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

描述（由申请人提供）：本研究旨在验证近红外光谱（NIRS）作为检测9-12岁自闭症谱系障碍（ASD）儿童激活和功能连接（FC）的替代成像方式。在执行控制和无任务的休息状态下，将检查FC。执行功能受损（EF）是ASD认知表型的核心，影响社会化、学习成绩和日常功能。EF包含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很重要的大脑区域，即前额叶和顶叶皮层，在目前ASD神经病理学的主流理论中占据中心地位，即ASD的额-后交流减少。在自闭症谱系障碍中，目前选择的测量这种交流的方式是功能性磁共振成像（fMRI）。它对运动伪影高度敏感，不能用于那些对限制性MR环境感到恐惧/焦虑的人。此外，较高的头部运动使FC测量偏向于连接不足，使得fMRI不适合用于高头部运动和恐惧/焦虑（如ASD）人群的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，可以通过验证近红外光谱作为测量皮层激活和FC的成像方式来解决。该建议使用近红外光谱作为fMRI的替代方案，不容易产生运动伪影，并且没有限制恐惧/焦虑的MR环境。拟议的实验将验证ASD受试者和对照组在额顶叶区域的执行负荷依赖性激活会有所不同的假设（目的1）；2)与对照组相比，ASD儿童的额-后侧FC较低（目的2）。此外，这些实验将验证ASD儿童和对照组在静息状态下的额-后侧FC存在差异的假设（目的3）。这项工作将验证的效用

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.