孤独症谱系障碍额顶失连接及其调控机制研究

Individuals with autism spectrum disorder (ASD) demonstrate deficits in social communication and social interaction and show restricted repetitive behaviors, interests, and activities. Its pathogenesis is still not clear. Recent research suggests that ASD is not caused by abnormal structure and function of single brain region, but is related to the abnormal connections among multiple brain regions. Our previous study found that modifying the excitability of parietal cortex may partially improve the core symptoms and cognitive functions of ASD. We hypothesize that frontal-parietal underconnectivity may be an important pathogenesis of ASD. Furthmore, by increasing the excitability of parietal cortex in ASD, it is expected to enhance afferent information from the parietal lobe to the frontal lobe, to improve the frontal-parietal decreased connection, so as to further improve the cognitive function and clinical symptoms. In this project, fMRI will be used to identify resting-state frontal-parietal functional connections in ASD. The accurate abnormal brain regions and frontal-parietal effective function of ASD patients will be delineated by magnetoencephalography (MEG). Furthermore, transcranial magnetic stimulation-electroencephalography (TMS-EEG) will be used to identify the frontal-parietal physiologic connection in ASD. After changing the excitability of the parietal cortex by repetitive transcranial magnetic stimulation (rTMS), the above mentioned methods will be applied again to explore the changes of abnormal brain regions and frontal-parietal connections in patients with ASD, to find the neurophysiological mechanisms of ASD, to elucidate the nature of the disease to some extent and to provide an important theoretical basis for neuromodulation therapy for ASD.

孤独症谱系障碍（ASD）是一组以社会交往障碍、刻板重复行为为特点的神经发育障碍性疾病，其发病机制尚不明确。研究显示，ASD并非单一脑区结构和功能异常导致，而与多个脑区间连接异常有关。我们前期研究结果显示，提高顶叶皮层兴奋性后可改善ASD核心症状和认知功能。我们推测额顶失连接有可能是ASD的重要发病机制，通过提高ASD顶叶皮层兴奋性，有望改善额顶失连接，从而改善患者认知功能和临床症状。本项目拟通过fMRI明确ASD额顶网络的功能连接，通过脑磁图解析额顶网络的有效连接，应用经颅磁刺激兼容的脑电图明确ASD患者额顶网络的生理连接；并在磁刺激提高顶叶兴奋性后应用上述手段探索ASD额顶连接变化模式，明确顶叶在额顶连接中的作用机制，试图发现ASD患者病理生理机制的关键环节，为在临床上开展神经调控治疗提供重要的理论依据。

孤独症谱系障碍（ASD）是一组以社会交往障碍、刻板重复行为为特点的神经发育障碍性疾病，其发病机制尚不明确。研究显示，ASD并非单一脑区结构和功能异常导致，而与多个脑区间连接异常有关。我们前期研究结果显示，提高顶叶皮层兴奋性后可改善ASD核心症状和认知功能。我们推测额顶失连接有可能是ASD的重要发病机制，通过提高ASD顶叶皮层兴奋性，有望改善额顶失连接，从而改善患者认知功能和临床症状。本课题通过脑电图网络分析等手段证实了ASD存在额顶叶、额枕叶失连接等脑网络异常模式，明确了顶叶皮层兴奋性改变后ASD脑网络改变模式及其与症状改善的关系，建立了ASD无创神经调控治疗的新靶点、新参数。初步建立了ASD早期诊断、疗效评价的客观生物学指标。