In a rapidly evolving world where technology, philosophy, and personal growth intersect, the concepts of cognitive liberty and expanding consciousness have captured the attention of individuals seeking to explore the depths of their own minds. At the core of this exploration lies the quest for personal freedom, self-discovery, and a deeper understanding of the human experience. In this blog post, we’ll delve into these intriguing concepts without focusing on drug-related aspects, shedding light on the transformative journey towards mental sovereignty and ethical expansion.
**Cognitive Liberty: Claiming the Right to Our Minds**
Cognitive liberty stands as a beacon of individual sovereignty over our thoughts, beliefs, and cognitive processes. It’s about embracing the power to shape our own perspectives and pursue knowledge without constraint. This concept goes beyond legal or political rights; it encompasses the idea that our mental faculties are essential to our identity and should be protected from undue external influence.
As we discuss cognitive liberty in a broader context, it becomes clear that it encompasses more than substances. It encompasses the ability to explore diverse ideas, engage in critical thinking, and shape our perceptions independently.
**Expanding Consciousness: The Inner Odyssey**
At the heart of cognitive liberty is the pursuit of expanding consciousness. This journey, often embarked upon through practices like meditation, mindfulness, and introspection, is about transcending the confines of routine awareness. It’s an odyssey that allows us to venture into the depths of our own minds, exploring the realms of creativity, insight, and connection to a larger universe.
Expanding consciousness isn’t limited to chemical alterations; it’s a holistic experience that encompasses philosophical, spiritual, and psychological growth. It encourages us to explore the boundaries of our perception and embrace the mysteries that lie beyond.
**Ethical Philosophy: Navigating the Inner Landscape Responsibly**
As we tread the path of cognitive exploration and expanding consciousness, ethical considerations become paramount. Ethical philosophy guides us in discerning our responsibilities as explorers of the mind. How do we navigate our inner landscape with respect for ourselves and others? How do we approach personal growth without infringing upon the rights and well-being of those around us?
Ethical exploration involves balancing our innate curiosity with a profound respect for the boundaries and well-being of others. It’s about fostering a compassionate and informed approach that ensures our quest for enlightenment contributes positively to our own lives and the greater community.
**Final Thoughts: Embracing the Journey**
Cognitive liberty and expanding consciousness are two facets of the intricate tapestry that makes us human. By recognizing our right to explore our own minds and pursuing the expansion of our awareness in ethical and responsible ways, we embark on a transformative journey of self-discovery, connection, and personal growth. This journey isn’t limited to any one method; it’s a vast landscape of potential waiting to be explored, understood, and cherished.
As we venture forward, let us remember that cognitive liberty and expanded consciousness are not merely abstract concepts, but living, breathing philosophies that encourage us to embrace the boundless potential of the human mind.
Explore. Question. Evolve.
**Title: Exploring Cognitive Liberty and Expanding Human Consciousness**
**Introduction:**
In a world where the realms of thought, consciousness, and personal freedom converge, the concept of cognitive liberty takes center stage. This dynamic principle is not only about the freedom of choice; it’s about the sovereignty of the mind itself. Delving into the realm of consciousness exploration, ethical philosophy, and the mind-body connection can empower individuals to expand their human experience without being tethered to external constraints. In this blog post, we’ll journey through the corridors of cognitive liberty and consciousness expansion, uncovering the potential for personal growth, intellectual exploration, and the pursuit of higher states of awareness.
**Cognitive Liberty: Nurturing the Garden of Thought:**
Cognitive liberty goes beyond the conventional understanding of personal freedom. It’s the notion that our thoughts, beliefs, and experiences belong solely to us, and no external entity has the authority to dictate or regulate them. This principle, closely intertwined with ethical philosophy, urges us to safeguard our cognitive realm from undue interference. In a world where information and ideas flow ceaselessly, cognitive liberty offers the foundation for critical thinking, self-expression, and open dialogue.
**Consciousness Exploration: Beyond the Horizon of Awareness:**
At the heart of cognitive liberty lies the opportunity for consciousness exploration. This journey involves venturing into the depths of our own minds, seeking to understand the intricacies of our thoughts and the expanses of our awareness. Through practices like mindfulness, meditation, and contemplation, we can unlock new perspectives and discover hidden facets of our consciousness. This form of personal growth allows us to break free from the limitations of routine thinking and explore the vast landscape of our inner worlds.
**Mind-Body Connection: Bridging the Gap:**
The intricate relationship between our mind and body shapes our perceptions, experiences, and responses to the world around us. Understanding this connection provides a gateway to cognitive enhancement and expanded consciousness. By nurturing both mental and physical well-being, we create an environment where cognitive liberty flourishes. Practices such as yoga, breathwork, and holistic health approaches contribute to harmonizing the mind-body connection, enabling us to access new dimensions of awareness.
**Expanding Human Consciousness: The Uncharted Horizons:**
As we embrace cognitive liberty and delve into consciousness exploration, we embark on a journey to expand human consciousness. This is not a mere intellectual exercise; it’s a transformational endeavor that awakens us to the potential of heightened states of awareness. By integrating philosophy, science, and personal experience, we can transcend the boundaries of ordinary consciousness and glimpse the extraordinary. It’s an evolution that empowers us to embrace the full spectrum of human potential.
**Conclusion:**
Cognitive liberty stands as a beacon of intellectual autonomy, inviting us to explore the intricacies of consciousness and embrace our capacity for growth and expansion. By nurturing the mind-body connection and delving into ethical philosophy, we pave the way for greater cognitive awareness. As we journey through the landscapes of thought, we redefine personal freedom, creating a tapestry of consciousness that is uniquely our own. In the pursuit of cognitive liberty, we unlock the doors to uncharted realms of human consciousness, and in doing so, we find liberation in the vast expanses of our own minds.
Title: **”Unlocking the Mind: Navigating Cognitive Liberty and Expanding Consciousness”**
In a world where our understanding of consciousness and the human mind is constantly evolving, the concept of cognitive liberty has gained significance as a gateway to exploring the depths of our inner experiences. Delving into altered states of consciousness and personal growth, the pursuit of cognitive liberty has taken on ethical and philosophical dimensions that extend far beyond the realm of substances. In this blog post, we’ll journey through the realms of cognitive liberty, consciousness exploration, and the ethical considerations that guide our pursuit of mind freedom.
**Cognitive Liberty: Beyond Boundaries**
Cognitive liberty, often referred to as the right to control one’s own mental processes and experiences, is a fundamental concept that opens doors to personal growth and self-discovery. At its core, cognitive liberty acknowledges that each individual should have the autonomy to explore the reaches of their consciousness without undue constraints. This exploration goes beyond traditional understandings of freedom; it’s an exploration of our inner worlds and the realization that our minds are landscapes ripe for discovery.
**The Odyssey of Consciousness Exploration**
Consciousness exploration, a key facet of cognitive liberty, invites us to embark on an odyssey within ourselves. Through practices such as meditation, mindfulness, and introspection, we can unlock altered states of consciousness that illuminate new perspectives on reality. This journey doesn’t rely on external substances; rather, it’s a mindful navigation of our thoughts, emotions, and perceptions. It’s a quest to better understand the intricate web of our consciousness and the infinite potential it holds.
**Ethical Philosophy: Guiding Our Path**
As we tread the path of cognitive liberty, ethical philosophy serves as our compass. We’re confronted with questions that challenge us to consider the implications of our actions on both ourselves and society. How do we responsibly wield our freedom to explore our minds? How do we ensure that our pursuits don’t infringe upon the well-being of others? Ethical considerations shape our approach to cognitive liberty, emphasizing respect for ourselves, others, and the interconnectedness of our experiences.
**Expanding Horizons, Expanding Humanity**
Expanding human consciousness is a journey of expanding our horizons and, in turn, expanding our humanity. By embracing cognitive liberty and consciously exploring our inner landscapes, we contribute to the ever-evolving tapestry of human understanding. Our discoveries become threads woven into the fabric of shared knowledge, fostering empathy, connection, and a deeper appreciation for the diversity of human experience.
**Cognitive Rights for the Future**
In the pursuit of cognitive liberty, we’re paving the way for cognitive rights to be recognized and protected. Just as we cherish freedom of speech and expression, cognitive rights could emerge as a cornerstone of our evolving societal framework. By championing cognitive liberty, we’re advocating for the importance of personal growth, self-awareness, and the exploration of consciousness as integral components of the human experience.
In conclusion, cognitive liberty transcends conventional boundaries and offers us a profound invitation to explore the limitless dimensions of our minds. As we embark on this journey of consciousness exploration, guided by ethical considerations, we contribute to the ongoing evolution of human understanding and interconnectedness. Let us embrace cognitive liberty as a catalyst for personal growth, connection, and the expansion of our shared humanity.
**Title: Exploring Cognitive Liberty: Navigating the Frontiers of Human Consciousness**
In a rapidly evolving world, the exploration of cognitive liberty and the depths of human consciousness has taken center stage. As we journey towards greater self-awareness and understanding, a multitude of fascinating concepts come into play. Let’s delve into the captivating realm of cognitive liberty without focusing on drug-related aspects, and discover how it influences personal growth, ethical philosophy, and the expansion of our cognitive horizons.
**Consciousness Exploration for Personal Growth**
Consciousness, that enigmatic phenomenon that defines our awareness, offers a vast landscape for exploration. In the pursuit of personal growth, understanding the various dimensions of consciousness becomes a transformative endeavor. Exploring altered states of consciousness, not limited to substances, can lead to insights about the mind’s capabilities and the limitless potential for self-improvement.
**Cognitive Enhancement and the Mind-Body Connection**
Cognitive enhancement is an exciting avenue of study that transcends the boundaries of conventional thought. It encompasses practices that harness the mind’s innate abilities to optimize cognitive functions. The mind-body connection, a cornerstone of cognitive liberty, allows us to explore techniques such as meditation, mindfulness, and cognitive exercises to unlock new levels of mental clarity and focus.
**Ethical Philosophy and Cognitive Rights**
As cognitive liberty paves the way for uncharted territories, questions of ethics and personal freedom emerge. Ethical philosophy enters the discussion as we contemplate the boundaries of our cognitive experiences. The concept of cognitive rights gains prominence, advocating for individuals’ autonomy over their consciousness and mental states, irrespective of their chosen path of exploration.
**The Neuroethical Implications of Expanding Consciousness**
Neuroethics, a field at the intersection of neuroscience and ethics, plays a crucial role in the pursuit of cognitive liberty. It grapples with the implications of altering consciousness and advocates for responsible exploration. The discourse surrounding neuroethics challenges us to consider the potential impacts of our actions on both our individual well-being and society at large.
**Embracing Cognitive Liberty: A Journey of Discovery**
In conclusion, cognitive liberty offers a multidimensional journey that extends far beyond its perceived associations with substance-related exploration. It encompasses personal growth, ethical considerations, and the intersection of mind and body. By embracing the diversity of cognitive experiences available to us, we embark on a profound journey of self-discovery and a deeper understanding of the complexities of human consciousness.
As we navigate the uncharted waters of cognitive liberty, we’re invited to challenge existing paradigms, explore the unexplored, and champion our right to explore the full spectrum of human consciousness in an ethical and mindful manner.
Keywords: Cognitive liberty, Consciousness exploration, Mind freedom, Psychedelic research, Altered states of consciousness, Personal growth and consciousness, Cognitive enhancement, Ethical philosophy, Drug policy reform, Mental sovereignty, Psychedelic therapy, Mind-body connection, Neuroethics, Expanding human consciousness, Cognitive rights
Pfefferbaum, B., Nitiéma, P., & Newman, E.. (2019). A Meta-analysis of Intervention Effects on Depression and/or Anxiety in Youth Exposed to Political Violence or Natural Disasters. Child and Youth Care Forum
“Background: meta-analyses of youth mass trauma intervention studies have focused primarily on posttraumatic stress even though depression and anxiety are common maladaptive outcomes that require intervention. objective: this meta-analysis examined youth mass trauma intervention effects on depression and anxiety relative to natural recovery and characteristics of the event, context, population, intervention, and intervention delivery that may have moderated these effects. method: a literature search identified 21 studies investigating the effectiveness of 24 randomized controlled trials with inactive controls (21 trials examined depression and 8 examined anxiety; 5 examined both). intervention effects were computed as hedge’s g estimates and combined using random effects models. moderator analysis computed intervention effect sizes across selected covariates. results: the summary intervention effect was not significant for either depression or anxiety. there were statistically significant effects for depression with interventions delivered following a natural disaster (g = 0.40; p = 0.0192) or in a high income country (g = 0.30; p = 0.0253) and with non-trauma-focused interventions (g = 0.29; p = 0.0155) and those delivered in more than eight sessions (g = 0.23; p = 0.0416). the effect for anxiety symptoms was significant only with non-trauma-focused interventions (g = 0.83; p = 0.0428). conclusions: given the prevalence of depression and anxiety post event, greater attention is warranted to develop and maximize the benefit of interventions for these outcomes. the findings suggest that trauma-focused interventions may need to be augmented with specific components directed at depression and/or anxiety.”
Pfefferbaum, B., Noffsinger, M. A., & Wind, L. H.. (2012). Issues in the assessment of Children’s coping in the context of mass trauma. Prehospital and Disaster Medicine
Pfefferbaum, B., Nitiéma, P., & Newman, E.. (2021). A critical review of effective child mass trauma interventions: What we know and do not know from the evidence. Behavioral Sciences
“Over the last 20 years, numerous interventions have been developed and evaluated for use with children exposed to mass trauma with six publications reporting meta-analyses of randomized controlled trials of child mass trauma interventions using inactive controls to examine intervention effects on posttraumatic stress, depression, anxiety, and functional impairment. the current report reviews the results of these meta-analytic studies to examine the status of the evidence for child mass trauma mental health interventions and to evaluate potential moderators of intervention effect and implications for practice. the meta-analyses reviewed for the current report revealed a small to medium overall effect of interventions on posttraumatic stress, a non-statistically significant to small overall effect on depression, a non-statistically significant overall effect on anxiety, and a small overall effect on functional impairment. the subgroup analyses suggest that interventions should be matched to the populations being served and to the context. additional research is needed to tailor future interventions to further address outcomes other than posttraumatic stress including depression, anxiety, and functional impairment.”
Pfefferbaum, B., Nitiéma, P., & Newman, E.. (2020). The Effect of Interventions on Functional Impairment in Youth Exposed to Mass Trauma: a Meta-Analysis. Journal of Child and Adolescent Trauma
“This study examined the benefit of psychosocial interventions on functional impairment in youth exposed to mass trauma. a random effects meta-analysis was used to estimate the overall effect in 15 intervention trials identified through a literature review. the moderator analysis examined how the effect of intervention differed across types of populations receiving the intervention (targeted or non-targeted samples), characteristics of intervention delivery (individual or group application and number of sessions), and the context of intervention administration (country income level). the results revealed a significant small effect on functional impairment (hedges’ g = 0.33; 95%ci = (0.16; 0.50); p = 0.0011). none of the moderators explained the heterogeneity in intervention effect, perhaps due to the small number of trials. the effect of the interventions on functional impairment and on posttraumatic stress were positively correlated. the current analysis provides preliminary evidence that interventions can improve functioning in youth exposed to mass trauma, but the mechanisms, moderators, and duration of benefit are yet unknown.”
Pfefferbaum, B., Nitiéma, P., Newman, E., & Patel, A.. (2019). The Benefit of Interventions to Reduce Posttraumatic Stress in Youth Exposed to Mass Trauma: A Review and Meta-Analysis. Prehospital and Disaster Medicine
“Numerous interventions to address posttraumatic stress (pts) in youth exposed to mass trauma have been delivered and evaluated. it remains unclear, however, which interventions work for whom and under what conditions. this report describes a meta-analysis of the effect of youth mass-trauma interventions on pts to determine if interventions were superior to inactive controls and describes a moderator analysis to examine whether the type of event, population characteristics, or income level of the country where the intervention was delivered may have affected the observed effect sizes. a comprehensive literature search identified randomized controlled trials (rcts) of youth mass-trauma interventions relative to inactive controls. the search identified 2,232 references, of which 25 rcts examining 27 trials (n = 4,662 participants) were included in this meta-analysis. intervention effects were computed as hedge’s g estimates and combined using a random effects model. moderator analyses were conducted to explain the observed heterogeneity among effect sizes using the following independent variables: disaster type (political violence versus natural disaster); sample type (targeted versus non-targeted); and income level of the country where the intervention was delivered (high-versus middle-versus low-income). the correlation between the estimates of the intervention effects on pts and on functional impairment was estimated. the overall treatment effect size was converted into a number needed to treat (nnt) for a practical interpretation. the overall intervention effect was statistically significant (g = 0.57; p <.0001), indicating that interventions had a medium beneficial effect on pts. none of the hypothesized moderators explained the heterogeneity among the intervention effects. estimates of the intervention effects on pts and on functional impairment were positively correlated (spearman’s r = 0.90; p <.0001), indicating a concomitant improvement in both outcomes. these findings confirm that interventions can alleviate pts and enhance functioning in children exposed to mass trauma. this study extends prior research by demonstrating improvement in pts with interventions delivered to targeted and non-targeted populations, regardless of the country income level. intervention populations and available resources should be considered when interpreting the results of intervention studies to inform recommendations for practice.”
Tarvydas, V. M., Levers, L. L., & Teahen, P. R.. (2017). Ethical Guidelines for Mass Trauma and Complex Humanitarian Emergencies. Journal of Counseling and Development
“Issues pertaining to trauma, especially mass trauma and complex humanitarian emergencies, are explored through the lens of ethical counseling guidelines. in mass trauma, particular attention must be paid to the experiences of both survivors and counselors to enhance understanding of ethical best practices and to emphasize the importance of contextual factors in framing effective responses to trauma and humanitarian crises. recommendations regarding ethical guidelines for counseling practice, clinical involvement, and training are offered.”
Pfefferbaum, B., Tucker, P., Nitiéma, P., Van Horn, R. L., Varma, V., Varma, Y., … Newman, E.. (2022). Inconclusive Findings in Studies of the Link Between Media Coverage of Mass Trauma and Depression in Children. Current Psychiatry Reports
“Purpose of review: this paper reports a review of the empirical research examining the association between mass trauma media contact and depression in children, the factors that may influence the association, and the difficulties encountered in the study of media effects on depression. recent findings: all of the included studies assessed general population samples. pre-covid-19 research focused primarily on television coverage alone or on multiple media forms including television, while covid-19 media studies examined various media forms including social media. most studies used cross-sectional design and non-probability sampling. the review revealed inconclusive findings across studies. summary: the study of mass trauma media effects on depression in children is complicated by a number of potential confounding factors and by the relatively high prevalence of depression in the general population. media contact was a relatively minor consideration among other interests in the extant studies which failed to explore numerous issues that warrant attention in future research.”
Meffert, S., & Ekblad, S.. (2013). Global mental health intervention research and mass trauma. Open Access Journal of Clinical Trials
Hobfoll, S. E., Watson, P., Bell, C. C., Bryant, R. A., Brymer, M. J., Friedman, M. J., … Ursano, R. J.. (2007). Five essential elements of immediate and mid-term mass trauma intervention: Empirical evidence. Psychiatry
“Given the devastation caused by disasters and mass violence, it is critical that intervention policy be based on the most updated research findings. however, to date, no evidence-based consensus has been reached supporting a clear set of recommendations for intervention during the immediate and the mid-term post mass trauma phases. because it is unlikely that there will be evidence in the near or mid-term future from clinical trials that cover the diversity of disaster and mass violence circumstances, we assembled a worldwide panel of experts on the study and treatment of those exposed to disaster and mass violence to extrapolate from related fields of research, and to gain consensus on intervention principles. we identified five empirically supported intervention principles that should be used to guide and inform intervention and prevention efforts at the early to mid-term stages. these are promoting: 1) a sense of safety, 2) calming, 3) a sense of self- and community efficacy, 4) connectedness, and 5) hope.”
Husain, M. I., Umer, M., Chaudhry, I. B., Husain, M. O., Rahman, R., Shakoor, S., … Husain, N.. (2021). Relationship between childhood trauma, personality, social support and depression in women attending general medical clinics in a low and middle-income country. Journal of Affective Disorders
“Background: associations between childhood trauma, personality, and major depressive disorder (mdd) have been well established in studies conducted in high-income countries. however, there are limited studies on these associations in low and middle-income countries (lmics), where mdd is highly prevalent. we assessed the relationships between childhood trauma, personality, and mdd in women in karachi, pakistan. method: in this cross-sectional study of 455 female patients attending general medical outpatient clinics, a diagnosis of mdd was confirmed using the structured clinical interview for dsm-iv (scid); retrospective reports of childhood trauma were collected using the childhood trauma questionnaire (ctq); and big five personality traits were assessed using the neo personality inventory revised (neo pi-r). other measures included the life events questionnaire (leq) and the multidimensional scale of perceived social support (mspss). factors independently associated with mdd were determined using logistic regression analyses. results: of the 455 women recruited between august 1, 2011 and july 31, 2013, 242 (53%) had a diagnosis of mdd. women with mdd were significantly more likely to be separated, had more stressful life events and higher ctq scores. higher perceived social support, conscientiousness and extraversion were independently associated with significantly reduced odds of mdd. there were no significant associations between ctq scores and any of the neo pi-r subscales. limitations: ratings of childhood trauma were based on retrospective recall. conclusion: mdd and a history of childhood trauma were highly prevalent in pakistani women attending general medical clinics. interventions to prevent childhood trauma and promote social support in women may improve public mental health in lmics like pakistan.”
Fuchshuber, J., & Unterrainer, H. F.. (2020). Childhood Trauma, Personality, and Substance Use Disorder: The Development of a Neuropsychoanalytic Addiction Model. Frontiers in Psychiatry
“Background: while traditional psychoanalysis has been criticized as insufficient for the treatment of substance use disorder (sud), recent progress in the field of neuropsychoanalysis has generated new and promising hypotheses regarding its etiology. however, empirical research applying this framework has been sparse. aim and scope: the present overview aims at developing and empirically validating a neuroscientifically informed psychodynamic framework regarding the etiology of sud. for this purpose, this review provides a concise overview of the most relevant historical and contemporary psychoanalytic theories on sud etiology. furthermore, the original research summarized in this paper consists of three studies investigating connections between childhood trauma, primary emotions, personality structure and attachment, as well as their relation to sud development and treatment. conclusions: the results highlight the empirical validity of the neuropsychoanalytic approach towards sud etiology. in particular, the findings underscore the conceptualization of sud as a disorder related to dysfunctional attachment and affect regulation abilities especially linked to increased sadness and anger dispositions, which mediated the relationship between sud and traumatic childhood relationships. based on these findings, a refined model of sud etiology is proposed, which should be tested in future studies.”
Stevanović, A., Frančišković, T., & Vermetten, E.. (2016). Relationship of early-life trauma, war-related trauma, personality traits, and PTSD symptom severity: A retrospective study on female civilian victims of war. European Journal of Psychotraumatology
“Background: consequences of war-related traumatisation have mostly been investigated in military and predominant male populations, while research on female civilian victims of war has been neglected. furthermore, research of post-war posttraumatic stress disorder (ptsd) inwomen has rarely included early-life trauma in their prediction models, so the contribution of trauma in childhood and early youth is still unexplored. objective: to examine the relationship of early-life trauma, war-related trauma, personality traits, and symptoms of posttraumatic stress among female civilian victims of the recent war in croatia. method: the cross-sectional study included 394 participants, 293 war-traumatised adult women civilians, and 101 women without war-related trauma. participants were recruited using the snowball sampling method. the applied instruments included the clinician-administrated ptsd scale (caps), the neo personality inventory-revised (neo-pi-r), thewar stressors assessment questionnaire (wsaq), and the early trauma inventory self report-short form (etisr-sf). a hierarchical multiple regression analysis was performed to assess the prediction model of ptsd symptom severity measured by caps score for current ptsd. results: the prevalence of current ptsd (caps cut-off score[1]65) in this cohort was 20.7%. the regression model that included age, early-life trauma, war-related trauma, neuroticism, and extraversion as statistically significant predictors explained 45.8% of variance in ptsd symptoms. conclusions: older age, exposure to early-life trauma, exposure to war-related traumatic events, high neuroticism, and low extraversion are independent factors associated with higher level of ptsd symptoms among women civilian victims of war.”
Yalch, M. M., Stewart, A. M., & Dehart, R. M.. (2021). Influence of Betrayal Trauma on Antisocial Personality Disorder Traits. Journal of Trauma and Dissociation
“Antisocial personality disorder (aspd) is linked to a number of social problems and accordingly is the focus of intensive empirical study. there is reason to believe that aspd is influenced at least in part by exposure to trauma, but there has been minimal research on the association between trauma and aspd traits. specifically, research has not examined how traumatic experiences with different degrees of interpersonal betrayal differentially influence aspd traits. this is notable in light of recent studies indicating that exposure to traumatic experiences high in betrayal (i.e., high betrayal trauma) is the primary predictor of borderline and narcissistic personality pathology. in this study, we examined the relative associations between high, medium, and low betrayal trauma and aspd traits in a sample recruited from amazon’s mechanical turk (n = 363) using structural equation modeling. results confirmed a strong association between trauma and aspd traits in general, although the influence of specific forms of trauma differed depending on both sex and how trauma was calculated (i.e., in terms of severity vs. exposure). in general, high betrayal trauma was the most consistent predictor of aspd traits for men, whereas medium and low betrayal traumas were more consistently associated with aspd traits for women. study findings extend research on betrayal trauma to more malevolent forms of personality pathology. sex differences in the influence of trauma across aspd traits suggest the possibility of sex-specific personality responses to trauma high in betrayal, a topic that can be addressed in the future research.”
Paris, J.. (1998). Does childhood trauma cause personality disorders in adults?. Canadian Journal of Psychiatry
“Objective: to examine the relationship between trauma in childhood and personality disorders in adulthood. method: a review of the literature was conducted. results: the reported associations between trauma and personality pathology are illuminated by the following research findings: 1) personality is heritable; 2) only a minority of patients with severe personality disorders report childhood trauma; and 3) children are generally resilient, and traumatic experiences do not consistently lead to psychopathology. conclusions: the role of trauma in the personality disorders is best understood in the context of gene-environment interactions.”
Bahari, A., Hasani, J., & Mashhadi Akbar Boojar, M.. (2021). Childhood trauma and type D personality: The endocrine and cardiovascular effects on stress reactivity. Journal of Health Psychology
“Both exaggerated and blunted cardiovascular stress reactions are associated with health problems. moreover, early life experiences and personality traits affect stress responses. regarding the childhood traumas and type d personality, this study aimed to compare the endocrine and cardiovascular reactions against acute laboratory stress. results showed that the simultaneous existence of childhood traumatic experiences and type d personality leads to exaggerated stress reactivity, while each factor results in a blunted cardiovascular response. although the cardiovascular responses are dampened in type d personality people, their endocrine reactions are exaggerated. the underlying mechanisms of blunted cardiovascular reactivity differ between childhood trauma and type d personality groups.”
Rutkowski, K., Dembińska, E., & Walczewska, J.. (2016). Effect of trauma onset on personality traits of politically persecuted victims. BMC Psychiatry
“Background: the hypothesis that traumatic experiences in early childhood impact personality formation and psychopathology is well known in psychology and psychiatry, but this is difficult to verify statistically in methodological terms. the aim of this study, conducted with politically persecuted poles, was to establish the influence of the time when trauma is experienced on the development of psychopathological symptoms. methods: the subjects were divided into two groups: those who had experienced trauma before age five (group 1) and those who experienced trauma at an older age (group 2). subjects in both groups suffered from chronic untreated post-traumatic stress disorder. in order to test the research hypothesis, the minnesota multiphasic personality inventory-2 profiles of both groups were compared using student’s t-test, and the mann-whitney u-test. results: statistically significant between-group differences were found for the f validity scale and the following clinical scales: hypochondriasis, depression, psychopathic deviate, psychasthenia, schizophrenia, and social introversion. all the significantly different scores were higher in the group traumatized in early childhood. people exposed to trauma under age five had profiles similar to those traumatized after age five, but they experienced their symptoms more intensely. conclusions: of clinical significance, higher scores on the psychasthenia, schizophrenia, and social introversion scales, especially on the psychopathic deviate scale, indicated pathology only in the early childhood trauma group. taken together, these symptoms lead to withdrawal and hindrance of social functioning. this outcome confirms the hypothesis of the influence of various early childhood factors (such as trauma) on personality formation and personality traits in adulthood.”
