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

使用 NIRS 研究 ASD 儿童工作记忆和抑制控制的神经基础

• 批准号: 8936908
• 负责人: Frank Anthony Fishburn
• 金额: $ 3.09万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8936908
• 关键词: Achievement; Address; Adolescent; Adult; Age; Anxiety; Area; Back; Behavior; Biological Markers; Brain; Brain Diseases; Brain imaging; Brain region; Child; Childhood; Cognitive; Communication; Data; Development; Diffuse; Disease; Elements; Environment; Executive Dysfunction; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Head; Infant; Intervention; Investigation; Language; Left; Letters; Measurement; Measures; Methods; Modality; Modeling; Morphologic artifacts; Motion; Near-Infrared Spectroscopy; Outcome; Parietal; Parietal Lobe; Phenotype; Population; Population Study; Prefrontal Cortex; Process; Research; Rest; School-Age Population; Schools; Short-Term Memory; Signal Transduction; Socialization; Standardization; Testing; Work; autism spectrum disorder; awake; base; biomarker development; developmental disease; executive function; imaging modality; innovation; neuropathology; public health relevance; relating to nervous system; research study; response; social cognition; theories; tool

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.

描述（由申请人提供）：本研究旨在验证近红外光谱（NIRS）作为一种替代成像方式，用于检查9-12岁ASD（自闭症谱系障碍）儿童的激活和功能连接（FC）。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，并影响社会化，学习成绩和日常功能。执行功能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）.对于EF重要的脑区域，即前额叶和顶叶皮质，在ASD神经病理学的当前主导理论中处于中心位置-ASD中的额-后沟通减少。目前ASD中用于测量这种通信的选择方式是功能性磁共振成像（fMRI）。它对运动伪影高度敏感，不能用于对受限MR环境感到恐惧/焦虑的患者。此外，较高的头部运动使FC测量偏向连接不足，使得fMRI不适合用于具有高头部运动和恐惧/焦虑（如ASD）的人群的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NIRS作为测量皮质激活和FC的成像方式来解决。该提案使用NIRS作为fMRI的替代方案，不太容易产生运动伪影，并且没有限制恐惧/焦虑的MR环境。 所提出的实验将检验以下假设：1）额顶叶区域中的执行负荷依赖性激活将在ASD受试者和对照者之间不同（目标1）; 2）额后部FC将在ASD儿童中相对于对照者较低（目标2）。此外，这些实验将检验以下假设：静息状态期间额后部FC将在ASD儿童和对照者之间不同（目标3）。这项工作将验证的效用， 近红外光谱，一个有前途的新的成像模式，用于表征ASD的功能连接性。这项研究将进一步加深我们对ASD神经基础的理解，并有助于未来生物标志物的开发。 这项研究是可行的，因为所有的预测都涉及皮层区域服从近红外光谱和强大的功能磁共振成像的特点。近红外光谱也已成功地用于检查皮质激活的ASD儿童的年龄相同的建议。申办者具有互补的专业知识，ASD，执行功能，静息状态（Vaidya博士-申办者）和NIRS信号和分析（Medvedev博士-共同申办者）。 这项工作的新元素是使用NIRS来检查ASD中1）负荷相关的激活变化; 2）任务诱发的FC; 3）静息状态FC; 4）从静息状态到任务状态的FC变化。这项工作促进了FC分析工具的开发（将通过NITRC免费传播），有助于新兴成像模式方法的标准化。