Abnormal Frontoparietal Network Connectivity Is Correlated with Motor Skill Ability in Children with Autism

Background: Children with autism spectrum disorder (ASD) frequently show abnormal motor signs early in development, and strong correspondence with social and communicative features of ASD render it a critical focus of study. Converging evidence has shown that children with ASD have marked impairment in the production of motor skills, termed dyspraxia. Neurobiological evidence of motor skill (praxis), taken from both healthy and impaired states, is by in large supported with the functional involvement of a dorsal frontoparietal (dFPN) cortical network. Although the dFPN abnormalities have been identified in ASD, there is little understanding of how dFPN connectivity affects praxis performance in children with ASD.

Objectives: Our aim was to test if dFPN connectivity is abnormal in children with ASD, and if dFPN connectivity is related to dyspraxia in children with ASD.

Methods: We acquired resting state functional magnetic resonance imaging (rsfMRI) scans from 162 children (81 ASD, 81 typically developing, TD) aged 8-12 years. Groups were balanced for age, socioeconomic status, handedness, and general ability index (GAI). Independent component analysis (ICA) was used to estimate functional connectivity. The dFPN was localized using spatial matching, with left-lateralized sources localized to premotor and parietal regions. Local maxima in the dFPN map were converted to ROIs, and implemented in a seed-based functional connectivity analysis with correction for sources of extraneous noise. We tested for brain-behavior relationships by including measures of gesture and imitation ability (Florida Apraxia Battery modified for children), motor coordination (movement assessment battery for children, MABC-2), social skills (social responsiveness scale, SRS), and ADOS as covariates of interest in the regression model (SPM12).

Results: ASD children were less accurate on gesture imitation than TD children (p < 0.0001). We observed a consistent increase in connectivity between right and left inferior parietal lobule (IPL) dFPN seeds and the default mode network (DMN) (p < 0.05, FWE). In ASD children, increased connectivity between left IPL and left somatosensory cortex and right precentral gyrus was correlated with gesture accuracy. Connectivity between left IPL and left dorsal premotor, somatosensory cortex, and right cerebellum was correlated with measures of gesture and manual dexterity performance (MABC-2). Further, connectivity between left IPL and premotor, parietal, insula, and cerebellum correlated with gesture and ADOS, while overlapping right prefrontal and premotor, and medial premotor regions correlated with SRS scores and gesture.

Conclusions: These results suggest that praxis deficit in ASD arises from reduced connectivity between the IPL and other within- and between-network regions. Reduction of left IPL connectivity may hinder imitation through reduced ability to carry out dexterous movement. The reduced asynchrony with DMN suggests that abnormal between-network connectivity may contribute to dyspraxia in children with ASD. Our findings further demonstrate the striking correspondence between brain connectivity related to motor skill, and overlapping connectivity related to ASD severity and social skills. These findings represent a step towards understanding the involvement of the dFPN in skilled behavior in ASD, with extension to abnormalities in core social and communicative behaviors.