This grant will develop high-performance naturalistic optical functional imaging instrumentation, paradigms, and computational tools for mapping typical and atypical brain development. An exemplar neurodevelopmental disorder, autism spectrum disorder (ASD), affects 1/54 children in the general population. Because early interventions in toddlers with ASD have been proven to result in improved outcomes, innovative methods for early detection of the alterations in brain function underlying ASD prior to manifestation of behavioral symptoms are necessary to advance treatment strategies and improve prognoses. Current brain mapping methods such as functional magnetic resonance imaging (fMRI) offer promising sensitivity to healthy development progression and to atypical ASD brain development, yet pose significant methodological challenges in studies of awake, interacting children due to the loud, claustrophobic environment and the requirement for children to stay still. Further, many imaging paradigms developed for adults are not naturalistic and do not translate well to children Optical neuroimaging, a promising potential surrogate to fMRI, can provide a much more naturalistic imaging experience than MRI. While traditional functional near infrared spectroscopy (fNIRS) systems had poor image quality due to sparse imaging arrays, newer high-density diffuse optical tomography (HD-DOT) systems have improved image quality. However, the large opto-electronic consoles and bulky fiber optics typically used with HD-DOT restrict head motion and require participants to remain stationary to avoid motion induced noise. This grant will develop a unique lightweight HD-DOT system the size of a bike helmet that leverages silicon photomultiplier (SiPM) detection to dramatically improve low light level performance. Naturalistic imaging paradigms aim to recapitulate real-life conditions more closely than traditional reductive protocols (e.g., flashing checkerboard patterns). Ideally, naturalistic paradigms use highly engaging multi-modal content and are particularly well suited for populations (e.g., young children) unable to make overt behavioral responses or perform a repetitive or predictable task. Naturalistic viewing paradigms employing movies or television shows enable repeatability and control over stimulus presentation while preserving greater ecological validity. While feasibility of rudimentary movie regressors have been shown with HD-DOT, the full complexity of movie viewing analyses that has been developed with fMRI has not yet been translated to HD-DOT. To complement movie viewing, we will also advance spontaneous brain activity mapping methods. Functional connectivity analysis of the brain at rest has become a dominant approach to human brain mapping. However, traditional FC analysis rests on bivariate correlation measures that are often susceptible to confounding physiological processes. In contrast, a multi-variate FC (MFC) analysis, developed in this grant for HD-DOT, has the potential to improve the spatial specificity, repeatability, and reliability of the network measures. The movie mapping will complement MFC by providing task localizers, a common feature of modern FC Studies.

Project Narrative: Innovative methods for early detection of the alterations in brain function underlying autism spectrum disorder prior to manifestation of behavioral symptoms are necessary to advance treatment strategies and improve prognoses. This grant will develop a high performance naturalistic optical neuroimaging device and complementary naturalistic functional imaging paradigms and analysis methods for mapping typical and atypical brain development.