See also: Edwin Black – IBM and the Holocaust: The Strategic Alliance Between Nazi Germany and America’s Most Powerful Corporation (2002)
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In December 2023, IBM released Quatum System 2
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Version 1
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Benthams Panopticon
Further References
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Armanski, Gerhard, Maschinen des Terrors: Das Lager (KZ und GULAG) in der Moderne. Munster: Verlag Westfalisches Dampfboot, 1993.
Austrian, Geoffrey D. Herman Hollerith: Forgotten Giant of Information Processing. New York: Columbia University Press, 1982.
Baumgartner, Andreas. Die vergessenen Frauen von Mauthausen: Die weiblichen Haftlinge des Konzentrationslagers Mauthausen und ihre Geschichte. Wien: Verlag Osterreich, 1997.
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Black, Edwin. The Transfer Agreement: The Dramatic Story of the Pact Between the Third Reich and Jewish Palestine. New York: Macmillan, 1984; Chicago: Dialog Press, 1999.
Borkin, Joseph. The Crime and Punishment of I.G. Farben. New York: The Free Press, 1978.
Bradsher, Greg, comp. Holocaust-Era Assets: A Finding Aid to Records at the National Archives at College Park, Maryland. National Archives and Records Administration, 1999.
Breitman, Richard. Official Secrets: What the Nazis Planned, What the British and Americans Knew. New York: Hill and Wang, 1998.
Browning, Christopher R. The Path to Genocide: Essays on Launching the Final Solution. New York: Cambridge University Press, 1992.
Brynen, Rex. Sanctuary and Survival: The PLO in Lebanon. Boulder: Westview Press, 1990.
Burleigh, Michael. Death and Deliverance: ‘Euthanasia’ in Germany,’ 1900-1945. New York: Cambridge University Press, 1994.
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Choldin, Harvey M. Looking for the Last Percent: The Controversy Over Census Undercounts. New Brunswick: Rutgers University Press, 1994.
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De Jong, L. Holland Fights the Nazis. London: Lindsay Drummon.
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Friedlander, Saul. Nazi Germany and the Jews. Volume 1: The Years of Persecution. New York: HarperCollins, 1997.
Garr, Doug. Lou Gerstner and the Business Turnaround of the Decade. New York: HarperCollins 1999.
Gilbert, Martin. The Holocaust: A History of the Jews of Europe During the Second World War. New York: Holt, Rinehart and Winston, 1985.
Goldhagen, Daniel Jonah. Hitler’s Willing Executioners: Ordinary Germans and the Holocaust. New York: Alfred A. Knopf, 1996; Vintage Books, 1997.
Gutman, Israel. Resistance: The Warsaw Ghetto Uprising. New York: Houghton Mifflin Company, 1994.
Gutman, Yisrael and Michael Berenbaum, eds. Anatomy of the Auschwitz Death Camp. Indianapolis: Indiana University Press, 1994; published in association with the United States Holocaust Memorial Museum, Washington, D.C.
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Hirschfeld, Gerhard. Nazi Rule and Dutch Collaboration: The Netherlands Under German Occupation, 1940-1945. Translated by Louise Willmot. New York: Berg, 1988.
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Ioanid, Radu. The Holocaust in Romania: The Destruction of Jews and Gypsies Under the Antonescu Regime, 1940-1944. Chicago: Ivan R. Dee, 2000.
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Kahn, Annette. Le Fichier. Paris: Robert Laffont, S.A., 1993.
Katsh, Abraham I., ed. and translator. Scroll of Agony: The Warsaw Diary of Chaim A. Kaplan. New York: The Macmillan Company, 1965.
Katsh, Abraham I., ed. and translator. The Warsaw Diary of Chaim A. Kaplan. New York: Collier Books, 1973.
Kermish, Joseph, ed. To Live With Honor and Die With Honor: Selected Documents from the Warsaw Ghetto Underground Archives “O.S.” [“Oneg Skabbath”] Jerusalem: Yad Vashem, 1986.
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Kleine Chronik der IBM Deutschland, IBM Corporation, 1993.
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Linden, Michael. IBM and the Holocaust: The Strategic Alliance Between Nazi Germany and America’s Most Powerful Corporation. New York: Crown Publishers, 2001.
Littman, Sol. IBM and the Holocaust: The Strategic Alliance Between Nazi Germany and America’s Most Powerful Corporation. Watson Publishing International, 2002.
Lochner, Louis P. What About Germany? New York: Dodd, Mead and Company, 1942.
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Miczek, Eva. At the Mercy of Strangers: Growing Up on the Edge of the Holocaust. Toronto: Bantam Books, 1998.
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Moeller van den Bruck, Arthur. Das Dritte Reich. Hamburg: Verlag Hanseatische Verlagsanstalt, 1931.
In this review we provide an analysis of recent literature reports on the synthesis and applications of stimuli-responsive polymeric and hybrid nanostructured particles in a range of sizes from nanometers to a few micrometers: nano- and microgels, core–shell structures, polymerosomes, block-copolymer micelles, and more complex architectures. The review consists of two major parts: synthesis and applications of nanoparticles in colloidal dispersions, thin films, delivery devices and sensors. We also broadly discuss potential directions for further developments of this research area.
