Mapping cerebellar connectivity to cognition in psychosis: Convergent evidence from fMRI and TMS.

IF 9.6 1区医学 Q1 NEUROSCIENCES

Biological Psychiatry Pub Date : 2025-07-03 DOI:10.1016/j.biopsych.2025.06.023

Hengyi Cao, Miklos Argyelan, Joanna Yan, Halil Aziz Velioglu, Franky Fang, Andrea Joanlanne, Simran Kang, Lara Prizgint, Jenna Schugart, Kadeem Brown, John Cholewa, Philip Watson, Sunny X Tang, Ricardo Carrion, Jose Rubio, Moein Foroughi, Todd Lencz, Anil K Malhotra

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引用次数: 0

Abstract

Background: Cerebellar dysfunction is strongly implicated in both cognition and psychosis, and the "cognitive dysmetria" hypothesis posits cognition as the intermediary in the pathway from cerebellar dysfunction to psychopathology. However, the nuanced cerebellum-behavior relationships in psychosis remain unclear. Establishing such link is crucial to understand cerebellar mechanisms and to identify treatment target for cognitive deficits in patients.

Methods: We studied 100 patients with early psychosis from the Human Connectome Project Early Psychosis study. Connectome-based predictive modeling was conducted to probe cognitive functions most predicted by cerebellar connectivity. Mediation analysis was performed to test a mediating role of cognition between cerebellar connectivity and symptoms. To further support the causality of the findings, we additionally recruited 16 psychotic patients for a 2-week randomized, sham-controlled cerebellar transcranial magnetic stimulation (TMS) trial.

Results: Cerebellar connectivity significantly predicted three cognitive functions, namely, verbal ability, working memory, and cognitive flexibility. Verbal ability fully mediated the relationship between cerebellar connectivity and negative symptoms, in particular alogia. While each cognitive function was predicted by a distinct cerebellar connectivity pattern, the left crus I/II appeared to be a common area with connectivity consistently predicting all three functions. Stimulating this region via TMS showed significantly improved cognitive composite score and medium-to-large effects on scores for memory, verbal, and executive functions.

Conclusions: These findings suggest a potential causal pathway from cerebellar connectivity to domain-specific cognitive deficits and psychopathology in schizophrenia. Moreover, they also point to the cerebellum as a potential target for the treatment of cognitive dysfunction in psychotic disorders.

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在精神病中绘制小脑连通性与认知：来自fMRI和TMS的趋同证据。

背景：小脑功能障碍与认知和精神病密切相关，“认知障碍”假说认为认知是小脑功能障碍到精神病理通路的中介。然而，精神病中小脑与行为的微妙关系仍不清楚。建立这种联系对于理解小脑机制和确定认知缺陷患者的治疗靶点至关重要。方法：我们研究了100例早期精神病患者，这些患者来自人类连接组计划早期精神病研究。采用基于连接体的预测建模方法对小脑连通性预测最多的认知功能进行探测。进行中介分析以检验认知在小脑连通性和症状之间的中介作用。为了进一步支持这些发现的因果关系，我们额外招募了16名精神病患者进行为期2周的随机、假对照小脑经颅磁刺激（TMS）试验。结果：小脑连通性显著预测语言能力、工作记忆和认知灵活性三项认知功能。语言能力完全介导了小脑连通性与阴性症状之间的关系，特别是痛症。虽然每一种认知功能都是通过不同的小脑连接模式来预测的，但左小腿I/II似乎是一个共同的区域，其连接一致地预测了所有三种功能。通过经颅磁刺激刺激这一区域，可以显著提高认知综合得分，并对记忆、言语和执行功能得分产生中等到较大的影响。结论：这些发现提示了一个潜在的因果途径，从小脑连接到特定领域的认知缺陷和精神分裂症的精神病理。此外，他们还指出，小脑是治疗精神障碍患者认知功能障碍的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biological Psychiatry 医学-精神病学

CiteScore

18.80

自引率

2.80%

发文量

1398

审稿时长

33 days

期刊介绍： Biological Psychiatry is an official journal of the Society of Biological Psychiatry and was established in 1969. It is the first journal in the Biological Psychiatry family, which also includes Biological Psychiatry: Cognitive Neuroscience and Neuroimaging and Biological Psychiatry: Global Open Science. The Society's main goal is to promote excellence in scientific research and education in the fields related to the nature, causes, mechanisms, and treatments of disorders pertaining to thought, emotion, and behavior. To fulfill this mission, Biological Psychiatry publishes peer-reviewed, rapid-publication articles that present new findings from original basic, translational, and clinical mechanistic research, ultimately advancing our understanding of psychiatric disorders and their treatment. The journal also encourages the submission of reviews and commentaries on current research and topics of interest.