Fung Hoki, Potash Ruby M, Krystal Andrew, Pizzagalli Diego A, Sacchet Matthew D
Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, 94143, USA.
Neuropsychopharmacology. 2025 May 13. doi: 10.1038/s41386-025-02125-z.
In our prior study involving a transdiagnostic sample of individuals with anhedonia, we showed that an 8-week administration of a selective κ-opioid receptor (KOR) antagonist enhanced fMRI ventral striatal activation during reward anticipation in the Monetary Incentive Delay task as compared to a placebo. However, individual differences in brain architecture may limit the translation of this finding to the context of precision medicine. Here, we adopted an individual-specific approach to elucidate the effects of selective KOR antagonism on cortical-subcortical reward circuits in individuals with anhedonia. Sixty-four participants with anhedonia (30 KOR Antagonist, 34 Placebo) who completed both pre- and post- treatment MRI scans in the FAST-MAS study were included in this analysis. Using an individualized-brain-systems-functional-brain-mapping approach, functional networks were mapped at the individual level, and individual-specific cortical patches and subcortical-cortical clusters were obtained. Statistical analyses were conducted to examine the pre- and post-treatment changes in patch and cluster sizes, as well as their relationships with clinical-cognitive measures. ROI analyses revealed a significant patch size decrease in the right medial posterior prefrontal cortex within the frontoparietal control network, and significant size increases in three right subcortical clusters - pallidum, amygdala, and thalamus - within the orbitofrontal-limbic network, following KOR antagonist treatment. In short, we applied recently developed computational neuroimaging approaches to examine changes in the individualized brain systems of FAST-MAS participants before and after eight weeks of KOR antagonist treatment for anhedonia. Our results revealed alterations in functional cortical patch and subcortical-cortical cluster sizes in anhedonia-related brain regions following KOR antagonist treatment.
在我们之前一项针对快感缺失个体的跨诊断样本研究中，我们发现，与安慰剂相比，连续8周给予选择性κ-阿片受体（KOR）拮抗剂可增强货币奖励延迟任务中奖励预期期间功能磁共振成像（fMRI）腹侧纹状体激活。然而，大脑结构的个体差异可能会限制这一发现转化到精准医学背景中。在此，我们采用个体特异性方法来阐明选择性KOR拮抗作用对快感缺失个体皮质-皮质下奖赏回路的影响。本分析纳入了64名在FAST-MAS研究中完成治疗前和治疗后MRI扫描的快感缺失参与者（30名接受KOR拮抗剂治疗，34名接受安慰剂治疗）。使用个体化脑系统功能脑图谱方法，在个体水平绘制功能网络，并获得个体特异性皮质区域和皮质下-皮质簇。进行统计分析以检查治疗前后区域和簇大小的变化，以及它们与临床认知指标的关系。感兴趣区（ROI）分析显示，KOR拮抗剂治疗后，额顶叶控制网络内右侧内侧前额叶后部皮质区域大小显著减小，眶额-边缘网络内右侧三个皮质下簇（苍白球、杏仁核和丘脑）大小显著增加。简而言之，我们应用最近开发的计算神经成像方法来检查FAST-MAS参与者在接受KOR拮抗剂治疗8周前后个体化脑系统的变化。我们的结果显示，KOR拮抗剂治疗后，快感缺失相关脑区的功能性皮质区域和皮质下-皮质簇大小发生了改变。
