Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial

伏隔核 酒精使用障碍 渴求 线索反应性 脑深部刺激 腹侧纹状体 心理学 功能磁共振成像 医学 上瘾 壳核 神经科学 精神科 纹状体 内科学 多巴胺 化学 疾病 生物化学 帕金森病
作者
Benjamin Davidson,Peter Giacobbe,Tony P. George,Sean M. Nestor,Jennifer S. Rabin,Maged Goubran,Alexander J Nyman,Anusha Baskaran,Ying Meng,Christopher B. Pople,Simon J. Graham,Fred Tam,Clement Hamani,Nir Lipsman
出处
期刊:Molecular Psychiatry [Springer Nature]
卷期号:27 (10): 3992-4000 被引量:34
标识
DOI:10.1038/s41380-022-01677-6
摘要

Alcohol use disorder (AUD) is a highly prevalent, often refractory, medical illness. The symptoms of AUD are driven by dysfunction in several neurocircuits centered on the nucleus accumbens (NAc). Case reports and animal studies suggest NAc-DBS may be an effective harm-reduction treatment in severe AUD. Six patients with severe, refractory AUD underwent NAc-DBS. Safety metrics and clinical outcomes were recorded. Positron emission tomography (FDG-PET) was used to measure glucose metabolism in the NAc at baseline and 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in NAc functional connectivity to the rest of the brain, as well as NAc and dorsal striatal reactivity to alcoholic visual cues. This study was registered with ClinicalTrials.gov, NCT03660124. All patients experienced a reduction in craving. There was a significant reduction in alcohol consumption, alcohol-related compulsivity, and anxiety at 12 months. There was no significant change in depression. FDG-PET analysis demonstrated reduced NAc metabolism by 6 months, which correlated with improvements in compulsive drinking behaviors. Clinical improvement correlated with reduced functional connectivity between the NAc and the visual association cortex. Active DBS was associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe, otherwise refractory AUD. It is associated with a reduction in cravings and addictive behavior. A potential mechanism underlying this process is a down-regulation of the NAc, a disruption of its functional connectivity to the visual association cortex, and interference of cue-elicited dorsal striatum reactivity. Trial Registration NCT03660124 ( www.clinicaltrials.gov ).
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