Sansone, R. A., & Sansone, L. A.. (2007). Childhood trauma, borderline personality, and eating disorders: A development cascade. Eating Disorders
“In this article, we discuss the nature and role of trauma in relationship to borderline personality disorder and eating disorders. as is clinically evident, trauma can result in a variety of psychological consequences. these consequences include both axis i and ii disorders. among the axis ii disorders, trauma appears to heighten the risk for the development of borderline, antisocial, avoidant, paranoid, and even schizotypal personality disorders. likewise, trauma may heighten the risk for developing an eating disorder. there appear to be complex inter-relationships among trauma, borderline personality disorder, and eating disorders. in this article, we attempt to summarize these inter-relationships.”
Green, K., & Browne, K.. (2020). Personality Disorder Traits, Trauma, and Risk in Perpetrators of Domestic Violence. International Journal of Offender Therapy and Comparative Criminology
“Crimes committed against partners and family members have devastating effects on victims. unfortunately, recidivism rates for offenders are high, and there is a need to establish risk factors that may be potential treatment targets. this study aimed to investigate childhood maltreatment, symptoms of trauma, and personality disorder (pd) traits in males convicted of domestic violence (dv) offences. data were extracted from the files of 40 males under the supervision of the probation service in the united kingdom. actual return to custody was recorded after a minimum follow-up of 6 months. self-reported childhood maltreatment was associated with increases in pd traits, posttraumatic symptoms, and assessed risk. however, maltreatment did not predict return to custody. tension-reducing behaviours and depressive symptoms predicted return to custody as did antisocial pd. these preliminary findings highlight important areas of future research, in particular, factors which may be relevant treatment targets in reducing the risk of recidivism.”
Li, Y., Lv, Q., Li, B., Luo, D., Sun, X., & Xu, J.. (2020). The role of trauma experiences, personality traits, and genotype in maintaining posttraumatic stress disorder symptoms among child survivors of the Wenchuan earthquake. BMC Psychiatry
“Background: posttraumatic stress disorder (ptsd) is the most prevalent type of psychiatric disorder among children after an earthquake. this study investigated the role of trauma experiences, personality traits, and genotype in the maintenance of ptsd symptoms. methods: in a previous large-scale epidemiological investigation 1 year after the wenchuan earthquake, 215 children with ptsd symptoms were selected at random with their blood samples collected. all of them were followed up, and their ptsd symptoms were assessed 3 years later. the adolescent version of the ucla ptsd reaction index, the earthquake exposure scale, and the junior eysenck personality questionnaire were used to determine ptsd symptoms, trauma experiences, and personality traits, respectively. we sequenced candidate genes involved in the regulation of long-term potentiation via nmda-type receptors to identify the related snp variations. results: being trapped for a longer period of time, feeling one’s own or a family member’s life to be in danger, losing a close family member or friend, extraversion, neuroticism, trkb, g72 and cntf were found to be associated with the maintenance of ptsd symptoms. conclusions: experiences, personality traits, and genotype influenced the maintenance of ptsd in child survivors who were considered to be followed up without medicine. this result could help to identify potential targets for treatment and promote the rational allocation of medical resources.”
Back, S. N., Flechsenhar, A., Bertsch, K., & Zettl, M.. (2021). Childhood Traumatic Experiences and Dimensional Models of Personality Disorder in DSM-5 and ICD-11: Opportunities and Challenges. Current Psychiatry Reports
“Purpose of review: childhood trauma is an important risk factor for the development of personality disorders (pds), yet most research has been devoted to categorical models of personality pathology. considering the introduction of a dimensional pd model with icd-11, we review current findings related to various forms of childhood trauma, and pds, operationalized in the form of personality functioning and maladaptive traits. we focus on the magnitude of associations and examine specific relationships between emotional and physical trauma with areas of personality functioning and single traits. recent findings: two studies showed a strong association between childhood trauma and personality dysfunction. seven studies, including clinical and forensic samples, demonstrated heterogeneous associations between various forms of childhood trauma and maladaptive traits. overall, four studies indicated a slightly stronger association between personality dysfunction, maladaptive trait expression, and higher levels of emotional trauma than for physical or sexual trauma. regarding specific trait domains and childhood trauma, most studies yielded the strongest associations for either psychoticism or detachment. summary: research on childhood trauma and dimensional pd models (i.e., personality functioning and traits) has the potential to contribute to a better understanding of their complex relationship. however, high intercorrelations among different types of childhood trauma, areas of personality functioning, and trait domains increase the difficulty of disentangling single effects. more research is needed including clinical and non-western samples, especially considering the upcoming icd-11 classification.”
Sheehan, A. E., Bounoua, N., Miglin, R., Spielberg, J. M., & Sadeh, N.. (2021). A multilevel examination of lifetime aggression: Integrating cortical thickness, personality pathology and trauma exposure. Social Cognitive and Affective Neuroscience
“Aggression represents a significant public health concern, causing serious physical and psychological harm. although many studies have sought to characterize the etiology of aggression, research on the contributions of risk factors that span multiple levels of analysis for explaining aggressive behavior is lacking. to address this gap, we investigated the direct and unique contributions of cortical thickness (level 1), pathological personality traits (level 2) and trauma exposure (level 3) for explaining lifetime physical aggression in a high-risk sample of community adults (n = 129, 47.3% men). first, the frequency of lifetime aggression was inversely associated with cortical thickness in regions of prefrontal and temporal cortices that have been implicated in executive functioning, inhibitory mechanisms and socio-emotional processing. further, aggression was positively associated with pathological personality traits (antagonism and disinhibition) and exposure to assaultive trauma. notably, all three levels of analysis (cortical thickness, pathological personality traits and assaultive trauma exposure) explained non-overlapping variance in aggressive behavior when examined simultaneously in integrative models. together, the findings provide a multilevel assessment of the biopsychosocial factors associated with the frequency of aggression. they also indicate that cortical thickness explains novel variance in these harmful behaviors not captured by well-established personality and environmental risk factors for aggression.”
Watkeys, O. J., Kremerskothen, K., Quidé, Y., Fullerton, J. M., & Green, M. J.. (2018). Glucocorticoid receptor gene (NR3C1) DNA methylation in association with trauma, psychopathology, transcript expression, or genotypic variation: A systematic review. Neuroscience and Biobehavioral Reviews
“The glucocorticoid receptor gene (nr3c1) is a critical component of the stress response system. cytosine methylation of nr3c1 has been repeatedly associated with trauma and mental disorders, including major depression, post-traumatic stress disorder, anxiety, and personality disorders, suggesting that nr3c1 methylation may play a role in stress-related psychopathology. we systematically reviewed 55 studies examining nr3c1 dna methylation in association with trauma exposure, psychopathology, gene expression, and/or common genetic variants. overall, a number of nr3c1 cpg sites were significantly associated with trauma or psychopathology, but significant findings were often inconsistent across studies. this lack of consistency is likely influenced by significant methodological variability – experimentally and analytically – across studies. selected common genetic variants show no significant effect on nr3c1 cpg methylation. in contrast, there was ample evidence linking increased methylation of nr3c1 to reduced expression of this gene. the inverse association between methylation and gene expression shown across eight out of ten studies supports the notion that methylation in the promoter region of nr3c1 is associated with transcriptional silencing.”
Light, A. E., Holt-Lunstad, J., Porter, C. L., & Light, K. C.. (2019). Early life trauma: An exploratory study of effects on OXTR and NR3C1 gene expression and nurturing self-efficacy in mothers of infants. International Journal of Psychophysiology
“Background: in animals, adverse early experience alters oxytocinergic and glucocorticoid activity and maternal behavior in adulthood. this preliminary study explored associations among childhood trauma (loss of a parent or sexual abuse in childhood), maternal self-efficacy, and leukocyte gene expression (mrna) of oxytocin and glucocorticoid receptors (oxtr and nr3c1) in mothers of infants. methods: 62 mothers (20 with early life trauma) with healthy 3-month old infants reported maternal self-efficacy, depression, infant temperament, and overall social support; the effects of early trauma on these measures were assessed. of these, 35 mothers (14 with early trauma) underwent blood draws after 2 infant feeding times; their oxtr and nr3c1 mrna was compared to a control group of 25 no-infant women without early trauma, and also was examined for associations with self-efficacy. results: oxtr mrna was increased in mothers of infants versus no-infant controls (p < 0.0003), and mothers with greatest prior maternal experience had higher oxtr than those with less experience (0–2 vs. 3+ older children, p < 0.033). mothers with early trauma and less maternal experience had lower oxtr mrna than no-trauma mothers (p < 0.029) and lower nr3c1 mrna than controls (p < 0.004). mothers with depression also had lower nr3c1 than other mothers (p < 0.003) but did not differ in oxtr. mothers with early trauma also reported their support network to be less helpful and more upsetting and unpredictable than other mothers (p < 0.035–p < 0.005). regarding maternal behavior, in mothers with early trauma, helpful support networks increased self-reported nurturing self-efficacy when babies were not fussy but decreased it with fussy babies (p < 0.05). support was unrelated to self-efficacy in no-trauma mothers. similarly, among mothers with low oxtr or nr3c1 (−1sd, most having early trauma and lower maternal experience), greater support was associated with lower self-efficacy (p < 0.05), while mothers with high oxtr or nr3c1 (+1sd) tended to have higher self-efficacy with greater support. conclusions: these preliminary findings need confirmation in a larger sample but suggest that childhood trauma influences maternal behavior and both oxtr and nr3c1 pathways in mothers of infants, and that both depression and prior maternal experience may be other important factors. effects on maternal behavior appear to require more complex modeling.”
de Assis Pinheiro, J., Freitas, F. V., Borçoi, A. R., Mendes, S. O., Conti, C. L., Arpini, J. K., … Alvares-da-Silva, A. M.. (2021). Alcohol consumption, depression, overweight and cortisol levels as determining factors for NR3C1 gene methylation. Scientific Reports
“The nr3c1 glucocorticoid receptor (gr) gene is a component of the stress response system, which can be regulated by epigenetic mechanisms. nr3c1 methylation has been associated with trauma and mental issues, including depression, post-traumatic stress, anxiety, and personality disorders. previous studies have reported that stressful events are involved in nr3c1 gene methylation, suggesting that its regulation under environmental effects is complex. the present study aimed to analyze associations involving stressors such as socioeconomic status, health conditions, and lifestyle in relation to nr3c1 methylation in adults. this study included 386 individual users of the brazilian public unified health system (sus), and evaluated socioeconomic and health conditions, body mass index, cortisol levels, and lifestyle. data were correlated with nr3c1 methylation, determined using dna pyrosequencing. the results showed that alcohol consumption, overweight, and high cortisol levels were related to nr3c1 demethylation, while depression was related to its methylation. habits, lifestyle, and health status may influence nr3c1 gene regulation via methylation, revealing the complexity of environmental impacts on nr3c1 methylation.”
Çetin, Ş., Sözeri-Varma, G., Çetin, G. O., Türel, S., Uğurlu, T. T., & Özdel, O.. (2022). The Relationship Between Methylation of the Glucocorticoid Receptor Gene (NR3C1) and Childhood Trauma and Alexithymia. Israel Journal of Psychiatry
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“Background: childhood traumas affect the hypothalamo-pituitary-adrenal (hpa) axis functions, and therefore emotional regulation response to stress. glucocorticoid receptor (gr) gene nr3c1 plays a key role in hpa axis. the aim of the study was to investigate the relationship between methylation of nr3c1 gene with childhood trauma and alexithymia in somatic symptom disorder (ssd) and major depressive disorder (mdd). methods: a total of 48 patients with ssd, 50 patients with mdd and 50 healthy controls were included in the study. mongomery-asberg depression rating scale (madrs), toronto alexithymia scale (tas-20), and the childhood trauma questionnaire (ctq) were applied to the participants. methylation levels of the nr3c1 gene were determined quantitatively in dna blood samples. results: tas-20 and ctq total scores were found to be the highest in patients with ssd. ctq scores were observed to be higher in ssd and mdd compared with the control group. nr3c1 gene methylation levels were found to be lowest in ssd and highest in mdd. there was no correlation between scores of tas-20 and nr3c1 methylation. high alexithymia level was predictive for ssd (or: 1.237, 95% ci: 1.018-1.504). high methylation levels increase the risk of mdd (or: 7.449, 95% ci: 3.702-14.986), decrease the risk of ssd (or: 0.00006 95% ci: 0.000-0.038). conclusion: our results show that emotion processing processes and gr methylation are different in both disorders. childhood trauma may be related to epigenetic changes in the gr gene. the type of epigenetic changes may result in vulnerability to different psychiatric disorders.”
Alexander, N., Kirschbaum, C., Wankerl, M., Stauch, B. J., Stalder, T., Steudte-Schmiedgen, S., … Miller, R.. (2018). Glucocorticoid receptor gene methylation moderates the association of childhood trauma and cortisol stress reactivity. Psychoneuroendocrinology
“Exposure to childhood trauma (ct) has been linked to sustained dysregulations of major stress response systems, including findings of both exaggerated and attenuated hypothalamus–pituitary–adrenal (hpa) axis activity. likewise, ct constitutes a common risk factor for a broad range of psychiatric conditions that involve distinct neuroendocrine profiles. in this study, we investigated the role of epigenetic variability in a stress-related gene as a potential mediator or moderator of such differential trajectories in ct survivors. for this, we screened adult volunteers for ct and recruited a healthy sample of 98 exposed (67 with mild-moderate, 31 with moderate-severe exposure) and 102 control individuals, with an equal number of males and females in each group. dna methylation (dnam) levels of the glucocorticoid receptor exon 1f promoter (nr3c1-1f) at functionally relevant sites were analyzed via bisulfite pyrosequencing from whole blood samples. participants were exposed to a laboratory stressor (trier social stress test) to assess salivary cortisol stress responses. the major finding of this study indicates that dnam in a biologically relevant region of nr3c1-1f moderates the specific direction of hpa-axis dysregulation (hypo- vs. hyperreactivity) in adults exposed to moderate-severe ct. those trauma survivors with increased nr3c1-1f dnam displayed, on average, 10.4 nmol/l (62.3%) higher peak cortisol levels in response to the tsst compared to those with low dnam. in contrast, unexposed and mildly-moderately exposed individuals displayed moderately sized cortisol stress responses irrespective of nr3c1-1f dnam. contrary to some prior work, however, our data provides no evidence for a direct association of ct and nr3c1-1f dnam status. according to this study, epigenetic changes of nr3c1-1f may provide a more in-depth understanding of the highly variable neuroendocrine and pathological sequelae of ct.”
Vangeel, E. B., Kempke, S., Bakusic, J., Godderis, L., Luyten, P., Van Heddegem, L., … Claes, S.. (2018). Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients. Journal of Psychosomatic Research
“Objective although the precise mechanisms are not yet understood, previous studies have suggested that chronic fatigue syndrome (cfs) is associated with hypothalamic-pituitary-adrenal (hpa) axis dysregulation and trauma in early childhood. consistent with findings suggesting that early life stress-induced dna methylation changes may underlie dysregulation of the hpa axis, we previously found evidence for the involvement of glucocorticoid receptor (gr) gene (nr3c1) methylation in whole blood of cfs patients. methods in the current study, we assessed nr3c1-1f region dna methylation status in peripheral blood from a new and independent sample of 80 female cfs patients and 91 female controls. in cfs patients, history of childhood trauma subtypes was evaluated using the childhood trauma questionnaire short form (ctq-sf). results although absolute methylation differences were small, the present study confirms our previous findings of nr3c1-1f dna hypomethylation at several cpg sites in cfs patients as compared to controls. following multiple testing correction, only cpg_8 remained significant (dna methylation difference: 1.3% versus 1.5%, p < 0.001). in addition, we found associations between dna methylation and severity of fatigue as well as with childhood emotional abuse in cfs patients, although these findings were not significant after correction for multiple testing. conclusions in conclusion, we replicated findings of nr3c1-1f dna hypomethylation in cfs patients versus controls. our results support the hypothesis of hpa axis dysregulation and enhanced gr sensitivity in cfs.”
Martín-Blanco, A., Ferrer, M., Soler, J., Salazar, J., Vega, D., Andión, O., … Pascual, J. C.. (2014). Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder. Journal of Psychiatric Research
Perroud, N., Dayer, A., Piguet, C., Nallet, A., Favre, S., Malafosse, A., & Aubry, J. M.. (2014). Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder. British Journal of Psychiatry
“Background early-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. this may be the consequence of a sustained alteration of the hypothalamic-pituitary-adrenal (hpa) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor (nr3c1). aims to investigate whether severity of childhood maltreatment isassociated with increased methylation of the exon 1f nr3c1 promoter in bipolar disorder. method a sample of people with bipolar disorder (n = 99) were assessed for childhood traumatic experiences. the percentage of nr3c1 methylation was measured for each participant.results the higher the number of trauma events, the higher was the percentage of nr3c1 methylation (β = 0.52, 95% ci 0.46-0.59, p”0.0001). the severity of each type of maltreatment (sexual, physical and emotional) was also associated with nr3c1 methylation status. conclusionsearly-life adversities have a sustained effect on the hpa axis through epigenetic processes and this effect may be measured in peripheral blood. this enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder. declaration of interest none.”
Straight, B., Fisher, G., Needham, B. L., Naugle, A., Olungah, C., Wanitjirattikal, P., … Lalancette, C.. (2021). Lifetime stress and war exposure timing may predict methylation changes at NR3C1 based on a pilot study in a warrior cohort in a small-scale society in Kenya. American Journal of Human Biology
“Objectives: candidate gene methylation studies of nr3c1 have identified associations with psychosocial adversity, including war trauma. this pilot study (sample sizes from 22 to 45 for primary analyses) examined nr3c1 methylation in a group of kenyan pastoralist young men in relation to culturally relevant traumatic experiences, including participation in coalitional lethal gun violence. methods: adolescent and young adult samburu men (‘warriors’) were recruited for participation. dna was obtained from whole saliva and methylation analyses performed using mass spectrometry. we performed a data reduction of variables from a standardized instrument of lifetime stress using a factor analysis and we assessed the association between the extracted factors with culturally relevant and cross-culturally comparative experiences. results: cumulative lifetime trauma exposure and forms of violence to which warriors are particularly susceptible were associated with dna methylation changes in the nr3c1 1f promoter region but not in the nr3c1 1d promoter region. however, sensitivity analyses revealed significant associations between individual cpg sites in both regions and cumulative stress exposures, war exposure timing, and war fatalities. conclusions: this study supports the importance of nr3c1 methylation changes in response to challenging life circumstances, including in a global south cultural context that contrasts in notable ways from global north contexts and from the starkly tragic examples of the rwandan genocide and war-associated rape explored in recent studies. timing of traumatic exposure and culturally salient means to measure enduring symptoms of trauma remain important considerations for dna methylation studies.”
Malhi, G. S., Das, P., Outhred, T., Dobson-Stone, C., Irwin, L., Gessler, D., … Mannie, Z.. (2019). Effect of stress gene-by-environment interactions on hippocampal volumes and cortisol secretion in adolescent girls. Australian and New Zealand Journal of Psychiatry
“Objective: adolescence is a time of increased susceptibility to environmental stress and mood disorders, and girls are particularly at risk. genes interacting with the environment (g × e) are implicated in hypothalamic-pituitary-adrenal axis dysregulation, hippocampal volume changes and risk or resilience to mood disorders. in this study, we assessed the effects of stress system g × e interactions on hippocampal volumes and cortisol secretion in adolescent girls. methods: we recruited 229 girls aged 12–18 years, and scans were obtained from 202 girls. of these, 76 had been exposed to higher emotional trauma (abuse or neglect). hippocampal volumes were measured using freesurfer and high-resolution structural magnetic resonance imaging scans. saliva samples were collected for measurement of cortisol levels and genotyping of stress system genes: fkbp5, nr3c1 (both n = 194) and nr3c2 (n = 193). results: among girls with the ‘g’ allelic variant of the nr3c1 gene, those who had been exposed to higher emotional trauma had significantly smaller left hippocampal volumes (n = 44; mean = 4069.58 mm 3 , standard deviation = 376.99) than girls who had been exposed to minimal emotional trauma with the same allelic variant (n = 69; mean = 4222.34 mm 3 , standard deviation = 366.74). conclusion: in healthy adolescents, interactions between emotional trauma and the ‘protective’ nr3c1 ‘gg’ variant seem to induce reductions in left hippocampal volumes. these g × e interactions suggest that vulnerability to mood disorders is perhaps driven by reduced ‘protection’ that may be specific to emotional trauma. this novel but preliminary evidence has implications for targeted prevention of mood disorders and prospective multimodal neuroimaging and longitudinal studies are now needed to investigate this possibility.”
Smart, C., Strathdee, G., Watson, S., Murgatroyd, C., & McAllister-Williams, R. H.. (2015). Early life trauma, depression and the glucocorticoid receptor gene-an epigenetic perspective. Psychological Medicine
“Hopes to identify genetic susceptibility loci accounting for the heritability seen in unipolar depression have not been fully realized. family history remains the ‘gold standard’ for both risk stratification and prognosis in complex phenotypes such as depression. meanwhile, the physiological mechanisms underlying life-event triggers for depression remain opaque. epigenetics, comprising heritable changes in gene expression other than alterations of the nucleotide sequence, may offer a way to deepen our understanding of the aetiology and pathophysiology of unipolar depression and optimize treatments. a heuristic target for exploring the relevance of epigenetic changes in unipolar depression is the hypothalamic-pituitary-adrenal (hpa) axis. the glucocorticoid receptor (gr) gene (nr3c1) has been found to be susceptible to epigenetic modification, specifically dna methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life. method. in this paper we discuss the progress that has been made by studies that have investigated the relationship between depression, early trauma, the hpa axis and the nr3c1 gene. difficulties with the design of these studies are also explored. results. future efforts will need to comprehensively address epigenetic natural histories at the population, tissue, cell and gene levels. the complex interactions between the epigenome, genome and environment, as well as ongoing nosological difficulties, also pose significant challenges. conclusions. the work that has been done so far is nevertheless encouraging and suggests potential mechanistic and biomarker roles for differential dna methylation patterns in nr3c1 as well as novel therapeutic targets.”
Qi, R., Luo, Y., Zhang, L., Weng, Y., Surento, W., Xu, Q., … Thompson, P. M.. (2021). Decreased functional connectivity of hippocampal subregions and methylation of the NR3C1 gene in Han Chinese adults who lost their only child. Psychological Medicine
“Background losing one’s only child is a major traumatic life event that may lead to post-traumatic stress disorder (ptsd); however, the underlying mechanisms of its psychological consequences remain poorly understood. here, we investigated subregional hippocampal functional connectivity (fc) networks based on resting-state functional magnetic resonance imaging and the deoxyribonucleic acid methylation of the human glucocorticoid receptor gene (nr3c1) in adults who had lost their only child. methods a total of 144 han chinese adults who had lost their only child (51 adults with ptsd and 93 non-ptsd adults [trauma-exposed controls]) and 50 controls without trauma exposure were included in this fmri study (age: 40-67 years). fcs between hippocampal subdivisions (four regions in each hemisphere: cornu ammonis1 [ca1], ca2, ca3, and dentate gyrus [dg]) and methylation levels of the nr3c1 gene were compared among the three groups. results trauma-exposed adults, regardless of ptsd diagnosis, had weaker positive fc between the left hippocampal ca1, left dg, and the posterior cingulate cortex, and weaker negative fc between the right ca1, right dg, and several frontal gyri, relative to healthy controls. compared to non-ptsd adults, ptsd adults showed decreased negative fc between the right ca1 region and the right middle/inferior frontal gyri (mfg/ifg), and decreased negative fc between the right dg and the right superior frontal gyrus and left mfg. both trauma-exposed groups showed lower methylation levels of the nr3c1 gene. conclusions adults who had lost their only child may experience disrupted hippocampal network connectivity and nr3c1 methylation status, regardless of whether they have developed ptsd.”
Schür, R. R., van Leeuwen, J. M. C., Houtepen, L. C., Joëls, M., Kahn, R. S., Boks, M. P., & Vinkers, C. H.. (2018). Glucocorticoid receptor exon 1 F methylation and the cortisol stress response in health and disease. Psychoneuroendocrinology
“Childhood trauma has been proposed to increase vulnerability to develop psychopathology in part through an altered cortisol stress response. research in rats has suggested that this effect is mediated by methylation in the glucocorticoid receptor 1 7 region (gr-1 7 or gr-1 f in humans), with higher methylation after poor maternal care leading to an increased cortisol stress response in adulthood. in humans, the associations between childhood trauma and gr-1 f methylation or the cortisol stress response are equivocal. remarkably, evidence for the relation between gr-1 f methylation and the cortisol stress response has been conflicting as well. to further explore this, we investigated the associations of peripheral gr-1 f methylation (52 cpgs) with the cortisol stress response (trier social stress test) and with childhood trauma in three independent studies (total n = 241) including healthy controls, patients with schizophrenia and bipolar disorder and unaffected siblings of patients with one of these disorders. we did not find any significant association between gr-1 f methylation and the cortisol stress response (areas under the curve) or childhood trauma, nor did we observe any group differences between patients, siblings and healthy controls. our findings do not support gr-1 f methylation as a proxy for the cortisol stress response, nor its link with childhood trauma or psychopathology. these results suggest that multifactorial models for stress-related psychopathology are needed. alternatively, future longitudinal studies may reveal gr-1 f methylation to be a useful parameter at an individual level.”
Yehuda, R., Flory, J. D., Bierer, L. M., Henn-Haase, C., Lehrner, A., Desarnaud, F., … Meaney, M. J.. (2015). Lower Methylation of Glucocorticoid Receptor Gene Promoter 1F in Peripheral Blood of Veterans with Posttraumatic Stress Disorder. Biological Psychiatry
“BACKGROUND: enhanced glucocorticoid receptor (gr) sensitivity is present in people with posttraumatic stress disorder (ptsd), but the molecular mechanisms of gr sensitivity are not understood. epigenetic factors have emerged as one potential mechanism that account for how trauma exposure leads to sustained ptsd symptoms given that ptsd develops in only a subset of trauma survivors. methods: cytosine methylation of a relevant promoter of the gr gene (nr3c1-1f promoter) and three functional neuroendocrine markers of hypothalamic-pituitary-adrenal axis function were examined in a sample of 122 combat veterans. results: lower nr3c1-1f promoter methylation in peripheral blood mononuclear cells (pbmcs) was observed in combat veterans with ptsd compared with combat-exposed veterans who did not develop ptsd. nr3c1-1f promoter methylation was also associated with three functional measures of glucocorticoid activity that have been associated with ptsd in combat veterans: pbmcs’ lysozyme inhibition on the lysozyme suppression test, plasma cortisol decline on the low-dose (.50 mg) dexamethasone suppression test, and 24-hour urinary cortisol excretion. finally, nr3c1-1f promoter methylation was inversely correlated with clinical markers and symptoms associated with ptsd. conclusions: alterations in nr3c1-1f promoter methylation may reflect enduring changes resulting from combat exposure that lead to functional neuroendocrine alterations. because epigenetic measures are thought to reflect enduring effects of environmental exposures, they may be useful in distinguishing combat-exposed veterans who do or do not develop ptsd.”
