In vivo whole- cortex marker of excitation- inhibition ratio indexes cortical maturation and cognitive ability in youth

• 成果类型: Article
• 署名作者: Zhang, Shaoshi; Larsen, Bart; Sydnor, Valerie J.; Zeng, Tianchu; An, Lijun; Yan, Xiaoxuan; Kong, Ru; Kong, Xiaolu; Gur, Ruben C.; Gur, Raquel E.; Moore, Tyler M.; Wolf, Daniel H.; Holmes, Avram J.; Xie, Yapei; Zhou, Juan Helen; Fortier, Marielle V.; Tan, Ai Peng; Gluckman, Peter; Chong, Yap Seng; Meaney, Michael J.; Deco, Gustavo; Satterthwaite, Theodore D.; Yeo, B. T. Thomas
• 署名单位: National University of Singapore; National University of Singapore; National University of Singapore; National University of Singapore; National University of Singapore; National University of Singapore; National University of Singapore; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Minnesota System; University of Minnesota Twin Cities; University of Pennsylvania; Rutgers University System; Rutgers University New Brunswick; Yale University; KK Women's & Children's Hospital; Agency for Science Technology & Research (A*STAR); A*STAR - Singapore Institute for Clinical Sciences (SICS); National University of Singapore; University of Auckland; National University of Singapore; McGill University; University of Barcelona; Pompeu Fabra University; ICREA; University of Barcelona; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9314
• DOI: 10.1073/pnas.2318641121
• 发表日期: 2024-06-04
• 关键词: critical period plasticity; human cerebral-cortex; functional connectivity; balance; network; mechanisms; SYSTEM; autism; cells; MODEL

摘要

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.