Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children

•The DMN is a potential endophenotype for social deficits in ASD.•This study used resting state functional MRI to probe the default mode network.•MPFC–PCC connection was reduced in strength in ASD and correlated with ASD severity.•Graph theory analysis showed that DMN had greater cross-network connectivity in ASD.•Findings support DMN as an ASD endophenotype and align with a GABA theory of ASD.

Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8–13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core—medial prefrontal cortex–posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD.