Functional connectivity in autism spectrum disorders

自闭症谱系障碍的功能连接

• 批准号: 8511121
• 负责人: James Christopher EDGAR
• 金额: $ 25.13万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-05 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8511121
• 关键词: Age; Area; Auditory; Auditory system; Autacoids; Autistic Disorder; Behavioral Sciences; Biological Neural Networks; Biomedical Engineering; Brain; Brain region; Child; Clinical; Clinical Trials; Communication; Communities; Computer software; Computers; Coupling; Data; Data Set; Electrophysiology (science); Expeditions; Fishes; Frequencies; Gender; Glutamates; Heterogeneity; Individual; Laboratories; Measures; Mental disorders; Methods; National Institute of Mental Health; Pattern; Pharmaceutical Preparations; Phase; Process; Psychologist; Publishing; Research; Research Personnel; Rest; Sampling; Source; Stimulus; Structure; Sum; Superior temporal gyrus; Symptoms; Synapses; Testing; Time; Treatment Efficacy; autism spectrum disorder; base; cognitive function; information processing; insight; interest; neural circuit; neuroimaging; neuropathology; new therapeutic target; public health relevance; relating to nervous system; social; software development; synaptic function; tool

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.

描述（由申请人提供）：神经病理学和神经影像学研究显示，自闭症患者的多个脑区存在非典型脑功能，可能与神经突触兴奋性和抑制性活动失衡有关。虽然自闭症中的突触过程不能进行非侵入性评估，但根据振荡功率、交叉频率耦合和功能连接来评估神经过程可以提供对这些突触过程的洞察。我们的实验室已经观察到自闭症谱系障碍（ASD）和典型发育（TD）儿童在静息状态以及处理听觉信息时的神经振荡活动的焦点差异。这些局灶性不规则性似乎具有临床意义，因为它们与症状和认知功能相关。需要更好地了解这些振荡不规则性，以开发针对ASD患者的大脑活动调节的治疗方法。我们假设ASD的振荡活动与非典型的局部交叉频率耦合（CFC）和长程功能连接（FC）有关。拟议的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来检查这些假设。这项研究的优势在于，根据我们实验室发表的和新出现的研究结果，对特定的假设进行了测试，而不是进行功能连接的“钓鱼远征”。总之，这项研究确定了自闭症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。鉴于临床试验的出现，重点是通过使用谷氨酸能和GABA能化合物来改变突触功能，在拟议的研究中确定的ASD中的CFC和FC过程将提供评估治疗疗效的候选定量方法。深入了解ASD的基本神经脑过程也可能提出新的治疗靶点（例如，恢复特定的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，供研究界使用。