Basal forebrain involvement in low-functioning autistic children: a voxel-based morphometry study

Abstract

Background and purpose: Imaging studies have revealed brain abnormalities in the regions involved in functions impaired in ASD (social relations, verbal and nonverbal communication, and adaptive behavior). We performed a VBM whole-brain analysis to assess the areas involved in autistic children with DD.

Materials and methods: Twenty-one developmentally delayed children with ASD (aged 3-10 years) were compared with 21 controls matched for age, sex, and sociocultural background. All ASD cases had been diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, with the Autism Diagnostic Observation Schedule-Generic, and the Autism Diagnostic Interview-Revised. The VBM data, covaried with intelligence quotient, age, and brain volume, were analyzed.

Results: ASD patients showed a pattern of regional GM reduction symmetrically affecting the basal forebrain, accumbens nucleus, cerebellar hemispheres, and perisylvian regions, including insula and putamen. Asymmetric involvement of GM was observed in other brain regions functionally connected to the basal forebrain, ie, an area located close to the medial and ventral surface of the frontal lobe. No regional WM differences were observed between the 2 groups. No significant differences between patients and controls were found regarding total brain volume, GM, and WM.

Conclusions: In children with ASD and DD, the novel finding of our VBM study was the demonstration of reduced GM volume in the basal forebrain and the areas connected with it. This system is involved in social behavior, communication, and cognitive skills. Whether the involvement of the basal forebrain is characteristic of ASD or is related to the DD present in our patients needs further investigation.

Fig 1.

Basal forebrain and accumbens nucleus volume differences between groups. GM volume differences between groups, overlaid on T1 images (consecutive coronal sections, rostral to caudal) showing the involvement of accumbens nucleus and basal forebrain. The relative decrease in GM attenuation observed in autistic subjects compared with controls is represented in a red-orange color scale. The statistical threshold is P < .05 (FDR corrected). L = left; R = right.

Fig 2.

GM volume differences between groups. GM volume differences between groups, overlaid on T1 images. The relative decrease in GM attenuation observed in autistic subjects compared with controls is represented in a red-orange color scale. The statistical threshold is P < .05 (FDR corrected).