Motornov, M., Roiter, Y., Tokarev, I., & Minko, S.. (2010). Stimuli-responsive nanoparticles, nanogels and capsules for integrated multifunctional intelligent systems. Progress in Polymer Science, 35(1–2), 174–211.
Buwalda, S. J., Boere, K. W. M., Dijkstra, P. J., Feijen, J., Vermonden, T., & Hennink, W. E.. (2014). Hydrogels in a historical perspective: From simple networks to smart materials. Journal of Controlled Release, 190, 254–273.
“Over the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. biomedical application of hydrogels was initially hindered by the toxicity of crosslinking agents and limitations of hydrogel formation under physiological conditions. emerging knowledge in polymer chemistry and increased understanding of biological processes resulted in the design of versatile materials and minimally invasive therapies. hydrogel matrices comprise a wide range of natural and synthetic polymers held together by a variety of physical or chemical crosslinks. with their capacity to embed pharmaceutical agents in their hydrophilic crosslinked network, hydrogels form promising materials for controlled drug release and tissue engineering. despite all their beneficial properties, there are still several challenges to overcome for clinical translation. in this review, we provide a historical overview of the developments in hydrogel research from simple networks to smart materials.”
Advances in the development of cyclodextrin-based nanogels/microgels for biomedical applications: Drug delivery and beyond 2022, Carbohydrate Polymers
Formation of ultrathin scarf-like micelles, ultrathin disk-like micelles and spherical micelles by self-assembly of polyurethane diblock copolymers 2022, Journal of Molecular Liquids
Inorganic/organic hybrid nanoparticles synthesized in a two-step radiation-driven process 2022, Radiation Physics and Chemistry
The influence of the functional end groups on the properties of polylactide-based materials 2022, Progress in Polymer Science
How molecular interactions tune the characteristic time of nanocomposite colloidal sensors 2022, Journal of Colloid and Interface Science
Psychoneuroimmunology (PNI), also referred to as psychoendoneuroimmunology (PENI) or psychoneuroendocrinoimmunology (PNEI), is the study of the interaction between psychological processes and the nervous and immune systems of the human body. It is a subfield of psychosomatic medicine. PNI takes an interdisciplinary approach, incorporating psychology, neuroscience, immunology, physiology, genetics, pharmacology, molecular biology, psychiatry, behavioral medicine, infectious diseases, endocrinology, and rheumatology.
The main interests of PNI are the interactions between the nervous and immune systems and the relationships between mental processes and health. PNI studies, among other things, the physiological functioning of the neuroimmune system in health and disease; disorders of the neuroimmune system (autoimmune diseases; hypersensitivities; immune deficiency); and the physical, chemical and physiological characteristics of the components of the neuroimmune system in vitro, in situ, and in vivo.
It is now clear that the cellular and molecular processes that make up our ‘immune system’ are also crucial to normal brain development and play a role in the pathoaetiology of many mental and physical disorders.
Troyer, E. A., Kohn, J. N., & Hong, S.. (2020). Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain, Behavior, and Immunity, 87, 34–39.
“The coronavirus disease 19 (covid-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals’ lives and organizations in virtually all social and economic sectors worldwide. fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. however, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; sars-cov-2), and the subsequent host immunologic response, on the human central nervous system (cns) and related outcomes are unknown. we discuss currently available evidence of covid-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. the potential mechanisms are also discussed, including viral and immunological underpinnings. therefore, prospective neuropsychiatric monitoring of individuals exposed to sars-cov-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of covid-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.”
Hamilton-West, K.. (2011). Psychobiological Processes in Health and Illness. Psychobiological Processes in Health and Illness. 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP United Kingdom: SAGE Publications Ltd
“Psychobiological processes in health and illness is an accessible and engaging introduction to the interrelationships between mind and body across a broad range of topics including infectious illness, autoimmunity, cancer and pain. taking a biopsychosocial approach, it brings together research from a number of disciplines including health psychology, psychoneuroimmunology and behavioral genetics. the textbook presents established theoretical models relevant to psychobiological processes in health and illness, as well as recent developments in systems, technologies and intervention methods.”
Mravec, B., Tibensky, M., & Horvathova, L.. (2020). Stress and cancer. Part II: Therapeutic implications for oncology. Journal of Neuroimmunology, 346, 577312.
“Accumulated evidence has confirmed the ability of stress to promote the induction and progression of cancer (for review see stress and cancer. part i: mechanisms mediating the effect of stressors on cancer). in support of this, data from clinical trials utilizing approaches that reduce stress-related signaling have shown prolonged survival of cancer patients. therefore, the question has arisen as to how we can utilize this knowledge in the daily treatment of cancer patients. the main aim of this review is to critically analyze data from studies utilizing psychotherapy or treatment by β-blockers on the survival of cancer patients. because these approaches, especially treatment by β-blockers, have been routinely used in clinical practice for decades in the treatment of non-cancer patients, their wider introduction into oncology might be realized in the near future.”
Pahlevi, R., Putra, S. T., & Sriyono, S.. (2017). Psychoneuroimmunology Approach to Improve Recovery Motivation, Decrease Cortisol and Blood Glucose of DM Type 2 Patients with Dhikr Therapy. Jurnal Ners, 12(1), 60–65.
