ABSTRACTAutism Spectrum Disorder (ASD) is associated with multiple complex abnormalities in functional brain connectivity measured with functional magnetic resonance imaging (fMRI). Despite much research in this area, to date, neuroimaging-based models are not able to characterize individuals with ASD with sufficient sensitivity and specificity; this is likely due to the heterogeneity and complexity of this disorder. Here we apply a data-driven subject-level approach, connectome-based predictive modeling, to resting-state fMRI data from a set of individuals from the Autism Brain Imaging Data Exchange. Using leave-one-subject-out and split-half analyses, we define two functional connectivity networks that predict continuous scores on the Social Responsiveness Scale (SRS) and Autism Diagnostic Observation Schedule (ADOS) and confirm that these networks generalize to novel subjects. Notably, these networks were found to share minimal anatomical overlap. Further, our results generalize to individuals for whom SRS/ADOS scores are unavailable, predicting worse scores for ASD than typically developing individuals. In addition, predicted SRS scores for individuals with attention-deficit/hyperactivity disorder (ADHD) from the ADHD-200 Consortium are linked to ADHD symptoms, supporting the hypothesis that the functional brain organization changes relevant to ASD severity share a component associated with attention. Finally, we explore the membership of predictive connections within conventional (atlas-based) functional networks. In summary, our results suggest that an individual’s functional connectivity profile contains information that supports dimensional, non-binary classification in ASD, aligning with the goals of precision medicine and individual-level diagnosis.
Mapping functional brain organization: Rethinking lesion symptom mapping and advanced neuroimaging methods in the understanding of human cognition