Neural basis of working memory and inhibitory control in ASD Children using NIRS

描述(由申请人提供)：这项研究旨在验证近红外光谱(NIRS)作为检查9-12岁患有自闭症谱系障碍(ASD)儿童的激活和功能连接(FC)的替代成像方式。FC将在执行控制和无任务休息状态下进行检查。执行功能受损(EF)是ASD认知表型的核心，影响社交、学业成绩和日常功能。EF包括服务于目标导向行为的过程，包括工作记忆(WM)和抑制控制(IC)。对EF重要的脑区，即前额叶和顶叶皮质，在当前ASD神经病理学的主导理论中居于中心位置，即ASD患者额后部沟通减少。ASD目前选择的测量这种沟通的方法是功能磁共振成像(FMRI)。它对运动伪影高度敏感，不能用于那些对受限的MR环境感到恐惧/焦虑的人。此外，较高的头部运动会使FC测量偏向连接不足，使得fMRI不太适合对患有高度头部运动和恐惧/焦虑的人群(如ASD)进行FC研究。这是寻找ASD功能性神经生物标志物的一个重要障碍，可以通过验证NIRS作为测量皮质激活和FC的成像手段来解决。该建议使用近红外光谱作为功能磁共振成像的替代方案，更不容易出现运动伪影，并且没有受限的恐惧/焦虑引发的磁共振环境。这些实验将检验如下假设：1)额顶区的执行负荷激活在ASD受试者和对照组(目标1)之间会有所不同；2)ASD儿童的额后部FC将低于对照组(目标2)。此外，这些实验将检验ASD儿童和对照组(目标3)在静息状态下的额后部FC不同的假设。这项工作将验证 NIRS是一种很有前途的新的成像手段，用于表征ASD的功能连接不典型。这项研究将进一步加深我们对ASD神经基础的理解，并为未来生物标记物的开发做出贡献。这项研究是可行的，因为所有的预测都涉及服从NIRS的大脑皮层区域，以及功能磁共振成像很好地表征的稳健效应。NIRS也被成功地用于检测相同年龄的ASD儿童的皮质激活情况。赞助商有互补的专业知识、自闭症、执行功能、静息状态(Vaidya博士赞助商)和近红外光谱信号和分析(梅德韦杰夫博士共同赞助商)。这项工作的新内容是使用近红外光谱检查1)负荷相关的激活变化；2)任务诱发的FC；3)静息状态的FC；4)ASD中FC从静息状态到任务状态的变化。这项工作促进了FC分析工具的开发(这些工具将通过NITRC免费传播)，有助于新出现的成像方式的方法标准化。

DESCRIPTION (provided by applicant): This research aims to validate Near-infrared spectroscopy (NIRS) as an alternative imaging modality for examining activation and functional connectivity (FC) in children age 9-12 with ASD (Autism Spectrum Disorders). FC will be examined during both executive control and a task-free resting state. Impaired executive function (EF) is central to the cognitive phenotype of ASD and influences socialization, school achievement, and everyday functioning. EF encompasses processes that serve goal- directed behavior, including working memory (WM) and inhibitory control (IC). Brain regions important for EF, namely prefrontal and parietal cortices figure centrally in the current dominant theory of neuropathology in ASD - that fronto-posterior communication is reduced in ASD. The current modality of choice in ASD for measuring such communication is functional magnetic resonance imaging (fMRI). It is highly sensitive to motion artifacts and cannot be used in those with fear/anxiety of the confining MR environment. Moreover, higher head motion biases FC measurement towards underconnectivity, making fMRI poorly suited for FC studies of populations with high head-motion and fear/anxiety such as ASD. This is a significant barrier in the search of functional neural biomarkers for ASD, which can be addressed by validating NIRS as an imaging modality for measuring cortical activation and FC. This proposal uses NIRS as an alternative to fMRI, being less prone to motion artifact and without the confining fear/anxiety-provoking MR environment. The proposed experiments will test the hypothesis that executive load-dependent 1) activation in fronto- parietal regions will differ between ASD subjects and controls (Aim 1); 2) fronto-posterior FC will be lower in ASD children relative to controls (Aim 2) Further, these experiments will test the hypothesis that fronto- posterior FC during the resting state will differ between ASD children and controls (Aim 3). This work will validate the utility of NIRS, a promising new imaging modality, for characterizing functional connectivity atypicalities in ASD. This research will further our understanding of the neural underpinnings of ASD and contribute to future biomarker development. This research is feasible in that all predictions concern cortical regions amenable to NIRS and robust effects well-characterized with fMRI. NIRS has also been used successfully for examining cortical activation in ASD children of the same ages as proposed. Sponsors have complementary expertise, ASD, executive function, resting-state (Dr. Vaidya - sponsor) and NIRS signal and analysis (Dr. Medvedev - co-sponsor). New elements of this work are the use of NIRS to examine 1) load-related activation change; 2) task- evoked FC; 3) resting-state FC; 4) change in FC from resting to task states, in ASD. This work prompts the development of FC analyses tools (which will be freely disseminated via NITRC) that contribute to standardization of methods for the emerging imaging modality.