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In this pre-registered study we demonstrate that a hidden subgroup within the general population\u2014people with synesthesia (e.g. who \u201chear\u201d colors)\u2014show a distinctive behavioral phenotype and wide-ranging differences in brain structure and function. We assess the performance of 13 different brain-based biomarkers (structural and functional MRI) for classifying synesthetes against general population samples, using machine learning models. The features in these models were derived from subject-specific parcellations of the cortex using the Human Connectome Project approach. All biomarkers performed above chance with intracortical myelin being a particularly strong predictor that has not been implicated in synesthesia before. Resting state data show widespread changes in the functional connectome (including less hub-based connectivity). These brain-based individual differences within the neurotypical population can be as large as those that differentiate neurotypical from clinical brain states.<\/jats:p>","DOI":"10.1093\/cercor\/bhae446","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T03:20:16Z","timestamp":1731727216000},"source":"Crossref","is-referenced-by-count":11,"title":["Synesthesia is linked to large and extensive differences in brain structure and function as determined by whole-brain biomarkers derived from the HCP (Human Connectome Project) cortical parcellation approach"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7007-1902","authenticated-orcid":false,"given":"Jamie","family":"Ward","sequence":"first","affiliation":[{"name":"School of Psychology and Sussex Neuroscience, University of Sussex , Brighton, BN1 9QH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Simner","sequence":"additional","affiliation":[{"name":"School of Psychology and Sussex Neuroscience, University of Sussex , Brighton, BN1 9QH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivor","family":"Simpson","sequence":"additional","affiliation":[{"name":"School of Engineering and Informatics, University of Sussex , Brighton, BN1 9QH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Rae","sequence":"additional","affiliation":[{"name":"School of Psychology and Sussex Neuroscience, University of Sussex , Brighton, BN1 9QH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"del Rio","sequence":"additional","affiliation":[{"name":"School of Psychology and Sussex Neuroscience, University of Sussex , Brighton, BN1 9QH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A","family":"Eccles","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Brighton and Sussex Medical School (BSMS) , Brighton, BN1 9QH,","place":["United Kingdom"]},{"name":"Neurodevelopmental Service, Sussex Partnership NHS Foundation Trust , Worthing, BN13 3EP,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Racey","sequence":"additional","affiliation":[{"name":"School of Psychology and Sussex Neuroscience, University of Sussex , Brighton, BN1 9QH,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"2024111603200460700_ref1","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/nrn3465","article-title":"Imaging structural co-variance between human brain regions","volume":"14","author":"Alexander-Bloch","year":"2013","journal-title":"Nat Rev Neurosci"},{"key":"2024111603200460700_ref2","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1111\/bjop.12050","article-title":"Assessing vividness of mental imagery: the Plymouth sensory imagery questionnaire","volume":"105","author":"Andrade","year":"2014","journal-title":"Br J Psychol"},{"key":"2024111603200460700_ref3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.tins.2008.03.007","article-title":"Synaesthesia and cortical connectivity","volume":"31","author":"Bargary","year":"2008","journal-title":"Trends Neurosci"},{"key":"2024111603200460700_ref4","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.cognition.2007.05.003","article-title":"Familial patterns and the origins of individual differences in synaesthesia","volume":"106","author":"Barnett","year":"2008","journal-title":"Cognition"},{"key":"2024111603200460700_ref5","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1068\/p220419","article-title":"Coloured speech perception: is synaesthesia what happens when modularity breaks down?","volume":"22","author":"Baron-Cohen","year":"1993","journal-title":"Perception"},{"key":"2024111603200460700_ref6","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/A:1005653411471","article-title":"The autism-spectrum quotient (aq): evidence from asperger syndrome\/high-functioning autism, males and females, scientists and mathematicians","volume":"31","author":"Baron-Cohen","year":"2001","journal-title":"J Autism Dev Disord"},{"key":"2024111603200460700_ref7","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1177\/0013164498058003002","article-title":"Raven\u2019s advanced progressive matrices: norms for first-year university students and the development of a short form","volume":"58","author":"Bors","year":"1998","journal-title":"Educ Psychol Meas"},{"key":"2024111603200460700_ref8","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1111\/bjop.12354","article-title":"Is there is a burden attached to synaesthesia? 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