Vangeel, E., Van Den Eede, F., Hompes, T., Izzi, B., Del Favero, J., Moorkens, G., … Claes, S.. (2015). Chronic fatigue syndrome and DNA hypomethylation of the glucocorticoid receptor gene promoter 1F Region: Associations with HPA Axis Hypofunction and childhood trauma. Psychosomatic Medicine
“Objectives: chronic fatigue syndrome (cfs) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (gr) sensitivity. in addition, childhood trauma is considered a major risk factor for the syndrome. this study examinesdna methylation of the gr gene (nr3c1) in cfs and associations with childhood sexual and physical trauma. methods: quantification of dna methylation within the 1f promoter region of nr3c1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls by using sequenom epityper. further, we examined the association of nr3c1-1f promoter methylation with the outcomes of the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test in a subset of the study population. mann-whitney u tests and spearman correlations were used for statistical analyses. results: overall nr3c1-1f dna methylation was lower in patients with cfs than in controls. after cytosine guanine dinucleotide (cpg)-specific analysis, cpg-1.5 remained significant after bonferroni correction (adjusted p = .0014).within the cfs group, overall methylation (p = 0.477, p = .016) and selective cpg units (cpg-1.5: p = 0.538, p = .007; cpg-12.13: p = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. there was no significant difference in nr3c1-1f methylation between traumatized and nontraumatized patients. conclusions:we found evidence of nr3c1 promoter hypomethylation in female patients with cfs and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (gr hypersuppression). however, we found no evidence of an additional effect of childhood trauma on cfs via alterations in nr3c1 methylation.”
Fiacco, S., Gardini, E. S., Mernone, L., Schick, L., & Ehlert, U.. (2019). DNA Methylation in Healthy Older Adults With a History of Childhood Adversity—Findings From the Women 40+ Healthy Aging Study. Frontiers in Psychiatry
“Background: adversity in early development seems to increase the risk of stress-related somatic disorders later in life. physiologically, functioning of the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes is often discussed as long-term mediators of risk. in particular, dna methylation in the glucocorticoid receptor gene promoter (nr3c1) has been associated with type and strength of early life adversity and subsequent effects on hpa axis signaling in humans. animal studies, moreover, suggest changes in dna methylation in the estrogen receptor gene (erα) upon early life adversity. we investigated the association of type and severity of childhood adversity with methylation in nr3c1 and erα and additionally considered associations between methylation and steroid hormone secretion. methods: the percentage of methylation within the nr3c1 promoter and the erα shore was investigated using dried blood spot samples of 103 healthy women aged 40–73 years. childhood adversity was examined with the childhood trauma questionnaire. linear regression analyses were performed with methylation as dependent variable and the experience of emotional abuse and neglect, physical abuse and neglect, and sexual abuse (compared to non-experience) as independent variables. all analyses were controlled for age, bmi, annual household income, and smoking status and were adjusted for multiple testing. results: overall, over 70% of the sample reported having experienced any kind of abuse or neglect of at least low intensity. there were no significant associations between childhood adversity and methylation in the nr3c1 promoter (all p >.10). participants reporting emotional abuse showed significantly higher methylation in the erα shore than those who did not (p =.001). additionally, higher levels of adversity were associated with higher levels of erα shore methylation (p =.001). conclusion: in healthy women, early life adversity does not seem to result in nr3c1 promoter hypermethylation in midlife and older age. this is the first study in humans to suggest that childhood adversity might, however, epigenetically modify the erα shore. further studies are needed to gain a better understanding of why some individuals remain healthy and others develop psychopathologies in the face of childhood adversity.”
Perroud, N., Paoloni-Giacobino, A., Prada, P., Olié, E., Salzmann, A., Nicastro, R., … Malafosse, A.. (2011). Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: A link with the severity and type of trauma. Translational Psychiatry
Womersley, J. S., Martin, L. I., van der Merwe, L., Seedat, S., & Hemmings, S. M. J.. (2018). Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents. Metabolic Brain Disease
“Anxiety sensitivity (as) is characterised by the fear of anxiety-related symptoms and is a risk factor for the development of anxiety-related disorders. we examined whether genetic variation in three stress response genes, crhr1, nr3c1, and fkbp5, interact with childhood trauma (ct) to predict as in south african adolescents. xhosa (n = 634) and coloured (n = 317) students completed self-report measures of as and ct, and a total of eighteen polymorphisms within crhr1, nr3c1, and fkbp5 were genotyped. differences in as based on genetic variation and ct were analysed within population and gender groups using multiple linear regression. associations were found between as and fkbp5 rs9296158 (p = 0.025) and rs737054 (p = 0.045) in coloured males. analysis of gene x ct interactions indicated that nr3c1 rs190488 cc-genotype, nr3c1 rs10482605 g-allele addition, and fkbp5 rs3800373 c-allele addition protect against as with increasing ct in xhosa females (p = 0.009), xhosa males (p = 0.036) and coloured males (p = 0.049), respectively. we identified two different protective single nucleotide polymorphism (snp) combinations in a four-snp crhr1 haplotype in coloured males. an analysis of the interaction between ct and a six-snp fkbp5 haplotype in coloured males revealed both protective and risk allelic combinations. our results provide evidence for the influence of both genetic variation in crhr1, nr3c1 and fkbp5, as well as ct x snp interactions, on as in south african adolescents. this study reinforces the importance of examining the influence of gene-environment (g x e) interactions within gender and population groups.”
Rovaris, D. L., Mota, N. R., Bertuzzi, G. P., Aroche, A. P., Callegari-Jacques, S. M., Guimarães, L. S. P., … Grassi-Oliveira, R.. (2015). Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment. Journal of Psychiatric Research
“The aim of this study was to analyze hypotheses-driven gene-environment and gene-gene interactions in smoked (crack) cocaine addiction by evaluating childhood neglect and polymorphisms in mineralocorticoid and glucocorticoid receptor genes (nr3c2 and nr3c1, respectively). one hundred thirty-nine crack/cocaine-addicted women who completed 3 weeks of follow-up during early abstinence composed our sample. childhood adversities were assessed using the childhood trauma questionnaire (ctq), and withdrawal symptoms were assessed using the cocaine selective severity assessment (cssa) scale. conditional logistic regression with counterfactuals and generalized estimating equation modeling were used to test gene-environment and gene-gene interactions. we found an interaction between the rs5522-val allele and childhood physical neglect, which altered the risk of crack/cocaine addiction (odds ratio=4.0, p=0.001). moreover, a nr3c2-nr3c1 interaction (p = 0.002) was found modulating the severity of crack/cocaine withdrawal symptoms. in the post hoc analysis, concomitant carriers of the nr3c2 rs5522-val and nr3c1 rs6198-g alleles showed lower overall severity scores when compared to other genotype groups (p-values ≤ 0.035). this gene-environment interaction is consistent with epidemiological and human experimental findings demonstrating a strong relationship between early life stress and the hypothalamic-pituitary-adrenal (hpa) axis dysregulation in cocaine addiction. additionally, this study extended in crack/cocaine addiction the findings previously reported for tobacco smoking involving an interaction between nr3c2 and nr3c1 genes.”
Holmes, L., Shutman, E., Chinaka, C., Deepika, K., Pelaez, L., & Dabney, K. W.. (2019). Aberrant epigenomic modulation of glucocorticoid receptor gene (NR3C1) in early life stress and major depressive disorder correlation: Systematic review and quantitative evidence synthesis. International Journal of Environmental Research and Public Health
“Early life stress (els) induced by psychological trauma, child maltreatment, maternal separation, and domestic violence predisposes to psycho-behavioral pathologies during adulthood, namely major depressive disorder (mdd), anxiety, and bipolar affective disorder. while environmental data are available in illustrating this association, data remain to be established on the epigenomic underpinning of the nexus between els and mdd predisposition. specifically, despite the observed aberrant epigenomic modulation of the nr3c1, a glucocorticoid receptor gene, in early social adversity and social threats in animal and human models, reliable scientific data for intervention mapping in reducing social adversity and improving human health is required. we sought to synthesize the findings of studies evaluating (a) epigenomic modulations, mainly dna methylation resulting in mdd following els, (b) epigenomic modifications associated with els, and (c) epigenomic alterations associated with mdd. a systematic review and quantitative evidence synthesis (qes) were utilized with the random effect meta-analytic procedure. the search strategy involved both the pubmed and hand search of relevant references. of the 1534 studies identified through electronic search, 592 studies were screened, 11 met the eligibility criteria for inclusion in the qes, and 5 examined els and mdd; 4 studies assessed epigenomic modulation and els, while 2 studies examined epigenomic modulations and mdd. the dense dna methylation of the 1f exon of the nr3c1, implying the hypermethylated region of the glucocorticoid receptor gene, was observed in the nexus between els and mdd, common effect size (ces) = 14.96, 95%ci, 10.06–19.85. with respect to epigenomic modulation associated with child els, hypermethylation was observed, ces = 23.2%, 95%ci, 8.00–38.48. in addition, marginal epigenomic alteration was indicated in mdd, where hypermethylation was associated with increased risk of mdd, ces = 2.12%, 95%ci, −0.63–4.86. substantial evidence supports the implication of nr3c1 and environmental interaction, mainly dna methylation, in the predisposition to mdd following els. this qes further supports aberrant epigenomic modulation identified in els as well as major depressive episodes involving dysfunctional glucocorticoid-mediated negative feedback as a result of allostatic overload. these findings recommend prospective investigation of social adversity and its predisposition to the mdd epidemic via aberrant…”
Grillault Laroche, D., Curis, E., Bellivier, F., Nepost, C., Courtin, C., Etain, B., & Marie-Claire, C.. (2020). Childhood maltreatment and HPA axis gene expression in bipolar disorders: A gene network analysis. Psychoneuroendocrinology
“Introduction: bipolar disorder (bd) is highly associated with childhood maltreatment (cm), the exposure to such early adversity being suggested to disrupt the expression of several biological pathways. this study aims at exploring associations between the mrna levels of 9 hpa axis genes in lymphoblastoid cell lines from patients with bd according to their self-reported exposure to cm. methods: the sample consisted of 33 caucasian patients with a diagnosis of bd type 1, assessed for the exposure to cm with the childhood trauma questionnaire (ctq). quantitative rt-pcr was performed on 9 transcripts of the hpa axis genes: dgkh, fkbp5, nr3c1, sgk1, sgk2, sgk3, ska2, stat5a and ucn. rt-qpcr data were analyzed using the method of disjoint gene networks with sarp.compo package for r. results: we found no associations between ctq total score and the amount of hpa axis transcripts neither in univariate analyses, nor with network analyses. emotional abuse (ea) was associated with a significant decreased expression of two transcripts, dgkh (p = 0.009) and nr3c1 (p = 0.04). this was confirmed by the disjoint network analysis, which showed that nr3c1 and dgkh were expressed differently from the rest of the hpa axis network in presence of emotional abuse. discussion: this study described the expression levels of a comprehensive set of hpa axis genes according to childhood maltreatment in a sample of patients with bd type 1 and suggested that emotional abuse decreased the expression of nr3c1 and dgkh. our results require further replication in independent larger samples.”
Sheerin, C. M., Lind, M. J., Bountress, K. E., Marraccini, M. E., Amstadter, A. B., Bacanu, S. A., & Nugent, N. R.. (2020). Meta-Analysis of Associations Between Hypothalamic-Pituitary-Adrenal Axis Genes and Risk of Posttraumatic Stress Disorder. Journal of Traumatic Stress
“The hypothalamic-pituitary-adrenal (hpa) axis has been of interest in attempts to identify genetic vulnerability for posttraumatic stress disorder (ptsd). although numerous hpa-axis genes have been implicated in candidate gene studies, the findings are mixed and interpretation is limited by study design and methodological inconsistencies. to address these inconsistencies in the ptsd candidate gene literature, we conducted meta-analyses of hpa-related genes from both a traditional single nucleotide polymorphism (snp)–level analysis and a gene-level analysis, using novel methods aggregating markers in the same gene. database searches (pubmed and psycinfo) identified 24 unique articles examining six hpa-axis genes in ptsd; analyses were conducted on four genes (adcyap1r1, crhr1, fkbp5, nr3c1) that met study eligibility criteria (original research, human subjects, main effect association study of selected genes, ptsd as an outcome, trauma-exposed control group) and had sufficient data and number of studies for use in meta-analysis, within 20 unique articles. findings from snp-level analyses indicated that two variants (rs9296158 in fkbp5 and rs258747 in nr3c1) were nominally associated with ptsd, ps =.001 and.001, respectively, following multiple testing correction. at the gene level, significant relations between ptsd and both nr3c1 and fkbp5 were detected and robust to sensitivity analyses. although study limitations exist (e.g., varied outcomes, inability to test moderators), taken together, these results provide support for fkbp5 and nr3c1 in risk for ptsd. overall, this work highlights the utility of meta-analyses in resolving discrepancies in the literature and the value of adopting gene-level approaches to investigate the etiology of ptsd.”
Peng, H., Zhu, Y., Strachan, E., Fowler, E., Bacus, T., Roy-Byrne, P., … Zhao, J.. (2018). Childhood Trauma, DNA Methylation of Stress-Related Genes, and Depression: Findings from Two Monozygotic Twin Studies. Psychosomatic Medicine
“Objective dna methylation has been associated with both early life stress and depression. this study examined the combined association of dna methylation at multiple cpg probes in five stress-related genes with depressive symptoms and tested whether these genes methylation mediated the association between childhood trauma and depression in two monozygotic (mz) twin studies. methods the current analysis comprised 119 mz twin pairs (84 male pairs [mean = 55 years] and 35 female pairs [mean = 36 years]). peripheral blood dna methylation of five stress-related genes (bdnf, nr3c1, slc6a4, maoa, and maob) was quantified by bisulfite pyrosequencing or 450k beadchip. we applied generalized poisson linear-mixed models to examine the association between each single cpg methylation and depressive symptoms. the joint associations of multiple cpgs in a single gene or all five stress-related genes as a pathway were tested by weighted truncated product method. mediation analysis was conducted to test the potential mediating effect of stress gene methylation on the relationship between childhood trauma and depressive symptoms. results multiple cpg probes showed nominal individual associations, but very few survived multiple testing. gene-based or gene-set approach, however, revealed significant joint associations of dna methylation in all five stress-related genes with depressive symptoms in both studies. moreover, two cpg probes in the bdnf and nr3c1 mediated approximately 20% of the association between childhood trauma and depressive symptoms. conclusions dna methylation at multiple cpg sites are jointly associated with depressive symptoms and partly mediates the association between childhood trauma and depression. our results highlight the importance of testing the combined effects of multiple cpg loci on complex traits and may unravel a molecular mechanism through which adverse early life experiences are biologically embedded.”
Nöthling, J., Malan-Müller, S., Abrahams, N., Hemmings, S. M. J., & Seedat, S.. (2020). Epigenetic alterations associated with childhood trauma and adult mental health outcomes: A systematic review. World Journal of Biological Psychiatry
“Objectives: multiple, chronic and repeated trauma exposure in childhood is associated with adverse mental health outcomes in adulthood. in this paper we synthesise the literature on epigenetic modifications in childhood trauma (ct) and the mediating effects of differential epigenetic mechanisms on the association between ct and the later onset of psychiatric disorders. methods: we reviewed the literature up to march 2018 in four databases: pubmed, web of science, ebscohost and scopus. non-human studies were excluded. all studies investigating ct exposure both in healthy adults (18years and older) and adults with psychiatric disorders were included. results: thirty-six publications were included. for mood disorders, methylation of the glucocorticoid receptor nr3c1 gene, specifically at the ngfi-a binding site in exon 1f, and correlation with ct was a robust finding. several studies documented differential methylation of slc6a4, bdnf, oxtr and fkbp5 in association with ct. common pathways identified include neuronal functioning and maintenance, immune and inflammatory processes, chromatin and histone modification, and transcription factor binding. conclusions: a variety of epigenetic mediators that lie on a common pathway between ct and psychiatric disorders have been identified, although longitudinal studies and consistency in methodological approach are needed to disentangle cause and effect associations.”
Brown, V.. (2021). Methylation of the glucocorticoid receptor gene NR3C1: a summary for clinicians working with children and families. BJPsych Open
“Aims it has been shown that the glucocorticoid receptor nr3c1 gene can be methylated (‘switched off’) in response to early adversity. methylation has also been linked to physiological changes in the body’s response to stress by changing the sensitivity of the hypothalamic-pituitary-adrenal (hpa) axis. in adults, associations have been made between nr3c1 methylation and borderline personality disorder, depression and post-traumatic stress disorder. environmental and social co-variates increase with lifespan so establishing cause and effect is difficult. studies in children, then, may illuminate patterns to inform current hypotheses. this paper reviews the literature on children and adolescents linking glucocorticoid gene receptor nr3c1 to the psychopathology of mental illness. findings are presented in an accessible manner to engage people less familiar with genetics and to inform frontline clinicians of this quickly growing area of research. method medline and psychinfo were searched for relevant peer-reviewed original research using the following keywords and associated mesh terms: nrc31, glucocorticoid receptor gene, methylation, epigenetics, child, adolescent, trauma, psychopathology, gene expression. result 14 studies were identified involving 5475 young people. degree of nr3c1 methylation was associated with severity of early life adversity. methylation was linked with psychopathology including borderline personality disorder, internalising symptoms and externalising symptoms with sex differences. the most consistent association was with depression. methylation seems to modulate the interaction between environment and genetics with the suggestion that the effect may be protective in some cases. however, longitudinal genetic sampling was only conducted in one study. conclusion heterogeneity of studies in the epigenetics field are discussed but should not detract from future possibilities. the hope is to identify therapeutic targets or monitor response to treatment as we work to better understand the biology of developmental psychology, mental illness and resilience. there is a growing understanding that epigenetic modifications likely change over time and clinical significance is most likely dictated by changes at multiple gene locations. thus future research may need to move away from single gene research typically employed in favour of longitudinal whole genome studies in larger population studies. it is time that clinician…”
Williams, C.. (2019). On ‘modified human agents’: John Lilly and the paranoid style in American neuroscience. History of the Human Sciences, 32(5), 84–107.
“The personal papers of the neurophysiologist john c. lilly at stanford university hold a classified paper he wrote in the late 1950s on the behavioural modification and control of ‘human agents’. the paper provides an unnerving prognosis of the future application of lilly’s research, then being carried out at the national institute of mental health. lilly claimed that the use of sensory isolation, electrostimulation of the brain, and the recording and mapping of brain activity could be used to gain ‘push-button’ control over motivation and behaviour. this research, wrote lilly, could eventually lead to ‘master-slave controls directly of one brain over another’. the paper is an explicit example of lilly’s preparedness to align his research towards cold war military aims. it is not, however, the research for which lilly is best known. during the 1960s and 1970s, lilly developed cult status as a far-out guru of consciousness exploration, promoting the use of psychedelics and sensory isolation tanks. lilly argued that, rather than being used as tools of brainwashing, these techniques could be employed by the individual to regain control of their own mind and retain a sense of agency over their thoughts and actions. this article examines the scientific, intellectual, and cultural relationship between the sciences of brainwashing and psychedelic mind alteration. through an analysis of lilly’s autobiographical writings, i also show how paranoid ideas about brainwashing and mind control provide an important lens for understanding the trajectory of lilly’s research.”
This article was adapted from a chapter of the PhD thesis Battles for the Mind: Brainwashing Altered States and the Politics of the Nervous System (1945-1970), completed at Birkbeck in 2018.
Abstract
The personal papers of the neurophysiologist John C. Lilly at Stanford University hold a classified paper he wrote in the late 1950s on the behavioural modification and control of ‘human agents’. The paper provides an unnerving prognosis of the future application of Lilly’s research, then being carried out at the National Institute of Mental Health. Lilly claimed that the use of sensory isolation, electrostimulation of the brain, and the recording and mapping of brain activity could be used to gain ‘push-button’ control over motivation and behaviour. This research, wrote Lilly, could eventually lead to ‘master- slave controls directly of one brain over another’. The paper is an explicit example of
Lilly’s preparedness to align his research towards Cold War military aims. It is not, however, the research for which Lilly is best known. During the 1960s and 1970s, Lilly developed cult status as a far-out guru of consciousness exploration, promoting the use of psychedelics and sensory isolation tanks. Lilly argued that, rather than being used as tools of brainwashing, these techniques could be employed by the individual to regain control of their own mind and retain a sense of agency over their thoughts and actions. This article examines the scientific, intellectual, and cultural relationship between the sciences of brainwashing and psychedelic mind alteration. Through an analysis of Lilly’s autobiographical writings, I also show how paranoid ideas about brainwashing and mind control provide an important lens for understanding the trajectory of Lilly’s research.
The ‘Cold War brainwashing scare’
Lilly’s appointment to the NIMH came shortly after a new term – brainwashing – had been introduced into the English language. The term was first used publicly by journalist Edward Hunter in an article for the Miami News (1950).7 In this article and in later works, Hunter claimed that by combining Pavlovian theory with modern technology, Russian and Chinese psychologists had developed powerful techniques for manipulating minds. Although it resonated with concerns about the growing global influence of communism, the term brainwashing would perhaps never have gained traction if it had not been for a series of scandals involving collaboration between American POWs and the Chinese enemy during the Korean War. Most famously, in 1952, Colonel Frank Schwable and 35 other captured US Air Force personnel publicly confessed to committing crimes of germ warfare against North Korea. Other accounts of collaboration at the hands of the Chinese, including the making of public anti-war and anti-McCarthy broadcasts, received widespread attention during the war. Perhaps most controversially, after a long-awaited armistice deal was agreed in 1953, one British and 21 American POWs refused to be repatriated after the war, choosing to relocate to communist China instead. It was widely reported that the soldiers had been exposed to sophisticated techniques of mental coercion based on Pavlovian science, similar to those reported to have been used to extract confessions for Soviet purge trials such as that of Cardinal József Mindszenty in 1949 (Carruthers, 2009).
Scholarship on this period has described the ‘Cold War brainwashing scare’, the ‘brainwashing idea’, and the ‘spectre of brainwashing’, as a central motif in postwar film and literature upon which myriad concerns about agency and influence were projected (for use of these phrases see, respectively, Carruthers, 1998; Reisch, 2012; Taylor, 2004). Whilst such scholarship has often described brainwashing as a ‘cultural fantasy’, the idea of brainwashing nonetheless had real effects, not least within the human sciences. In the early 1950s, building on investigations carried out since the Second World War, the CIA established its notorious MKULTRA programme, which aimed, in the words of its former director Sidney Gottlieb, to ‘investigate whether and how it was possible to modify an individual’s behaviour by covert means’ (Marks, 1978: 57). What the historian Alfred McCoy has called ‘the Manhattan Project of the mind’ was fuelled by a dual sense of hubris about the CIA’s own research and development potential and paranoia about the capabilities of the enemy, enhanced, as it were, by the semi-tangible reports of enemy scientific projects within what Melley has called the ‘covert sphere’ (McCoy, 2006; Melley, 2012).
According to his own memoirs, Lilly had long been interested in questions of behavioural control. It was reportedly his reading of Aldous Huxley’s Brave New World in 1934 and its portrayal of the misuse of the human sciences that influenced his decision to major in biology rather than physics as a student (Lilly, 1997: 57). Although Lilly has somewhat successfully cultivated an image of himself as someone who resisted the lure of military and intelligence funding, like many of his peers, his work and career was heavily shaped by the wider forces shaping the human sciences after the war (Lutz, 1997; McCoy, 2006).
*Lilly, ‘Special Considerations of Modified Human Agents as Reconnaissance and Intelligence Devices (Committee D, Intelligence and Reconnaissance)’, Lilly Papers, Box 54, Folder 17. Exactly when and where this paper was delivered is unclear. In his paper on human manipulation, Lilly implies that both papers were presented at the same place or at connected events: ‘In the following discussion I wish to mention a few human cases; a later supplement will mention certain non-human species as possible agents.’ It is likely that this work or similar was presented at the Pentagon meeting discussed in Lilly’s memoirs (Lilly, 1997: 93–5). According to a former intelligence official’s description of this meeting ‘Dr. Lilly stated that the potential of this technique in “brain-washing” or interrogation or in the field of controlling the actions of humans and animals is almost limitless’: memorandum, Jones to Deloach, 2, FBI personal file, as quoted in Burnett (2016). However, an old inventory for Lilly’s archive from 1992 includes the entry ‘Manuscript of Presentation Given to GAP Symposium on Brainwashing Entitled: “Special Considerations of Modified Human Agents as Reconnaissance and Intelligence Devices”: November 1956’, suggesting that Lilly may have delivered this paper at a meeting for the Group for the Advancement of Psychiatry, which we know he attended (Group for the Advancement of Psychiatry, 1956). Yet this is further complicated by the fact that both papers include references dated as late as 1958, suggesting the papers in the archive were presented after 1956.
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@book{book:{91532088},
title = {Operation Mind Control},
author = {Walter Bowart},
isbn = {0440167558; 9780440167556},
year = {1978},
url = {libgen.li/file.php?md5=5b759b56e154df6303bb47b051dfb3db}}
This text is an excerpt from a chapter of Bärtås and Ekman’s collection of essays Orienterarsjukan och andra berättelser.
URL: biblioteket.stockholm.se/titel/516229
—
The letter from Professor Delgado carries two insignias. One is made of Hebrew letters on what looks like a Torah scroll. Under the scroll it says “lux et veritas”—light and truth. The other insignia reads “Investigacion Ramon y Cajal.” In our letter to him, we have explained that we are two artists who have been studying his “astonishing research,” and that we are interested in his views on the relationship between humans and machines. José M.R. Delgado has written that he will be most happy to receive us at his home in Madrid.
Delgado’s name is a constant on various conspiracy websites dedicated to the topic of mind control; those with names like The Government Psychiatric Torture Site, Mind Control Forum, and Parascope. The Internet has in fact become the medium of conspiracy theorists. The network functions as an endless library where the very web structure lends itself to a conspiratorial frame of mind. The idea that every phenomenon and person can be connected to another phenomenon and person is the seed of the conspiracy theorist’s claim to “make the connections between things,” track the flow of power, and show how everything hangs together within some larger murky context.
Before traveling to Madrid, we get a hold of Physical Control of the Mind: Toward a Psychocivilized Society, the 1969 Delgado book most often cited on the Net. The book has has been gathering dust for 30 years at the university’s psychology library: it has never been cracked open. It is a disturbing book, less because of its photographs of animal experiments than because of the triumphal tone of the writing. Delgado discusses how we have managed to tame and civilize our surrounding nature. Now it is time to civilize our inner being. The scientist sees himself on the verge of a new era where humans will undergo “psycho-civilization” by linking their brains directly to machines.
“Ramon y Cajal”—the name on one of the two insignia—is referred to in Delgado’s book. Cajal was a famous histologist who became the young Delgado’s mentor and inspiration. In his acknowledgements, Delgado cites Cajal’s telling claim that “knowledge of the physicochemical basis of memory, feelings, and reason would make man the true master of creation, that his most transcendental accomplishment would be the conquering of his own brain.”1
Professor Delgado is now 85 and lives in a suburb of Madrid. Madrid is also the home of an anonymous group of people who call themselves Nosman, and are dedicated to gathering information about Delgado and his career. We e-mail Nosman and receive some awkwardly written responses that oscillate between warnings about the Spanish security agencies and suspicious questions about us and our interest in Delgado. For some reason, they refuse to meet with us but give us Delgado’s email address anyway. Delgado, on the other hand, responds immediately when we get to Madrid. He is very eager to invite us to lunch.
It was at Madrid University that Delgado began his research on pain and pleasure as the means of behavior control. After World War II, he became the head of the Department of neuropsychiatry at Yale’s medical school. In 1966, he became a professor in physiology. By that time, he had further developed the research of the Swiss physiologist and Nobel Prize winner Walter Rudolph Hess who had used electric stimulation to chart how different parts of the brain control different motor functions.