“Introduction: blood glucose levels are controlled when the management of diabetes success. positive perception of the strength of the spiritual aspect will improve the motivation of patients with type 2 diabetes to control it. the purpose of this study was to determine the effect of dhikr based on psychoneuroimmunology (pni) on blood glucose levels of patients with type 2 diabetes.methods: this study used quasi-experiment with pre-test and post-test control group design. samples were taken from the population of patients with type 2 diabetes who were hospitalized in the internal medicine rumkital dr. ramelan surabaya with purposive sampling techniques. data taken include the general characteristics of respondents, cures motivation, cortisol levels and fasting blood glucose levels. collecting data using questionnaires and laboratory test, then analyzed using paired t-test and independent t-test, with α value <0.05.results: statistical test showed that the motivation to recover increased (p = 0.001), cortisol levels fall (p = 0.058) and a drop in blood glucose levels (p = 0.028) after administration of dhikr therapy in patients with diabetes mellitus type 2. there was a significant difference in increased of recovery motivation between patient conduct zikr therapy and patient cared (p = 0,000).conclusion: dhikr therapy increases the motivation of patients with type 2 diabetes by strengthening awareness and spirituality belief in allah make positive stress perception. positive stress perception will affect the stress response and improved regulation of blood glucose through the hpa axis to suppress the secretion of crh, acth, and cortisol.”
Mathews, H. L., & Janusek, L. W.. (2011). Epigenetics and psychoneuroimmunology: Mechanisms and models. Brain, Behavior, and Immunity, 25(1), 25–39.
Labanski, A., Langhorst, J., Engler, H., & Elsenbruch, S.. (2020). Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge. Psychoneuroendocrinology, 111, 104501.
“The broad role of stress in the brain-gut axis is widely acknowledged, with implications for multiple prevalent health conditions that are characterized by chronic gastrointestinal symptoms. these include the functional gastrointestinal disorders (fgid), such as irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel diseases (ibd) like ulcerative colitis and crohn’s disease. although the afferent and efferent pathways linking the gut and the brain are modulated by stress, the fields of neurogastroenterology and psychoneuroendocrinology (pne)/ psychoneuroimmunology (pni) remain only loosely connected. we aim to contribute to bringing these fields closer together by drawing attention to a fascinating, evolving research area, targeting an audience with a strong interest in the role of stress in health and disease. to this end, this review introduces the concept of the brain-gut axis and its major pathways, and provides a brief introduction to epidemiological and clinical aspects of fgids and ibd. from an interdisciplinary pne/pni perspective, we then detail current knowledge regarding the role of chronic and acute stress in the pathophysiology of fgid and ibd. we provide an overview of evidence regarding non-pharmacological treatment approaches that target central or peripheral stress mechanisms, and conclude with future directions, particularly those arising from recent advances in the neurosciences and discoveries surrounding the gut microbiota.”
Leckman, J. F.. (2014). Commentary: What does immunology have to do with brain development and psychopathology? – A commentary on O’Connor et al. (2014). Journal of Child Psychology and Psychiatry and Allied Disciplines
Segerstrom, S. C., Glover, D. A., Craske, M. G., & Fahey, J. L.. (1999). Worry Affects the Immune Response to Phobic Fear. Brain, Behavior, and Immunity, 13(2), 80–92.
“Worry, the cognitive enumeration and anticipation of potential future negative events, is associated with autonomic dysregulation, which may in turn have implications for the immune system. people endorsing high (n = 7) and normal levels of trait worry (n = 8) were briefly exposed to a phobic stimulus and the autonomic and immune responses and recovery were assessed. a time-matched control group (n = 6) was not exposed to any stimulus. both worry groups showed increased heart rate and skin conductance in response to phobic fear. however, only the normal worry group showed a concomitant increase in natural killer cells in peripheral blood. patterns of change during the follow-up period suggested that phobic fear had disrupted a normal circadian increase in natural killer cells. adrenergic and hypothalamus-pituitary-adrenal mechanisms may be responsible for the differences between high and normal worry groups in their natural killer cell response to and recovery from phobic fear.”
Aziez Chettoum, Kamilia Guedri, Zouhir Djerrou, Rachid Mosbah, Latifa Khattabi, Abir Boumaaza, & Wissam Benferdi. (2020). Distribution of leukocyte subpopulation among students threatened by failure. International Journal of Research in Pharmaceutical Sciences, 11(3), 3807–3812.
“Psychoneuroimmunology or the study of the relationships between the brain and the immune system is an area of research that has experienced significant development over the decade. stress does not appear without consequences on the state of health, the role of fears, emotions and significant constraints in the appearance of organic and mental diseases. in this research, we studied the effect of stress and anxiety during exams at the end of the academic year (2018/2019) on the distribution of leukocyte subpopulations and the immune system, questionnaires has been completed by student volunteers, to estimate the anxio-depressive comorbidities through the (hads) test during and outside exams, and in the same time we asked them for a blood sample the next morning day to carry out some biological assays (cbc). we also found that stress during exams caused a change in the distribution of different types of white blood cells, a total decrease in white blood cell counts with neutropenia and lymphopenia were found in students during exams compared to controls, and an increase in monocyte and other types of polymorphonuclear levels in students during exams compared to controls. other tests measuring the effects of stress on specific functions of the immune system can be used.”
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
Show/hide publication abstract
“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
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“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
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“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.”
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
How strangely will the Tools of a Tyrant pervert the plain Meaning of Words!
