Functional connectivity in autism spectrum disorders

描述（由申请人提供）：神经病理学和神经影像学研究显示自闭症患者在多个脑区具有非典型脑功能，可能与神经突触兴奋性和抑制性活动的不平衡有关。虽然自闭症的突触过程不能进行无创评估，但从振荡功率、交叉频率耦合和功能连通性方面评估神经过程可以深入了解这些突触过程。我们的实验室观察了自闭症谱系障碍（ASD）儿童和正常发育（TD）儿童在静息状态和处理听觉信息时神经振荡活动的局灶性差异。这些局灶性不规则似乎具有临床意义，因为它们与症状和认知功能有关。我们需要更好地了解这些振荡的不规则性，从而开发出量身定制的治疗方法来调节ASD患者的大脑活动。我们假设ASD的振荡活动与非典型局部交叉频率耦合（CFC）和远程功能连接（FC）有关。提出的R21通过评估ASD （N = 150）和TD对照组（N = 150+）的静息状态和听觉系统CFC和FC来检验这些假设。这项研究的优势在于，它不是进行功能连接的“钓鱼考察”，而是根据我们实验室已发表的和新出现的发现，对特定的假设进行了测试。综上所述，本研究确定了自闭症中连接异常的具体特征和模式，以更好地了解自闭症的大脑过程。鉴于通过使用谷氨酸能和氨基丁酸能化合物来改变突触功能的临床试验的出现，本研究中确定的ASD中的CFC和FC过程将提供评估治疗效果的候选定量手段。对ASD的基本神经脑过程的深入了解也可能提出新的治疗靶点（例如，恢复特定局部和远程神经动力学的药物）。此外，在研究结束时，我们将开发一套MATLAB全脑CFC和FC工具，这些工具将提供给研究界。

DESCRIPTION (provided by applicant): Neuropathology and neuroimaging studies show atypical brain function in multiple brain regions in autism, likely associated with imbalances in excitatory and inhibitory activity at the neural synapse. Although synaptic processes in autism cannot be non-invasively assessed, assessment of neural processes in terms of oscillatory power, cross-frequency coupling, and functional connectivity can provide insight into these synaptic processes. Our laboratory has observed focal differences in neural oscillatory activity between children with autism spectrum disorders (ASD) and typically developing (TD) controls in the resting state as well as when processing auditory information. These focal irregularities appear to have clinical implications, as they were associated with symptoms and cognitive function. A better understanding of these oscillatory irregularities is needed to develop treatments tailored to modulate brain activity in ASD. We hypothesize that oscillatory activity in ASD is associated with atypical local cross-frequency coupling (CFC) and long-range functional connectivity (FC). The proposed R21 examines these hypotheses by assessing resting-state and auditory system CFC and FC in ASD (N = 150) and TD controls (N = 150+). A strength of the study is that rather than undertaking a functional connectivity 'fishing expedition', specific hypotheses are tested, based on our laboratory's published and emerging findings. In sum, the proposed study determines the specific character and pattern of connectivity abnormalities in autism to better understand brain processes in autism. Given the emergence of clinical trials focusing on modifying synaptic function via the use of glutamatergic and GABAergic compounds, the CFC and FC processes in ASD identified in the proposed study will provide a candidate quantitative means of assessing treatment efficacy. Obtaining insights into basic neural brain processes in ASD will likely also suggest new therapeutic targets (e.g., drugs that restore specific local and long-range neural dynamics). Furthermore, by the end of the study, we will have developed a set of MATLAB whole-brain CFC and FC tools that will be made available to the research community.