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.
Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.
Proc Natl Acad Sci U S A. 2024 Jun 4;121(23):e2318641121. doi: 10.1073/pnas.2318641121. Epub 2024 May 30.
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.
大脑功能的健康需要平衡的兴奋-抑制比（E/I 比）。皮质整体 E/I 比的正常发育尚不清楚。在这里，我们通过将一个大规模的生物物理上合理的电路模型拟合到静息状态功能磁共振成像（fMRI）数据，无创地估计了一个整体皮质 E/I 比的假定标志物。我们首先确认我们的模型在人类连接组计划中产生了现实的大脑动力学。接下来，我们表明，所估计的 E/I 比标志物对 fMRI 期间的γ-氨基丁酸（GABA）激动剂苯二氮䓬类药物阿普唑仑敏感。阿普唑仑诱导的 E/I 变化与苯二氮䓬受体密度的正电子发射断层扫描测量在空间上一致。然后，我们研究了 E/I 比标志物与神经发育之间的关系。我们发现，E/I 比标志物在青少年期间在大脑皮质中不均匀地下降，与感觉运动系统相比，关联系统的下降幅度最大。重要的是，在具有相同年龄的儿童中，较低的 E/I 比标志物（尤其是在联合皮层中）与更好的认知表现相关。这一结果在北美（8.2 至 23.0 岁）和亚洲（7.2 至 7.9 岁）队列中得到了复制，这表明更成熟的 E/I 比指标可以在正常发育过程中提高认知能力。总体而言，我们的发现为研究 E/I 轨迹的破坏如何导致青少年时期出现的精神病理学中的认知功能障碍开辟了道路。
