Reduced integration and differentiation of the imitation network in autism: A combined functional connectivity magnetic resonance imaging and diffusion-weighted imaging study

• Published in: Annals of neurology Vol. 78; no. 6; pp. 958 - 969
• Main Authors: Fishman, Inna, Datko, Michael, Cabrera, Yuliana, Carper, Ruth A., Müller, Ralph-Axel
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.12.2015; Wiley Subscription Services, Inc
• Subjects: Adolescent; Autism; Autism Spectrum Disorder - pathology; Autism Spectrum Disorder - physiopathology; Cerebral Cortex - pathology; Cerebral Cortex - physiopathology; Child; Connectome; Diffusion; Diffusion Magnetic Resonance Imaging - methods; Female; Humans; Imitative Behavior - physiology; Magnetic Resonance Imaging - methods; Male; Nerve Net - pathology; Nerve Net - physiopathology; NMR; Nuclear magnetic resonance
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.24533

Objective Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but few studies have integrated functional with structural connectivity measures. This multimodal investigation examined functional and structural connectivity of the imitation network in children and adolescents with ASD, and its links with clinical symptoms. Methods Resting state functional magnetic resonance imaging and diffusion‐weighted imaging were performed in 35 participants with ASD and 35 typically developing controls, aged 8 to 17 years, matched for age, gender, intelligence quotient, and head motion. Results Within‐network analyses revealed overall reduced functional connectivity (FC) between distributed imitation regions in the ASD group. Whole brain analyses showed that underconnectivity in ASD occurred exclusively in regions belonging to the imitation network, whereas overconnectivity was observed between imitation nodes and extraneous regions. Structurally, reduced fractional anisotropy and increased mean diffusivity were found in white matter tracts directly connecting key imitation regions with atypical FC in ASD. These differences in microstructural organization of white matter correlated with weaker FC and greater ASD symptomatology. Interpretation Findings demonstrate atypical connectivity of the brain network supporting imitation in ASD, characterized by a highly specific pattern. This pattern of underconnectivity within, but overconnectivity outside the functional network is in contrast with typical development and suggests reduced network integration and differentiation in ASD. Our findings also indicate that atypical connectivity of the imitation network may contribute to ASD clinical symptoms, highlighting the role of this fundamental social cognition ability in the pathophysiology of ASD. Ann Neurol 2015;78:958–969