— Samuel Adams
Archon (Greek: ἄρχων, romanized: árchōn) is the Greek term for “ruler”. Cognate derivatives are, e.g., terms such as:
monarchy
dyarchy
hierarchy
patriarchy/matriarchy
gynarchy
autarchy
anarchy (etymology discussed subsequently in more detail)
According to Aristotle’s Constitution of the Athenians (78-c. 100), the power and influence of the king first devolved to the archons, and these offices were filled from the aristocracy by elections on a decennial basis. Archon Eponymos was the primary magistrate, the Polemarch referred to the head of the armed forces, and the Archon Basileus was in charge of the religious aspects of society.
Various fraternities and sororities use the title of archon or variations on it. Some Gnostic sects used this term for demons associated with the planetspheres.
3-D computer rendering of an “archon”
The term anarchy is the negation of the term archon (i.e., the negatory prefix *a). It thus means “without a ruler/master”, i.e., human beings that do not accept a master and who do not allow others to rule over them (they are not slaves to anyone). Importantly, this derivation should not be confused with “chaos or without rules”. Anarchy simply is the negation of slavery.
Niemand ist mehr Sklave, als der sich für frei hält, ohne es zu sein. ‘
~ Johann Wolfgang von Goethe
(Transl.: None are more hopelessly enslaved than those who falsely believe they are free.)
Human beings who are anarchists are thus literally beings that do not accept to be ruled by archons, i.e., they are free and cannot be ruled and suppressed by external forces (they only subordinate themselves to natural law, viz., the timeless universal metaphysical foundation of morality and ethics; cf. the Kantian categorical imperative).
Act only according to that maxim whereby you can at the same time will that it should become a universal law.
— Immanuel Kant, Grounding for the Metaphysics of Morals (1785)
In this context a quotation by the freedom fighter Malcolm X is of great pertinence.
He asked the following quintessential question concerning the highest of all virtues:
What is the price of freedom?
Answer
Death.
P.S. This does not imply that one has to die to be free, but it means that one has to be willing to risk once own life for the greatest of all goods, viz., the ultimate expression of human potential: Absolute Freedom.
If one is not willing to go “all in” one has lost the quest for freedom a priori because one is not willing to risk what it takes to achieve it. Fear is the inhibitor of freedom. Death is the mother of all fears. Ergo, overcoming the irrational fear of death is a condicio sine qua non for the obtainment of superordinate transcendental values.
Non-cooperation with evil is a sacred duty.
~ Mahatma Gandhi
Freedom comes with wisdom, intrinsically. They are inseparable, and no society wants people to be free. The communist society, the fascist society, the capitalist society, the Hindu, the Mohammedan, the Christian – no society likes people to use their own intelligence because the moment they start using their intelligence they become dangerous – dangerous to the establishment, dangerous to the people who are in power, dangerous to the “haves”; dangerous to all kinds of oppression, exploitation, suppression; dangerous to the churches, dangerous to the states, dangerous to the nations.
In fact, a wise man is afire, alive, aflame. He would like rather to die than to be enslaved. Death will not matter much to him, but he cannot sell his life to all kinds of stupidities, to all kinds of stupid people. He cannot serve them. Hence, the societies down the ages have been supplying you with false knowing. That’s the very function of your schools, colleges, universities.
They don’t serve you, remember, they serve the past, they serve the vested interests. Of course, they go on puffing your ego up bigger and bigger, they go on giving you more and more degrees. Your name becomes longer and longer, but only the name – you go on becoming shorter and shorter. A point comes where there are only certificates and the man has disappeared. First the man carries the certificates, then the certificates carry the man. The man is long dead.
~Osho
Jacobsen, A.. (2015). The Pentagon’s brain : an uncensored history of DARPA, America’s top secret military research agency. Little, Brown US
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“First edition. since its inception in 1958, the defense advanced research projects agency, or darpa, has grown to become the defense department’s most secret, most powerful, and most controversial military science research and development agency. created by president eisenhower to prevent another sputnik, and to focus primarily on defensive programs against nuclear weapons, the agency–and its imagination and scope–has expanded enormously with each passing year. from agent orange in vietnam to insect-sized drones in use today, from the earliest networked computers and the internet to smart rockets and war zones under 24-hour video surveillance, darpa is responsible for innovations that have changed the course of war, national security, and strategic planning at the highest levels. to uncover the secret history of darpa in action, journalist annie jacobsen tracked down key players in darpa’s smart weapons program, past and present; neuroscientists building an artificial brain, cell biologists working on limb regeneration, the nobel laureate who invented the laser. from darpa’s earliest defensive advances to hundreds of ongoing programs, jacobsen exposes both sides of the darpa coin: the fantastic technological advances from which we all benefit, and the darker side drawn up in a race for military supremacy. based on information from inside sources, exclusive interviews, private documents, and declassified memos, the pentagon’s brain reads like science fiction but is absolutely true, a groundbreaking look behind the scenes at the clandestine intersection of science and the american military.–publisher information. the cold war : the evil thing ; war games and computing machines ; vast weapons systems of the future ; emergency plans ; sixteen hundred seconds until doomsday ; psychological operations — the vietnam war : techniques and gadgets ; rand and coin ; command and control ; motivation and morale ; the jasons enter vietnam ; the electronic fence ; the end of vietnam — operations other than war : rise of the machines ; star wars and tank wars ; the gulf war and operations other than war ; biological weapons ; transforming humans for war — the war on terror : terror strikes ; total information awareness ; ied war ; combat zones that see ; human terrain — future war : drone wars ; brain wars ; the pentagon’s brain.”
