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.
This investigation will provide new information about how functional connectivity during executive control and during a task-free state differ between children with and without ASD, using a new emerging brain imaging modality, near-infrared spectroscopy. This information will refine models of functional neuropathology of ASD, an important step towards the development of biomarkers for ASD.
