Self Representation and Frontal Brain Structure in Children with ASD

Background: Children with Autism Spectrum Disorder (ASD) have delayed development of self-representation. While typically developing children achieve self representation by age 2, children with ASD achieve self representation at later ages.  The development of self representation is associated with structural changes in white matter in frontal brain regions. Children with ASD have increased frontal white matter relative to typically developing children.  The deficits in self representation in ASD may be associated with alterations in frontal white matter volumes.

Objectives: We tested the hypothesis that increased white matter in frontal brain regions would be associated with deficits in self representation in children with ASD.

Methods: High resolution T1 images were obtained on 10 children with ASD (mean age 4.5 years) using a 1.5 T GE Signa System. Voxel-based morphometry (VBM) was performed using statistical parametric mapping software (SPM8). Preprocessing of images included spatial normalization, segmentation of white matter (WM) and gray matter (GM), modulation to adjust for volume changes during normalization, and smoothing.  Region of interest (ROI) analyses were performed by applying brain masks (Wake Forrest University Atlas) to the whole frontal lobe, as well as to regions defined by Brodmann Areas (BA).  Ratios of partial frontal volumes to the whole frontal lobe volume were obtained.  Within two weeks of the MRI scanning, self representation was assessed by obtaining scaled scores for the behaviors of mirror recognition, use of personal pronouns, and pretend play involving another person.  These three behaviors were combined into a scaled self representation score (SRS).  Severity of the signs of ASD were obtained by the Autism Diagnostic Observation Schedule (ADOS-G).

Results: The associations between self representation and brain volume were assessed by R² (Pearson correlation squared).  Strong associations were found between SRS and WM volume in both left and right whole brain (R² > .4) in that greater volumes were associated with lower self representation scores.  ROI analyses showed that the associations were located in left BA 10 and 11 (R² > .5), as well as both left and right BA 4 and 6 (R² > .4).  Strong associations between ADOS-G total score and WM volume were found in left and right whole brain (R² > .4), with regional associations in BA 8 and 9 (R²_left> .6, R²_right > .4), and in BA 4 and 6 (R²_left > .6, R²_right > .35).  Strong associations were found between ADOS-G and GM volume in left and right whole frontal lobe (R² > .45), with regional associations in BA 10 and 11 (R²_left > .5, R²_right > .6), as well as left and right BA 8 and 9 (R² > .6).  In both GM and WM analyses, greater volumes were associated with higher ADOS-G scores.

Conclusions: Regional increases in white matter in frontal brain area are associated with deficits in self representation in children with ASD as well as with increased behavioral signs of ASD.  The delays in self representation are implicated in the delays in social development.