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.

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.

Accelerated repetitive transcranial magnetic stimulation does not influence grey matter volumes in regions related to alcohol relapse: An open-label exploratory study.

The application of repetitive transcranial magnetic stimulation (rTMS) to prevent relapse in alcohol addiction is currently being evaluated. However, how rTMS may influence the related brain processes is far from clear. Here we wanted to investigate whether baseline grey matter volume (GMV) can predict relapse and whether 15 accelerated high-frequency (HF)- rTMS sessions may influence GMV in areas related to relapse. Voxel-based morphometric (VBM) measurements were used to compare baseline GMV of 22 detoxified, hospitalized, alcohol-dependent patients with 22 age and gender matched healthy control subjects. Only patients received 15 accelerated HF-rTMS sessions at the right dorsolateral prefrontal cortex (DLPFC) followed by VBM measurements. Relapse rates were assessed four weeks after the end of the stimulation protocol. At baseline, alcohol-dependent patients overall showed less GMV in diffuse brain areas compared to healthy controls. Relapsers compared to abstainers displayed larger GMV decreases, especially in brain midline structures, insular, hippocampal, and amygdalar areas. Accelerated HF-rTMS treatment had no significant effect on GMV in alcohol-dependent patients, regardless of the relapse state. Although an accelerated HF-rTMS treatment protocol did not influence GMV in alcohol-dependent patients, baseline GMV predicted future relapse.

Facing temptation: The neural correlates of gambling availability during sports picture exposure.

Nowadays, sports betting has become increasingly available and easy to engage in. Here we examined the neural responses to stimuli that represent sporting events available for betting as compared to sporting events without a gambling opportunity. We used a cue exposure task in which football (soccer) fans (N = 42) viewed cues depicting scheduled football games that would occur shortly after the scanning session. In the "betting" condition, participants were instructed to choose, at the end of each block, the game (and the team) they wanted to bet on. In the "watching" condition, participants chose the game they would prefer to watch. After the scanning session, participants completed posttask rating questionnaires assessing, for each cue, their level of confidence about the team they believed would win and how much they would enjoy watching the game. We found that stimuli representing sport events available for betting elicited higher fronto-striatal activation, as well as higher insular cortex activity and functional connectivity, than sport events without a gambling opportunity. Moreover, games rated with more confidence towards the winning team resulted in greater brain activations within regions involved in affective decision-making (ventromedial prefrontal cortex), cognitive inhibitory control (medial and superior frontal gyri) and reward processing (ventral and dorsal striatum). Altogether, these novel findings offer a sensible simulation of how the high availability of sports betting in today's environment impacts on the reward and cognitive control systems. Future studies are needed to extend the present findings to a sample of football fans that includes a samilar proportion of female and male participants.

Accelerated HF-rTMS Protocol has a Rate-Dependent Effect on dACC Activation in Alcohol-Dependent Patients: An Open-Label Feasibility Study.

