{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:41:32Z","timestamp":1793378492454,"version":"4.5.0"},"posted":{"date-parts":[[2025,10,2]]},"group-title":"Neuroscience","reference-count":89,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["MH121095"],"award-info":[{"award-number":["MH121095"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["MH138347"],"award-info":[{"award-number":["MH138347"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["EB034720"],"award-info":[{"award-number":["EB034720"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  A key assumption of the NIMH\u2019s RDoC framework is that disordered circuits in the brain should manifest in observable behaviors, including psychiatric symptomatology and cognitive deficits. However, how disordered circuitry impacts multiple behaviors remains poorly understood. Connectome-based predictive modeling (CPM) applied to functional MRI connectivity data can identify networks associated with specific behavioral measures across individuals. Prediction strength reflects how closely a measure relates to network connectivity, while derived networks provide evidence of where an individual\u2019s disordered circuits are located. Using CPM, we predicted a broad range of self-reported clinical and objective cognitive measures in a large, transdiagnostic sample with extensive fMRI data (n = 317). Prediction performance varied substantially across instruments, with objective cognitive tests yielding stronger models than self-reported clinical measures (\n                  <jats:italic>p<\/jats:italic>\n                  &lt; 0.001). To test whether circuits underlying cognitive deficits related to symptomatology reside in regions where networks overlap, we examined the prediction strength of these sparsely shared circuits. Their connectivity strongly predicted cognitive performance and were primarily localized within the frontoparietal network and between the frontoparietal and default mode networks. These findings reveal how much various behavioral measures reflect brain networks and how circuits within the shared network space contribute to cognitive deficits associated with symptomatology.\n                <\/jats:p>","DOI":"10.1101\/2025.10.02.680080","type":"posted-content","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T07:25:10Z","timestamp":1759476310000},"source":"Crossref","is-referenced-by-count":0,"title":["Transdiagnostic connectome-based predictive modeling reveals where circuits related to self-reported clinical symptoms impinge upon brain networks supporting cognition"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7087-7965","authenticated-orcid":false,"given":"Alexander J","family":"Simon","sequence":"first","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Samardzija","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santino","family":"Iannone","sequence":"additional","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flor Parra","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saloni","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyuze","family":"Tokoglu","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maolin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagriti","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira Y","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Q","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Sanacora","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3103-5228","authenticated-orcid":false,"given":"Scott W.","family":"Woods","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod H.","family":"Srihari","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin","family":"Scheinost","sequence":"additional","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT, USA"},{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5661-9521","authenticated-orcid":false,"given":"R. 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