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      The Neurobiological Mechanism of Chemical Aversion (Emetic) Therapy for Alcohol Use Disorder: An fMRI Study

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          Abstract

          A recent NIH epidemiology study found the lifetime prevalence of alcohol use disorder in the United States to be 29%. Alcohol drinking behavior is strongly “learned” via pleasure center activation/reinforcement. Alcohol craving is a powerful desire to drink alcoholic beverages. Craving was added as one of the defining criteria for alcohol use disorder in DSM5, and craving reduction is becoming an increasingly important treatment goal. In the current study, patients with alcohol use disorder received 10 days of inpatient multi-modal treatments at Schick Shadel Hospital (SSH) of Seattle. The treatments included five chemical aversion conditioning sessions that associated alcohol cues (and alcohol) with nausea and emesis. All patients met DSM4 criteria for alcohol use disorder, were heavy drinkers, and reported craving alcohol pre-treatment. Craving reduction was one of the primary treatment goals. This is the first fMRI study to measure the effects of chemical aversion therapy on alcohol craving-related brain activity. Patients were recruited as subjects for the University of Washington (UW) brain scan study following SSH admission but before treatment onset. Prior to treatment, patients reported craving/desire for alcohol. After treatment (after four SSH chemical aversion treatments, again after five SSH chemical treatments, 30 and 90-days post-discharge), these same patients reported avoidance/aversion to alcohol. Most of the participants (69%) reported being still sober 12 months post-treatment. Consistent with a craving reduction mechanism of how chemical aversion therapy facilitates sobriety, results of the UW fMRI brain scans showed significant pre- to post-treatment reductions in craving-related brain activity in the occipital cortex. Additional fMRI brain scan studies are needed to further explore the neurobiological mechanism of chemical aversion therapy treatment for alcohol use disorder, and other substance use disorders for which chemical aversion therapy is used (e.g., opioid dependence and cocaine dependence). Substance use disorders are estimated to affect well over one billion people worldwide.

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          Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI.

          This study investigated the neural correlates of virtual reality analgesia. Virtual reality significantly reduced subjective pain ratings (i.e. analgesia). Using fMRI, pain-related brain activity was measured for each participant during conditions of no virtual reality and during virtual reality (order randomized). As predicted, virtual reality significantly reduced pain-related brain activity in all five regions of interest; the anterior cingulate cortex, primary and secondary somatosensory cortex, insula, and thalamus (p<0.002, corrected). Results showed direct modulation of human brain pain responses by virtual reality distraction. Copyright 2004 Lippincott Williams and Wilkins
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            The analgesic effects of opioids and immersive virtual reality distraction: evidence from subjective and functional brain imaging assessments.

            Immersive virtual reality (VR) is a novel form of distraction analgesia, yet its effects on pain-related brain activity when used adjunctively with opioid analgesics are unknown. We used subjective pain ratings and functional magnetic resonance imaging to measure pain and pain-related brain activity in subjects receiving opioid and/or VR distraction. Healthy subjects (n = 9) received thermal pain stimulation and were exposed to four intervention conditions in a within-subjects design: (a) control (no analgesia), (b) opioid administration [hydromorphone (4 ng/mL target plasma level)], (c) immersive VR distraction, and (d) combined opioid + VR. Outcomes included subjective pain reports (0-10 labeled graphic rating scales) and blood oxygen level-dependent assessments of brain activity in five specific, pain-related regions of interest. Opioid alone significantly reduced subjective pain unpleasantness ratings (P < 0.05) and significantly reduced pain-related brain activity in the insula (P < 0.05) and thalamus (P < 0.05). VR alone significantly reduced both worst pain (P < 0.01) and pain unpleasantness (P < 0.01) and significantly reduced pain-related brain activity in the insula (P < 0.05), thalamus (P < 0.05), and SS2 (P < 0.05). Combined opioid + VR reduced pain reports more effectively than did opioid alone on all subjective pain measures (P < 0.01). Patterns of pain-related blood oxygen level-dependent activity were consistent with subjective analgesic reports. These subjective pain reports and objective functional magnetic resonance imaging results demonstrate converging evidence for the analgesic efficacy of opioid administration alone and VR distraction alone. Furthermore, patterns of pain-related brain activity support the significant subjective analgesic effects of VR distraction when used as an adjunct to opioid analgesia. These results provide preliminary data to support the clinical use of multimodal (e.g., combined pharmacologic and nonpharmacologic) analgesic techniques.
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              Relapse Prevention

              Relapse prevention (RP) is an important component of alcoholism treatment. The RP model proposed by Marlatt and Gordon suggests that both immediate determinants (e.g., high-risk situations, coping skills, outcome expectancies, and the abstinence violation effect) and covert antecedents (e.g., lifestyle factors and urges and cravings) can contribute to relapse. The RP model also incorporates numerous specific and global intervention strategies that allow therapist and client to address each step of the relapse process. Specific interventions include identifying specific high-risk situations for each client and enhancing the client’s skills for coping with those situations, increasing the client’s self-efficacy, eliminating myths regarding alcohol’s effects, managing lapses, and restructuring the client’s perceptions of the relapse process. Global strategies comprise balancing the client’s lifestyle and helping him or her develop positive addictions, employing stimulus control techniques and urge-management techniques, and developing relapse road maps. Several studies have provided theoretical and practical support for the RP model.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                28 September 2017
                2017
                : 11
                : 182
                Affiliations
                [1] 1Department of Medical Research, Schick Shadel Hospital , Seattle, WA, United States
                [2] 2Department of Radiology, Integrated Brain Imaging Center, University of Washington , Seattle, WA, United States
                [3] 3Human Photonics Lab, Mechanical Engineering, University of Washington , Seattle, WA, United States
                Author notes

                Edited by: Antonella Gasbarri, University of L'Aquila, Italy

                Reviewed by: Eun Lee, Yonsei University, South Korea; Gabriel Rubio, Hospital Universitario 12 De Octubre, Spain

                *Correspondence: Hunter G. Hoffman hoontair@ 123456gmail.com
                Article
                10.3389/fnbeh.2017.00182
                5625029
                c8652747-5b31-49eb-bb1a-3435d908bb6e
                Copyright © 2017 Elkins, Richards, Nielsen, Repass, Stahlbrandt and Hoffman.

                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) or licensor 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
                : 30 July 2017
                : 13 September 2017
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 38, Pages: 8, Words: 6393
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01GM042725
                Award ID: R01AR054115
                Award ID: R01-DA026438
                Categories
                Neuroscience
                Original Research

                Neurosciences
                alcohol,opioid,craving,fmri,aversive conditioning,alcohol treatment,addiction,craving-related brain activity

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