Atypical Functional Connectivity of Amygdala Related to Reduced Symptom Severity in Children With Autism

Abstract

Converging evidence indicates that brain abnormalities in autism spectrum disorders (ASDs) involve atypical network connectivity. Given the central role of social deficits in the ASD phenotype, this investigation examined functional connectivity of the amygdala-a brain structure critically involved in processing of social information-in children and adolescents with ASDs, as well as age-dependent changes and links with clinical symptoms. Resting-state functional magnetic resonance imaging (rs-fMRI) data from 55 participants with ASDs and 50 typically developing (TD) controls, aged 7 to 17 years, were included. Groups were matched for age, gender, IQ, and head motion. Functional connectivity MRI (fcMRI) analysis was applied to examine intrinsic functional connectivity (iFC) of the amygdala, including cross-sectional tests of age-related changes. Direct between-group comparisons revealed reduced functional connectivity between bilateral amygdalae and left inferior occipital cortex, accompanied by greater connectivity between right amygdala and right sensorimotor cortex in the ASD group. This atypical pattern of amygdala connectivity was associated with decreased symptom severity and better overall functioning, as specifically seen in an ASD subgroup with the most atypical amygdala iFC but the least impaired social functioning. Age-related strengthening of amygdala-prefrontal connectivity, as observed in the TD group, was not detected in children with ASDs. Findings support aberrant network sculpting in ASDs, specifically atypical integration between amygdala and primary sensorimotor circuits. Paradoxical links between atypical iFC and behavioral measures suggest that abnormal amygdala functional connections may be compensatory in some individuals with ASDs.