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

Abstract

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 language function is minimal. Yet insights from functional MRI are absent. Here we report results from a first study of intrinsic connectivity in nine non- or minimally verbal children with autism spectrum disorder scanned under sedation with propofol, along with eight typically developing children (scanned awake), using resting-state functional MRI. We targeted both functional connectivity and anatomically constrained, generative effective connectivity in speech and language regions, the insula and associated networks and the hippocampus. Identical analyses were applied to an independent resting-state MRI dataset of healthy adults scanned both under propofol and while awake, to evaluate sedation confounds. Non- or minimally verbal children with autism spectrum disorder, compared to their neurotypical peers, showed a widespread pattern of hypoconnectivity in auditory speech perception, fronto-temporal and semantic processing regions, which extended further to the insula and the hippocampus. Effective connectivity results selectively replicated these patterns, which correlated with Autism Diagnostic Observation Schedule behavioural scores within the group of non- or minimally verbal children with autism spectrum disorder. This hypoconnectivity pattern extended neither to the adults scanned under propofol, nor to the visual cortex used as a control region in non- or minimally verbal children with autism spectrum disorder, supporting that this pattern of results is not 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.