Hypofunctional Connectivity Between the Posterior Cingulate Cortex and Ventromedial Prefrontal Cortex in Autism: Evidence from Coordinate-based Imaging Meta-analysis

Background: Underconnectivity in the posterior cingulate cortex (PCC) may be associated with a weakened ability to interpret social signals in autism spectrum disorder (ASD) and result in cognitive inflexibility - a hallmark feature of ASD. However, previous neuroimaging studies using resting-state functional magnetic resonance imaging in ASD reported inconsistent findings on functional connectivity of the PCC. This study investigated the aberrant resting-state functional connectivity of the PCC in ASD using multilevel kernel density analysis.

Methods: Online databases (MEDLINE/PubMed) were searched for PCC-based functional connectivity in ASD. Ten studies (501 subjects; 161 reported foci) met the inclusion criteria of this meta-analysis.

Results: We found one consistent and strong abnormal functional connectivity of ASD during the resting state, which was the hypoconnectivity between the PCC and ventromedial prefrontal cortex (VMPFC). Importantly, the Jackknife sensitivity analysis revealed that the VMPFC cluster was stably hypoconnected with the PCC in ASD (maximum spatial overlap rate: 100%).

Conclusions: The reduced PCC-VMPFC functional coupling may provide an early insight into the effects of ASD on multiple dimensions of functioning, including higher-order cognitive and complex social functions.