{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:49:52Z","timestamp":1791978592765,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["343923\/Z\/26\/Z"],"award-info":[{"award-number":["343923\/Z\/26\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Analyses of neuroimaging data increasingly leverage the distribution of neurotransmitter receptors derived from positron emission tomography (PET) to bridge the gap between micro\u2010 and macro\u2010scale brain function. However, these receptor maps are highly spatially overlapping, which can give rise to interpretive and analytical challenges. Here, we systematically investigate the impact of spatial collinearity among PET maps in the context of Receptor\u2010Enriched Analysis of functional Connectivity by Targets (REACT), a method that uses receptor maps as spatial regressors to derive subject\u2010level molecular\u2010enriched functional connectivity networks. Exhaustive combinatorial analysis across 19 receptor and transporter maps showed that collinearity scales rapidly with the number of receptors modelled simultaneously, and that the underlying correlation structure was relatively stable across parcellation scales, reflecting the intrinsic organisation of neurotransmitter systems. Using test\u2013retest fMRI data from the Human Connectome Project, we demonstrate that modelling greater numbers of receptors degrades the reliability of molecular\u2010enriched networks derived from conventional multivariate REACT models, and that collinearity among receptor maps drives this degradation. An alternative univariate approach, in which each receptor is modelled independently, yielded more reliable networks and, when applied to a within\u2010subjects study of LSD compared to placebo, better recovered the role of the 5\u2010HT\n                    <jats:sub>2A<\/jats:sub>\n                    receptor in LSD's neural effects. These findings identify spatial collinearity as a fundamental constraint on multivariate molecular\u2010enriched network estimation. We therefore recommend univariate models as the default, with multivariate models used only where specifically motivated and reported alongside the univariate result.\n                  <\/jats:p>","DOI":"10.1002\/hbm.70645","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:35:51Z","timestamp":1789965351000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial Collinearity Constrains Multivariate Molecular\u2010Enriched Network Estimation"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-5987","authenticated-orcid":false,"given":"Timothy","family":"Lawn","sequence":"first","affiliation":[{"name":"Oxford Centre for Integrative Neuroimaging, Department of Experimental Psychology University of Oxford  Oxford UK"},{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0269-8559","authenticated-orcid":false,"given":"Johan","family":"Nakuci","sequence":"additional","affiliation":[{"name":"U.S. Army DEVCOM Army Research Laboratory  Adelphi Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-1941","authenticated-orcid":false,"given":"Steve C. R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Turkheimer","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1152-5323","authenticated-orcid":false,"given":"Mitul A.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.05.070"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.09.025"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2017.00108"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010023\u201000752\u20103"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyac075"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2003.822821"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471725153"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1039\u201008.2008"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/02698811231211154"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.151"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","unstructured":"Bryant A. 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