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.
摘要:
平衡的兴奋-抑制比(E/I比)对于健康的脑功能是关键的。皮质全E/I比率的规范发展仍然未知。这里,我们通过对静息状态功能MRI(fMRI)数据进行大规模生物物理可信回路模型拟合,来无创地估计全皮质E/I比值的推定标记.我们首先确认我们的模型在人类Connectome项目中生成了现实的大脑动力学。接下来,我们表明,在fMRI过程中,估计的E/I比率标记对γ-氨基丁酸(GABA)激动剂苯二氮卓阿普唑仑敏感。阿普唑仑诱导的E/I变化在空间上与苯二氮卓受体密度的正电子发射断层扫描测量一致。然后,我们研究了E/I比值标记与神经发育之间的关系。我们发现E/I比值标记在青年时期在大脑皮层中不均匀地下降,相对于联想系统,感觉运动系统的减少最大。重要的是,在相同实际年龄的儿童中,较低的E/I比值标记(尤其是在联想皮层中)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)人群中复制,表明更成熟的E/I比指标改善了规范发展过程中的认知。总的来说,我们的研究结果为研究E/I轨迹中断如何导致青年时期出现的精神病理学认知功能障碍打开了大门.