After a series of spectacular experiments on animals in Bermuda, Delgado wrote: “If you insert electrodes directly into the brains of cats and apes, they will behave like electronic toys. A whole series of motor functions can be triggered based on which button the experimenter pushes. This applies to all body parts: front and back paws, the tail, the hind parts, the head, and the ears.”
Using electrostimulation in a group of gibbon apes, Delgado succeeded in dismantling the usual power structure within the group. He gave a female ape with a low ranking a control box connected to electrodes that were implanted in the group’s alpha male, and the female learned to use the box to turn the alpha male on and off at will.
The electrodes were inserted into the ape’s brain and connected to an instrument that Delgado called the stimoceiver. The stimoceiver was an ideal instrument for two-way communication. Researchers could affect and at the same time register activity in the brain. From earlier prototypes where the lab animals were connected with wires, a remote control model was later developed that could send and receive signals over FM waves. The device was developed from the telemetric equipment used to send signals to and from astronauts in space. “We have already established radio contact with space; it is now time to establish contact with the human brain,”—a recurring refrain in Delgado’s articles.
The taxi lets us out in an upscale suburb of Madrid where a light rain is falling on the brick houses. A church service has just finished and people in Burberry clothes are streaming out of a strange concrete church. At the entrance of the apartment building where Delgado lives, we are met by a fashionable and exuberant American woman of indeterminable age. The woman, who is Delgado’s wife, talks nonstop in the elevator that opens directly into the apartment. The apartment is decorated in a fussy, bourgeois style. If it were not such a bleak day, the view would extend all the way to the Pardo Mountains. Delgado gives us a very cordial welcome. He is a proper old gentleman with sharp, intelligent eyes.
Delgado says that he has had a nightmare about our visit and woke up crying in the middle of the night. In the dream, we had showed up barefoot and in short sleeve shirts and had proceeded to gulp down all of his meringues. An hour later, we are seated at the marble table in his dining room and are served meringues and strawberry tarts after a large meal. We do not want to have more than one meringue each.
In a CNN special from 1985 called “Electro-magnetic Weapons and Mind Control,” the reporter claims that Delgado’s experiments were limited to animals. Nor is there anything in the texts on the various websites that indicates how far Delgado went in his research. His experiments on humans seem to have fallen into a strange collective amnesia. But anyone can walk into any well-stocked American medical library and take out Delgado’s own reports and articles on the subject. There we can find his own candid, open descriptions of how he moved on from experimenting on animals to humans. In an article called “Radio Control Behavior” in the February 1969 issue of The Journal of Nervous and Mental Disease, Delgado, Dr. Mark, and several other colleagues describe what was the first clinical use of Intracerebral Radio Stimulation (IRS) on a human being. The stimoceiver itself only weighed 70 grams and was held fast by a bandage. One of the patients hid her stimoceiver with a wig because the experiments lasted days or weeks. The patients were scrutinized thoroughly. Everything they said was taped, their EEG was recorded, and they were photographed at regular intervals in order to document changes in their facial expressions.
In one of the article’s photographs, we see two of the subjects engaged in “spontaneous activity.” They are both girls with bandages over their heads. The girl in the background is holding something to her mouth, perhaps a harmonica. The other girl is bent over a guitar. Delgado’s colleague, Dr. Mark, is smiling at them. Mark had already achieved some notoriety at this time by claiming that all anti-social behavior is caused by brain damage. His recommendation had been the mass scanning of the American population in order to detect such damage in time and “correct” it.
Delgado and Mark’s article offers short descriptions of the patients who have had the device affixed to their brain. A black fourteen-year-old girl on the border of developmental disability who grew up in a foster home suddenly goes into a fury that leads to the death of her two stepsisters. A thirty-five-year old white industrial designer who ends up killing his wife and children flies into a rage when other motorists try to overtake him and he chases them and tries to run them off the road. Their aggressive behavior is supposed to be registered by the stimoceiver in the way a seismograph registers the earth’s tremors and the same stimoceiver is then to “turn them off” via the FM transmitter.
Delgado bombards us with a steady stream of anecdotes, scientific comments, and provocative rhetorical questions that are only interrupted by occasional tender comments directed to his wife. He tells of his work at the Ramon y Cajal Institute in the 1930s. In order to save a few paltry pennies, he would take a short cut through the zoo on his way to and from work. He would wander through the zoo alone at dawn and dusk and would hear lions and tigers roaring in this jungle in the city. After the War, he came to conquer nature in his own way in Bermuda. Even his wife was delighted to see the alpha male gibbon collapse when the underlings pushed the control lever. “Do you remember how we thought of Franco?” says his wife. “Imagine being able to turn off the Generalisimo.” Delgado responds “But who could have put the electrodes into the dictator? With electromagnetic radiation we could have controlled the dictator from a distance. We did some experiments at Yale where we influenced the brain from up to 30 meters away.”
One of the most important reasons why we wanted to meet Delgado is that we imagined him and his activities as belonging to a borderland between fiction and reality, between science and madness. People in psychotic states of mind often feel themselves controlled by foreign voices or spend their lives trying to prove that they have had a transmitter implanted inside their skulls that dictates their actions and thoughts all day and night. We ask Delgado what he thinks of the fact that his research provides a realistic edge to such fantasies.
He answers that he has on several occasions been contacted by strangers who say they want to have their implants removed and also that he has been sued by people he has never seen. Delgado is silent about the article that appeared in the Spanish monthly magazine Tiempo last year, where he was interviewed about exactly such accusations. The Tiempo reporter claimed that Delgado has ties with the Spanish secret police.
Delgado stretches out after the strawberry tarts. He has come to think of a case in Pittsburg in the 1950s where a robber was offered a milder sentence in exchange for being lobotomized. “I was operating electrodes into people’s brains at that time together with my good friend David Koskoff.” It was Koskoff who carried out the lobotomy on the robber. The patient was quiet for a while after the operation but then reverted to carrying out robberies again. In despair over his own unreliability, he decided to take his own life. He wrote a suicide note addressed to Dr. Koskoff: “Doctor, all your work has been in vain. I am an incompetent man and a criminal. I am taking my life but I am shooting myself in the heart and not the head. I donate my brain to you for research.”
Delgado’s wife puts her arm on his shoulder and says “And very little has happened since then, dear. There are still lots of bums running around.” The comment makes us both look away.
A moment later, we are sitting on the sofa. Delgado admits that not one useful application of the stimoceiver has come out of his research. “We knew too little about the brain. It is much too complicated to be controlled. We never knew which parts of the brain we were stimulating with the stimoceiver. We didn’t even manage to prevent epileptic attacks, which we thought would be the simplest of things. We never found the area where epilepsy attacks originate.” He says all of this without a trace of bitterness, as if in passing.
We are surprised by his casual attitude toward the stimoceiver, which in the 1960s and 70s was heralded as a great contribution to science. To demonstrate the power of their invention, Delgado and his colleagues orchestrated violent scenes in the lab. In her book, The Brain Changers: Scientists and the New Mind Control, Maya Pine describes a film where Dr. Mark attaches a stimoceiver to an electrode in a woman’s brain:
As the film opens, the patient, a rather attractive young woman, is seen playing the guitar and singing “Puff, the Magic Dragon.” A psychiatrist sits a few feet away. She seems undisturbed by the bandages that cover her head like a tight hood, from her forehead to the back of her neck. Then a mild electric current is sent from another room, stimulating one of the electrodes in her right amygdala. Immediately, she stops singing, the brainwave tracings from her amygdala begin to show spikes, a sign of seizure activity. She stares blankly ahead. Suddenly she grabs her guitar and smashes it against the wall, narrowly missing the psychiatrist’s head.2
The same incident was described in one of Delgado’s own articles. This experiment was repeated three days in a row.
If there were any problems with the experiments for Delgado, these were not ethical in nature but technical. How do you replicate the lab situation in society? How do you cut off the electricity to the stimoceiver? How do you avoid scarring and inflammation where the stimoceiver enters the brain? But the problems did not provoke any doubts about the supposed success of the stimoceiver. In the long run, the technique could be used to make people happy from a distance.
“When did you stop the stimoceiver experiments?” we ask him. To our surprise, he responds indignantly that he has yet to do so. “After Yale, I have continued my experiments here in Spain, both on animals and on humans.” Delgado’s pragmatism does another pirouette and we are beginning to have trouble following him.
Delgado pours coffee with his trembling hands. Spanish guitar music from the stereo fills the silence. We look together through the three recent collection of essays that Delgado has placed in front of us. Their publication dates range from 1979 up to this year. There is no emphasis on neurophysiology in any of them. Instead, they address questions of learning and upbringing from a more general psychological point of view.
Until the end of the 70s, Delgado and his colleagues were considered conquerors of an unknown territory, a wild and expansive jungle, the landscape of the brain and the soul. Apparently Delgado never got very far into the jungle, which proved to be much too thick and impenetrable. He has apparently retired without any regrets. He has instead started to cultivate his own garden. “My new book is going to be called The Education of My Grandchildren and Myself.”
We ask if it is possible to learn to interpret the electrical language of the brain and mention the Swedish science journalist Göran Frankel’s interview with Delgado back in 1977.3 In the interview Delgado claims that it is only a question of time before we connect the brain directly into computers that can communicate with the brain’s electrical language.
Delgado makes a dismissive gesture and looks at us as if we are numskulls. “It is impossible to decode the brain’s language. We can obviously manipulate different forms of electrical activity but what does that prove?” When we ask him about his colleague, Dr. Robert G. Heath, who claimed to be able to cure schizophrenic patients with electrostimulation, Delgado breaks into a patronizing smile and says, “Yes, yes, you’re supposed to have a box on your stomach with cables coming out of it that attach to electrodes in your brain and you stimulate yourself. It never worked.”
We lead him to a discussion of his own patients. Delgado interrupts us: “I have never done experiments on people.” For a moment, we wonder if we’ll have to take out one of his own scientific articles and hold it in front of him as evidence. We start to look for our file with hundreds of medical reports and articles. “You have to understand,” he says. “There are incredibly stringent rules around experimenting on humans. All the experiments I was involved in had a therapeutic goal. They were for the patients’ best.”
In one of the Yale reports in our file, there is a description of an experiment on an epileptic mental patient. The report states that the woman has been in asylums for a long time, she is worried about her daughter, and suffers from economic hardship. Electrodes measuring 12 centimeters have been stuck into her brain, 5 centimeters of them inside the brain tissue. She is interviewed while being given periodic electrical stimulation. The woman is tossed between various emotional states and finds that strange words are coming to her mind. She experiences pain and sexual desire. At the end of the interview, she becomes flirty and her language becomes coarse, only to be ashamed later and ask to be excused for words that she felt had come to her from outside. The woman has been transformed into a speaking doll that unwillingly gives voice to her brain’s every whim.
Delgado, who had previously been so flattered by two artists being interested in his work, now seems to be looking at us with new eyes. Who are we? And what do we want? His tone is short and sharp. The temperature in the apartment has dropped a few degrees.
In Physical Control of the Mind, Delgado proudly sums up how he has “used electrodes implanted for days or months to block thought, speech, and movement, or to trigger joy, laughter, friendliness, verbal activity, generosity, fear, hallucinations, and memory.” With this in mind, we ask him what therapeutic results came from these experiments. “As a whole, they didn’t result in any methods, except in the case of patients with chronic pain.”
Delgado in his apartment in Madrid. Video still courtesy of Magnus Bärtås.
He looks at the clock and says that we only have five minutes left. But we do not want to abandon our questions about the patients. What happened to them? How long were the implants in their brains? Delgado now becomes somewhat vague. He says that it was other researchers that left the implants in for a long time, not him or Dr. Heath, and he does not recall which patients it was. The electrodes were taken out of his own patients after a couple of days and did not cause any injuries. “We killed maybe a few hundred neurons when we inserted the electrodes. But the brain has millions of neurons.”
When Delgado spoke in the 60s of “the precise interface between brain and machine,” it gave rise to a number of far-fetched military visions. His research was also mainly funded by military institutions such as the Office of Naval Research and the Air Force AeroMedical Research Laboratory.
In the US, the CIA and government research in (and use of) different means of behavior control was made public in a series of congressional hearings in 1974 as well as in a Senate investigation three years later. Witnesses offered a glimpse of the CIA’s astonishing experiments in the so-called MK-Ultra program. The list of MK-Ultra experiments is like a group photo of the extended family of behavioral technologies: hypnosis, drugs, psychological testing, sleep research, brain research, electromagnetism, lie detection. The specific operations had very imaginative names: Sleeping Beauty, Project Pandora, Woodpecker, Artichoke, Operation Midnight Climax.
One of MK-Ultra’s fields of interest was electromagnetic fields and their effect on human beings. In 1962 it was discovered that the Russians had directed microwave radiation at the American embassy in Moscow with the hope of penetrating through to the ambassador’s office. The CIA immediately mounted an investigation under the codename Project Pandora. Concurrently with his research on the stimoceiver, Delgado had begun research on electro-magnetic radiation and its capacity for influencing people’s consciousness, and there is speculation that Delgado may have been involved in Project Pandora.
The CIA arranged for apes to be brought to the embassy. When the apes were examined after a period of being radiated, it was discovered that they had undergone changes in their chromosomes and blood. The personnel at the embassy was later reported to have increased white blood cell counts of up to 40 percent. The Boston Globe reported that the ambassador himself suffered not only from bloody eyes and chronic headaches but also from a blood disease resembling leukemia.
We take up Delgado’s research on electromagnetic fields and their effect on people. “I could later do with electro-magnetic radiation what I did with the stimoceiver. It’s much better because there’s no need for surgery,” he explains. “I could make apes go to sleep. But I stopped that line of research fifteen years ago. But I’m sure they’ve done a lot more research on this in both the US and Russia.”
We understand now that Delgado thinks the meeting ought to come to an end. We ask him about Project Pandora and he confirms the story of the Moscow Signal without any hesitation but he denies being involved in the operation.
In 1972, an article citing Delgado’s views was presented at Congress’s MK-Ultra hearings:
We need a program of psychosurgery for political control of our society. The purpose is physical control of the mind. Everyone who deviates from the given norm can be surgically manipulated. The individual may think that the most important reality is his own existence, but this is only his personal point of view. This lacks historical perspective Man does not have the right to develop his own mind. This kind of liberal orientation has great appeal. We must electrically control the brain. Some day armies and generals will be controlled by electric stimulation of the brain.4
When we confront him with this statement, he falls silent for a second. His crystal-clear memory of a moment ago suddenly evaporates. A fog sweeps in, the words become hard to get out. He does not recall ever being called to Congress. And he has no desire to acknowledge the kinds of statements we have just mentioned. For a second, Delgado becomes a very old and fragile man. But in the next moment, he is standing up straight again and has shaken off all these unpleasantries. Now he is in a hurry. He has to meet his sick sister-in-law. We try to secure a second meeting but he is evasive and talks about the vagaries of the weather and trips to his country house. Out the door in a cloud of cigar smoke, the taxi takes us back to Madrid.
Translated by Sina Najafi
This article was corrected on 29 November 2014. Since publishing this article in Cabinet no. 2 (Spring 2001), several errors have come to our attention. Together, these support Delgado’s claim that he never appeared before Congress or made the statement that the authors attributed to him. Delgado never testified before Congress during the MK-Ultra hearings, which in fact took place not in 1974 but in 1977. Neither is his name present in any of the transcripts of the hearings. Additionally, as far as we have been able to determine, the cited statement does not exist in this form in any of Delgado’s publications, though some of the phrases do occur in his book Physical Control of the Mind. The sole reference to Delgado in the Congressional Record that we have been able to locate appears in Dr. Peter Breggin’s “The Return of Lobotomy and Psychosurgery.” This article, which was critical of Delgado’s methods, was entered into the Congressional Record on 24 February 1972. We regret the errors.
Schleim, S.. (2021). Neurorights in History: A Contemporary Review of José M. R. Delgado’s “Physical Control of the Mind” (1969) and Elliot S. Valenstein’s “Brain Control” (1973). Frontiers in Human Neuroscience, 15
“Scholars from various disciplines discuss the ethical, legal, and social implications of neurotechnology. some have proposed four concrete ‘neurorights’. this review presents the research of two pioneers in brain stimulation from the 1950s to 1970s, josé m. r. delgado and elliot s. valenstein, who also reflected upon the ethical, legal, and social aspects of their and other scientists’ related research. delgado even formulated the vision ‘toward a psychocivilized society’ where brain stimulation is used to control, in particular, citizens’ aggressive and violent behavior. valenstein, by contrast, believed that the brain is not organized in such a way to allow the control or even removal of only negative processes without at the same time diminishing desirable ones. the paper also describes how animal and human experimentation on brain stimulation was carried out in that time period. it concludes with a contemporary perspective on the relevance of neurotechnology for neuroethics, neurolaw, and neurorights, including two recent examples for brain-computer interfaces.”
Vera, J. A., & Martínez-Sánchez, F.. (2016). Ethics, science and mind control: J. M. Rodríguez-Delgado’s legacy. Spanish Journal of Psychology
“This work analyses the evolution of the scientific visibility of the neurophysiologist josé manuel rodríguez delgado. it examines the longitudinal evolution from 1955 to 2013 of an article (delgado, roberts, & miller, 1954) studying the neurological basis of learning and motivation and compares it with a coetaneous article (olds & milner, 1954) with a similar subject and methodology. both studies have been essential in psychology. this work analyses the number of times each article has been cited between 1955-1984 and 1985-2013. the results show that the visibility of james olds and peter milner’s article (expressed in number of citations between 1955-1984 and 1985-2013) has longitudinally increased (p <.001), whereas the number of citations received by josé manuel rodríguez delgado et al.’s article has significantly reduced (p <.001). the results are discussed and the low visibility of delgado’s article is explained through historical and social factors, including the growing concern about compliance with bioethical and research guidelines and the controversial media projection of the spanish scientist, not by the intrinsic value or the scientific repercussion of the compared articles.”
Sultanov, M.. (2019). Brain-Computer Interfaces: From Past to Future. American Journal of Biomedical Science & Research
“More than 100 years ago, scientists were interested in the capabilities of the brain and tried to understand whether it is possible to somehow influence it. in 1875, english doctor richard caton managed to register a weak electric field on the surface of the brain of rabbits and monkeys. then there was a lot of discovery and research, but only in 1950, josé manuel rodríguez delgado, a professor of physiology at yale university, invented the device, which could be implanted in the brain and controlled by radio signals. ”
Wilder, J.. (1971). Physical Control of the Mind. Toward a Psychocivilized Society. American Journal of Psychotherapy
“Http://en.wikipedia.org/wiki/jos%c3%a9_manuel_rodriguez_delgado josé manuel rodriguez delgado from wikipedia, the free encyclopedia jump to: navigation, search ‘jose delgado’ redirects here. for the comic book character, see gangbuster. text document with red question mark.svg tthis article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. please improve this article by introducing more precise citations where appropriate. (may 2010) dr. josé manuel rodriguez delgado (born august 8, 1915) is a spanish professor of physiology at yale university, famed for his research into mind control through electrical stimulation of regions in the brain. contents [hide] * 1 biography * 2 research * 3 references * 4 further reading * 5 external links [edit] biography delgado was born in ronda, spain in 1915. he received a doctor of medicine degree from the university of madrid just before the outbreak of the spanish civil war, in which he served as a medical corpsman on the republican side. after the war he had to repeat his m.d. degree, and then took a ph.d. at the cajal institute in madrid. ”
Blackwell, B.. (2012). Jose Manuel Rodriguez Delgado. Neuropsychopharmacology
“Presents an obituary of jose manuel rodriguez delgado (1915-2011). jose enrolled in madrid medical school in 1933 to study both medicine and physiology. in 1936, the spanish civil war erupted, his mentor juan negri fled the country and jose joined the republican side as a medical corpsman. from 1942 to 1950, he began research in neurophysiology on selective brain ablation and electrical stimulation in animals, published 14 articles and won several prizes. in 1950, delgado won a scholarship to the yale university in the department of physiology under the direction of john fulton whose pioneer work on pre-frontal lobotomy in chimpanzees encouraged the portuguese psychiatrist egas moniz to perform the operation in schizophrenic patients, for which he received the noble prize in 1949. delgado positioned himself between growing disapproval of mutilating brain surgery and his own belief that electrical stimulation of specific brain areas was scientifically superior to oral administration of drugs whose effects were mitigated by liver metabolism, the blood-brain barrier, and uncertain distribution. in the last years of his life, jose and his wife returned to america and lived in san diego where he died unheralded. unjustly treated and harshly judged by segments of the public and his profession, jose delgado’s ground breaking research, benevolent philosophy, and memory deserve better recognition. his career trajectory may provide budding scientists with a cautionary note about the pitfalls of mingling science with philosophy. (psycinfo database record (c) 2016 apa, all rights reserved)”
Faria, M.. (2013). Violence, mental illness, and the brain – A brief history of psychosurgery: Part 3 – From deep brain stimulation to amygdalotomy for violent behavior, seizures, and pathological aggression in humans. Surgical Neurology International
“In the final installment to this three-part, essay-editorial on psychosurgery, we relate the history of deep brain stimulation (dbs) in humans and glimpse the phenomenal body of work conducted by dr. jose delgado at yale university from the 1950s to the 1970s. the inception of the national commission for the protection of human subjects of biomedical and behavioral research (1974-1978) is briefly discussed as it pertains to the ‘determination of the secretary of health, education and welfare regarding the recommendations and guidelines on psychosurgery.’ the controversial work – namely recording of brain activity, dbs, and amygdalotomy for intractable psychomotor seizures in patients with uncontrolled violence – conducted by drs. vernon h. mark and frank ervin is recounted. this final chapter recapitulates advances in neuroscience and neuroradiology in the evaluation of violent individuals and ends with a brief discussion of the problem of uncontrolled rage and ‘pathologic aggression’ in today’s modern society – as violence persists, and in response, we move toward authoritarianism, with less freedom and even less dignity.”
Marzullo, T. C.. (2017). The Missing Manuscript of Dr. Jose Delgado’s Radio Controlled Bulls.. Journal of Undergraduate Neuroscience Education : JUNE : A Publication of FUN, Faculty for Undergraduate Neuroscience
Show/hide publication abstract
“Neuroscience systems level courses teach: 1) the role of neuroanatomical structures of the brain for perception, movement, and cognition; 2) methods to manipulate and study the brain including lesions, electrophysiological recordings, microstimulation, optogenetics, and pharmacology; 3) proper interpretation of behavioral data to deduce brain circuit operation; and 4) the similarities, differences, and ethics of animal models and their relation to human physiology. these four topics come together quite dramatically in dr. jose delgado’s 1960s famous experiments on the neural correlates of aggression in which he stopped bulls in mid-charge by electrically stimulating basal ganglia and thalamic structures. technical documentation on these experiments is famously difficult to find. here i translate and discuss a spanish language article written by dr. delgado in 1981 for an encyclopedia on bull fighting published in madrid. here dr. delgado appears to give the most complete explanation of his experiments on microstimulation of bovine brains. dr. delgado’s motivations, methods, and his interpretation of the bull experiments are summarized, as well as some accompanying information from his 1970 english language book: ‘physical control of the mind.’ this review of dr. delgado’s written work on the bull experiments can provide a resource to educators and students who desire to learn more about and interpret the attention-calling experiments that dr. delgado did on a ranch in andalucía over 50 years ago.”
Zemelman, B. V.. (2017). Uncovering key neurons for manipulation in mammals. In Optogenetics: From Neuronal Function to Mapping and Disease Biology
“Introduction in one guise or another, directed manipulation of brain function can be traced back decades. while much has been made of francis crick’s musings in the 1990s on the potential power of selective neuronal stimulation (crick, 1999), remarkably effective – albeit controversial – in vivo experiments had been conducted by jose delgado nearly 30 years earlier. working with large mammals and primates, delgado demonstrated that many properties attributed to the primitive brain (maclean, 1990; panksepp, 2004) – sleep, nurture, hunger and aggression – could be modified by stimulating narrowly circumscribed groups of neurons, including by ‘remote control’ (delgado, 1964; delgado, 1969). these studies motivated ever more troubling attempts at psychosurgery in the form of localized electrical stimulation in order to diagnose, condition and treat human subjects suffering from behavioral and psychiatric disorders (heath, monroe and mickle, 1955; king, 1961; sweet, ervin and mark, 1969). current selective activation techniques, however, stem from efforts to image, rather than perturb, brain function. the advent of fluorescent protein-based cellular markers and reporters in the late 1990s represented a critical advance in combining the convenience of light with the precision of genetic encoding. such sensors helped catalyze our plan to design a method for stimulating neurons, as opposed to passively monitoring them. our 2001 overview of optical sensors ends with this prescient hypothesis: ‘… schemes [that] localize the response to illumination could [feed] patterns of distributed activity … directly into a genetically circumscribed population of neurons, irrespective of the anatomical location of its members or their connection to sensory input. perhaps the ability to probe defined groups of neurons with [light] will hold the key to an understanding of neural systems’ (zemelman and miesenböck, 2001). these sentences succinctly frame the revolution that would take place in experimental neuroscience over the following 15 years. while the tools for selective photoactivation of neurons have benefitted from numerous much-needed refinements, chief among them the cloning of channelrhodopsin (nagel et al., 2003), the prediction that light and a heterologous light receptor could be used to dissect neuronal mechanisms in vivo has been exhaustively validated across numerous systems and species.”
Peter, N., & Kleinjung, T.. (2019). Neuromodulation for tinnitus treatment: an overview of invasive and non-invasive techniques. Journal of Zhejiang University: Science B
“Tinnitus is defined as a perception of sound without any external sound source. chronic tinnitus is a frequent condition that can affect the quality of life. so far, no causal cure for tinnitus has been documented, and most pharmacologic and psychosomatic treatment modalities aim to diminish tinnitus’ impact on the quality of life. neuromodulation, a novel therapeutic modality, which aims at alternating nerve activity through a targeted delivery of a stimulus, has emerged as a potential option in tinnitus treatment. this review provides a brief overview of the current neuromodulation techniques as tinnitus treatment options. the main intention is to provide updated knowledge especially for medical professionals counselling tinnitus patients in this emerging field of medicine. non-invasive methods such as repetitive transcranial magnetic stimulation, transcranial electrical stimulation, neurofeedback, and transcutaneous vagus nerve stimulation were included, as well as invasive methods such as implanted vagus nerve stimulation and invasive brain stimulation. some of these neuromodulation techniques revealed promising results; nevertheless, further research is needed, especially regarding the pathophysiological principle as to how these neuromodulation techniques work and what neuronal change they induce. various studies suggest that individually different brain states and networks are involved in the generation and perception of tinnitus. therefore, in the future, individually tailored neuromodulation strategies could be a promising approach in tinnitus treatment for achieving a more substantial and longer lasting improvement of complaints.”
Fomenko, A., Neudorfer, C., Dallapiazza, R. F., Kalia, S. K., & Lozano, A. M.. (2018). Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications. Brain Stimulation
“Background: there is an emerging need for noninvasive neuromodulation techniques to improve patient outcomes while minimizing adverse events and morbidity. low-intensity focused ultrasound (lifus) is gaining traction as a non-surgical experimental approach of modulating brain activity. several lifus sonication parameters have been found to potentiate neural firing, suppress cortical and epileptic discharges, and alter behavior when delivered to cortical and subcortical mammalian brain regions. objective: this review introduces the elements of an effective sonication protocol and summarizes key preclinical studies on lifus as a neuromodulation modality. the state of the art in human ultrasound neuromodulation is then comprehensively summarized, and current hypotheses regarding the underlying mechanism of action on neural activity are presented. methods: peer-reviewed literature on human ultrasound neuromodulation was obtained by searching several electronic databases. the abstracts of all reports were read and publications which examined low-intensity transcranial ultrasound applied to human subjects were selected for review. results: lifus can noninvasively influence human brain activity by suppressing cortical evoked potentials, influencing cortical oscillatory dynamics, and altering outcomes of sensory/motor tasks compared to sham sonication. proposed mechanisms include cavitation, direct effects on neural ion channels, and plasma membrane deformation. conclusions: though optimal sonication paradigms and transcranial delivery methods are still being established, future applications may include non-invasive human brain mapping experiments, and nonsurgical treatments for functional neurological disorders.”
