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
{"title":"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。","authors":"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","doi":"10.1016/j.biopsych.2025.06.023","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mapping cerebellar connectivity to cognition in psychosis: Convergent evidence from fMRI and TMS.\",\"authors\":\"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\",\"doi\":\"10.1016/j.biopsych.2025.06.023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":8918,\"journal\":{\"name\":\"Biological Psychiatry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":9.6000,\"publicationDate\":\"2025-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.biopsych.2025.06.023\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.biopsych.2025.06.023","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Mapping cerebellar connectivity to cognition in psychosis: Convergent evidence from fMRI and TMS.
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.
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.
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