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      Closed Loop Deep Brain Stimulation for PTSD, Addiction, and Disorders of Affective Facial Interpretation: Review and Discussion of Potential Biomarkers and Stimulation Paradigms

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          Abstract

          The treatment of psychiatric diseases with Deep Brain Stimulation (DBS) is becoming more of a reality as studies proliferate the indications and targets for therapies. Opinions on the initial failures of DBS trials for some psychiatric diseases point to a certain lack of finesse in using an Open Loop DBS (OLDBS) system in these dynamic, cyclical pathologies. OLDBS delivers monomorphic input into dysfunctional brain circuits with modulation of that input via human interface at discrete time points with no interim modulation or adaptation to the changing circuit dynamics. Closed Loop DBS (CLDBS) promises dynamic, intrinsic circuit modulation based on individual physiologic biomarkers of dysfunction. Discussed here are several psychiatric diseases which may be amenable to CLDBS paradigms as the neurophysiologic dysfunction is stochastic and not static. Post-Traumatic Stress Disorder (PTSD) has several peripheral and central physiologic and neurologic changes preceding stereotyped hyper-activation behavioral responses. Biomarkers for CLDBS potentially include skin conductance changes indicating changes in the sympathetic nervous system, changes in serum and central neurotransmitter concentrations, and limbic circuit activation. Chemical dependency and addiction have been demonstrated to be improved with both ablation and DBS of the Nucleus Accumbens and as a serendipitous side effect of movement disorder treatment. Potential peripheral biomarkers are similar to those proposed for PTSD with possible use of environmental and geolocation based cues, peripheral signs of physiologic arousal, and individual changes in central circuit patterns. Non-substance addiction disorders have also been serendipitously treated in patients with OLDBS for movement disorders. As more is learned about these behavioral addictions, DBS targets and effectors will be identified. Finally, discussed is the use of facial recognition software to modulate activation of inappropriate responses for psychiatric diseases in which misinterpretation of social cues feature prominently. These include Autism Spectrum Disorder, PTSD, and Schizophrenia—all of which have a common feature of dysfunctional interpretation of facial affective clues. Technological advances and improvements in circuit-based, individual-specific, real-time adaptable modulation, forecast functional neurosurgery treatments for heretofore treatment-resistant behavioral diseases.

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          Introduction to behavioral addictions.

          Several behaviors, besides psychoactive substance ingestion, produce short-term reward that may engender persistent behavior, despite knowledge of adverse consequences, i.e., diminished control over the behavior. These disorders have historically been conceptualized in several ways. One view posits these disorders as lying along an impulsive-compulsive spectrum, with some classified as impulse control disorders. An alternate, but not mutually exclusive, conceptualization considers the disorders as non-substance or "behavioral" addictions. Inform the discussion on the relationship between psychoactive substance and behavioral addictions. We review data illustrating similarities and differences between impulse control disorders or behavioral addictions and substance addictions. This topic is particularly relevant to the optimal classification of these disorders in the forthcoming fifth edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Growing evidence suggests that behavioral addictions resemble substance addictions in many domains, including natural history, phenomenology, tolerance, comorbidity, overlapping genetic contribution, neurobiological mechanisms, and response to treatment, supporting the DSM-V Task Force proposed new category of Addiction and Related Disorders encompassing both substance use disorders and non-substance addictions. Current data suggest that this combined category may be appropriate for pathological gambling and a few other better studied behavioral addictions, e.g., Internet addiction. There is currently insufficient data to justify any classification of other proposed behavioral addictions. Proper categorization of behavioral addictions or impulse control disorders has substantial implications for the development of improved prevention and treatment strategies.
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            Is there a common molecular pathway for addiction?

            Drugs of abuse have very different acute mechanisms of action but converge on the brain's reward pathways by producing a series of common functional effects after both acute and chronic administration. Some similar actions occur for natural rewards as well. Researchers are making progress in understanding the molecular and cellular basis of these common effects. A major goal for future research is to determine whether such common underpinnings of addiction can be exploited for the development of more effective treatments for a wide range of addictive disorders.
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              Addiction circuitry in the human brain.

              A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                04 May 2018
                2018
                : 12
                : 300
                Affiliations
                [1] 1Division of Neurosurgery, Banner University Medical Center , Tucson, AZ, United States
                [2] 2Neurosurgery Service, VA Greater Los Angeles Healthcare System , Los Angeles, CA, United States
                [3] 3Department of Neurosurgery, University of California, Los Angeles , Los Angeles, CA, United States
                Author notes

                Edited by: Jonathan Miller, University Hospitals Case Medical Center, United States

                Reviewed by: George C. McConnell, Stevens Institute of Technology, United States; Ali Yadollahpour, Ahvaz Jundishapur University of Medical Sciences, Iran

                *Correspondence: Jean-Phillipe Langevin Jlangevin@ 123456mednet.ucla.edu

                This article was submitted to Neuroprosthetics, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2018.00300
                5945819
                29780303
                07294fbf-5632-46c9-8684-0540d2b51997
                Copyright © 2018 Bina and Langevin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 November 2017
                : 18 April 2018
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 162, Pages: 13, Words: 10916
                Categories
                Neuroscience
                Review

                Neurosciences
                closed-loop dbs,ptsd,addiction,facial recognition software,autism,schizophrenia,functional neurosurgery

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