Brock, D. G., & Demitrack, M. A.. (2014). Therapeutic neuromodulation: Overview of a novel treatment platform. Psychiatric Annals
Pathak, Y. J., Greenleaf, W., Verhagen Metman, L., Kubben, P., Sarma, S., Pepin, B., … Ross, E.. (2021). Digital Health Integration With Neuromodulation Therapies: The Future of Patient-Centric Innovation in Neuromodulation. Frontiers in Digital Health
“Digital health can drive patient-centric innovation in neuromodulation by leveraging current tools to identify response predictors and digital biomarkers. iterative technological evolution has led us to an ideal point to integrate digital health with neuromodulation. here, we provide an overview of the digital health building-blocks, the status of advanced neuromodulation technologies, and future applications for neuromodulation with digital health integration.”
Velasco, F.. (2000). Neuromodulation: An overview. Archives of Medical Research
“For over two centuries, electricity has been known to induce modification of neural and nerve fiber activity and has been proposed to be used to treat some neurological dysfunctions. the new era of the use of electrical current in the treatment of neurological symptoms began in 1967 with the use of totally implanted devices that deliver a controlled amount of electricity on a precise structure within the nervous systems and was first used to control pain. extensive research has been carried out ever since to elucidate the mechanism of action of this treatment and extend its indication for the treatment of the other neurological symptoms. so far, there is evidence that the treatment is safe and efficient for long periods of time, as it does not induce permanent damage to the stimulated structure. most likely, electrical current at the parameters used for therapeutic purpose induces an inhibition of the structure on which it is applied. however, this may be accompanied by either inhibition or excitation of anatomically related structures. for this reason, it seems more convenient to refer to this type of therapy as neuromodulation.a review of the historical development of this fascinating area is presented, with special attention to the evidence derived from experimental work on the parameters that electrical current must maintain to avoid damage to the underlying tissue. copyright (c) 2000 imss.”
Tanagho, E. A.. (2012). Neuromodulation and neurostimulation: Overview and future potential. Translational Andrology and Urology
“Pediatric movement disorders are heterogeneous and complex disorders with various aetiologies. these are broadly classified as hypo and hyperkinetic disorders. genetic causes of basal ganglia dysfunction or direct injuries to the basal ganglia mark the genesis of these abnormal movements. the management of pediatric movement disorders is multidisciplinary with pharmacotherapy as the first line of management along with physical therapy. patients resistant to medications are candidates for invasive neuromodulation which is an upcoming treatment modality in pediatric movement disorders. deep brain stimulation of basal ganglia and thalamic nuclei are associated with promising symptomatic benefit with reduction in disability and improvement in quality of life of these children. in this article, we have reviewed the management of pediatric movement disorders with emphasis on neuromodulation i.e., deep brain stimulation.”
Roy, H., Offiah, I., & Dua, A.. (2018). Neuromodulation for pelvic and urogenital pain. Brain Sciences
“Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. in cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. however, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. the aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. however, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes.”
N., P., & T., K.. (2019). Neuromodulation for tinnitus treatment: an overview of invasive and non-invasive techniques. Journal of Zhejiang University: Science B
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“Tinnitus is defined as a perception of sound without any external sound source. chronic tinnitus is a frequent condition that can affect the quality of life. so far, no causal cure for tinnitus has been documented, and most pharmacologic and psychosomatic treatment modalities aim to diminish tinnitus’ impact on the quality of life. neuromodulation, a novel therapeutic modality, which aims at alternating nerve activity through a targeted delivery of a stimulus, has emerged as a potential option in tinnitus treatment. this review provides a brief overview of the current neuromodulation techniques as tinnitus treatment options. the main intention is to provide updated knowledge especially for medical professionals counselling tinnitus patients in this emerging field of medicine. non-invasive methods such as repetitive transcranial magnetic stimulation, transcranial electrical stimulation, neurofeedback, and transcutaneous vagus nerve stimulation were included, as well as invasive methods such as implanted vagus nerve stimulation and invasive brain stimulation. some of these neuromodulation techniques revealed promising results; nevertheless, further research is needed, especially regarding the pathophysiological principle as to how these neuromodulation techniques work and what neuronal change they induce. various studies suggest that individually different brain states and networks are involved in the generation and perception of tinnitus. therefore, in the future, individually tailored neuromodulation strategies could be a promising approach in tinnitus treatment for achieving a more substantial and longer lasting improvement of complaints.”
McCormick, D. A., & Nusbaum, M. P.. (2014). Editorial overview: Neuromodulation: Tuning the properties of neurons, networks and behavior. Current Opinion in Neurobiology
“Neuromodulation is a clinical tool used for treating chronic neuropathic pain by transmitting controlled physical energy to the pre-identified neural targets in the central nervous system. its drug-free, nonaddictive, and improved targeting characteristics have attracted increasing attention among neuroscience research and clinical practices. this article provides a brief overview of the neuropathic pain and pharmacological routines for treatment, summarizes both the invasive and noninvasive neuromodulation modalities for pain management, and highlights an emerging brain stimulation technology, transcranial focused ultrasound (tfus), with a focus on ultrasound transducer devices and the achieved neuromodulation effects and applications on pain management. practical considerations of spatial guidance for tfus are discussed for clinical applications. the safety of transcranial ultrasound neuromodulation and its future prospectives on pain management are also discussed.”
(2019). An overview on Neuromodulation. Case Medical Research
Waldron, N. H., Fudim, M., Mathew, J. P., & Piccini, J. P.. (2019). Neuromodulation for the Treatment of Heart Rhythm Disorders. JACC: Basic to Translational Science
“There is an increasing recognition of the importance of interactions between the heart and the autonomic nervous system in the pathophysiology of arrhythmias. these interactions play a role in both the initiation and maintenance of arrhythmias and are important in both atrial and ventricular arrhythmia. given the importance of the autonomic nervous system in the pathophysiology of arrhythmias, there has been notable effort in the field to improve existing therapies and pioneer additional interventions directed at cardiac-autonomic targets. the interventions are targeted to multiple and different anatomic targets across the neurocardiac axis. the purpose of this review is to provide an overview of the rationale for neuromodulation in the treatment of arrhythmias and to review the specific treatments under evaluation and development for the treatment of both atrial fibrillation and ventricular arrhythmias.”
Luigjes, J., Breteler, R., Vanneste, S., & de Ridder, D.. (2013). [Neuromodulation as an intervention for addiction: overview and future prospects].. Tijdschrift Voor Psychiatrie
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“BACKGROUND in recent years several neuromodulation techniques have been introduced as interventions for addiction. aim to review and discuss studies that have investigated the effects of treating addiction by means of electroencephalography (eeg) neurofeedback, real-time functional magnetic resonance imaging (rt-fmri) neurofeedback, transcranial magnetic stimulation/transcranial direct current stimulation (tms/tdcs) and deep brain stimulation (dbs). method we reviewed the literature, focusing on dutch studies in particular. results studies using eeg neurofeedback were shown to have positive effects on drug use, treatment compliance, and cue reactivity in patients with cocaine and alcohol dependence. a pilot study investigating the effects of rt-fmri neurofeedback on nicotine dependent patients showed that modulation of the anterior cingulate cortex can decrease smokers’ craving for nicotine. in several studies decreased craving was found in alcohol dependent patients after tms or tdcs stimulation of the anterior cingulate cortex or the dorsolateral prefrontal cortex. the first dbs pilot studies suggest that the nucleus accumbens is a promising target region for the treatment of alcohol and heroin dependence. conclusion neuromodulation provides us with a unique opportunity to directly apply neuroscientific knowledge to the treatment of addiction. however, more research is needed to ensure the efficacy, safety and feasibility of the various neuromodulation techniques that are now available.”
Brunoni, A. R., Teng, C. T., Correa, C., Imamura, M., Brasil-Neto, J. P., Boechat, R., … Fregni, F.. (2010). Neuromodulation approaches for the treatment of major depression: Challenges and recommendations from a working group meeting. Arquivos de Neuro-Psiquiatria
“The use of neuromodulation as a treatment for major depressive disorder (mdd) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ect) such as transcranial magnetic stimulation (tms), transcranial direct current stimulation (tdcs), deep brain stimulation (dbs), and vagus nerve stimulation (vns). method: we convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of mdd. results: the state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of mdd; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in mdd associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. discussion: ect is the first-line treatment for severe depression. tms and tdcs are strategies with a relative benign profile of side effects; however, while tms effects are comparable to antidepressant drugs for treating mdd; further research is needed to establish the role of tdcs. dbs and vns are invasive strategies with a possible role in treatment-resistant depression. in summary, mdd is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.”
Antony, A. B., Mazzola, A. J., Dhaliwal, G. S., & Hunter, C. W.. (2019). Neurostimulation for the treatment of chronic head and facial pain: A literature review. Pain Physician
“Background: head and facial pain is a common and often difficult to treat disorder. routine treatments sometimes fail to provide acceptable relief, leaving the patient searching for something else, including narcotics and surgery. recently, neuromodulation has been expanding to provide another option. secondary to its potentially temporary nature and relatively manageable risk profile, several reviews have suggested trialing neuromodulation prior to starting narcotics or invasive permanent surgeries. there is evidence that neuromodulation can make a difference in those patients with intractable severe craniofacial pain. objectives: to provide a basic overview of the anatomy, epidemiology, pathophysiology and common treatments of several common head and facial disorders. furthermore, to demonstrate the suggested mechanisms of neuromodulation and the evidence currently existing for the use of neuromodulation. methods: a comprehensive review was performed regarding the available literature through targeting articles reporting on the use of neuromodulation to treat pain of the head and face. results: we compiled and discuss the current evidence available in treating head and facial pain. the strongest evidence currently for neuromodulation is for occipital nerve stimulation for migraine, transcutaneous vagal nerve stimulation for migraine and cluster headache, sphenopalatine ganglion microstimulation for cluster headache, and transcutaneous supraorbital and supratrochlear nerve stimulation for migraine. in addition, there is moderate evidence for occipital nerve stimulation in treating occipital neuralgia. limitations: neuromodulation has been trialed and is promising in several craniofacial pain disorders; however, there remains a need for large-scale, randomized, placebo-controlled clinical trials to further evaluate the efficacy and safety of most treatments. much of the current data relies on case reports without randomization or placebo controls. conclusions: with advancing techniques and technology, neuromodulation can be promising in treating intractable pain of the head and face. although more randomized controlled trials are warranted, the current literature supports the use of neuromodulation in intractable craniofacial pain.”
Schluter, R. S., Daams, J. G., Van Holst, R. J., & Goudriaan, A. E.. (2018). Effects of non-invasive neuromodulation on executive and other cognitive functions in addictive disorders: A systematic review. Frontiers in Neuroscience
“Background: in order to improve the current treatment of addictive disorders non-invasive neuromodulation over the dorsolateral prefrontal cortex (dlpfc) has gained attention. the dlpfc is crucially involved in executive functioning, functions which are related to the course of addictive disorders. non-invasive stimulation of the dlpfc may lead to changes in executive functioning. currently an overview of effects of neuromodulation on these functions is lacking. therefore, this systematic review addresses the effects of non-invasive neuromodulation on executive functioning in addictive disorders. methods: the current review is conducted and reported in accordance with the preferred reporting items for systematic reviews and meta-analyses for protocols 2015 (prisma-p 2015) guidelines and has been registered in prospero international prospective register of systematic reviews (www.crd.york.ac.uk/prospero/, registration number: crd42018084157). original articles were searched using the ovid medline, embase and psycinfo database. results: the systematic search resulted in 1,228 unique studies, of which sixteen were included in the current review. some of these studies do not address the classic definition of executive functions, but another cognitive function. however, they were included in this review since the field is small and still under development and we aim to give an inclusive overview in its broadest sense. the following executive and other cognitive functioning domains were assessed: attention, cognitive flexibility, response inhibition, memory and learning, problem solving, social cognition, risk taking, cognitive bias modification and overall executive functioning. the executive function domain most positively affected was social cognition followed by memory & learning, response inhibition, cognitive flexibility and attention. conclusions: the studies addressed in the current review used a large variability of stimulation protocols and study designs which complicates comparability of the results. nevertheless, the results of these studies are promising in light of improvement of current treatment. therefore, we recommend future studies that compare the effect of different types of stimulation, stimulation sides and number of stimulation sessions in larger clinical trials. this will significantly increase the comparability of the studies and thereby accelerate and clarify the conclusion on whether non-invasive neuromodulation is an effec…”
Hunter, C. W., Stovall, B., Chen, G., Carlson, J., & Levy, R.. (2018). Anatomy, pathophysiology and interventional therapies for chronic pelvic pain: A review. Pain Physician
“Background: chronic pelvic pain (cpp) represents a group of poorly understood disorders that are often refractory to conventional treatment. referral to pain management typically occurs later in the continuum of care; as such, many of the injections and nerve blocks commonly prescribed for such patients are potentially limited in efficacy. while neuromodulation is conventionally considered the next algorithmic step in the treatment of chronic pain after injections fail, there is a common perception that neuromodulation is largely ineffective for cpp conditions. however, there is evidence that suggests neuromodulation may in fact be a viable treatment option for this particular patient population when utilized properly. objectives: to provide a basic overview of the pathophysiology of cpp and the relevant neuroanatomy as it pertains to various available treatment options, as well as the techniques and potential targets for neuromodulation. study design: literature review. setting: private practice, academic and hospital setting. methods: a comprehensive review of the available literature was performed targeting publications focused on cpp and various techniques for utilizing neuromodulation to treat it. results: neuromodulation is an established treatment modalities, however its usefulness as it relates to treating cpp has typically been drawn into question. in this literature review, we discuss the efficacy of various techniques for treating cpp with neuromodulation. limitations: evidence to support the various treatments, while encouraging, is based on small studies and case series. large-scale randomized, placebo-controlled clinical trials are warranted to evaluate the clinical efficacy and safety of the different treatments described, particularly neuromodulation. conclusions: in addition to the percutaneous, injection-based treatments described herein, neuromodulation remains a plausible option for recalcitrant cases that fail to respond to more conventional means.”
Powell, K., Shah, K., Hao, C., Wu, Y.-C., John, A., Narayan, R. K., & Li, C.. (2019). Neuromodulation as a new avenue for resuscitation in hemorrhagic shock. Bioelectronic Medicine
“Hemorrhagic shock (hs), a major cause of early death from trauma, accounts for around 40% of mortality, with 33–56% of these deaths occurring before the patient reaches a medical facility. intravenous fluid therapy and blood transfusions are the cornerstone of treating hs. however, these options may not be available soon after the injury, resulting in death or a poorer quality of survival. therefore, new strategies are needed to manage hs patients before they can receive definitive care. recently, various forms of neuromodulation have been investigated as possible supplementary treatments for hs in the prehospital phase of care. here, we provide an overview of neuromodulation methods that show promise to treat hs, such as vagus nerve stimulation, electroacupuncture, trigeminal nerve stimulation, and phrenic nerve stimulation and outline their possible mechanisms in the treatment of hs. although all of these approaches are only validated in the preclinical models of hs and are yet to be translated to clinical settings, they clearly represent a paradigm shift in the way that this deadly condition is managed in the future.”
Fletcher, N.. (2020). An overview of sacral neuromodulation: A treatment for patients with symptoms of lower urinary tract dysfunction. British Journal of Nursing
“This article provides an introduction to patient selection for, and the processes involved in, sacral neuromodulation (snm) device implantation as a treatment for urinary symptoms. snm has been an option to treat lower urinary tract dysfunction for more than 20 years and is a treatment for both overactive bladder syndrome (oab) and female non obstructed chronic urinary retention (fcur). it is recognised by the national institute for health and care excellence as a therapeutic option for oab and fcur. snm has its place in the pathway for the treatment of both conditions and, in the correctly assessed patient, can be the last option before considering major surgical intervention.”
Shin, S. S., & Pelled, G.. (2017). Novel neuromodulation techniques to assess interhemispheric communication in neural injury and neurodegenerative diseases. Frontiers in Neural Circuits
“Interhemispheric interaction has a major role in various neurobehavioral functions. its disruption is a major contributor to the pathological changes in the setting of brain injury such as traumatic brain injury, peripheral nerve injury, and stroke, as well as neurodegenerative diseases. because interhemispheric interaction has a crucial role in functional consequence in these neuropathological states, a review of noninvasive and state-of-the-art molecular based neuromodulation methods that focus on or have the potential to elucidate interhemispheric interaction have been performed. this yielded approximately 170 relevant articles on human subjects or animal models. there has been a recent surge of reports on noninvasive methods such as transcranial magnetic stimulation and transcranial direct current stimulation. since these are noninvasive techniques with little to no side effects, their widespread use in clinical studies can be easily justified. the overview of novel neuromodulation methods and how they can be applied to study the role of interhemispheric communication in neural injury and neurodegenerative disease is provided. additionally, the potential of each method in therapeutic use as well as investigating the pathophysiology of interhemispheric interaction in neurodegenerative diseases and brain injury is discussed. new technologies such as transcranial magnetic stimulation or transcranial direct current stimulation could have a great impact in understanding interhemispheric pathophysiology associated with acquired injury and neurodegenerative diseases, as well as designing improved rehabilitation therapies. also, advances in molecular based neuromodulation techniques such as optogenetics and other chemical, thermal, and magnetic based methods provide new capabilities to stimulate or inhibit a specific brain location and a specific neuronal population.”
Abboud, H., Hill, E., Siddiqui, J., Serra, A., & Walter, B.. (2017). Neuromodulation in multiple sclerosis. Multiple Sclerosis
“Neuromodulation, or the utilization of advanced technology for targeted electrical or chemical neuronal stimulation or inhibition, has been expanding in several neurological subspecialties. in the past decades, immune-modulating therapy has been the main focus of multiple sclerosis (ms) research with little attention to neuromodulation. however, with the recent advances in disease-modifying therapies, it is time to shift the focus of ms research to neuromodulation and restoration of function as with other neurological subspecialties. preliminary research supports the value of intrathecal baclofen pump and functional electrical stimulation in improving spasticity and motor function in ms patients. deep brain stimulation can improve ms-related tremor and trigeminal neuralgia. spinal cord stimulation has been shown to be effective against ms-related pain and bladder dysfunction. bladder overactivity also responds to sacral neuromodulation and posterior tibial nerve stimulation. despite limited data in ms, transcranial magnetic stimulation and brain–computer interface are promising neuromodulatory techniques for symptom mitigation and neurorehabilitation of ms patients. in this review, we provide an overview of the available neuromodulatory techniques and the evidence for their use in ms.”
Tohyama, S., Walker, M. R., Sammartino, F., Krishna, V., & Hodaie, M.. (2020). The Utility of Diffusion Tensor Imaging in Neuromodulation: Moving Beyond Conventional Magnetic Resonance Imaging. Neuromodulation
“Objectives: conventional targeting methods for neuromodulation therapies are insufficient for visualizing targets along white matter pathways and localizing targets in patient-specific space. diffusion tensor imaging (dti) holds promise for enhancing neuromodulation targeting by allowing detailed visualization of white matter tracts and their connections on an individual level. material and methods: we review the literature on dti and neuromodulation, focusing on clinical studies that have utilized dti tractography for surgical neuromodulation planning. this primarily includes the growing number of studies on tractography-guided targeting in deep brain stimulation as well as magnetic resonance-guided focused ultrasound. results: in this review, we discuss three main topics: 1) an overview of the basic principles of dti, its metrics, and tractography, 2) the evolution and utility of dti to better guide neuromodulation targets, and 3) the ability of dti to investigate structural connectivity and brain networks, and how such a network perspective may be an integral part of identifying new or optimal neuromodulation targets. conclusion: there is increasing evidence that dti is superior to conventional targeting methods with respect to improving brain stimulation therapies. dti has the ability to better define anatomical targets by allowing detailed visualization of white matter tracts and localizing targets based on individual anatomy. network analyses can lead to the identification of new or optimal stimulation targets based on understanding how target regions are connected. the integration of dti as part of routine mri and surgical planning offers a more personalized approach to therapy and may be an important path for the future of neuromodulation.”
Lakatos, P., Gross, J., & Thut, G.. (2019). A New Unifying Account of the Roles of Neuronal Entrainment. Current Biology
“Rhythms are a fundamental and defining feature of neuronal activity in animals including humans. this rhythmic brain activity interacts in complex ways with rhythms in the internal and external environment through the phenomenon of ‘neuronal entrainment’, which is attracting increasing attention due to its suggested role in a multitude of sensory and cognitive processes. some senses, such as touch and vision, sample the environment rhythmically, while others, like audition, are faced with mostly rhythmic inputs. entrainment couples rhythmic brain activity to external and internal rhythmic events, serving fine-grained routing and modulation of external and internal signals across multiple spatial and temporal hierarchies. this interaction between a brain and its environment can be experimentally investigated and even modified by rhythmic sensory stimuli or invasive and non-invasive neuromodulation techniques. we provide a comprehensive overview of the topic and propose a theoretical framework of how neuronal entrainment dynamically structures information from incoming neuronal, bodily and environmental sources. we discuss the different types of neuronal entrainment, the conceptual advances in the field, and converging evidence for general principles. lakatos, gross, and thut review the evidence for neuronal entrainment by environmental, self-produced, and neuromodulatory rhythms, which leads them to propose a new, unifying account of the role of neuronal entrainment in the selection and structuring of information – taking into account the brain in a wider context.”
Vlaicu, A., & Bustuchina Vlaicu, M.. (2020). New neuromodulation techniques for treatment resistant depression. International Journal of Psychiatry in Clinical Practice
“In the treatment of depression, when pharmacotherapy, psychotherapy and the oldest brain stimulation techniques are deadlocked, the emergence of new therapies is a necessary development. the field of neuromodulation is very broad and controversial. this article provides an overview of current progress in the technological advances in neuromodulation and neurostimulation treatments for treatment-resistant depression: magnetic seizure therapy; focal electrically administered seizure therapy; low field magnetic stimulation; transcranial pulsed electromagnetic fields; transcranial direct current stimulation; epidural cortical stimulation; trigeminal nerve stimulation; transcutaneous vagus nerve stimulation; transcranial focussed ultrasound; near infra-red transcranial radiation; closed loop stimulation. the role of new interventions is expanding, probably with more efficacy. nowadays, still under experimentation, neuromodulation will probably revolutionise the field of neuroscience. at present, major efforts are still necessary before that these therapies are likely to become widespread.key points there is a critical need for new therapies for treatment resistant depression. newer therapies are expanding. in the future, these therapies, as an evidence-based adjunctive treatments, could offer a good therapeutic choice for the patients with a trd. the current trend in the new neuromodulation therapies is to apply a personalised treatment. these news therapies can be complementary. that treatment approaches can provide clinically significant benefits.”
Yang, X., McGlynn, E., Das, R., Paşca, S. P., Cui, B., & Heidari, H.. (2021). Nanotechnology Enables Novel Modalities for Neuromodulation. Advanced Materials
“Neuromodulation is of great importance both as a fundamental neuroscience research tool for analyzing and understanding the brain function, and as a therapeutic avenue for treating brain disorders. here, an overview of conceptual and technical progress in developing neuromodulation strategies is provided, and it is suggested that recent advances in nanotechnology are enabling novel neuromodulation modalities with less invasiveness, improved biointerfaces, deeper penetration, and higher spatiotemporal precision. the use of nanotechnology and the employment of versatile nanomaterials and nanoscale devices with tailored physical properties have led to considerable research progress. to conclude, an outlook discussing current challenges and future directions for next-generation neuromodulation modalities is presented.”
Ramirez-Zamora, A., Giordano, J. J., Gunduz, A., Brown, P., Sanchez, J. C., Foote, K. D., … Okun, M. S.. (2018). Evolving applications, technological challenges and future opportunities in neuromodulation: Proceedings of the fifth annual deep brain stimulation think tank. Frontiers in Neuroscience
“The annual deep brain stimulation (dbs) think tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. the proceedings of the fifth think tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including parkinson’s disease, dystonia, essential tremor, tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. the report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. specifically, this year’s meeting focused on technical developments in dbs, design considerations for dbs electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive dbs (closed-loop systems), updates on national institutes of health and darpa dbs programs of the brain initiative, and neuroethical and policy issues arising in and from dbs research and applications in practice.”
Goudriaan, A. E., & Schluter, R. S.. (2019). Non-invasive Neuromodulation in Problem Gambling: What Are the Odds?. Current Addiction Reports
“Purpose of review: non-invasive neuromodulation as a potential therapeutic target in addiction treatment is a fast-growing, but nascent research field. with gambling disorder as the first behavioral addiction, the goal of this review is to provide an overview of the current state-of-the-art of neuromodulation in substance use disorders and gambling disorder. recent findings: only a few neuromodulation studies in gambling disorder are present, most of these are single-session studies. effects of rtms on craving have been described, but large placebo effects are also present, indicating a need for larger, blinded, multiple-session neuromodulation trials. summary: the field of neuromodulation in gambling is in its infancy, given the limited number of studies, with small sample sizes. the effects that neuromodulation can have on diminishing craving and improving cognitive functions in substance use disorders are promising. as these factors also play a role in relapse in gambling disorder, these findings in suds indicate that investment in larger studies in gambling disorder, focusing on both clinically relevant outcome measures and on intermediate working mechanisms like craving and cognitive functions, is warranted.”
Elias, G. J. B., Boutet, A., Parmar, R., Wong, E. H. Y., Germann, J., Loh, A., … Bhat, V.. (2021). Neuromodulatory treatments for psychiatric disease: A comprehensive survey of the clinical trial landscape. Brain Stimulation
“Background: numerous neuromodulatory therapies are currently under investigation or in clinical use for the treatment of psychiatric conditions. objective/hypothesis: we sought to catalogue past and present human research studies on psychiatric neuromodulation and identify relevant trends in this field. methods: clinicaltrials.gov (www.clinicaltrials.gov/) and the international clinical trials registry platform (www.who.int/ictrp/en/) were queried in march 2020 for trials assessing the outcome of neuromodulation for psychiatric disorders. relevant trials were categorized by variables such as neuromodulation modality, country, brain target, publication status, design, and funding source. results: from 72,086 initial search results, 1252 unique trials were identified. the number of trials registered annually has consistently increased. half of all trials were active and a quarter have translated to publications. the largest proportion of trials involved depression (45%), schizophrenia (18%), and substance use disorders (14%). trials spanned 37 countries; china, the second largest contributor (13%) after the united states (28%), has increased its output substantially in recent years. over 75% of trials involved non-convulsive non-invasive modalities (e.g., transcranial magnetic stimulation), while convulsive (e.g., electroconvulsive therapy) and invasive modalities (e.g., deep brain stimulation) were less represented. 72% of trials featured approved or cleared interventions. characteristic inter-modality differences were observed with respect to enrollment size, trial design/phase, and funding. dorsolateral prefrontal cortex accounted for over half of focal neuromodulation trial targets. the proportion of trials examining biological correlates of neuromodulation has increased. conclusion(s): these results provide a comprehensive overview of the state of psychiatric neuromodulation research, revealing the growing scope and internationalism of this field.”
