{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:26:51Z","timestamp":1785432411476,"version":"3.56.0"},"posted":{"date-parts":[[2025,6,6]]},"group-title":"Neuroscience","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["2112455"],"award-info":[{"award-number":["2112455"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2316421"],"award-info":[{"award-number":["2316421"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1U24 RR021992"],"award-info":[{"award-number":["1U24 RR021992"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1U24 RR025736-01"],"award-info":[{"award-number":["1U24 RR025736-01"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R01MH130595"],"award-info":[{"award-number":["1R01MH130595"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Disrupted large-scale brain network interactions are a hallmark of schizophrenia, yet the circuit-level mechanisms underlying cognitive deficits remain incompletely understood. In particular, cortico\u2013thalamo\u2013cerebellar circuitry has been implicated in \u201ccognitive dysmetria,\u201d but its functional organization across subdomains has not been fully characterized. Here, we apply a flexible multimodal data fusion framework (aNy-way independent component analysis) to integrate 4D domain-specific resting-state fMRI data from the cortex, thalamus, and cerebellum. Using a large discovery cohort (FBIRN, N=311) and two independent replication datasets (COBRE, N=148; MPRC, N=364), we identify a robust cortico\u2013thalamo\u2013cerebellar circuit involving higher-order thalamic nuclei, visual cortex, default mode network, and cerebellar posterior regions. This circuit shows altered connectivity in schizophrenia, characterized by reduced anticorrelation between thalamus and cortex, and is consistently associated with cognitive impairments, including processing speed, working memory, and reasoning deficits across cohorts. Importantly, these findings are largely replicated across independent cohorts. Together, these results provide data-driven evidence for a cortico\u2013thalamo\u2013cerebellar mechanism underlying cognitive dysfunction in schizophrenia, supporting the cognitive dysmetria hypothesis. This work also demonstrates the utility of aNy-way independent component analysis for identifying clinically relevant brain circuits in psychiatric disorders.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Identified cortico\u2013thalamo\u2013cerebellar circuits in schizophrenia<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Altered thalamocortical interactions differentiated schizophrenia<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Circuit alterations were associated with cognitive impairment<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Findings are replicated across three independent multisite datasets<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Multidomain fusion enabled subdomain-specific circuit characterization<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.02.657541","type":"posted-content","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T05:05:14Z","timestamp":1749186314000},"source":"Crossref","is-referenced-by-count":0,"title":["Cortico\u2013thalamo\u2013cerebellar circuit disruptions underlying cognitive deficits in schizophrenia: a multi-cohort multidomain fusion study"],"prefix":"10.64898","author":[{"given":"KuaiKuai","family":"Duan","sequence":"first","affiliation":[{"name":"Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, USA"},{"name":"Marcus Autism Center, Children\u2019s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA"},{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogers F.","family":"Silva","sequence":"additional","affiliation":[{"name":"Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Abdur","family":"Rahaman","sequence":"additional","affiliation":[{"name":"Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, USA"},{"name":"Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zening","family":"Fu","sequence":"additional","affiliation":[{"name":"Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kochunov","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center Houston, TX, 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo G.M.","family":"van Erp","sequence":"additional","affiliation":[{"name":"Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California"},{"name":"Center for the Neurobiology of Learning and Memory, University of California Irvine, 309 Qureshey Research Lab, Irvine, CA, 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Shultz","sequence":"additional","affiliation":[{"name":"Marcus Autism Center, Children\u2019s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA"},{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vince D.","family":"Calhoun","sequence":"additional","affiliation":[{"name":"Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of 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