Moreno, J. D.. (2012). Mind wars : brain science and the military in the twenty-first century. Bellevue Literary Press
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“Minority report meets dr. strangelove in the true story of how neuroscience and related technologies are shaping national defense. acknowledgments; introduction; 1. darpa on your mind; 2. of machines and men; 3. mind games; 4. how to think about the brain; 5. brain reading; 6. building better soldiers; 7. enter the nonlethals; 8. toward an ethics of neurosecurity; sources; index; about the author.”
Miranda, R. A., Casebeer, W. D., Hein, A. M., Judy, J. W., Krotkov, E. P., Laabs, T. L., … Ling, G. S. F.. (2014). DARPA-funded efforts in the development of novel brain-computer interface technologies.. Journal of Neuroscience Methods, 244, 52–67.
“The defense advanced research projects agency (darpa) has funded innovative scientific research and technology developments in the field of brain-computer interfaces (bci) since the 1970s. this review highlights some of darpa’s major advances in the field of bci, particularly those made in recent years. two broad categories of darpa programs are presented with respect to the ultimate goals of supporting the nation’s warfighters: (1) bci efforts aimed at restoring neural and/or behavioral function, and (2) bci efforts aimed at improving human training and performance. the programs discussed are synergistic and complementary to one another, and, moreover, promote interdisciplinary collaborations among researchers, engineers, and clinicians. finally, this review includes a summary of some of the remaining challenges for the field of bci, as well as the goals of new darpa efforts in this domain.”
Sir Francis Galton, was an English Victorian era statistician, polymath, sociologist, psychologist, anthropologist, eugenicist, tropical explorer, geographer, inventor, meteorologist, proto-geneticist, and psychometrician. He was knighted in 1909.
Galton produced over 340 papers and books. He also created the statistical concept of correlation and widely promoted regression toward the mean. He was the first to apply statistical methods to the study of human differences and inheritance of intelligence, and introduced the use of questionnaires and surveys for collecting data on human communities, which he needed for genealogical and biographical works and for his anthropometric studies.
He was a pioneer in eugenics, coining the term itself and the phrase “nature versus nurture”. His book Hereditary Genius (1869) was the first social scientific attempt to study genius and greatness.
As an investigator of the human mind, he founded psychometrics (the science of measuring mental faculties) and differential psychology and the lexical hypothesis of personality. He devised a method for classifying fingerprints that proved useful in forensic science. He also conducted research on the power of prayer, concluding it had none by its null effects on the longevity of those prayed for. His quest for the scientific principles of diverse phenomena extended even to the optimal method for making tea.
LibriVox
Hereditary Genius
A biographical summary of the pre-eminent men of Britain grouped by profession. The extensive survey draws from information including college graduation, reputation during career, fellowships, and even known relatives. Includes discussions on findings and observations as well as referenced appendices. - Summary by Leon Harvey
„We enter the Reichstag to arm ourselves with democracy’s weapons. If democracy is foolish enough to give us free railway passes and salaries, that is its problem… We are coming neither as friends or neutrals. We come as enemies! As the wolf attacks the sheep, so come we.“ — Joseph Goebbels
„The people’s community must not be a mere phrase, but a revolutionary achievement following from the radical carrying out of the basic life needs of the working class. A ruthless battle against corruption! A war against exploitation, freedom for the workers! The elimination of all economic-capitalist influences on national policy. Maintaining a rotten economic system has nothing to do with nationalism, which is an affirmation of the Fatherland.“ — Joseph Goebbels
A lesser known fact is that Goebbels stratagems were “inspired” by Edward Bernays (who authored the book entitled “Propaganda” in 1928).
Bernays stated the following in his 1965 autobiography:
They were using my books as the basis for a destructive campaign against the Jews of Germany. This shocked me, but I knew any human activity can be used for social purposes or misused for antisocial ones.
Further References
Doob, L. W.. (1950). Goebbels’ Principles of Propaganda. Public Opinion Quarterly
“For almost a dozen years german propaganda minister goebbels was recognized as a master of his trade by those who fought and by those who acclaimed the nazi state. this article, based on both the published and unpublished portions of goebbels’ diary, summarizes the major propaganda principles which he followed.”
Meyer, M., & Welch, D.. (2006). Propaganda and the German Cinema, 1933-1945. The History Teacher
“This is the most comprehensive analysis to date of nazi film propaganda in its political, social, and economic contexts, from the pre-war cinema as it fell under the control of the propaganda minister, joseph goebbels, through to the end of the second world war. david welch studies more than one hundred films of all types, identifying those aspects of nazi ideology that were concealed in the framework of popular entertainment.”
