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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,6,4]]},"abstract":"<jats:p>A balanced excitation-inhibition ratio (E\/I ratio) is critical for healthy brain function. Normative development of cortex-wide E\/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E\/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E\/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E\/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E\/I ratio marker and neurodevelopment. We find that the E\/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E\/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E\/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E\/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth.<\/jats:p>","DOI":"10.1073\/pnas.2318641121","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T13:15:51Z","timestamp":1717074951000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":68,"title":["In vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6352-9150","authenticated-orcid":false,"given":"Shaoshi","family":"Zhang","sequence":"first","affiliation":[{"name":"Centre for Sleep and Cognition and Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore"},{"name":"Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore"},{"name":"N.1 Institute for Health, National University of Singapore, Singapore 117456, Singapore"},{"name":"Integrative Sciences and Engineering Programme, National University of Singapore, Singapore 119077, Singapore"},{"name":"Department of Medicine, Human Potential Translational Research Programme &amp; Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Signapore 117456, Signapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7896-4342","authenticated-orcid":false,"given":"Bart","family":"Larsen","sequence":"additional","affiliation":[{"name":"Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA 19104"},{"name":"Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104"},{"name":"Lifespan Brain Institute of Penn Medicine and Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104"},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie J.","family":"Sydnor","sequence":"additional","affiliation":[{"name":"Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA 19104"},{"name":"Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104"},{"name":"Lifespan Brain Institute of Penn Medicine and Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianchu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Centre for Sleep and Cognition and Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore"},{"name":"Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore"},{"name":"N.1 Institute for Health, National University of Singapore, Singapore 117456, Singapore"},{"name":"Department of Medicine, Human Potential Translational Research Programme &amp; Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Signapore 117456, Signapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1030-4625","authenticated-orcid":false,"given":"Lijun","family":"An","sequence":"additional","affiliation":[{"name":"Centre for Sleep and Cognition and Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore"},{"name":"Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore"},{"name":"N.1 Institute for Health, National University of Singapore, Singapore 117456, Singapore"},{"name":"Department of Medicine, Human Potential Translational Research Programme &amp; Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Signapore 117456, Signapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Yan","sequence":"additional","affiliation":[{"name":"Centre for Sleep and Cognition and Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore"},{"name":"Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore"},{"name":"N.1 Institute for Health, National University of Singapore, Singapore 117456, Singapore"},{"name":"Integrative Sciences and Engineering Programme, National University of Singapore, Singapore 119077, Singapore"},{"name":"Department of Medicine, Human Potential Translational Research Programme &amp; 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