Downloaded from http://journals.lww.com/ectjournal by BhDMf5ePHKbH4TTImqenVOm0oSGVjfT8+QfybSiEeIDq6xP4E/IuDwXh2M/arltAT6mS6Ed0IOs= on 08/23/2018 tDCS in Addiction and Impulse Control Disorders Olivia M. Lapenta, PhD,*† Lucas M. Marques, MSc,* Gabriel G. Rego, MSc,* William E. Comfort, PhD,* and Paulo S. Boggio, PhD* Abstract: The study of addiction and impulsion control disorders has shown that behaviors of seeking and consumption of addictive substances are subserved by neurobiological alterations specifically related to brain networks for reward, stress, and executive control, representing the brain's adaptation to the continued use of an addictive substance. In parallel, stud- ies using neuromodulation techniques such as transcranial direct current stimulation (tDCS) have demonstrated promising effects in modulating cognitive and motor functions. This review aims to describe the neurobiol- ogy of addiction and some of the most relevant cognitive models of addic- tive behavior and to clarify how tDCS application modulates the intake and craving for several addictive substances, such as food, alcohol, nicotine, co- caine, crack, methamphetamine, and cannabis. We also discuss the positive and null outcomes of the use of this neuromodulatory technique in the treatment of addiction disorders resulting from the use of these substances. The reviewed findings lead us to conclude that tDCS interventions hold several promising clinical avenues in addiction and impulsive control. However, methodological investigations are necessary for undercover opti- mal parameters before implementing its clinical application. Key Words: addiction, cognitive control, impulse disorders, dual-process model, substance abuse, transcranial direct current stimulation (J ECT 2018;34: 182–192) N oninvasive brain stimulation tools have been increasingly ap- plied in clinical and research settings when investigating 3 main goals: (i) identifying the brain areas involved in cognitive and motor processes, (ii.) describing the cognitive and biological mechanisms of neuroplasticity, and (iii.) improving behavioral and cognitive function in healthy participants and individuals suf- fering from neurological and neuropsychiatric disorders. 1,2 Some promising results from the effects of brain stimulation on executive functioning 3,4 have prompted several researchers to investigate the potential for neuromodulation of addiction behav- iors because of common underlying mechanisms of decision mak- ing and impulsivity. 5 Transcranial direct current stimulation (tDCS) has been the method of choice in this area because of its low cost, ease of use, safety and portability and because of previ- ous extensive investigations of its therapeutic utility. 6 The mechanism of action for tDCS occurs through the prolonged ap- plication of weak, electric current through 2 scalp electrodes, leading to cortical hypopolarization or hyperpolarization in ac- cordance to prespecified parameters. 7,8 Specifically, for addictive behavior, anodal tDCS application over the dorsolateral prefron- tal cortex (DLPFC) may enhance the cognitive control compo- nent of executive functioning, therefore reducing craving as well as the probability of relapse toward substance abuse. The neuromodulation of frontal circuitry may regulate the release of dopamine and norepinephrine possibly by means of top-down control mechanisms in the prefrontal cortex (PFC) over inhibitory control and reward mechanisms, which are likely dys- functional in such disorders. 9 This would explain effects such as re- duced craving for alcohol, 10 food, 11 nicotine, 12 and other addictive substances. 4,13–15 This review therefore aims to highlight the neuro- biological underpinnings of addiction and several cognitive models that have been proposed to explain addictive behavior in order to clarify how tDCS is able to modulate the intake and craving for sev- eral substances. Furthermore, we summarize some previous find- ings of frontal tDCS application in the treatment of distinct form of addictive behavior; we seek to specify the most successful pa- rameters for stimulation in this context and to identify any remain- ing gaps in this field for future trends in basic and clinical research. COGNITIVE AND NEUROBIOLOGICAL MODELS OF ADDICTION Addiction can be defined as a compulsive pattern of seeking and using addictive substances, even when one is consciously aware of their potential for harm (known as a binge or intoxication phase). It may be accompanied by several negative emotional states following abstinence such as hypohedonia, dysphoria, and distress (a withdrawal/negative affect phase) and a heightened propensity to relapse even after long periods of abstinence (a preoccupation/anticipation phase). These symptoms occur in con- junction with neurobiological alterations specifically related to brain networks for reward, stress, and executive control. 16 The regular consumption of different substances can lead to ad- diction in several distinct ways through modulation of the brain and body. The dopaminergic circuitry has been extensively studied in ad- diction for being directly linked to motivation and goal-directed be- havior 16,17 and activated in response to environmental cues, with a key role in habit formation and compulsive drug seeking and abuse, which are frequently unresponsive to conscious control. 16,18 Animal models have demonstrated that the ventral tegmental area, the source of many dopaminergic cell bodies in the brain, and the nucleus accumbens (NAcc), which is innervated by ventral tegmental area dopaminergic cells and broadly responsible for re- ward prediction, show adaptive structural and functional changes due to heightened incentive-sensitization to particular substances and/or related cues in the environment. These adaptive changes can indirectly lead to altered neurotransmitter production/release and changes in circuitry plasticity (CREB 19 ). Consequently, sub- stance abuse becomes associated with an enhanced release of neurotransmitters. In turn, the individual's brain circuitry adapts to an increase in dopamine secretion, and low levels may result From the *Social and Cognitive Neuroscience Laboratory and Developmental Disorders Program, Center for Health and Biological Sciences, Mackenzie Presbyterian University, São Paulo, Brazil; and †The MARCS Institute for Brain, Behaviour & Development, Western Sydney University, Penrith New South Wales, Australia. Received for publication March 2, 2018; accepted July 11, 2018. Reprints: Paulo S. Boggio, PhD, Social and Cognitive Neuroscience Laboratory and Developmental Disorders Program, Center for Health and Biological Sciences, Mackenzie Presbyterian University, Rua Piauí, 181, 10 andar, São Paulo, SP, Brazil 01241-001 (e‐mail: boggio@mackenzie.br or psboggio@gmail.com). L.M.M. is supported by a PhD grant (no. 2017/06136-2, São Paulo Research Foundation [FAPESP]). G.G.R. is supported by a PhD grant (no. 2015/ 18713-9, FAPESP). W.E.C. is supported by a postdoctoral grant (no. 2017/ 12752-8). P.S.B. is a CNPq research fellow (311641/2015-6). All authors contributed to manuscript writing and approved the final version of the manuscript for submission. The authors have no conflicts of interest or financial disclosures to report. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000541 SPECIAL ISSUE ON tDCS 182 www.ectjournal.com Journal of ECT • Volume 34, Number 3, September 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.