Doshi, P. P., Russo, M., & Doshi, P. K.. (2021). Practice Trends of Neuromodulation Therapies for Pain and Spasticity in India. Neuromodulation
“Background: neuromodulation has been successfully used globally to address severe refractory chronic pain for over five decades. compared to the wide acceptance that it enjoys in united states and europe, it is fairly underutilized in asia, including india. objectives: we conducted the first systematic nationwide survey to provide an overview of neuromodulation in the past 20 years to investigate the practice trends for severe refractory chronic pain and barriers for the uptake of neuromodulation therapies for pain in india. design: a 20-point detailed questionnaire survey was sent out for online completion in august 2020 to practitioners in india involved in interventions for pain. the survey was completed by 112 practitioners (10% return rate). the response data collected were analyzed, tabulated, and presented as percentages. results: the average duration of pain practice in india for the majority of respondents was less than a decade. about 70% of practitioners expressed that they manage severe refractory pain without neuromodulation. this survey confirms that neuromodulation is grossly underutilized for pain, comprising only 10% of total neuromodulation implants performed per annum in india. the most common indications were neuropathic pain (45%) and failed back surgery syndrome (42%). the respondents expressed the main barriers to be related to the cost (85%); lack of awareness (68%) and lack of good training (59%). more than 50% of respondents also expressed difficulty of access to neuromodulation therapies for pain and acceptance by patients. conclusion: the younger generation of pain practitioners in india is becoming more aware and convinced about the role of neuromodulation to alleviate severe pain and suffering. an all-round approach combining improved training, awareness at various levels, more flexible options of newer technology and reimbursement approval can positively influence its use. this can be achieved with the collective efforts of physicians, insurers, industry, and focused academic activities of clinical societies.”
Ward, M., Doran, J., Paskhover, B., & Mammis, A.. (2018). The 50 Most Cited Articles in Invasive Neuromodulation. World Neurosurgery
“Objective: bibliometric analysis is a commonly used analytic tool for objective determination of the most influential and peer-recognized articles within a given field. this study is the first bibliometric analysis of the literature in the field of invasive neuromodulation, excluding deep brain stimulation. the objectives of this study are to identify the 50 most cited articles in invasive neuromodulation, provide an overview of the literature to assist in clinical education, and evaluate the effect of impact factor on manuscript recognition. methods: bibliometric analysis was performed using the science citation index from the institute for scientific information, accessed through the web of science. search terms relevant to the field of invasive neuromodulation were used to identify the 50 most cited journal articles between 1900 and 2016. results: the median number of citations was 236 (range, 173–578). the most common topics among the articles were vagus nerve stimulation (n = 24), spinal cord stimulation (n = 9), and motor cortex stimulation (n = 6). median journal impact factor was 5.57. most of these articles (n = 19) contained level i, ii, or iii evidence. conclusions: this analysis provides a brief look into the most cited articles within the field, many of which evaluated innovated procedures and therapies that helped to drive surgical neuromodulation forward. these landmark articles contain vital clinical and educational information that remains relevant to clinicians and students within the field and provide insight into areas of expanding research. journal impact factor may play a significant role in determining the literary relevance and general awareness of invasive neuromodulation studies.”
Starling, A.. (2018). Noninvasive neuromodulation in migraine and cluster headache. Current Opinion in Neurology
“Purpose of review the purpose of this narrative review is to provide an overview of the currently available noninvasive neuromodulation devices for the treatment of migraine and cluster headache. recent findings over the last decade, several noninvasive devices have undergone development and clinical trials to evaluate efficacy and safety. based on this body of work, single-pulse transcranial magnetic stimulation, transcutaneous supraorbital neurostimulation, and noninvasive vagal nerve stimulation devices have been cleared by the united states food and drug administration and are available for clinical use for the treatment of primary headache disorders. summary overall, these novel noninvasive devices appear to be safe, well tolerated, and have demonstrated promising results in clinical trials in both migraine and cluster headache. this narrative review will provide a summary and update of the proposed mechanisms of action, evidence, safety, and future directions of various currently available modalities of noninvasive neuromodulation for the treatment of migraine and cluster headache.”
Senova, S., Fomenko, A., Gondard, E., & Lozano, A. M.. (2020). Anatomy and function of the fornix in the context of its potential as a therapeutic target. Journal of Neurology, Neurosurgery and Psychiatry
“The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play a key role in cognition and episodic memory recall. as the most prevalent cause of dementia, alzheimer’s disease (ad) dramatically impairs the quality of life of patients and imposes a significant societal burden on the healthcare system. as an established treatment for movement disorders, deep brain stimulation (dbs) is currently being investigated in preclinical and clinical studies for treatment of memory impairment in ad by modulating fornix activity. optimal target and stimulation parameters to potentially rescue memory deficits have yet to be determined. the aim of this review is to consolidate the structural and functional aspects of the fornix in the context of neuromodulation for memory deficits. we first present an anatomical and functional overview of the fibres and structures interconnected by the fornix. recent evidence from preclinical models suggests that the fornix is subdivided into two distinct functional axes: a septohippocampal pathway and a subiculothalamic pathway. each pathway’s target and origin structures are presented, followed by a discussion of their oscillatory dynamics and functional connectivity. overall, neuromodulation of each pathway of the fornix is discussed in the context of evidence-based forniceal dbs strategies. it is not yet known whether driving fornix activity can enhance cognition-optimal target and stimulation parameters to rescue memory deficits have yet to be determined.”
Doesborg, P., & Haan, J.. (2018). Cluster headache: New targets and options for treatment. F1000Research
“Cluster headache is a severe headache disorder with considerable impact on quality of life. the pathophysiology of the disease remains poorly understood. with few specific targets for treatment, current guidelines mainly include off-label treatment with medication. however, new targets for possible treatment options are emerging. calcitonin gene-related peptide (cgrp)-targeted medication could become the first (cluster) headache-specific treatment option. other exciting new treatment options include invasive and non-invasive neuromodulation techniques. here, we provide a short overview of new targets and treatment options that are being investigated for cluster headache.”
Gardner, J.. (2017). Securing a future for responsible neuromodulation in children: The importance of maintaining a broad clinical gaze. European Journal of Paediatric Neurology
“Aim this perspective paper provides an overview of several key tensions and challenges within the social context of neuromodulation, and it suggests a means of securing the future of paediatric neuromodulation in light of these. results tensions and challenges relate to: the considerable clinical and economic need for new therapies to manage neurological diseases; significant commercial involvement in the field; funding pressures; public perceptions (particularly unrealistic expectations); and the emerging responsible research and innovation initiative. this paper argues that managing these challenges and tensions requires that clinicians working within the field adopt what could be called a broad clinical gaze. this paper will define the broad clinical gaze, and it will propose several ways in which a broad clinical gaze can be – and indeed is being – operationalised in recent advances in neuromodulation in children. these include the use of multidisciplinary and interdisciplinary clinical team structures, the adoption of clinical assessment tools that capture day-to-day functionality, and the use of patient registries. conclusion by adopting a broad clinical gaze, clinicians and investigators can ensure that the field as a whole can responsibly and ethically deliver on its significant clinical potential.”
Crockett, M. J., & Fehr, E.. (2014). Social brains on drugs: Tools for neuromodulation in social neuroscience. Social Cognitive and Affective Neuroscience
Edwards, C. A., Kouzani, A., Lee, K. H., & Ross, E. K.. (2017). Neurostimulation Devices for the Treatment of Neurologic Disorders. Mayo Clinic Proceedings
“Rapid advancements in neurostimulation technologies are providing relief to an unprecedented number of patients affected by debilitating neurologic and psychiatric disorders. neurostimulation therapies include invasive and noninvasive approaches that involve the application of electrical stimulation to drive neural function within a circuit. this review focuses on established invasive electrical stimulation systems used clinically to induce therapeutic neuromodulation of dysfunctional neural circuitry. these implantable neurostimulation systems target specific deep subcortical, cortical, spinal, cranial, and peripheral nerve structures to modulate neuronal activity, providing therapeutic effects for a myriad of neuropsychiatric disorders. recent advances in neurotechnologies and neuroimaging, along with an increased understanding of neurocircuitry, are factors contributing to the rapid rise in the use of neurostimulation therapies to treat an increasingly wide range of neurologic and psychiatric disorders. electrical stimulation technologies are evolving after remaining fairly stagnant for the past 30 years, moving toward potential closed-loop therapeutic control systems with the ability to deliver stimulation with higher spatial resolution to provide continuous customized neuromodulation for optimal clinical outcomes. even so, there is still much to be learned about disease pathogenesis of these neurodegenerative and psychiatric disorders and the latent mechanisms of neurostimulation that provide therapeutic relief. this review provides an overview of the increasingly common stimulation systems, their clinical indications, and enabling technologies.”
Rimmele, F., & Jürgens, T. P.. (2020). Neuromodulation in primary headaches: current evidence and integration into clinical practice. Current Opinion in Neurology
“PURPOSE of review: neuromodulatory approaches add to our armamentarium of therapeutic tools for the treatment of primary headaches. this review provides a comprehensive overview of current controlled studies on the different neuromodulation techniques and recommendations for clinical practice. recent findings: evidence for efficacy of transcutaneous vagal nerve stimulation (tvns) is limited to acute use in migraine with ambiguous results and episodic cluster headache as well as chronic cluster headache if applied in addition to conventional treatment. transcutaneous stimulation of the supraorbital and supratrochlear nerve was effective in both acute and preventive stimulation (the latter with ambiguous results) in episodic migraines. thus, invasive procedures should be reserved for severe and refractory cases only. occipital nerve stimulation for chronic refractory cluster headache is the only available invasive approach with a conformité européenne mark. summary: neuromodulation can complement conventional therapy, with noninvasive procedures being used preferably. given the limited number of studies for each modality and the lack of head-to-head studies, it is difficult to place neuromodulation techniques in a conventional treatment algorithm.”
La Rosa, V. L., Platania, A., Ciebiera, M., Garzon, S., Jȩdra, R., Ponta, M., & Buttice, S.. (2019). A comparison of sacral neuromodulation vs. transvaginal electrical stimulation for the treatment of refractory overactive bladder: The impact on quality of life, body image, sexual function, and emotional well-being. Przeglad Menopauzalny
“Overactive bladder syndrome (oab) is defined by the presence of urinary urgency, with or without urge incontinence, usually accompanied by an increase in urinary frequency and nocturia in the absence of urinary tract infections (uti) or other diseases. the overall prevalence of oab symptoms in the female population is reported to be 16.6% and increases with advancing age and menopause. the aetiology of oab is not fully understood and is likely to affect a heterogeneous population of patients due to changes to their central and peripheral nervous systems. although oab is frequently associated with female sexual dysfunction (fsd), its real impact on sexual function in women has been evaluated only in a few studies. the first line of treatment for oab includes behavioural modification and physical therapy, either as monotherapies or in combination. many patients who have not had success in managing their symptoms with more conservative therapies may decide to resort to third-line treatments for refractory oab. these treatments include neuromodulation therapies, particularly transvaginal electrical stimulation (tes) and sacral neuromodulation (sn). the aim of this short commentary is to provide an overview of the effectiveness of these treatments and of their impact on quality of life, body image, sexual function, and emotional well-being.”
Pericolini, M., Miget, G., Hentzen, C., Finazzi Agrò, E., Chesnel, C., Lagnau, P., … Amarenco, G.. (2021). Cortical, Spinal, Sacral, and Peripheral Neuromodulations as Therapeutic Approaches for the Treatment of Lower Urinary Tract Symptoms in Multiple Sclerosis Patients: A Review. Neuromodulation
“Introduction: multiple sclerosis (ms) is often associated with urological disorders, mainly urinary incontinence and retention, the management of which being necessary to improve patient’s quality of life (qol) and to reduce potential urological complications. besides the classical treatments based mainly on anticholinergics and/or self-catheterization, several neuromodulation techniques have been tried in recent years to improve these urinary disorders. by this review, we aim at providing an overview of neuromodulation and electrostimulation approaches to manage urinary symptoms in ms patients. materials and methods: a literature search using medline was performed. only papers in english, and describing the effects of neuromodulation in ms patients, were considered. results: a total of 18 studies met inclusion criteria and were reviewed. of them, four related to sacral neuromodulation (snm), seven to percutaneous tibial nerve stimulation (ptns), six to spinal cord stimulation (scs), and one to transcranial magnetic stimulation (tms). discussion: ptns and snm seem to be effective and safe therapeutic options for treating lower urinary tract symptoms in ms patients principally in case of overactive bladder (oab) symptoms. similarly, also scs and tms have been shown to be effective, despite the very limited number of patients and the small number of studies found in the literature. interestingly, these techniques are effective even in patients who do not respond well to conservative therapies, such as anticholinergics. furthermore, given their safety and efficacy, stimulations such as ptns could be considered as a first-line treatment for oab in ms patients, also considering that they are often preferred by patients to other commonly used treatments.”
Pauwels, N., Willemse, C., Hellemans, S., Komen, N., Van den Broeck, S., Roenen, J., … De Schepper, H.. (2021). The role of neuromodulation in chronic functional constipation: A systematic review. Acta Gastro-Enterologica Belgica
“Background: chronic functional constipation is a highly prevalent disorder in which, when conservative measures fail to relieve symptoms, surgical interventions are sometimes indicated. in recent years, neuromodulation for the treatment of functional constipation has gained interest but its role and effectiveness are still unclear. the purpose of this review is to provide a systematic overview on the current literature on the different modalities of neurostimulation and their effect on chronic functional constipation in adults as reported in the literature. methods: a search in the literature for articles concerning the effect of different types of neuromodulation on constipation was performed in pubmed using extensive search terms for the different modalities of neuromodulation. studies and trials were checked for eligibility. for all types of neuromodulation together, 27 articles were included. results: 17 studies were included on snm (sacral nerve modulation). although multiple studies show positive results on the effect of snm in constipation, double-blind crossover rct’s (randomised controlled trials) showed no significant effect. 3 studies were included for tsns (transcutaneous sacral nerve stimulation), 2 for ptns (percutaneous tibial nerve stimulation) and 2 for ttns (transcutaneous tibial nerve stimulation). studies and trials on these modalities of neuromodulation reported ambiguous results on statistical significance of the effect. for transcutaneous ifc (interferential current therapy) 2 studies were included, which both reported a statistically significant effect on all outcomes. conclusion: the beneficial effect of neuromodulation in chronic functional constipation remains questionable. however, neuro-modulation might be worth considering in patients refractory to treatment before turning to more invasive measures. future research should shed more light on the effects of neuromodulation in constipation. (acta gastroenterol. belg., 2021, 84, 467-476).”
Azad, T. D., Veeravagu, A., & Steinberg, G. K.. (2016). Neurorestoration after stroke. Neurosurgical Focus
“Recent advancements in stem cell biology and neuromodulation have ushered in a battery of new neurorestorative therapies for ischemic stroke. while the understanding of stroke pathophysiology has matured, the ability to restore patients’ quality of life remains inadequate. new therapeutic approaches, including cell transplantation and neurostimulation, focus on reestablishing the circuits disrupted by ischemia through multidimensional mechanisms to improve neuroplasticity and remodeling. the authors provide a broad overview of stroke pathophysiology and existing therapies to highlight the scientific and clinical implications of neurorestorative therapies for stroke.”
de Wall, L. L., & Heesakkers, J. P. F. A.. (2017). Effectiveness of percutaneous tibial nerve stimulation in the treatment of overactive bladder syndrome. Research and Reports in Urology
“Overactive bladder syndrome (oab) is a common condition affecting adults and children worldwide, resulting in a substantial economic and psychological burden. percutaneous tibial nerve stimulation (ptns) is derived from acupuncture used in chinese traditional medicine and was first described in the early 1980s. it is a neuromodulation technique used to modulate bladder function and facilitate storage. being a minimally invasive, easily applicable, but time-consuming treatment, future developments with implantable devices might be the solution for the logistical problems and economic burden associated with ptns on the long term. this nonsystematic review provides a current overview on ptns and its effectiveness in the treatment of oab for both adults and children.”
Ramirez-Zamora, A., Giordano, J., Boyden, E. S., Gradinaru, V., Gunduz, A., Starr, P. A., … Okun, M. S.. (2019). Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics. In Frontiers in Neuroscience
“The annual deep brain stimulation (dbs) think tank aims to create an opportunity for a multidisciplinary discussion in the field of neuromodulation to examine developments, opportunities and challenges in the field. the proceedings of the sixth annual think tank recapitulate progress in applications of neurotechnology, neurophysiology, and emerging techniques for the treatment of a range of psychiatric and neurological conditions including parkinson’s disease, essential tremor, tourette syndrome, epilepsy, cognitive disorders, and addiction. each section of this overview provides insight about the understanding of neuromodulation for specific disease and discusses current challenges and future directions. this year’s report addresses key issues in implementing advanced neurophysiological techniques, evolving use of novel modulation techniques to deliver dbs, ans improved neuroimaging techniques. the proceedings also offer insights into the new era of brain network neuromodulation and connectomic dbs to define and target dysfunctional brain networks. the proceedings also focused on innovations in applications and understanding of adaptive dbs (closed-loop systems), the use and applications of optogenetics in the field of neurostimulation and the need to develop databases for dbs indications. finally, updates on neuroethical, legal, social, and policy issues relevant to dbs research are discussed.”
Klooster, D. C. W., de Louw, A. J. A., Aldenkamp, A. P., Besseling, R. M. H., Mestrom, R. M. C., Carrette, S., … Boon, P.. (2016). Technical aspects of neurostimulation: Focus on equipment, electric field modeling, and stimulation protocols. Neuroscience and Biobehavioral Reviews
“Neuromodulation is a field of science, medicine, and bioengineering that encompasses implantable and non-implantable technologies for the purpose of improving quality of life and functioning of humans. brain neuromodulation involves different neurostimulation techniques: transcranial magnetic stimulation (tms), transcranial direct current stimulation (tdcs), vagus nerve stimulation (vns), and deep brain stimulation (dbs), which are being used both to study their effects on cognitive brain functions and to treat neuropsychiatric disorders. the mechanisms of action of neurostimulation remain incompletely understood. insight into the technical basis of neurostimulation might be a first step towards a more profound understanding of these mechanisms, which might lead to improved clinical outcome and therapeutic potential. this review provides an overview of the technical basis of neurostimulation focusing on the equipment, the present understanding of induced electric fields, and the stimulation protocols. the review is written from a technical perspective aimed at supporting the use of neurostimulation in clinical practice.”
De Ridder, D., Manning, P., Cape, G., Vanneste, S., Langguth, B., & Glue, P.. (2016). Pathophysiology-Based Neuromodulation for Addictions: An Overview. In Neuropathology of Drug Addictions and Substance Misuse
“Treatments for addiction are of limited effectivity and characterized by high relapse rates, requiring the development of novel pathophysiology-based treatment approaches. one such option is to use neuromodulation. neuromodulation can be defined as the use of techniques to focally induce directed neuroplasticity. both nonsurgical and surgical neuromodulation have been experimentally used for the suppression of craving. noninvasive techniques used include transcranial magnetic stimulation, transcranial electrical stimulation, and neurofeedback. surgical neuromodulation techniques involve lesioning and electrical stimulation via implanted electrodes. most studies using noninvasive stimulation have investigated the dorsolateral prefrontal cortex as the target. the two brain areas most commonly used as targets for lesioning are the anterior cingulate and nucleus accumbens. for implanted electrodes the nucleus accumbens and subthalamic nucleus have been investigated. the targets used can be linked to brain circuits involved in craving or withdrawal. for noninvasive neuromodulation no long-term studies have been performed and for implanted electrodes only small case series have been reported. thus even if results seem to be promising, they still have to be considered preliminary.”
Lo, P. A., Huang, K., Zhou, Q., Humayun, M. S., & Yue, L.. (2020). Ultrasonic retinal neuromodulation and acoustic retinal prosthesis. Micromachines
“Ultrasound is an emerging method for non-invasive neuromodulation. studies in the past have demonstrated that ultrasound can reversibly activate and inhibit neural activities in the brain. recent research shows the possibility of using ultrasound ranging from 0.5 to 43 mhz in acoustic frequency to activate the retinal neurons without causing detectable damages to the cells. this review recapitulates pilot studies that explored retinal responses to the ultrasound exposure, discusses the advantages and limitations of the ultrasonic stimulation, and offers an overview of engineering perspectives in developing an acoustic retinal prosthesis. for comparison, this article also presents studies in the ultrasonic stimulation of the visual cortex. despite that, the summarized research is still in an early stage; ultrasonic retinal stimulation appears to be a viable technology that exhibits enormous therapeutic potential for non-invasive vision restoration.”
Krauss, J. K., Lipsman, N., Aziz, T., Boutet, A., Brown, P., Chang, J. W., … Lozano, A. M.. (2021). Technology of deep brain stimulation: current status and future directions. Nature Reviews Neurology
“Deep brain stimulation (dbs) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. dbs is a standard of care in parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and alzheimer disease. modern dbs systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how dbs is viewed and delivered to patients. breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of dbs. in this review, we provide a comprehensive overview of the technical development of dbs, from its origins to its future. understanding the evolution of dbs technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.”
S., V., & D., D. R.. (2012). Noninvasive and invasive neuromodulation for the treatment of tinnitus: An overview. Neuromodulation
Show/hide publication abstract
“Objective: nonpulsatile tinnitus is an auditory phantom percept characterized as a tone, or a noise-like sound such as a hissing or buzzing sound or polyphonic, in the absence of any objective physical sound source. although advances have been made in symptomatic pharmacologic and nonpharmacologic treatments, these treatments are unable to eliminate the tinnitus sensation in most patients. a novel approach using noninvasive and invasive neuromodulation has emerged as an interesting and promising modality for tinnitus relief. methodology: we review noninvasive neuromodulation techniques including transcranial magnetic stimulation, transcranial direct current stimulation, transcutaneous electrical nerve stimulation, and cortical neurofeedback, as well as invasive neuromodulation techniques including auditory cortex stimulation, dorsolateral prefrontal cortex stimulation, subcutaneous occipital nerve stimulation, and deep brain stimulation, as potential treatments of tinnitus. conclusion: although the different techniques introduced revealed promising results, further research is needed to better understand how these techniques work and how the brain responds to neuromodulation. more sophisticated stimulation regimens and parameters should be developed to dynamically stimulate various regions at different frequencies and intensities, physiologically tailored to the patient’s brain state in an attempt to maximize efficacy. (copyright) 2012 international neuromodulation society.”
Kaczmarek, K. A.. (2017). The Portable Neuromodulation Stimulator (PoNS) for neurorehabilitation. Scientia Iranica
“The portable neuromodulation stimulator (pons) is a compact, self-contained device that delivers a fixed sequence of dc-balanced voltage pulses to the anterior-dorsal tongue through a matrix of 143 gold-plated electrodes. this form of stimulation is being investigated as a possible aid to rehabilitation of motor, cognitive, and emotional symptoms resulting from a range of neurological disorders of traumatic, degenerative, or developmental origin. this article provides a technical overview of the pons device as well as a summary of applications research to date.”
Somani, A., & Kar, S. K.. (2019). Efficacy of repetitive transcranial magnetic stimulation in treatment-resistant depression: The evidence thus far. General Psychiatry
“Depression is a common mental disorder, which attributes to significant morbidity, disability and burden of care. a significant number of patients with depression still remain symptomatic after adequate trials of antidepressant treatment as well as psychotherapy, which is often referred to as treatment-resistant depression. neuromodulation techniques-like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation (tms) and transcranial direct current stimulation, may be useful augmenting techniques in depression, mostly recommended for treatment-resistant cases. robust evidence exists regarding the efficacy of electroconvulsive therapy in the management of treatment-resistant depression; however, other techniques are understudied. tms has been increasingly studied in various psychiatric disorders including depression. it has been approved by the us food and drug administration for use in major depressive disorder. over the past two decades, tms has been studied in diverse groups of the population with depression using several research designs. this article gives an overview of the efficacy of repetitive tms in treatment-resistant depression with the recent evidence.”
Meng, Y., Hynynen, K., & Lipsman, N.. (2021). Applications of focused ultrasound in the brain: from thermoablation to drug delivery. Nature Reviews Neurology
“Focused ultrasound (fus) is a disruptive medical technology, and its implementation in the clinic represents the culmination of decades of research. lying at the convergence of physics, engineering, imaging, biology and neuroscience, fus offers the ability to non-invasively and precisely intervene in key circuits that drive common and challenging brain conditions. the actions of fus in the brain take many forms, ranging from transient blood–brain barrier opening and neuromodulation to permanent thermoablation. over the past 5 years, we have seen a dramatic expansion of indications for and experience with fus in humans, with a resultant exponential increase in academic and public interest in the technology. applications now span the clinical spectrum in neurological and psychiatric diseases, with insights still emerging from preclinical models and human trials. in this review, we provide a comprehensive overview of therapeutic ultrasound and its current and emerging indications in the brain. we examine the potential impact of fus on the landscape of brain therapies as well as the challenges facing further advancement and broader adoption of this promising minimally invasive therapeutic alternative.”
Coman, A., Skårderud, F., Reas, D. L., & Hofmann, B. M.. (2014). The ethics of neuromodulation for anorexia nervosa: A focus on rTMS. Journal of Eating Disorders
“Objective: recently there has been emerging clinical and research interest in the application of deep brain stimulation (dbs) and repetitive transcranial magnetic stimulation (rtms) to the treatment of anorexia nervosa (an). to our knowledge, few studies have discussed ethical aspects associated with the increased use of neuromodulation in an, some of which are quite specific to an, despite the rapid development and dissemination of these new technologies.method: we provide a brief overview of three published rtms studies for an and discuss ethical issues involved in the use of neuromodulation for an.results: in contrast to neurosurgery or dbs, rtms is a less invasive technique, with less associated risk, and thus has greater potential to become a more widespread augmentation or add-on therapy for an. new therapeutic procedures are promising, yet they raise ethical questions regarding informed consent and patient selection. illness-specific issues surrounding authenticity and autonomy are important to consider, ensuring an ethical approach to treatment for patients with an.discussion: we argue that ethical investigations for neuromodulation techniques are timely and important, and discussions should go beyond the immediate goals of patient safety, consent, and risk and benefit, to consider broader ethical concepts such as authenticity and autonomy.”
Herremans, S. C., & Baeken, C.. (2017). Clinical effects of non-invasive neuromodulation techniques in substance use disorder: An overview. Tijdschrift Voor Psychiatrie
Show/hide publication abstract
“BACKGROUND substance dependence is a chronic disorder that is difficult to treat. non-invasive stimulation techniques may have beneficial effects on the course of the illness. aim to provide an overview of studies that evaluate the clinical effects that transcranial magnetic stimulation (tms) and transcranial direct current stimulation (tdcs) have on patients with substance use disorders. method we performed an extensive search of the literature, using pubmed. results most studies showed that both tms and tdcshavea beneficial effect on clinical outcomes. however, the effects seemed to wear off over time, even if tms and tdcs had been administered to patients over several sessions. conclusion in terms of efficacy, we award a level b qualification to both tms and tdcs, which means that we regard both techniques as’very probably efficient’.”
Tyler, W. J.. (2011). Noninvasive neuromodulation with ultrasound? A continuum mechanics hypothesis. Neuroscientist
Yamamoto, K., Elias, G. J. B., Beyn, M. E., Zemmar, A., Loh, A., Sarica, C., … Lozano, A. M.. (2021). Neuromodulation for Pain: A Comprehensive Survey and Systematic Review of Clinical Trials and Connectomic Analysis of Brain Targets. Stereotactic and Functional Neurosurgery
“Background: chronic pain is a debilitating condition that imposes a tremendous burden on health-care systems around the world. while frontline treatments for chronic pain involve pharmacological and psychological approaches, neuromodulation can be considered for treatment-resistant cases. neuromodulatory approaches for pain are diverse in both modality and target and their mechanism of action is incompletely understood. objectives: the objectives of this study were to (i) understand the current landscape of pain neuromodulation research through a comprehensive survey of past and current registered clinical trials (ii) investigate the network underpinnings of these neuromodulatory treatments by performing a connectomic mapping analysis of cortical and subcortical brain targets that have been stimulated for pain relief. methods: a search for clinical trials involving pain neuromodulation was conducted using 2 major trial databases (clinicaltrials.gov and the international clinical trials registry platform). trials were categorized by variables and analyzed to gain an overview of the contemporary research landscape. additionally, a connectomic mapping analysis was performed to investigate the network connectivity patterns of analgesic brain stimulation targets using a normative connectome based on a functional magnetic resonance imaging dataset. results: in total, 487 relevant clinical trials were identified. noninvasive cortical stimulation and spinal cord stimulation trials represented 49.3 and 43.7% of this count, respectively, while deep brain stimulation trials accounted for <3%. the mapping analysis revealed that superficial target connectomics overlapped with deep target connectomics, suggesting a common pain network across the targets. conclusions: research for pain neuromodulation is a rapidly growing field. our connectomic network analysis reinforced existing knowledge of the pain matrix, identifying both well-described hubs and more obscure structures. further studies are needed to decode the circuits underlying pain relief and determine the most effective targets for neuromodulatory treatment.”
