Fehring Daniel J, Morrison-Ham Jordan, Cobden Annalee L, Mahlberg Justin, Gao Mengxia, Kelly Claire E, Sangchooli Arshiya, Stoliker Devon, Giddens Emily, Quinn Brody, Cholewick Antonia, Pacheco Luiza Bonfim, Razi Adeel, Albein-Urios Natalia, Verdejo-Garcia Antonio
School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia.
Monash Biomedical Imaging, Monash University, Clayton, VIC, Australia.
Contemp Clin Trials Commun. 2025 Jun 30;46:101515. doi: 10.1016/j.conctc.2025.101515. eCollection 2025 Aug.
Excessive alcohol consumption is a global health concern, with an estimated 400 million people living with alcohol use disorder (AUD). Current treatments for AUD have limited efficacy and fail to address its diverse neurobiological underpinnings. There are at least two cortico-striatal circuits relevant to AUD neurobiology: a weakened dorsolateral prefrontal cortex (dlPFC) pathway, and a heightened ventromedial prefrontal cortex (vmPFC) pathway.
This trial aims to examine whether deep transcranial magnetic stimulation (dTMS) can recalibrate the neurocircuitry disrupted in AUD as a proof-of-concept for its therapeutic potential. We will assess the capacity of two theta-burst stimulation protocols to modify neuroimaging and behavioral indices of AUD-related neurocircuitry alterations.
We will conduct a randomized, single-blind, sham-controlled crossover trial with 30 adults with moderate to severe AUD (aged 18-49). Participants will receive two doses of active or sham dTMS (for 2 sessions; 7 days apart; order counterbalanced) targeting the dlPFC or vmPFC with intermittent or continuous theta-burst stimulation, respectively.
Primary, secondary, and exploratory outcomes (i.e., stimulation-induced changes in neural circuit connectivity, executive control/decision-making, and craving-related emotions, respectively) will be collected before and after each dTMS dose. Additional exploratory outcomes (daily craving experiences and weekly alcohol consumption) will be collected across a 90-day period from the first session.
This trial innovates by utilizing distinct dTMS approaches to specifically target two functionally segregated neurocircuitries disrupted in AUD. Results will inform the development of a larger-scale trial by establishing optimal therapeutic approaches for AUD.
过量饮酒是一个全球关注的健康问题，估计有4亿人患有酒精使用障碍（AUD）。目前针对AUD的治疗效果有限，且未能解决其多样的神经生物学基础。与AUD神经生物学相关的至少有两条皮质-纹状体回路：一条是背外侧前额叶皮质（dlPFC）通路减弱，另一条是腹内侧前额叶皮质（vmPFC）通路增强。
本试验旨在研究深部经颅磁刺激（dTMS）是否可以重新校准AUD中被破坏的神经回路，以此作为其治疗潜力的概念验证。我们将评估两种theta爆发刺激方案改变与AUD相关神经回路改变的神经影像学和行为指标的能力。
我们将对30名年龄在18至49岁之间的中重度AUD成年人进行一项随机、单盲、假对照交叉试验。参与者将接受两剂活性或假dTMS（共2次治疗；间隔7天；顺序平衡），分别采用间歇性或连续性theta爆发刺激，靶向dlPFC或vmPFC。
将在每次dTMS剂量前后收集主要、次要和探索性结果（即分别为刺激引起的神经回路连接性、执行控制/决策以及与渴望相关情绪的变化）。在从第一次治疗开始的90天内，还将收集其他探索性结果（每日渴望体验和每周饮酒量）。
本试验的创新之处在于利用不同的dTMS方法，专门针对AUD中两条功能上分离的、被破坏的神经回路。研究结果将通过确定AUD的最佳治疗方法，为开展更大规模的试验提供依据。
