Biernacki Kathryn, Goldstein Rita Z, Güth Malte R, Alia-Klein Nelly, Cole Sally, Ray Suchismita, Baker Travis E
Center for Molecular and Behavioral Neuroscience, Rutgers University-Newark, Newark, NJ, USA.
National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA.
Transl Psychiatry. 2025 Sep 3;15(1):340. doi: 10.1038/s41398-025-03569-z.
Abnormalities in goal-directed behavior, mediated by mesocorticolimbic reward system, contribute to worse clinical outcomes including higher risk of treatment dropout and drug relapse in opioid users (OU). Despite efforts to counteract such neural alterations, brain-based interventions for this disorder remain ineffective. In this sham-controlled randomized study, we report the initial results on the efficacy of transcranial magnetic stimulus (TMS) in normalizing reward functioning in this population. During a reward-based choice task, we applied robot-assisted 10-Hz TMS to the prefrontal cortex in OU (Active = 16, Sham = 18) and matched healthy controls (HC, Active = 22, Sham = 24) while we recorded the reward positivity - an electrophysiological signal believed to index sensitivity of the anterior midcingulate cortex (MCC) to rewards. A robotic arm positioned a TMS coil over a prefrontal cortex target, and 50 pulses were delivered at 10-Hz before every 10 trials (2000 pulses, 400 trials). Our results revealed an interaction between TMS (Active vs Sham) and Group (OU vs HC) (F = 6.9, p = 0.01, η = 0.09). First, in the Sham TMS condition, OU exhibited a blunted reward positivity compared to HC (p = 0.01, d = 0.84). Second, OU receiving active TMS displayed a larger reward positivity compared to OU receiving sham (p = 0. 003, d = 0.98), and no differences were observed between OU and HC (p = 0.42, d = 0.17) or HC receiving sham (p = 0.48, d = 0.11). We envision that targeting a specific frontal-cingulate reward pathway is an important first step to maintain long-terms effect of TMS on MCC reward function, which may enhance treatment success through the maintenance of treatment goals.
由中脑边缘奖赏系统介导的目标导向行为异常，会导致更差的临床结果，包括阿片类药物使用者（OU）治疗中断和药物复发的风险更高。尽管人们努力对抗这种神经改变，但针对这种疾病的基于大脑的干预措施仍然无效。在这项假对照随机研究中，我们报告了经颅磁刺激（TMS）使该人群奖赏功能正常化的疗效的初步结果。在基于奖赏的选择任务中，我们对OU组（主动组 = 16人，假刺激组 = 18人）和匹配的健康对照组（HC，主动组 = 22人，假刺激组 = 24人）的前额叶皮层应用机器人辅助的10赫兹TMS，同时记录奖赏正波——一种被认为可指示前扣带中部皮质（MCC）对奖赏敏感性的电生理信号。一个机械臂将TMS线圈放置在前额叶皮层目标上方，每10次试验前以10赫兹的频率发送50个脉冲（共2000个脉冲，400次试验）。我们的结果揭示了TMS（主动刺激与假刺激）和组别（OU组与HC组）之间的交互作用（F = 6.9，p = 0.01，η = 0.09）。首先，在假刺激TMS条件下，与HC组相比，OU组的奖赏正波减弱（p = 0.01，d = 0.84）。其次，接受主动TMS的OU组与接受假刺激的OU组相比，表现出更大的奖赏正波（p = 0.003，d = 0.98），并且在OU组与HC组之间（p = 0.42，d = 0.17）或接受假刺激的HC组之间（p = 0.48，d = 0.11）未观察到差异。我们设想，针对特定的额叶 - 扣带回奖赏通路是维持TMS对MCC奖赏功能长期影响的重要第一步，这可能通过维持治疗目标来提高治疗成功率。
