{Reference Type}: Journal Article
{Title}: In vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth.
{Author}: Zhang S;Larsen B;Sydnor VJ;Zeng T;An L;Yan X;Kong R;Kong X;Gur RC;Gur RE;Moore TM;Wolf DH;Holmes AJ;Xie Y;Zhou JH;Fortier MV;Tan AP;Gluckman P;Chong YS;Meaney MJ;Deco G;Satterthwaite TD;Yeo BTT;
{Journal}: Proc Natl Acad Sci U S A
{Volume}: 121
{Issue}: 23
{Year}: 2024 Jun 4
{Factor}: 12.779
{DOI}: 10.1073/pnas.2318641121
{Abstract}: 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.