%0 Journal Article
%T In vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth.
%A Zhang S
%A Larsen B
%A Sydnor VJ
%A Zeng T
%A An L
%A Yan X
%A Kong R
%A Kong X
%A Gur RC
%A Gur RE
%A Moore TM
%A Wolf DH
%A Holmes AJ
%A Xie Y
%A Zhou JH
%A Fortier MV
%A Tan AP
%A Gluckman P
%A Chong YS
%A Meaney MJ
%A Deco G
%A Satterthwaite TD
%A Yeo BTT
%J Proc Natl Acad Sci U S A
%V 121
%N 23
%D 2024 Jun 4
%M 38814872
%F 12.779
%R 10.1073/pnas.2318641121
%X 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.