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      Both active and sham low-frequency rTMS single sessions over the right DLPFC decrease cue-induced cravings among pathological gamblers seeking treatment: A randomized, double-blind, sham-controlled crossover trial

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          Abstract

          Background

          Craving is a core symptom of addictive disorders, such as pathological gambling for example. Over the last decade, several studies have assessed the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the addiction field, which triggers the dorsolateral prefrontal cortex (DLPFC) to decrease craving. The STIMJEU study investigated whether a single session of low-frequency (LF, i.e., 1 Hz) rTMS applied to the right DLPFC reduced cue-induced gambling craving in a sample of treatment-seeking pathological gamblers.

          Methods

          Thirty patients received both active and sham rTMS in random order and were blinded to the condition in a within-subject crossover design. Outcome measures included self-reported gambling craving (Visual Analog Scale and Gambling Craving Scale) and physiological measures (heart rate and blood pressure).

          Results

          The rTMS sessions were associated with a significant decrease in the gambling urge, regardless of whether the session was active or sham. When controlling cue-induced craving levels, no effects were observed on craving for active rTMS. Overall, rTMS was well-tolerated, and the credibility of the sham procedure was assessed and appeared to be appropriate.

          Conclusions

          We failed to demonstrate the specific efficacy of one session of LF rTMS to decrease cue-induced craving in pathological gamblers. A strong placebo-effect and rTMS parameters may partly explain these results. Yet, we are convinced that rTMS remains a promising therapeutic method. Further studies are required to examine its potential effect.

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          Most cited references 53

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          Prefrontal-striatal pathway underlies cognitive regulation of craving.

          The ability to control craving for substances that offer immediate rewards but whose long-term consumption may pose serious risks lies at the root of substance use disorders and is critical for mental and physical health. Despite its importance, the neural systems supporting this ability remain unclear. Here, we investigated this issue using functional imaging to examine neural activity in cigarette smokers, the most prevalent substance-dependent population in the United States, as they used cognitive strategies to regulate craving for cigarettes and food. We found that the cognitive down-regulation of craving was associated with (i) activity in regions previously associated with regulating emotion in particular and cognitive control in general, including dorsomedial, dorsolateral, and ventrolateral prefrontal cortices, and (ii) decreased activity in regions previously associated with craving, including the ventral striatum, subgenual cingulate, amygdala, and ventral tegmental area. Decreases in craving correlated with decreases in ventral striatum activity and increases in dorsolateral prefrontal cortex activity, with ventral striatal activity fully mediating the relationship between lateral prefrontal cortex and reported craving. These results provide insight into the mechanisms that enable cognitive strategies to effectively regulate craving, suggesting that it involves neural dynamics parallel to those involved in regulating other emotions. In so doing, this study provides a methodological tool and conceptual foundation for studying this ability across substance using populations and developing more effective treatments for substance use disorders.
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            Cue-induced brain activity in pathological gamblers.

            Previous studies using functional magnetic resonance imaging (fMRI) have identified differential brain activity in healthy subjects performing gambling tasks and in pathological gambling (PG) subjects when exposed to motivational and emotional predecessors for gambling as well as during gambling or response inhibition tasks. The goal of the present study was to determine if PG subjects exhibit differential brain activity when exposed to visual gambling cues. Ten male DSM-IV-TR PG subjects and 10 matched healthy control subjects underwent fMRI during visual presentations of gambling-related video alternating with video of nature scenes. Pathological gambling subjects and control subjects exhibited overlap in areas of brain activity in response to the visual gambling cues; however, compared with control subjects, PG subjects exhibited significantly greater activity in the right dorsolateral prefrontal cortex (DLPFC), including the inferior and medial frontal gyri, the right parahippocampal gyrus, and left occipital cortex, including the fusiform gyrus. Pathological gambling subjects also reported a significant increase in mean craving for gambling after the study. Post hoc analyses revealed a dissociation in visual processing stream (dorsal vs. ventral) activation by subject group and cue type. These findings may represent a component of cue-induced craving for gambling or conditioned behavior that could underlie pathological gambling.
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              Effects of non-invasive neurostimulation on craving: a meta-analysis.

              This meta-analysis was conducted to evaluate the available evidence regarding the effects of non-invasive neurostimulation of the dorsolateral prefrontal cortex (DLPFC), on craving in substance dependence and craving for high palatable food. Non-invasive neurostimulation techniques were restricted to repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS). A total of 17 eligible studies were identified. Random effects analysis revealed a pooled standardized effect size (Hedge's g) of 0.476 (CI: 0.316-0.636), indicating a medium effect size favouring active non-invasive neurostimulation over sham stimulation in the reduction of craving (z=5.832, p<0.001). No significant differences were found between rTMS and tDCS, between the various substances of abuse and between substances of abuse and food, or between left and right DLPFC stimulation. In conclusion, this meta-analysis provides the first clear evidence that non-invasive neurostimulation of the DLPFC decreases craving levels in substance dependence. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                jba
                JBA
                Journal of Behavioral Addictions
                J Behav Addict
                Akadémiai Kiadó (Budapest )
                2062-5871
                2063-5303
                20 February 2018
                March 2018
                : 7
                : 1
                : 126-136
                Affiliations
                [ 1 ]Psychiatry Neuromodulation Unit, Addictology and Liaison Psychiatry Department, CHU Nantes , Nantes, France
                [ 2 ]Faculty of Sport Sciences, Laboratory “Movement, Interactions, Performance” (E.A. 4334), University of Nantes , Nantes, France
                [ 3 ] SPHERE MethodS in Patients-centered outcomes and HEalth ResEarch, Université de Nantes, Université de Tours , Nantes, France
                [ 4 ]Pathological Gambling Treatment Unit, Addictology and Liaison Psychiatry Department, CHU Nantes , Nantes, France
                Author notes
                [* ]Corresponding author: Marie Grall-Bronnec; Pathological Gambling Unit, Addictology and Liaison Psychiatry Department, Centre Hospitalier Universitaire, 85 rue Saint Jacques, 44093 Nantes cedex 1, France; Phone: +33 2 40 84 61 16; Fax: +33 2 40 84 61 18; E-mail: marie.bronnec@ 123456chu-nantes.fr
                Article
                10.1556/2006.7.2018.14
                6035030
                29463098
                © 2018 The Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.

                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 54, Pages: 11
                Funding
                Funding sources: The STIMJEU study was funded by a grant from the University Hospital of Nantes (Internal call for tenders, 2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                FULL-LENGTH REPORT

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