BACKGROUND: The application of accelerated high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) could be a potential treatment option for alcohol-dependent patients and may result in a faster clinical response. In this open-label HF-rTMS feasibility study, we wanted to replicate previous findings of baseline brain activation as a predictor of relapse, and to evaluate how this intervention influences the relapse neurocircuit of "treatment-seeking" alcohol-dependent patients, by means of functional magnetic resonance imaging (fMRI) cue-exposure paradigms. Because relapsing patients have a diminished resilience of the emotion regulation/cognitive control system, before HF-rTMS treatment, we expected lower neuronal activation of especially the ventromedial prefrontal cortex and anterior cingulate cortex (ACC) during the presentation of alcohol-related cues in these patients. The relapse neurocircuit should be modified after accelerated HF-rTMS treatment, only in those patients who did not relapse. METHODS: After being administered a single sham-controlled HF-rTMS session (20 Hz to 110% motor threshold), 19 alcohol-dependent patients received an accelerated HF-rTMS protocol, consisting of 14 right dorsolateral prefrontal cortical sessions spread over 3 days. Before and after stimulation, during fMRI patients were confronted with a block and an event-related alcoholic cue-exposure paradigm. Relapse was defined as the consumption of any amount of alcohol within 4 weeks after the stimulation. A region of interest analysis was performed to evaluate how HF-rTMS exerts its effect. RESULTS: After 4 weeks, 13 of 19 patients had already consumed alcohol. When abstainers were compared to patients who had relapsed, we found higher dorsal ACC (dACC) activation at baseline, but only during the blocked cue-exposure paradigm. The effects of HF-rTMS on dACC blood oxygen level-dependent response were negatively correlated with the baseline dACC activation. Due to susceptibility artifacts located at the ventral cortical aspects in 6 of our participants, reliable data were only obtained for the ACC. CONCLUSIONS: Our data indicate that higher baseline dACC activation may serve as a protective mechanism regarding relapse. For the first time, it is demonstrated that accelerated HF-rTMS treatment influences dACC activation in a rate-dependent manner: the lower the baseline dACC activation, the more dACC activity was increased after HF-rTMS treatment.

The Impact of Accelerated Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Cue-Reactivity: An fMRI Study on Craving in Recently Detoxified Alcohol-Dependent Patients.

In alcohol-dependent patients craving is a difficult-to-treat phenomenon. It has been suggested that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may have beneficial effects. However, exactly how this application exerts its effect on the underlying craving neurocircuit is currently unclear. In an effort to induce alcohol craving and to maximize detection of HF-rTMS effects to cue-induced alcohol craving, patients were exposed to a block and event-related alcohol cue-reactivity paradigm while being scanned with fMRI. Hence, we assessed the effect of right dorsolateral prefrontal cortex (DLPFC) stimulation on cue-induced and general alcohol craving, and the related craving neurocircuit. Twenty-six recently detoxified alcohol-dependent patients were included. First, we evaluated the impact of one sham-controlled stimulation session. Second, we examined the effect of accelerated right DLPFC HF-rTMS treatment: here patients received 15 sessions in an open label accelerated design, spread over 4 consecutive days. General craving significantly decreased after 15 active HF-rTMS sessions. However, cue-induced alcohol craving was not altered. Our brain imaging results did not show that the cue-exposure affected the underlying craving neurocircuit after both one and fifteen active HF-rTMS sessions. Yet, brain activation changes after one and 15 HF-rTMS sessions, respectively, were observed in regions associated with the extended reward system and the default mode network, but only during the presentation of the event-related paradigm. Our findings indicate that accelerated HF-rTMS applied to the right DLPFC does not manifestly affect the craving neurocircuit during an alcohol-related cue-exposure, but instead it may influence the attentional network.

The current perspective of neuromodulation techniques in the treatment of alcohol addiction: a systematic review.

BACKGROUND: Alcohol dependency can be considered as a chronic mental disorder characterized by frequent relapses even when treated with appropriate medical or psychotherapeutic interventions. Here, the efficacy of different neuromodulation techniques in alcohol addiction, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), vagal nerve stimulation (VNS) and electroconvulsive therapy (ECT) is critically evaluated. METHODS: A broad literature search on electronic databases such as NCBI PubMed, the Web of Knowledge, the Cochrane Library was conducted. Additionally, we searched recent handbooks on neuromodulation and/or addiction. RESULTS: Studies investigating these neuromodulation techniques in alcohol addiction remain to date rather limited and especially tDCS and rTMS applications have been investigated. Overall, the clinical effects seem modest. The use of VNS and ECT has yet to be investigated in alcohol dependent patients. CONCLUSIONS: Neuromodulation techniques have only recently been subject to investigation in alcohol addiction and methodological differences between the few studies restrict clear-cut conclusions. Nevertheless, the scarce results encourage further investigation in alcohol addiction.