Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia, Rovereto, Italy.
Department of Psychology, University of Cyprus, Nicosia, Cyprus.
Elife. 2020 Aug 4;9:e55684. doi: 10.7554/eLife.55684.
Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently.
兴奋-抑制（E:I）失衡被认为是自闭症的一个重要病理生理机制。自闭症更常影响男性，而与性别相关的机制（例如 X 连锁基因、雄激素激素）可以影响 E:I 平衡。这表明 E:I 失衡可能会对男性和女性的自闭症产生不同的影响。通过对小鼠进行计算机模拟和体内化学遗传操作的组合，我们首先表明，从 fMRI BOLD 信号估计的时间序列指标，Hurst 指数（H），可以作为突触 E:I 比值潜在变化的指标。在自闭症中，我们发现男性自闭症患者的内侧前额叶皮层（MPFC）中的 H 值降低，表明兴奋增加，但女性自闭症患者则没有。MPFC 的 H 值越来越完整，也与更好地掩饰社交沟通困难的行为能力相关，但仅在女性自闭症患者中。这项工作表明，BOLD 中的 H 可以指标突触 E:I 比值，并且 E:I 失衡对男性和女性自闭症的影响不同。