Propaganda and mass persuasion: a historical encyclopedia, 1500 to the present. (2013). Choice Reviews Online
“This fascinating survey provides a comprehensive introduction to propaganda, its changing nature, its practitioners, and its impact on the past five centuries of world history. written by leading experts, it covers the masters of the art from joseph goebbels to mohandas gandhi and examines enormously influential works of persuasion such as ‘uncle tom’s cabin,’ techniques such as films and posters, and key concepts like black propaganda and brainwashing. case studies reveal the role of mass persuasion during the reformation, and wars throughout history. regional studies cover propaganda superpowers, such as russia, china, and the united states, as well as little-known propaganda campaigns in southeast asia, ireland, and scandinavia. the book traces the evolution of propaganda from the era of printed handbills to computer fakery, and profiles such brilliant practitioners of the art as third reich film director leni riefenstahl and 19th-century cartoonist thomas nast, whose works helped to bring the notorious boss tweed to justice.”
Herf, J.. (2005). The “jewish War”: Goebbels and the antisemitic campaigns of the Nazi propaganda ministry. Holocaust and Genocide Studies
“How the nazi leadership translated radical antisemitism into a narrative of an innocent, besieged germany striking back at an ‘international jewry’ it accused of starting and prolonging world war ii forms the subject of this study. in the nazis’ paranoid conspiracy theory ‘jewry’ comprised powers behind the scenes in london, moscow, and washington. in response to the ‘war of extermination’ that jewry had supposedly launched against germany, the nazi leadership publicly threatened to ‘exterminate’ and ‘annihilate’ the jews as an act of justified retaliation. in their minds and in their policy, the ideological connection between the ‘final solution’ and the second world war was inherent, rather than contingent. the following analysis suggests why a centuries-old hatred led to mass murder between 1941 and 1945.”
Welch, D.. (1993). Manufacturing a consensus: Nazi propaganda and the building of a ‘national community’ (volksgemeinschaft). Contemporary European History
“The point has to be made at once that any attempt to quantify public reaction to nazi propaganda is fraught with difficulties. accurate measurement of the effectiveness of nazi propaganda is weakened by the absence of public opinion surveys and the fact that, in a society that resorted so readily to coercions and terror, reported opinion did not necessarily reflect the true feelings and moods of the public, especially if these views were opposed to the regime. nevertheless, to state that public opinion in the third reich ceased to exist is not strictly true. after the nazi ‘seizure of power’ in 1933, propaganda minister joseph goebbels stressed the importance of co-ordinating propaganda with other activities. in a dictatorship, propaganda must address itself to large masses of people and attempt to move them to a uniformity of opinion and action. but the nazis also understood that propaganda is of little value in isolation. to some extent this explains why goebbels impressed on all his staff at the ministry of popular enlightenment and propaganda the imperative necessity constantly to gauge public moods. goebbels therefore regularly received (as did all the ruling élites) extraordinarily detailed reports from the secret police (sd reports) about the mood of the people and would frequently quote these in his diary. hitler, too, was familiar with these reports, and his recorded determination to avoid increasing food prices at all costs for fear that this would undermine the regime’s popularity suggests a political sensitivity to public opinion. to assure themselves of continued popular support was an unwavering concern of the nazi leadership, and of hitler and goebbels in particular.”
George Lakoff could write a book on the “conceptual metaphor” employed in the title of the whitepaper. George Orwell is turning in his grave (the “digital algorithmic ministry of truth”).
Here are the “three foundational pillars” of the whitepaper (expressis verbis):
Improve our products so they continue to make quality count;
Counteract malicious actors seeking to spread disinformation;
Give people context about the information they see.
“F the metaphorical understanding of a situation functions in two parts irst, there is a widespread, relatively fixed set of metaphors that structure how fc we think. for example, a decision to go to war might be seen as a form o ost-benefit analysis, where war is justified …”
Steuter, E., & Wills, D.. (2008). At war with metaphor. Nueva York: Rowman and …
“BACKGROUND:pedomorphism is the retention of ancestrally juvenile traits by adults in a descendant taxon. despite its importance for evolutionary change, there are few examples of a molecular basis for this phenomenon. notothenioids represent one of the best described species flocks among marine fishes, but their diversity is currently threatened by the rapidly changing antarctic climate. notothenioid evolutionary history is characterized by parallel radiations from a benthic ancestor to pelagic predators, which was accompanied by the appearance of several pedomorphic traits, including the reduction of skeletal mineralization that resulted in increased buoyancy.results:we compared craniofacial skeletal development in two pelagic notothenioids, chaenocephalus aceratus and pleuragramma antarcticum, to that in a benthic species, notothenia coriiceps, and two outgroups, the threespine stickleback and the zebrafish. relative to these other species, pelagic notothenioids exhibited a delay in pharyngeal bone development, which was associated with discrete heterochronic shifts in skeletal gene expression that were consistent with persistence of the chondrogenic program and a delay in the osteogenic program during larval development. morphological analysis also revealed a bias toward the development of anterior and ventral elements of the notothenioid pharyngeal skeleton relative to dorsal and posterior elements.conclusions:our data support the hypothesis that early shifts in the relative timing of craniofacial skeletal gene expression may have had a significant impact on the adaptive radiation of antarctic notothenioids into pelagic habitats.”
