Functional Connectivity of the Ventromedial Prefrontal Cortex In Children with Autism Spectrum Disorders

Background:  Several lines of research have implicated abnormal neural connectivity as a possible etiological mechanism in Autism Spectrum Disorders (ASD).  Prior studies have found various alterations in functional connectivity, as assessed by resting-state fMRI, in individuals with ASDs.  For instance, several studies have noted abnormalities in functional connectivity of the default mode network, potentially involved self-referential cognition and theory of mind.  However, few studies have investigated functional connectivity in children with autism, to begin to address the developmental relevance of these alterations.

Objectives:  To assess large-scale cortical functional connectivity in children with and without autism, using resting-state fMRI.

Methods:  Resting-state fMRI data was collected in 25 typically developing (TD) children (age 8-17), 25 children with ASDs, and 50 typical adults.  Maps of functional connectivity were computed in each group, using a range of seeds defined functionally using a portion of the adult dataset.  Seeds included regions of the default mode, fronto-parietal attention, cingulo-insular control, and other networks.  These maps were compared between TD and ASD groups.

Results:  Overal, long-range cortical functional connections were largely similar in the TD and ASD groups, with few differences found.  However, we do find a striking difference in the functional connectivity of the ventromedial prefrontal cortex (vmPFC), particularly with other regions of the ventral default mode network subnetwork, such as parahippocampal and retrosplenial cortices.

Conclusions: In contrast with prior reports of global underconnectivity in individuals with ASD, cortical functional connectivity appears to be largely intact in children with ASD.  However, there is a marked reduction of connectivity of vmPFC, particularly with regions of the default mode network.  This may relate to prior findings of vmPFC-lesion-like behavioral abnormalities in ASD, and fMRI results indicating altered response properties of vmPFC.