Hennessey, D. B., Hoag, N., & Gani, J.. (2017). Impact of bladder dysfunction in the management of post radical prostatectomy stress urinary incontinence-a review. Translational Andrology and Urology
“Bladder dysfunction is a relatively common urodynamic finding post radical prostatectomy (rp). it can be the sole cause of post prostatectomy incontinence (ppi) or may be found in association with stress urinary incontinence (sui). the aim of this review is to provide a comprehensive review of the diagnosis and different treatments of post rp bladder dysfunction. a comprehensive literature review using medical search engines was performed. the search included a combination of the following terms, ppi, detrusor overactivity (do), detrusor underactivity (du), impaired compliance, anticholinergic, onabotulinumtoxina (botox®) and sacral neuromodulation (snm). definitions, general overview and management options were extracted from the relevant medical literature. do, du and impaired compliance are common and may occur alone or in combination with sui. in some patients the conditions exist pre rp, in others they arise due to denervation and surgical changes. do can be treated with anticholinergics, botox® and snm. do may need to be treated before sui surgery. du may be a contraindication to male sling surgery as some patients may go into urinary retention. severely impaired bladder compliance may be a contraindication to sui surgery as the upper tracts may be at risk. each individual dysfunction may affect the outcome of ppi treatments and clinicians should be alert to managing bladder dysfunction in ppi patients.”
Urits, I., Schwartz, R., Smoots, D., Koop, L., Veeravelli, S., Orhurhu, V., … Viswanath, O.. (2020). Peripheral neuromodulation for the management of headache. Anesthesiology and Pain Medicine
“Context: neuromodulation is an expanding field of study for headache treatment to reduce pain by targeting structures within the nervous system that are commonly involved in headache pathophysiology, such as the vagus nerve (vns), occipital nerves, or sphenopalatine ganglion (spg) for stimulation. pharmaceutical medical therapies for abortive and prophylactic treatment, such as triptans, nsaids, beta-blockers, tcas, and antiepileptics, are effective for some individuals, but the role that technology plays in investigating other therapeutic modalities is essential. peripheral neuromodulation has gained popularity and fda approval for use in treating certain headaches and migraine headache conditions, particularly in those who are refractory to treatment. early trials found fda approved neurostimulatory implant devices, including cephaly and springtms, improved patient-oriented outcomes with reductions in headaches per month (frequency) and severity. evidence acquisition: this was a narrative review. the sources for this review are as follows: searching on pubmed, google scholar, medline, and sciencedirect from 1990 – 2019 using keywords: peripheral neuromodulation, headache, vagus nerve, occipital nerves, sphenopalatine ganglion. results: the first noninvasive neurostimulator device approved for migraine treatment was the cefaly device, an external trigeminal nerve stimulation device (e-tns) that transcutaneously excites the supratrochlear and supraorbital branches of the ophthalmic nerve. the second noninvasive neurostimulation device receiving fda approval was the single-pulse transcranial magnetic stimulator, springtms, positioned at the occiput to treat migraine with aura. gammacore is a handheld transcutaneous vagal nerve stimulator applied directly to the neck at home by the patient for treatment of cluster headache (ch) and migraine. several other devices are in development for the treatment of headaches and target headache evolution at different levels and inputs. the scion device is a caloric vestibular stimulator (cvs) which interfaces with the user through a set of small cones resting in the ear canal on either side and held in place by modified over-ear headphones. the pulsante spg microstimulator is a patient-controlled device implanted in the patient’s upper jaw via an hour-long oral procedure to target the sphenopalatine ganglion. the occipital nerve stimulator (ons) is an invasive neuromodulation device for headache treatment that consist…”
Robbins, M. S., & Burch, R.. (2021). Preventive Migraine Treatment. CONTINUUM Lifelong Learning in Neurology
“PURPOSE of review this article provides an overview of preventive interventions for migraine, including when to start and how to choose a treatment, pharmacologic options (both older oral treatments and new monoclonal antibodies to calcitonin gene-related peptide [cgrp] or its receptor), nonpharmacologic treatment such as neuromodulation, and preventive treatment of refractory migraine. recent findings the migraine preventive treatment landscape has been transformed by the development of monoclonal antibodies targeting cgrp or its receptor. these treatments, which are given subcutaneously or intravenously monthly or quarterly, have high efficacy and were well tolerated in clinical trials. emerging real-world studies have found higher rates of adverse events than were seen in clinical trials. they are currently recommended for use if two traditional preventive therapies have proven inadequate. since the commonly cited 2012 american headache society/american academy of neurology migraine prevention guidelines were released, clinical trials supporting the preventive use of lisinopril, candesartan, and memantine have been published. neuromodulation devices, including external trigeminal nerve stimulation and single-pulse transcranial magnetic stimulation devices, have modest evidence to support preventive use. the american headache society/american academy of neurology guidelines for the preventive treatment of migraine are currently being updated. a new class of oral cgrp receptor antagonists (gepants) is being tested for migraine prevention. summary successful preventive treatment of migraine reduces disease burden and improves quality of life. many pharmacologic and nonpharmacologic treatment options are available for the prevention of migraine, including newer therapies aimed at the cgrp pathway as well as older treatments with good evidence for efficacy. multiple treatment trials may be required to find the best preventive for an individual patient.”
Ahmed, A. I., & Lucas, J. D.. (2020). Spinal cord injury: pathophysiology and strategies for regeneration. Orthopaedics and Trauma
“Spinal cord injury (sci) is regarded as a devastating irreversible process leading to high morbidity and dependence. the pathophysiology is complex resulting in changes in the spinal cord in the acute phase, followed by sub-acute and chronic changes. this leads to cell death, glial scar formation and the inability to regenerate. nevertheless, many strategies for regeneration are being actively pursued, including cell therapy, drug delivery and neuromodulation. several of these strategies are in current clinical trials. this review aims to give an overview of the current understanding of the injury process and the potential treatment strategies for sci.”
Argiolas, A., & Melis, M. R.. (1995). Neuromodulation of penile erection: an overview of the role of neurotransmitters and neuropeptides. Progress in Neurobiology
Mohammad, S. S., Paget, S. P., & Dale, R. C.. (2019). Current therapies and therapeutic decision making for childhood-onset movement disorders. Movement Disorders
Rajan, R., Skorvanek, M., Magocova, V., Siddiqui, J., Alsinaidi, O., Shinawi, H., … Bajwa, J.. (2020). Neuromodulation Options and Patient Selection for Parkinson’s Disease. In Neurology India
“Neuromodulation therapies, including deep brain stimulation (dbs) and pump therapies, are currently the standard of care for pd patients with advanced disease and motor complications that are difficult to control with medical management alone. the quest for alternate lesser invasive approaches led to the development of several novel therapies like intrajejunal levodopa infusions (ijli), continuous subcutaneous apomorphine infusions (csai) and magnetic resonance guided focused ultrasound (mrgfus) in recent years. to achieve good outcomes with any of these therapeutic modalities, careful patient selection, multidisciplinary evaluation and technical expertise are equally important. in this review, we will provide an overview of the neuromodulation strategies currently available for pd, emphasizing on patient selection and choosing among the various strategies.”
Dean, O. M., Gliddon, E., Van Rheenen, T. E., Giorlando, F., Davidson, S. K., Kaur, M., … Williams, L. J.. (2018). An update on adjunctive treatment options for bipolar disorder. Bipolar Disorders
“Objectives: bipolar disorder is a complex illness often requiring combinations of therapies to successfully treat symptoms. in recent years, there have been significant advancements in a number of therapies for bipolar disorder. it is therefore timely to provide an overview of current adjunctive therapeutic options to help treating clinicians to inform their patients and work towards optimal outcomes. methods: publications were identified from pubmed searches on bipolar disorder and pharmacotherapy, nutraceuticals, hormone therapy, psychoeducation, interpersonal and social rhythm therapy, cognitive remediation, mindfulness, e-health and brain stimulation techniques. relevant articles in these areas were selected for further review. this paper provides a narrative review of adjunctive treatment options and is not a systematic review of the literature. results: a number of pharmacotherapeutic, psychological and neuromodulation treatment options are available. these have varying efficacy but all have shown benefit to people with bipolar disorder. due to the complex nature of treating the disorder, combination treatments are often required. adjunctive treatments to traditional pharmacological and psychological therapies are proving useful in closing the gap between initial symptom remission and full functional recovery. conclusions: given that response to monotherapy is often inadequate, combination regimens for bipolar disorder are typical. correspondingly, psychiatric research is working towards a better understanding of the disorder’s underlying biology. therefore, treatment options are changing and adjunctive therapies are being increasingly recognized as providing significant tools to improve patient outcomes. towards this end, this paper provides an overview of novel treatments that may improve clinical outcomes for people with bipolar disorder.”
Moisset, X., Lanteri-Minet, M., & Fontaine, D.. (2020). Neurostimulation methods in the treatment of chronic pain. Journal of Neural Transmission
“The goal of this narrative review was to give an up-to-date overview of the peripheral and central neurostimulation methods that can be used to treat chronic pain. special focus has been given to three pain conditions: neuropathic pain, nociplastic pain and primary headaches. both non-invasive and invasive techniques are briefly presented together with their pain relief potentials. for non-invasive stimulation techniques, data concerning transcutaneous electrical nerve stimulation (tens), transcranial direct current stimulation (tdcs), repetitive transcranial magnetic stimulation (rtms), remote electrical neuromodulation (ren) and vagus nerve stimulation (vns) are provided. concerning invasive stimulation techniques, occipital nerve stimulation (ons), vagus nerve stimulation (vns), epidural motor cortex stimulation (emcs), spinal cord stimulation (scs) and deep brain stimulation (dbs) are presented. the action mode of all these techniques is only partly understood but can be very different from one technique to the other. patients’ selection is still a challenge. recent consensus-based guidelines for clinical practice are presented when available. the development of closed-loop devices could be of interest in the future, although the clinical benefit over open loop is not proven yet.”
Erőss, L., Entz, L., & Fabó, D.. (2015). Invasive neuromodulation in the treatment of drug-resistant epilepsies. Orvosi Hetilap
“Neuromodulation is one of the most developing new disciplines of medical science, which examines how electrical, chemical and mechanical interventions can modulate or change the functioning of the central and peripheral nervous system. neuromodulation is a reversible form of therapy which uses electrical or mechanical stimulation or centrallydelivered drugs to modulate the abnormal function of the central nervous system in pain, spasticity, epilepsy, movement and psychiatric disorders, and certain cardiac, incontinency, visual and auditory diseases. neuromodulation therapy has two major branches. non-invasive neuromodulation includes transcranial magnetic simulation, direct current stimulation and transcutaneous electric nerve stimulation. invasive neuromodulation includes deep brain stimulation, cortical stimulation, spinal cord stimulation, peripheral nerve stimulation, sacral nerve simulation, and subcutan stimulation. in this article the authors overview the apparently available neural interface technologies in epilepsy surgery.”
Ashina, M., Buse, D. C., Ashina, H., Pozo-Rosich, P., Peres, M. F. P., Lee, M. J., … Dodick, D. W.. (2021). Migraine: integrated approaches to clinical management and emerging treatments. The Lancet
“Migraine is a highly disabling neurological disorder that directly affects more than 1 billion individuals worldwide. available treatment options differ between countries and include acute, preventive, and non-pharmacological therapies. because of major progress in the understanding of migraine pathogenesis, novel mechanism-based medications have emerged and expanded the armamentarium of treatments. we provide a comprehensive overview of the current standard of care that will enable informed clinical management. first, we discuss the efficacy, tolerability, and safety profile of various pharmacological therapies for acute and preventive treatment of migraine. second, we review the current knowledge on non-pharmacological therapies, such as neuromodulation and biobehavioural approaches, which can be used for a multidisciplinary approach to clinical management. third, we emphasise that any effective treatment strategy starts with building a therapeutic plan tailored to individual clinical characteristics, preferences, and needs. finally, we explore the outlook of emerging mechanism-based treatments that could address unmet challenges in clinical management of migraine.”
All, A. H., Zeng, X., Teh, D. B. L., Yi, Z., Prasad, A., Ishizuka, T., … Liu, X.. (2019). Expanding the Toolbox of Upconversion Nanoparticles for In Vivo Optogenetics and Neuromodulation. Advanced Materials
“Optogenetics is an optical technique that exploits visible light for selective neuromodulation with spatio-temporal precision. despite enormous effort, the effective stimulation of targeted neurons, which are located in deeper structures of the nervous system, by visible light, remains a technical challenge. compared to visible light, near-infrared illumination offers a higher depth of tissue penetration owing to a lower degree of light attenuation. herein, an overview of advances in developing new modalities for neural circuitry modulation utilizing upconversion-nanoparticle-mediated optogenetics is presented. these developments have led to minimally invasive optical stimulation and inhibition of neurons with substantially improved selectivity, sensitivity, and spatial resolution. the focus is to provide a comprehensive review of the mechanistic basis for evaluating upconversion parameters, which will be useful in designing, executing, and reporting optogenetic experiments.”
Fandel, T., & Tanagho, E. A.. (2005). Neuromodulation in voiding dysfunction: A historical overview of neurostimulation and its application. Urologic Clinics of North America
“This article presents a historical overview of neurostimulation and its application in voiding dysfunction.”
Zbar, A. P.. (2014). Sacral neuromodulation and peripheral nerve stimulation in patients with anal incontinence: An overview of techniques, complications and troubleshooting. Gastroenterology Report
“4 sacral neuromodulation (snm) therapy has revolutionized the management of many forms of anal incontinence, with an expanded use and a medium-term efficacy of 75% overall. this review discusses the technique of snm therapy, along with its complications and troubleshooting and a discussion of the early data pertaining to peripheral posterior tibial nerve stimulation in incontinent patients. future work needs to define the predictive factors for neurostimulatory success, along with the likely mechanisms of action of their therapeutic action.”
Karri, J., Singh, M., Orhurhu, V., Joshi, M., & Abd-Elsayed, A.. (2020). Pain Syndromes Secondary to Cluneal Nerve Entrapment. Current Pain and Headache Reports
“Purpose of review: the purpose of this review is to provide an overview of the cluneal nerves, present a summary of pain syndromes secondary to clunealgia, and evaluate current literature for diagnostic and treatment modalities. recent findings: multiple trials and studies have reported success with numerous modalities ranging from nerve blocks, neuroablation, and even peripheral neuromodulation with varying degrees of clinical benefit. summary: cluneal nerve entrapment or chronic impingement can cause buttock pain or referred pain to nearby areas including the lower back, pelvic area, or even the lower extremities. clunealgias and associated pain syndromes can often be challenging to diagnose and differentiate. an appreciation of the pathophysiology of clunealgias can assist with patient selection for interventional pain strategies targeted towards the cluneal nerves, including nerve blocks, neuroablation, and peripheral neuromodulation. more research is needed to better delineate the efficacy of these procedures for clunealgias.”
“Infrared neuromodulation (inm) is a branch of photobiomodulation that offers direct or indirect control of cellular activity through elevation of temperature in a spatially confined region of the target tissue. research on inm started about 15 ago and is gradually attracting the attention of the neuroscience community, as numerous experimental studies have provided firm evidence on the safe and reproducible excitation and inhibition of neuronal firing in both in vitro and in vivo conditions. however, its biophysical mechanism is not fully understood and several engineered interfaces have been created to investigate infrared stimulation in both the peripheral and central nervous system. in this review, recent applications and present knowledge on the effects of inm on cellular activity are summarized, and an overview of the technical approaches to deliver infrared light to cells and to interrogate the optically evoked response is provided. the micro- and nanoengineered interfaces used to investigate the influence of inm are described in detail.”
Zhu, A., Qureshi, A. A., Kozin, E. D., & Lee, D. J.. (2020). Concepts in Neural Stimulation: Electrical and Optical Modulation of the Auditory Pathways. Otolaryngologic Clinics of North America
“Understanding the mechanisms of neural stimulation is necessary to improve the management of sensory disorders. neurons can be artificially stimulated using electrical current, or with newer stimulation modalities, including optogenetics. electrical stimulation forms the basis for all neuroprosthetic devices that are used clinically. off-target stimulation and poor implant performance remain concerns for patients with electrically based neuroprosthetic devices. optogenetic techniques may improve cranial nerve stimulation strategies used by various neuroprostheses and result in better patient outcomes. this article reviews the fundamentals of neural stimulation and provides an overview of recent major advancements in light-based neuromodulation.””
LeBeau, F. E. N., El Manira, A., & Griller, S.. (2005). Tuning the network: Modulation of neuronal microcircuits in the spinal cord and hippocampus. Trends in Neurosciences
“Purpose: the purpose of this article is to provide an overview of the current status of neural signal processing techniques for closed-loop neuromodulation. methods: first we described overall structure of closed-loop neuromodulation systems. then, the techniques for the stimulus artifact removal were explained, and the methods for neural state monitoring and biomarker extraction were described. finally, the current status of neuromodulation based on neural signal processing was provided in detail. results: closed-loop neuromodulation system automatically adjusts stimulation parameters based on the brain response in real time. adequate tools for signal sensing and signal processing can be used to obtain meaningful biomarkers reflecting the state of neural systems. especially, an appropriate neural signal processing technique can optimize the details of stimulation for effective treatment of target disease. conclusions: neural signal-based biomarkers reflecting the pathophysiological statuses of patients are essential for closedloop neuromodulation, and they should be developed from an understanding of the relationship between clinical states and neural signals.”
Hoffmann, J., & May, A.. (2019). Neuromodulation for the treatment of primary headache syndromes. Expert Review of Neurotherapeutics
“Introduction: neuromodulation techniques play an increasing role in the treatment of primary headaches. while initially reserved for refractory cases they are now increasingly taken into consideration in earlier treatment phases and in non-refractory situations. one of the main reasons for this paradigm shift is that most neuromodulation techniques are better tolerated as compared to the majority of pharmacological approaches. however, these techniques have their limitations that should be considered. areas covered: the review provides an overview of the available techniques and their therapeutic rationale as well as on the evidence for their efficacy and their limitations. the review covers these aspects for non-invasive vagal nerve stimulation, sphenopalatine ganglion stimulation, external trigeminal nerve stimulation, occipital nerve stimulation as well as single-pulse and repetitive-pulse transcranial magnetic stimulation. expert commentary: most of the evidence is based on open-label studies. sham devices used in controlled studies remain problematic as they either do not produce the paresthesias perceived during stimulation or induce some degree of stimulation. invasive techniques require a surgical intervention with all the potential complications that may arise. in summary, some of the techniques provide an effective expansion of available treatment options but their indication should be thoroughly evaluated before treatment is considered.”
Martens, F. M. J., & Sievert, K. D.. (2020). Neurostimulation in neurogenic patients. Current Opinion in Urology
“Purpose of reviewto provide an overview of available electrical stimulation devices in neurogenic patients with lower urinary tract disease.recent findingsit is advocated to do more studies in neurogenic patients as results seem promising and useful but most studies did not include neurogenic patients or neurogenic patients were not analyzed or reported separately. most studies included a small heterogenous neurogenic group with multiple pathophysiologic origin focusing on effect of a treatment instead of results of a treatment in a specific neurogenic group. neuromodulation or stimulation has the advantage that it acts on different organs, like bladder and bowel, so can treat neurogenic patients, who mostly suffer from multiple organ failure.summarybrindley procedure, sacral neuromodulation (snm) and posterior tibial nerve stimulation (ptns) are available for a while already. the brindley procedure (including sacral anterior root stimulation in combination with a rhizotomy of posterior sacral roots) is developed for selected spinal cord injury patient with a complete spinal injury, and has shown results for many years in neurogenic patients. an alternative to the rhizotomy is not established yet. snm and ptns are other modalities that are used in nonneurogenic patients, but are not yet indicated and much studied in neurogenic patients.”
Harmsen, I. E., Elias, G. J. B., Beyn, M. E., Boutet, A., Pancholi, A., Germann, J., … Lozano, A. M.. (2020). Clinical trials for deep brain stimulation: Current state of affairs. Brain Stimulation
“Background: deep brain stimulation (dbs) is a surgical neuromodulation procedure with a historically wide range of possible therapeutic indications, including movement disorders, neuropsychiatric conditions, and cognitive disorders. ongoing research in this field is critical to gain further insights into the mechanisms of dbs, to discover novel brain targets for new and existing indications, and to refine targeting and post-operative programming techniques for the optimization of therapeutic outcomes. objective: to update on the state of dbs-related clinical human research by cataloging and summarizing clinical trials that have been completed or are currently ongoing in this field worldwide. methods: a search was conducted for clinical trials pertaining to dbs, currently listed on the clinicaltrials.gov database. trials were analyzed to generate a detailed overview of ongoing dbs-related research. specifically, trials were categorized by trial start date, study completion status, clinical phase, projected subject enrollment, disorder, brain target, country of origin, device manufacturer, funding source, and study topic. results: in total, 384 relevant clinical trials were identified. the trials spanned 28 different disorders across 26 distinct brain targets, with almost 40% of trials being for conditions other than movement disorders. the majority of dbs trials have been us-based (41.9% of studies) but many countries are becoming increasingly active. the ratio of investigator-sponsored to industry-sponsored trials was 3:1. emphasizing the need to better understand the mechanism of action of dbs, one-third of the studies predominantly focus on imaging or electrophysiological changes associated with dbs. conclusions: this overview of current dbs-related clinical trials provides insight into the status of dbs research and what we can anticipate in the future concerning new brain targets, indications, techniques, and developing a better understanding of the mechanisms of action of dbs.”
Chen, Y., Tang, T., & Erdek, M. A.. (2019). Advanced Image-Guided Procedures for Painful Spine. Neuroimaging Clinics of North America
“In addition to basic image-guided injections, there are many advanced procedures to address the challenges of spine pain. patients with debilitating symptoms are offered relief, a shorter recovery period, and fewer potential complications. pain arises from numerous sites along the spine, presenting as spine pain or radiculopathy. this article is an overview of advanced techniques in this rapidly progressing field, including neuromodulation, radiofrequency thermocoagulation, discography, intradiscal thermocoagulation, and percutaneous image-guided lumbar decompression; and it highlights etiologic factors and their relationship to therapeutic technique and clinical evidence.”
Mishra, S., Kumar, A., Padmanabhan, P., & Gulyás, B.. (2021). Neurophysiological correlates of cognition as revealed by virtual reality: Delving the brain with a synergistic approach. Brain Sciences
“The synergy of perceptual psychology, technology, and neuroscience can be used to comprehend how virtual reality affects cognition of human brain. numerous studies have used neuroimaging modalities to assess the cognitive state and response of the brain with various external stimulations. the virtual reality-based devices are well known to incur visual, auditory, and haptic induced perceptions. neurophysiological recordings together with virtual stimulations can assist in correlating humans’ physiological perception with response in the environment designed virtually. the effective combination of these two has been utilized to study human behavior, spatial navigation performance, and spatial presence, to name a few. moreover, virtual reality-based devices can be evaluated for the neurophysiological correlates of cognition through neurophysiological recordings. challenges exist in the integration of real-time neuronal signals with virtual reality-based devices, and enhancing the experience together with real-time feedback and control through neuronal sig-nals. this article provides an overview of neurophysiological correlates of cognition as revealed by virtual reality experience, together with a description of perception and virtual reality-based neuromodulation, various applications, and existing challenges in this field of research.”
Christen, M., & Müller, S.. (2017). Editorial: The Clinical and Ethical Practice of Neuromodulation – Deep Brain Stimulation and Beyond. Frontiers in Integrative Neuroscience
“Neuromodulation is among the fastest-growing areas of medicine, involving many diverse specialties and affecting hundreds of thousands of patients with numerous disorders worldwide. it can briefly be described as the science of how electrical, chemical, and mechanical interventions can modulate the nervous system function. a prominent example of neuromodulation is deep brain stimulation (dbs), an intervention that reflects a fundamental shift in the understanding of neurological and psychiatric diseases: namely as resulting from a dysfunctional activity pattern in a defined neuronal network that can be normalized by targeted stimulation. the application of dbs has grown remarkably and more than 130,000 patients worldwide have obtained a dbs intervention in the past 30 years—most of them for treating movement disorders. these numbers will grow further for several reasons. first, dbs is investigated for various novel neurological and psychiatric indications. second, current research suggests that stimulation may be more beneficial if it is applied earlier in the course of the disease, especially for parkinsonian patients. third, the number of countries, centers, and companies that get involved in this field is steadily increasing. this frontiers research topics provides an overview on the current discussion beyond basic research in dbs and other brain stimulation technologies. researchers from clinical disciplines (e.g., neurology, neurosurgery, and psychiatry), neuroethics, social science, law, and economics who are working on broader clinical and social issues related to dbs and related neuromodulation technologies have contributed to this research topic. in the following, we provide a brief overview on the content of the e-book on ” the clinical and ethical practice of neuromodulation – deep brain stimulation and beyond. ” the paper from ineichen and christen exemplifies the impressive publication activity in the field. they analyzed more than 7,000 papers published between 1991 and 2014 on dbs using quantitative methods. the study confirms known trends within the field such as the emergence of psychiatric indications with a particular focus on depression and the increasing discussion of complex side-effects such as personality changes. other findings are more surprising, e.g., that hardware-related issues are far more robustly connected to ethical issues compared to impulsivity, concrete side-effects or death/suicide. this indicates that the bioethica…”
Stakenborg, N., & Boeckxstaens, G. E.. (2021). Bioelectronics in the brain-gut axis: Focus on inflammatory bowel disease (IBD). International Immunology
“Accumulating evidence shows that intestinal homeostasis is mediated by cross-talk between the nervous system, enteric neurons and immune cells, together forming specialized neuroimmune units at distinct anatomical locations within the gut. in this review, we will particularly discuss how the intrinsic and extrinsic neuronal circuitry regulates macrophage function and phenotype in the gut during homeostasis and aberrant inflammation, such as observed in inflammatory bowel disease (ibd). furthermore, we will provide an overview of basic and translational ibd research using these neuronal circuits as a novel therapeutic tool. finally, we will highlight the different challenges ahead to make bioelectronic neuromodulation a standard treatment for intestinal immune-mediated diseases.”
Serrano-Munoz, D., Taylor, J., Megia-Garcia, A., & Gomez-Soriano, J.. (2019). Neuromodulation for neurorehabilitation of motor disorders for stroke and spinal cord injury: An overview. Neuromodulation
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“The international neuromodulation society has defined therapeutic neuromodulation as ‘the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body’ (1). therapeutic neuromodulation can improve functional recovery and relieve neurological symptoms associated with stroke and spinal cord injury (sci), which has been highlighted by a tenfold increase in the number of studies cited in this field (institute for scientific information, january 2019). however, the overall quality of these studies needs to be assessed to facilitate better evidence-based choices about health interventions, especially as recent advances in this field has attracted intense online media attention (altmetric. bodleian oxford library, january 2019). in this workshop leading international researchers in the field of therapeutic neuromodulation for sci and stroke will present their latest results for improving motor system neurorehabilitation using both invasive and non-invasive neuromodulation techniques, ranging from repetitive magnetic motor cortex, transcutaneous spinal and deep brain cerebellum stimulation. each speaker will highlight the clinical impact of their research line and the priority areas that need to be addressed for further technical development. results from a systematic review of non-invasive transcutaneous spinal cord stimulation for sci motor neurorehabilitation will be presented, with a special emphasis on stimulation parameters, clinical trial design and outcome measures. finally, two ongoing research projects at the hospital nacional de paraplejicos and the universidad castilla-la mancha will be introduced to the audience. the neurotrain project will apply lumbosacral transcutaneous electrical spinal stimulation in combination with intensive cycling, with the aim of potentiating gait function and controlling spasticity for patients with incomplete sci. in parallel the recode project will assess how non-invasive transcutaneous spinal and transcortical direct current stimulation, synchronized with robotic exoskeletons, can potentiate gait rehabilitation after sci.”