Thibodeau, P. H., Hendricks, R. K., & Boroditsky, L.. (2017). How Linguistic Metaphor Scaffolds Reasoning. Trends in Cognitive Sciences
“Language helps people communicate and think. precise and accurate language would seem best suited to achieve these goals. but a close look at the way people actually talk reveals an abundance of apparent imprecision in the form of metaphor: ideas are ‘light bulbs’, crime is a ‘virus’, and cancer is an ‘enemy’ in a ‘war’. in this article, we review recent evidence that metaphoric language can facilitate communication and shape thinking even though it is literally false. we first discuss recent experiments showing that linguistic metaphor can guide thought and behavior. then we explore the conditions under which metaphors are most influential. throughout, we highlight theoretical and practical implications, as well as key challenges and opportunities for future research. metaphors pervade discussions of abstract concepts and complex issues: ideas are ‘light bulbs’, crime is a ‘virus’, and cancer is an ‘enemy’ in a ‘war’. at a process level, metaphors, like analogies, involve structure mapping, in which relational structure from the source domain is leveraged for thinking about the target domain. metaphors influence how people think about the topics they describe by shaping how people attend to, remember, and process information. the effects of metaphor on reasoning are not simply the result of lexical priming. metaphors can covertly influence how people think. that is, people are not always aware that they have been influenced by a metaphor.”
Hülsse, R., & Spencer, A.. (2008). The metaphor of terror: Terrorism studies and the constructivist turn. Security Dialogue
“Terrorism studies is fascinated with the terrorist actor. though this may seem natural, the present article argues that a different perspective can be fruitful. from a constructivist point of view, terrorism is a social construction. the terrorist actor is a product of discourse, and hence discourse is the logical starting point for terrorism research. in particular, it is the discourse of the terrorists’ adversaries that constitutes terrorist motivations, strategies, organizational structures and goals. hence, the article suggests a shift of perspective in terrorism studies – from an actor-centred to a discourse-centred perspective. it develops a discourse approach that emphasizes the crucial role of metaphors in the making of reality. to illustrate this approach, the metaphorical construction of al-qaeda in the german popular press in the aftermath of the terrorist attacks in new york and washington ( 2001), madrid ( 2004) and london ( 2005) is analysed. terrorism was first constituted as war, but from 2004 onwards the principal metaphor shifted from war to crime, constructing al-qaeda as a criminal rather than a military organization. this shift has transformed al-qaeda from an external to an internal threat, which has entailed a shift in counter-terrorism practices from a military to a judicial response.”
Ferrari, F.. (2007). Metaphor at work in the analysis of political discourse: Investigating a “preventive war” persuasion strategy. Discourse and Society
“The crucial historical moment represented by post 9/11 may undoubtedly be considered responsible for the subsequent hardening of american political rhetoric. and yet, the sudden increase of consensus catalysed by george w. bush and the consequences of his international policy bring his modus persuadendi up for discussion. the aim of this article is to present a framework for a metaphor-based critical analysis of persuasion in political discourse. our object of observation is george w. bush’s public speeches to the nation (2001–4). more specifically, the analysis is focused on the persuasion strategy enacted to promote the preventive war in iraq. in our approach, conceptual metaphor as related to emotion constitutes the fundamental argumentative feature and crucial tool to address the matter of persuasion in text, contributing to identifying both the ideological root and the persuasive strategy of a given discourse in the long run. synthesis of our results shows the potentialities of metaphor as a privileged cognitive tool for abstracting and constructing discourse strategies.”
Thibodeau, P., Mcclelland, J. L., & Boroditsky, L.. (2009). When a bad metaphor may not be a victimless crime : The role of metaphor in social policy. Proceedings of the Annual Meeting of the Cognitive Science Society
“Metaphors are pervasive in our discussions of abstract and complex ideas (lakoff & johnson, 1980), and have been shown to be instrumental in problem solving and building new conceptual structure (e.g., gentner & gentner, 1983; nersessian, 1992; boroditsky, 2000). in this paper we look at the role of metaphor in framing social issues. our language for discussing war, crime, politics, healthcare, and the economy is suffused with metaphor (schön, 1993; lakoff, 2002). does the way we reason about such important issues as crime, war or the economy depend on the metaphors we use to talk about these topics? might changing metaphors lead us to different conceptions and in turn different social policies? in this paper we focused on the domain of crime and asked whether two different metaphorical systems we have for talking about crime can lead people to different ways of approaching and reasoning about it. we find that framing the issue of crime metaphorically as a predator yielded systematically different suggestions for solving the crime problem than when crime was described as a virus. we then present a connectionist model that explores the mechanistic underpinnings of the role of metaphor.”
Spencer, A.. (2012). The social construction of terrorism: Media, metaphors and policy implications. Journal of International Relations and Development
“The article illustrates a constructivist understanding of studying terrorism and counter-terrorism by applying metaphor analysis to a british tabloid media discourse on terrorism between 2001 and 2005 in the sun newspaper. it identifies four conceptual metaphors constituting terrorism as a war, a crime, an uncivilised evil and as a disease, and it illustrates how these understandings make certain counter-terrorism policies such as a military response, judicial measures or immigration policies acceptable while at the same time excluding from consideration other options, such as negotiations. it thereby re-emphasises that a metaphorical understanding of political phenomena such as terrorism can give international relations insights into how certain policies become possible while others remain outside of the range of options thought to be appropriate.”
