Brain function in language and associated networks in non- or minimally verbal children

Language is universal in humans, develops robustly in infancy, and is rarely absent entirely in aphasia following strokes. Non- or minimally verbal children, in whom language has not developed by school-age in either production or comprehension, thus provide an unparalleled window into the human brain when it is deprived of language function. Yet insights from functional MRI are absent. Here we report results from a first study of intrinsic connectivity in 9 non- or minimally verbal children with autism spectrum disorder (nvASD) scanned under sedation with propofol along with 8 typically developing children (scanned awake), using resting-state (rs) fMRI. We targeted both functional (FC) and anatomically constrained, generative effective connectivity (GEC) in the speech and language networks, the insula and associated networks, and the hippocampus. Identical analyses were applied to an independent rsMRI dataset of healthy adults scanned both under propofol and while awake, to evaluate sedation confounds. NvASDs compared to their neurotypical peers showed a widespread pattern of hypoconnectivity in auditory speech perception, frontotemporal, and semantic processing regions, which extended further to the insula, and the hippocampus. GEC results selectively replicated these patterns, which correlated with autism diagnostic observation schedule (ADOS) behavioral scores within the nvASD group. This hypoconnectivity pattern extended neither to the adults scanned under propofol, nor to the visual cortex used as control region in nvASD, suggesting that this pattern of results could not be explained by sedation. Together, this first evidence from intrinsic connectivity reveals a broad pattern of underconnectivity across key cognitive networks, which provides a neural correlate for the significant breakdown of language-related cognitive functions in this population.