Civelli, O.. (2012). Orphan GPCRs and Neuromodulation. Neuron
“Most g protein-coupled receptors (gpcrs) started as orphan gpcrs. matching them to known neuromodulators led to the elucidation of the broad diversity of the neuroreceptor families. moreover, orphan gpcrs have also been used as targets to discover novel neuromodulators. these discoveries have had profound impact on our understanding of brain function. here, i present an overview of how some of the novel neuropeptides have enlarged our comprehension of responses that direct sleep/wakefulness, the onset of obesity and the feeding response. i also discuss other advances gained from orphan gpcr studies such as the concept of specificity in neuromodulation or of receptors acting as sensors instead of synaptic transmitters. finally, i suggest that the recently discovered neuromodulators may hold the keys to our understanding of higher brain functions and psychiatric disorders.”
Wagner, T., Valero-Cabre, A., & Pascual-Leone, A.. (2007). Noninvasive human brain stimulation. Annual Review of Biomedical Engineering
“Modulation of the peripheral nervous system (pns) has a great potential for therapeutic intervention as well as restore bodily functions. recent interest has focused on autonomic nerves, as they regulate extensive functions implicated in organ physiology, chronic disease state and appear tractable to targeted modulation of discrete nerve units. therapeutic interventions based on specific bioelectronic neuromodulation depend on reliable neural interface to stimulate and record autonomic nerves. furthermore, the function of stimulation and recording requires energy which should be delivered to the interface. due to the physiological and anatomical challenges of autonomic nerves, various forms of this active neural interface need to be developed to achieve next generation of neural interface for bioelectronic medicine. in this article, we present an overview of the state-of-the-art for peripheral neural interface technology in relation to autonomic nerves. also, we reveal the current status of wireless neural interface for peripheral nerve applications. recent studies of a novel concept of self-sustainable neural interface without battery and electronic components are presented. finally, the recent results of non-invasive stimulation such as ultrasound and magnetic stimulation are covered and the perspective of the future research direction is provided.”
Linster, C.. (2014). Neuromodulation: Overview. In Encyclopedia of Computational Neuroscience
Lakatos, P., Gross, J., & Thut, G.. (2019). Review A New Unifying Account of the Roles of Neuronal. Current Biology
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“Rhythms are a fundamental and defining feature of neuronal activity in animals including humans. this rhyth- mic brain activity interacts in complex ways with rhythms in the internal and external environment through the phenomenon of ‘neuronal entrainment’, which is attracting increasing attention due to its suggested role in a multitude of sensory and cognitive processes. some senses, such as touch and vision, sample the environ- ment rhythmically, while others, like audition, are faced with mostly rhythmic inputs. entrainment couples rhythmic brain activity to external and internal rhythmic events, serving fine-grained routing and modulation of external and internal signals across multiple spatial and temporal hierarchies. this interaction between a brain and its environment can be experimentally investigated and even modified by rhythmic sensory stimuli or invasive and non-invasive neuromodulation techniques. we provide a comprehensive overview of the topic and propose a theoretical framework of how neuronal entrainment dynamically structures information from incoming neuronal, bodily and environmental sources. we discuss the different types of neuronal entrainment, the conceptual advances in the field, and converging evidence for general principles.”
Bartoli, F., Burnstock, G., Crocamo, C., & Carrà, G.. (2020). Purinergic signaling and related biomarkers in depression. Brain Sciences
“It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. the purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. in this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine-and atp-mediated signaling at p1 and p2 receptors, respectively. furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. in particular, a2a and p2x7 receptors have been identified as potential targets for depression treatment. preclinical studies highlight that both selective a2a and p2x7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. in particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.”
Fellous, J. M., & Linster, C.. (1998). Computational Models of Neuromodulation. Neural Computation
“Computational modeling of neural substrates provides an excellent theoretical framework for the understanding of the computational roles of neuromodulation. in this review, we illustrate, with a large number of modeling studies, the specific computations performed by neuromodulation in the context of various neural models of invertebrate and vertebrate preparations. we base our characterization of neuromodulations on their computational and functional roles rather than on anatomical or chemical criteria. we review the main framework in which neuromodulation has been studied theoretically (central pattern generation and oscillations, sensory processing, memory and information integration). finally, we present a detailed mathematical overview of how neuromodulation has been implemented at the single cell and network levels in modeling studies. overall, neuromodulation is found to increase and control computational complexity.”
Chaudhry, S. R., Stadlbauer, A., Buchfelder, M., & Kinfe, T. M.. (2021). Melatonin moderates the triangle of chronic pain, sleep architecture and immunometabolic traffic. Biomedicines
“Preclinical as well as human studies indicate that melatonin is essential for a physiological sleep state, promotes analgesia and is involved in immunometabolic signaling by regulating neuroin-flammatory pathways. experimental and clinical neuromodulation studies for chronic pain treatment suggest that neurostimulation therapies such as spinal cord stimulation, vagus nerve stimulation and dorsal root ganglion stimulation have an impact on circulating inflammatory mediators in blood, cerebrospinal fluid and saliva. herein, we provide an overview of current literature relevant for the shared pathways of sleep, pain and immunometabolism and elaborate the impact of melatonin on the crossroad of sleep, chronic pain and immunometabolism. furthermore, we discuss the potential of melatonin as an adjunct to neurostimulation therapies. in this narrative review, we addressed these questions using the following search terms: melatonin, sleep, immunometabolism, obesity, chronic pain, neuromodulation, neurostimulation, neuroinflammation, molecular inflammatory phenotyping. so far, the majority of the published literature is derived from experimental studies and studies specifically assessing these relationships in context to neurostimulation are sparse. thus, the adjunct potential of melatonin in clinical neurostimulation has not been evaluated under the umbrella of randomized-controlled trials and deserves increased attention as melatonin interacts and shares pathways relevant for noninvasive and invasive neurostimulation therapies.”
Konofagou, E.. (2018). Focused ultrasound for modulation of the central and peripheral nervous system. The Journal of the Acoustical Society of America
“Noninvasive neuromodulation has been the preferred option of neurological treatment but noninvasive approaches fall short when it comes to depth penetration. ultrasound modulation has been shown feasible in several species including humans both in vitro and in vivo. in this paper, an overview of our group’s ultrasound neuromodulation in both the central (cns) and the peripheral (pns) nervous systems will be provided. in cns, both motor- and sensory-related responses have been elicited in mice in vivo both in ipsilateral and contralateral limbs and pupils, respectively. the success are was highly correlated with the applied intensity and pressure in both the limb movement and ocular changes. the brain regions targeted were the somatosensory and visual cortex for the limb movement and the superior colliculus and locus coeruleus for the pupil dilation. in pns, stimulation and inhibition of the sciatic nerve with fus was elicited at different ultrasound parameters in vivo. displacement of the nerve highly cor…”
Byron, N., Semenova, A., & Sakata, S.. (2021). Mutual interactions between brain states and Alzheimer’s disease pathology: A focus on gamma and slow oscillations. Biology
“Brain state varies from moment to moment. while brain state can be defined by ongoing neuronal population activity, such as neuronal oscillations, this is tightly coupled with certain behavioural or vigilant states. in recent decades, abnormalities in brain state have been recognised as biomarkers of various brain diseases and disorders. intriguingly, accumulating evidence also demonstrates mutual interactions between brain states and disease pathologies: while abnormalities in brain state arise during disease progression, manipulations of brain state can modify disease pathology, suggesting a therapeutic potential. in this review, by focusing on alzheimer’s disease (ad), the most common form of dementia, we provide an overview of how brain states change in ad patients and mouse models, and how controlling brain states can modify ad pathology. specifically, we summarise the relationship between ad and changes in gamma and slow oscillations. as pathological changes in these oscillations correlate with ad pathology, manipulations of either gamma or slow oscillations can modify ad pathology in mouse models. we argue that neuromodulation approaches to target brain states are a promising non-pharmacological intervention for neurodegenerative diseases.”
Kohan, L., McKenna, C., & Irwin, A.. (2020). Ilioinguinal Neuropathy. Current Pain and Headache Reports
“Purpose of review: the purpose of this review is to present an overview of ilioinguinal (il) neuralgia and evaluate the current literature. recent findings: treatment of il neuralgia includes pharmacotherapies, perineural injections, radiofrequency ablation, cryoablation, neuromodulation, and neurectomy. the efficacy of these therapies varies considerably. summary: il neuralgia is a common pain disorder characterized by pain in the lower abdomen and upper thigh. while various modalities can be used in the treatment of il neuralgia, the efficacy of these modalities is at times limited. dorsal root ganglion stimulation exhibits promise in the treatment of il neuralgia. more research is needed to better address the needs of patients suffering from this disorder.”
Chen, S. P., & Ayata, C.. (2017). Novel Therapeutic Targets Against Spreading Depression. Headache
“Migraine is among the most prevalent and disabling neurological diseases in the world. cortical spreading depression (sd) is an intense wave of neuronal and glial depolarization underlying migraine aura, and a headache trigger, which has been used as an experimental platform for drug screening in migraine. here, we provide an overview of novel therapeutic targets that show promise to suppress sd, such as acid-sensing ion channels, casein kinase iδ, p2x7-pannexin 1 complex, and neuromodulation, and outline the experimental models and essential quality measures for rigorous and reproducible efficacy testing.”
Ekhtiari, H., Tavakoli, H., Addolorato, G., Baeken, C., Bonci, A., Campanella, S., … Hanlon, C. A.. (2019). Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead. Neuroscience and Biobehavioral Reviews
“There is growing interest in non-invasive brain stimulation (nibs) as a novel treatment option for substance-use disorders (suds). recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent fda-approval of nibs treatments for mental health disorders that share overlapping pathology with suds. as with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tes) and transcranial-magnetic (tms) stimulation applied in suds. this consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. the goal of this effort is to provide the community with guidelines for best practices in tes/tms sud research. we hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.”
Fridén, J., House, J., Keith, M., Schibli, S., & van Zyl, N.. (2021). Improving hand function after spinal cord injury. Journal of Hand Surgery: European Volume
“Nerve transfer surgery has expanded reconstructive options for restoring upper extremity function following spinal cord injury. by adding new motor donors to the pool already available through tendon transfers, the effectiveness of treatment should improve. planning which procedures and in which order to perform, along with their details must be delineated. to meet these demands, refined diagnostics are needed, along with awareness of the remaining challenges to restore intrinsic muscle function and to address spasticity and its consequences. this article summaries recent advances in surgical reanimation of upper extremity motor control, together with an overview of the development of neuro-prosthetic and neuromodulation techniques to modify recovery or substitute for functional losses after spinal cord injuries.”
Anderson, N. D., & Craik, F. I. M.. (2017). 50 years of cognitive aging theory. Journals of Gerontology – Series B Psychological Sciences and Social Sciences
“Objectives: the objectives of this introduction to the journal of gerontology: psychological sciences special issue on ‘50 years of cognitive aging theory’ are to provide a brief overview of cognitive aging research prior to 1965 and to highlight significant developments in cognitive aging theory over the last 50 years. method: historical and recent theories of cognitive aging were reviewed, with a particular focus on those not directly covered by the articles included in this special issue. results: prior to 1965, cognitive aging research was predominantly descriptive, identifying what aspects of intellectual functioning are affected in older compared with younger adults. since the mid-1960s, there has been an increasing interest in how and why specific components of cognitive domains are differentially affected in aging and a growing focus on cognitive aging neuroscience. discussion: significant advances have taken place in our theoretical understanding of how and why certain components of cognitive functioning are or are not affected by aging. we also know much more now than we did 50 years ago about the underlying neural mechanisms of these changes. the next 50 years undoubtedly will bring new theories, as well as new tools (e.g., neuroimaging advances, neuromodulation, and technology), that will further our understanding of cognitive aging.”
Martin-Sanchez, F., & Maojo, V.. (2009). Biomedical Informatics and the Convergence of Nano-Bio-Info-Cogno (NBIC) Technologies. Yearbook of Medical Informatics
“Objectives to analyze the role that biomedical informatics could play in the application of the nbic converging technologies in the medical field and raise awareness of these new areas throughout the biomedical informatics community.”
Abstract
Objectives: To analyze the role that biomedical informatics could play in the application of the NBIC Converging Technologies in the medical field and raise awareness of these new areas throughout the Biomedical Informatics community.
Methods: Review of the literature and analysis of the reference documents in this domain from the biomedical informatics perspective. Detailing existing developments showing that partial convergence of technologies have already yielded relevant results in biomedicine (such as bioinformatics or biochips). Input from current projects in which the authors are involved is also used.
Results: Information processing is a key issue in enabling the convergence of NBIC technologies. Researchers in biomedical informatics are in a privileged position to participate and actively develop this new scientific direction. The experience of biomedical informaticians in five decades of research in the medical area and their involvement in the completion of the Human and other genome projects will help them participate in a similar role for the development of applications of converging technologies -particularly in nanomedicine.
Conclusions: The proposed convergence will bring bridges between traditional disciplines. Particular attention should be placed on the ethical, legal, and social issues raised by the NBIC convergence. These technologies provide new directions for research and education in Biomedical Informatics placing a greater emphasis in multidisciplinary approaches.
Rebholz-Schuhman D, Cameron G, Clark D, van Mulligen E, Coatrieux JL, Del Hoyo Barbolla E, Martin-Sanchez F, Milanesi L, Porro I, Beltrame F, Tollis I, Van der Lei J.BMC Bioinformatics. 2007 Mar 8;8 Suppl 1(Suppl 1):S18. doi: 10.1186/1471-2105-8-S1-S18.PMID: 17430562Free PMC article.Review.
Developments in biotechnology and neuroscience have the potential to unleash an engineering of human beings previously inconceivable. Proper ethical governance and a new understanding of humanism, are necessary to steer these technological developments in the direction of supporting sustainable, just and peaceful futures. Such futures will depend on open data, open science and an expanded understanding of the right to education to include the right to data, to information and to the protection of privacy.
UNESO, International Commission on the Futures of Education, p.8 et seq.
“It is, however, essential that eugenics should be brought entirely within the borders of science, for, as already indicated, in the not very remote future the problem of improving the average quality of human beings is likely to become urgent; and this can only be accomplished by applying the findings of a truly scientific eugenics.”
Sir Julian Sorell Huxley
From UNESCO Its Purpose and Its Philosophy
Daniel J simon, C. F. C. (1999). Gorilla in our midst – reference. Gorillas in Our Midst: Sustained, Inattentional Blindness for Dynamic Events – Perception.
Simons, D. J. (2010).
Monkeying around with the Gorillas in Our Midst: Familiarity with an Inattentional-Blindness Task Does Not Improve the Detection of Unexpected Events. I-Perception, 1(1), 3–6. doi.org/10.1068/i03865
5G map: www.nperf.com/de/map/5g
5G has been developed by the US/Israeli military as a weapon to disperse crowds (directed energy beams which are harmful to biological organisms). It has been used twice during the illegal Irak-war. There are virtually no studies about the safety of 5G and it can be regarded as a social experiment without consensus and control-group. The 60Ghz frequency interferes with oxygen absorption of hemoglobin.
Tretyakov, M. Y., Koshelev, M. A., Dorovskikh, V. V., Makarov, D. S., & Rosenkranz, P. W. (2005). 60-GHz oxygen band: precise broadening and central frequencies of fine-structure lines, absolute absorption profile at atmospheric pressure, and revision of mixing coefficients. Journal of Molecular Spectroscopy, 231(1), 1–14. doi.org/10.1016/j.jms.2004.11.011
PhysicalControloftheMind: Toward a Psycho-civilized Society by José M. R. Delgado. Publication date 1969
Electronic technology has reached a high level of sophistication,
and two-way radio commJ’nication with automobiles, airplanes,
and outer space vehicles is commonplace today. The
notable lag in development of similar instrumentation for communciation with the depth of the brain reflects the already
mentioned unbalanced evolution of our technological civilization,
which seems more interested in accumulating power than
in understanding and influencing the basic mechanisms of the
human mind.
This gap is now being filled, and as Figures 4 and 5 show, it
is already possible to equip animals or human beings with
minute instruments called “stimoceivers” for radio transmission
and reception of electrical messages to and from the brain in
completely unrestrained subjects. Microminiaturization of the
instrument’s electronic components permits control of all parameters of excitation for radio stimulation of three different points
within the brain and also telemetric recording of three channels
of intracerebral electrical activity. In animals, the stimoceiver
may be anchored to the skull, and different members of a colony
can be studied without disturbing their spontaneous relations
within a group. Behavior such as aggression can be evoked or
inhibited. In patients, the stimoceiver may be strapped to the
head bandage, permitting electrical stimulation and monitoring
of intracerebral activity without disturbing spontaneous activities.
p. 39 “Demselben Zweck einer Verdeckung eigener Ziele und Absichten dient eine Angsterzeugung durch propagandistische Deklaration einer großen Gefahr X, der die Bevölkerung durch einen »Kampf gegen X« entschlossen entgegentreten müsse. Eine derartige propagandistische Warnung begleiten die staatlichen Apparate durch »die gegenwärtig alles beherrschende Verheißung des Schutzes vor Terrorismus und Bösem aller Art«.38 X kann dabei so ziemlich alles sein, was sich irgendwie wirksam zur Angsterzeugung nutzen lässt. X kann also für »Kommunismus« stehen, für Migranten, »Sozialschmarotzer«, Terrorismus, Fake News und Desinformation, Rechtspopulismus, Islamismus oder für irgendetwas anderes. Durch die propagandistische Ausrufung eines »Kampfes gegen X« lassen sich in »kapitalistischen Demokratien« gleichzeitig mehrere von den Zentren der Macht gewünschte Ziele erreichen: Zum einen wird der für Machtzwecke nutzbare Rohstoff »Angst« produziert, zudem lässt sich die Aufmerksamkeit sehr wirksam auf Ablenkziele richten, und schließlich lassen sich unter dem Vorwand eines Kampfes gegen X demokratische Strukturen abbauen und auf allen Ebenen der Exekutive und Legislative autoritäre Strukturen etablieren.”
“Jean baudrillard is one of the most celebrated and most controversial of contemporary social theorists. this major work, appearing in english for the first time, occupies a central place in the rethinking of the humanities and social sciences around the idea of postmodernism. it leads the reader on an exhilarating tour encompassing the end of marxism, the enchantment of fashion, symbolism about sex and the body, and the relations between economic exchange and death. most significantly, the book represents baudrillard’s fullest elaboration of the concept of the three orders of the simulacra, defining the historical passage from production to reproduction to simulation.”
Baudrillard, J., & Glaser, S. F.. (1994). Simulacrum and Simulation (The Body, In Theory: Histories of Cultural Materialism). The Body, In Theory: Histories of Cultural Materialism
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“Fvinoly@webvisual.com, 02/16/97, rating=10: essential postmodern text baudrillard provides us with a clear explanation of the concept of simulations and simulacra–the copy without the original. from this postmodern landmark, he gives us specific examples of his theory that are a pleasure to read. chapters on ‘the china syndrome’, ‘holograms’, and ‘the animals’, among others, begin to define our roles in postmodern society and our relationships with our environment and ourselves. each chapter gives you a new, fascinating perspective, that culminates and reaches full circle with his final discussion of ‘nihilism’. table of contents the precession of simulacra history: a retro scenario holocaust the china syndrome apocalypse now the beaubourg effect: implosion and deterrence hypermarket and hypercommodity the implosion of meaning in the media absolute advertising, ground-zero advertising clone story holograms crash simulacra and science fiction the animals: territory and metamorphoses the remainder the spiraling cadaver value’s last tango on nihilism”
Baudrillard, J.. (1994). Simulacra and simulation / by Jean Baudrillard ; translated by Sheila Faria Glaser. Idea
“Scholars have recently paid increasing attention to china’s ‘mega events’ as a form of image management striving to influence future world order. in this article, the author examines china’s recent world fair, expo 2010 shanghai china, and argues that we need to move beyond the reading of mega events as simple representation and ideology and read it also as simulation and simulacra. reading the chinese world fair as a simulacrum of world order can provide different ways of relating ‘the west’ to its ‘other country’ china. the author examines this relation through asking what it means to be the fair: where is the world fair? when is the world fair? who is the world fair? reading the world/fair as simulacrum disrupts the fair’s notions of inside and outside, now and then, subject and object to the point where these terms are no longer workable.”
Croissant, J. L.. (2006). The new sexual technobody: Viagra in the hyperreal world. Sexualities
“This essay, based on the work of baudrillard and other critical theorists of culture and technology, describes how viagra and related products are creating not just new standards for men and women’s sexual performance, but new forms of hypersexual’ reality/hyperreal sexuality. considering television advertisements and framed around metaphors of landscape, internet spam’ advertisements for sexual performance enhancing products (both mechanical and chemical), and bodybuilding magazine representations of the body and sexuality, it is apparent that sexual expression in these genres is both constrained and yet exceeds its boundaries. sexuality is represented in these media as heterosexual, penetrative, and never to be imperfect in any way. the body itself, perhaps aging or flawed, is represented as incapable of achieving these ends reliably without pharmaceutical means. i argue that viagra and other sexual pharmaceuticals are best understood as hyperreal or hypernatural (reflecting baudrillard’s 1994 work, simulacra and simulation), as simulacra that bear no relation to reality’. sexual pharmaceutical advertisements refer to an unmedicated imaginary that assumes a unity where there is diversity, and conflates the means and ends of sexual technique.”
Butterfield, B.. (2007). Ethical Value and Negative Aesthetics: Reconsidering the Baudrillard-Ballard Connection. PMLA
“Like today’s masses, the characters in j. g. ballard’s crash are fascinated by what jean baudrillard calls the accident, especially when it involves the death of a celebrity. ballard’s characters, however, reenact their accidents as sexual rituals of a marriage between technology and death that are beyond the realm of moral judgment, making crash sci-fi, hypothetical, unrealistic. calling crash ‘the first great novel of the universe of simulation,’ jean baudrillard has drawn heavy criticism for missing the alleged moral point, both in crash and in the still-real world. as a fiction writer, ballard is given a wide moral berth, but when baudrillard’s theory turns sci-fi, the question of ethical boundaries is broached, and leniency is less likely. in defense of baudrillard, i read him, like ballard, in the nietzschean tradition of a purposefully amoral, negative aestheticism, which i argue is of value to ethics and radical politics in a world governed by instrumental simulacra.; the characters of j. g. ballard’s ‘crash’ are fascinated by what jean baudrillard calls the accident. butterfield reads baudrillard like ballard in the nietzschean tradition of a purposefully amoral, negative aestheticism, which he argues is of value to ethics and radical politics in a world governed by instrumental simulacra.;”
Constable, C.. (2006). Baudrillard reloaded: Interrelating philosophy and film via the Matrix Trilogy. Screen
“The extensive writing on the philosophical aspects of the matrix trilogy raises the problems inherent to the interrelation of philosophy/theory and film texts in an acute form. the films are often treated as an introduction to diverse and difficult concepts meaning that – at best – they function as examples to make the theories accessible. at worst, they are castigated for being insufficiently critical and presented as pseudo-philosophy. in contrast, this article will demonstrate that the scenarios offered by the matrix trilogy form an active dialogue with postmodern philosophy, changing the construction of key philosophical concepts. tracing such a dialogue involves the development of a new model for interrelating philosophical and filmic texts. the first part of the article sets out a new methodology, drawing on the work of french feminist philosopher michele le doeuff. the article focuses on the imagery that characterizes/defines baudrillard’s concept of the hyperreal in simulacra and simulation. this is accompanied by an examination of the ways in which the matrix trilogy takes up key images, such as the mirror and aspects of greek mythology. the final part addresses the films’ presentation of value – a departure from its baudrillardian source – which sustains a radical reconceptualization of the hyperreal.”
Massumi, B.. (1987). Realer than Real: The Simulacrum According to Deleuze and Guattari. Copyright
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“There is a seductive image of contemporary culture circulating today. our world, jean baudrillard tells us, has been launched into hyperspace in a kind of postmodern apocalypse. the airless atmosphere has asphyxiated the referent, leaving us satellites in aimless orbit around an empty center. we breathe an ether of floating images that no longer bear a relation to any reality whatsoever.1 that, according to baudrillard, is simulation: the substitution of signs of the real for the real.2 in hyperreality, signs no longer represent or refer to an external model. they stand for nothing but themselves, and refer only to other signs. they are to some extent distinguishable, in the way the phonemes of language are, by a combinatory of minute binary distinctions.3 but postmodernism stutters. in the absence of any gravitational pull to ground them, images accelerate and tend to run together. they become interchangeable. any term can be substituted for any other: utter indetermination.4 faced with this homogeneous surface of syntagmatic slippage, we are left speechless. we can only gape in fascination.5 for the secret of the process is beyond our grasp. meaning has imploded. there is no longer any external model, but there is an immanent one. to the syntagmatic surface of slippage there corresponds an invisible paradigmatic dimension that creates those minimally differentiated signs only in order for them to blur together in a pleasureless orgy of exchange and circulation. hidden in the images is a kind of genetic code responsible for their generation.6 meaning is out of reach and out of sight, but not be cause it has receded into the distance. it is because the code has been miniaturized. objects are images, images are signs, signs are information, and information fits on a chip. everything reduces to a molecular binarism. the generalized digitality of the computerized society.7 and so we gape. we cannot be said to be passive exactly, because all polarity, including the active/passive dichotomy, has disappeared. we have no earth to center us, but we ourselves function as a ground-in the electrical sense.8 we do not act, but neither do we merely receive. we absorb through our open eyes and mouths. we neutralize the play of energized images in the mass entropy of the silent majority. it makes for a fun read. but do we really have no other choice than being a naive realist or being a sponge? deleuze and guattari open a third way. although it is never developed at l…”
Rennett, M.. (2009). Baudrillard and The Joe Schmo Show. The International Journal of Baudrillard Studies
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“Reality television is a euphemism. although audience members may believe they are seeing what happens when people stop being polite and start being real, nothing could be further from the truth. a vh1 expose, reality tv secrets revealed, divulges many of the techniques used by the producers of these shows to get the story they want including recreating actions that were not originally caught on tape, combining audio and video from separate times together, and acting out pre-planned storylines. reality tv viewers and critics, as well as television and media scholars, have debated the reality of these programs ever since the genre became a popular part of the american zeitgeist in the late 1990s. through editing techniques, the producers can exaggerate elements from an individual’s personality to construct a persona that audiences can rapidly identify. the discussion of these tactics leads me to a question: if reality television does not present reality, as it purports to do, then what is it actually showing? as jean baudrillard notes, ‘reality television [gives] the illusion of a real world, an exterior world, despite the fact that each world is the exact image of the other’ (2005:181). by using the words ‘illusion’ and ‘exact image,’ baudrillard points to reality tv programs as mere simulacra of the real world and which produce a hyperreality — not unlike his famous example of disneyland (baudrillard, 2002a:23, 96). as baudrillard argues, hyperreality is created through the process of simulation in which images of reality are turned into simulacra, copies which are so powerful that they erase the original. the constructed character personalities seen on reality tv reflect baudrillard’s discussion of simulacra. adapted from the source document.”
Baudrillard, J.. (1972). Simulacra & Simulation* precession of simulacra. Postmodern American Fiction: A Norton Anthology
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“DEFINICIÓ d’hiperrealitat: the generation by models of a real without origin or reality (pag?) o ‘a real without origin or reality’ p1”