At war with metaphor: media, propaganda, and racism in the war on terror. (2013). Choice Reviews Online
“A valuable contribution to our growing understanding of the ways in which we talk ourselves into war, genocide, and other crimes against humanity. it causes us to wonder what might happen if we had the courage to deal with our rivalries and conflicts in a realistic manner rather than dehumanizing and demonizing those we consider enemies. ” —sam keen, author of faces of the enemy when photographs documenting the torture and humiliation of prisoners at abu ghraib came to the attention of a horrified public, national and international voices were raised in shock, asking how this happened. at war with metaphor offers an answer, arguing that the abuses of abu ghraib were part of a systemic continuum of dehumanization. this continuum has its roots in our public discussions of the war on terror and the metaphors through which they are repeatedly framed. arguing earnestly and incisively that these metaphors, if left unexamined, bind us into a cycle of violence that will only be intensified by a responsive violence of metaphor, erin steuter and deborah wills examine compelling examples of the images of animal, insect, and disease that inform, shape, and limit our understand-ing of the war on terror. tying these images to historical and contemporary uses of propaganda through a readable, accessible analysis of media filters, at war with metaphor vividly explores how news media, including political cartoons and talk radio, are enmeshed in these damaging, dehumanizing metaphors. analyzing media through the lenses of race and orientalism, the book invites us to hold our media and ourselves accountable for the choices we make in talking war and making enemies.”
Kövecses, Z.. (2016). Conceptual metaphor theory. In The Routledge Handbook of Metaphor and Language
“In a radical departure from theories based on digital, amodal accounts of cognition and language, lakoff and johnson (1980) proposed an account of metaphor as fundamentally conceptual, arguing that familiar linguistic metaphors are but surface manifestations of underlying conceptual relationships. they claimed that most conceptual thought is metaphorical, and conceptual domains are instantiated and expressed in families of conceptual metaphors, such as ‘more is u’, ‘emotionallyintimate is physically close’, ‘argument is war’, ‘love is a journey’, and ‘theories are buildings’. these conceptual metaphors number in the hundreds (gibbs, 1994b; lakoff and johnson, 1999), and they combine to serve as the foundation for new metaphors. for many of these families of metaphors lakoff and johnson trace the underlying metaphor to a literal concept based on embodied physical experience.”
Navaro-Yashin, Y.. (2009). Affective spaces, melancholic objects: Ruination and the production of anthropological knowledge. Journal of the Royal Anthropological Institute
“This article critically engages with recent theoretical writings on affect and non-human agency by way of studying the emotive energies discharged by properties and objects appropriated during war from members of the so-called ‘enemy’ community. the ethnographic material comes from long-term fieldwork in northern cyprus, focusing on how it feels to live with the objects and within the ruins left behind by the other, now displaced, community. i study turkish-cypriots’ relations to houses, land, and objects that they appropriated from the greek-cypriots during the war of 1974 and the subsequent partition of cyprus. my ethnographic material leads me to reflect critically on the object-centred philosophy of actor network theory and on the affective turn in the human sciences after the work of gilles deleuze. with the metaphor of ‘ruination’, i study what goes amiss in scholarly declarations of theoretical turns or shifts. instead, proposing an anthropologically engaged theory of affect through an ethnographic reflection on spatial and material melancholia, i argue that ethnography, in its most productive moments, is trans-paradigmatic. retaining what has been ruined as still needful of consideration, i suggest an approach which merges theories of affect and subjectivity as well as of language and materiality.”
Koller, V., Hardie, A., Rayson, P., & Semino, E.. (2008). Using a semantic annotation tool for the analysis of metaphor in discourse. Metaphorik.De
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“This paper describes the application of semantic annotation software for analysing metaphor in corpora of different genres. in particular, we outline three projects analysing religion and politics metaphors in corporate mission statements, the war metaphor in business magazines, and machine and living organism metaphors in a novel and in a second collection of business magazine articles. this research was guided by the hypotheses that a) semantic tags allocated by the software can correspond to source domains of metaphoric expressions, and b) that more conventional metaphors feature a source domain tag as first choice in the type’s semantic profile. the tagger was adapted to better serve the needs of metaphor research and automate to a greater extent the extraction of first choice and secondary semantic domains. two of the three studies represent re-analyses of previous manual and/or lexical corpus-based investigations, and findings indicate that semantic annotation can yield more comprehensive results. in”
Yanık, L. K.. (2009). The Metamorphosis of Metaphors of Vision: “Bridging” Turkey’s Location, Role and Identity After the End of the Cold War. Geopolitics
“During the cold war, ‘buffer’ or ‘bastion’ seemed a popular metaphor to describe turkey. after the cold war, ‘bridge,’ (and, to some extent, the ‘crossroad’) metaphor started to dominate the turkish foreign policy dışcourse. this article traces the use of ‘bridge’ metaphor in this dışcourse in the post-cold war period by the turkish foreign policy elite. it develops two arguments. first, the word bridge is a ‘metaphor of vision’ combining turkey’s perceived geographical exceptionalism with an identity and a role at the international level. as a ‘metaphor of vision,’ the employment of the word ‘bridge’ highlighted turkey’s liminality and justified some of its foreign policy actions to eurasia and then to the middle east. second, because the bridge metaphor was used in different context to justify different foreign policy choices, its meaning has changed, illustrating that metaphors are not static constructs. it concludes by sayıng that the continuous use of ‘bridge’ metaphor might reinforce turkey’s ‘liminality,’ placing turkey in a less classifiable category than the regular ‘othering’ practices.”
