Effects of Frontopolar TMS in Alcohol Craving

Alcohol dependence (AD) is a prevalent and debilitating condition characterized by a chronic inability to control alcohol consumption despite adverse consequences. Current treatment options have limited efficacy, highlighting the pressing need for innovative approaches. Continuous Theta Burst Stimulation (cTBS) is a form of transcranial magnetic stimulation (TMS) that has shown promise in modulating brain activity associated with craving and addiction.

This study aims to explore the effects of cTBS applied over the left frontopolar cortex on psychological, physiological, and neurobiological markers of alcohol craving in patients with AD. Specifically, this study will assess TMS-induced changes in psychological alcohol craving using the Penn Alcohol Craving Scale (PACS), and physiological alcohol craving using physiological craving markers, including heart rate (HR), skin temperature (ST) and skin conductance (SC), and their changes during Virtual Reality Cue Exposure and Craving Assessment (VR-CECA) before and after the TMS intervention. Additionally, the study aims to explore the relationship between neurobiological craving markers utilizing baseline structural and functional brain connectivity as assessed by magnetic resonance imaging (MRI) and TMS-induced changes in psychological and physiological alcohol craving.

This study aims to include a total of 34 patients aged 18-65 years with an ICD-10 diagnosis of AD. All participants undergo 15 sessions of accelerated cTBS targeting the left frontopolar cortex over five consecutive days using neuronavigation based on individual MRI scans. Clinical (questionnaires, diagnostic interviews) and behavioural (VR-CECA) assessments are conducted at two time points: pre-TMS intervention and post-TMS intervention. Structural and functional MRI scans are acquired before the TMS intervention to assess individual brain connectivity.

The primary outcome will be the TMS-induced change in psychological alcohol craving assessed with the PACS. Secondary outcomes include TMS-induced changes in physiological craving markers (HR, ST, and SC) during VR-CECA and TMS-induced changes and psychopathological states that will be assessed through a battery of clinical questionnaires.

This study hypothesizes that frontopolar cTBS will reduce psychological and physiological alcohol craving in patients with AD. Additionally, this study expects that baseline structural and functional connectivity will predict TMS-induced changes in physiological alcohol craving, providing insights into individual brain network variability on the effect of frontopolar cTBS.

This study aims to advance the understanding of the neurophysiological mechanisms underlying craving in AD and the identification of potential biomarkers for predicting psychological and physiological craving reductions. If successful, this could lead to more targeted and effective interventions for AD, ultimately improving patient outcomes.

• TMS-induced change in heart rate (BPM) during virtual reality alcohol cue exposure [Срок оценки: HR is continuously recorded during VR alcohol cue exposure sessions conducted on Day 1 (prior to the first TMS session) and Day 5 (following the final TMS session), allowing assessment of TMS-induced changes in physiological craving response.]
• TMS-induced change in skin conductance (µS) during Virtual reality alcohol cue exposure [Срок оценки: SC is continuously recorded during VR alcohol cue exposure sessions conducted on Day 1 (prior to the first TMS session) and Day 5 (following the final TMS session), allowing assessment of TMS-induced changes in physiological craving response.]
• TMS-induced change in skin temperature (°C) during Virtual reality alcohol cue exposure [Срок оценки: ST is continuously recorded during VR alcohol cue exposure sessions conducted on Day 1 (prior to the first TMS session) and Day 5 (following the final TMS session), allowing assessment of TMS-induced changes in physiological craving response.]
• TMS-induced change in self-reported craving during VR exposure using Visual Analogue Scale (VAS) [Срок оценки: Day 1 (pre-TMS; pre-VR and post-VR) and Day 5 (post-TMS; pre-VR and post-VR)]
• TMS-induced change in self-reported craving assessed with the Mannheimer Craving Scale (MaCS) [Срок оценки: The MaCS will be assessed at baseline before the start of the TMS Intervention (Pre-TMS, Day 0) and after the final TMS session (post-TMS, Day 5)]
• TMS-induced change in self-reported psychological craving assessed by the Craving-Automatized-Scale-Alcohol (CAS-A) [Срок оценки: The CAS-A will be assessed at baseline before the start of the TMS Intervention (Pre-TMS, Day 0) and after the final TMS session (post-TMS, Day 5)]
• Correlation between baseline brain connectivity and changes in heart rate (BPM) increase during VR [Срок оценки: MRI and, therefore, structural and functional connectivity is assessed at baseline (Day 0) and heart rate change during VR sessions before TMS intervention (Day 1) and after the final TMS intervention (Day 5)]
• TMS-induced changes in clinician-reported depressive symptoms using the MADRS [Срок оценки: The MADRS will be assessed at baseline before the start of the TMS Intervention (Pre-TMS, Day 0) and after the final TMS session (post-TMS, Day 5)]