Reduced Gyral Window and Corpus Callosum Size in Autism: Possible Macroscopic Correlates of a Minicolumnopathy

Background: Minicolumnar changes that generalize throughout a significant portion of the cortex have macroscopic structural correlates that may be visualized with modern structural neuroimaging techniques. Minicolumns in the brains of autistic patients were narrower and more numerous per linear length of tissue section examined as compared to controls. Since the minicolumn re-iterates itself millions of times throughout the brain, variations in the total number and width of minicolumns can result in macroscopic changes of the brain’s surface area and/or gyrification. Furthermore, proper integration of supernumerary minicolumns, both into corresponding segregates and their lateralized hemispheric homologues, requires their interconnectivity via association and commissural fibers.

Objectives: In this study, a series of autistic patients were studied for gross morphometric parameters related to minicolumnar pathology: cortical thickness (t), gray/white matter ratio (G:W), corpus callosum shape (CC) and cross-section (CCx), cortical folding, adjusted for age (GI_adj), and median white matter depth (w), as a proxy measurement for gyral window.

Methods: Fourteen male subjects between 8 and 38 years of age were recruited from across the. DSM-III-R and the Autism Diagnostic Interview (ADI) criteria were used to define autism, autistic disorders, and pervasive developmental delay. Twenty eight male, non-autistic individuals, matched 2:1 with patients for age and handedness, were recruited for comparison. Subjects were scanned on a 1.5 T GE MRI using IR and FLASH volume sequences. Images were preprocessed to reduce scanner noise. A deformable model was fit to the white matter surface of each brain, and morphometric parameters were computed from this model (w, CC) or directly from the MRI slices (GI_adj, t, CCx, G:W).

Results: There was a significant difference between the gyral window of autistic and normal control subjects. The cumulative distribution functions (CDF) of individual patients cluster tightly around the average CDF for their respective diagnostic categories. The gyral window w averaged 2.4 mm in autism and 5.8 mm in controls, and w was highly correlated with CC within diagnostic categories (R² = 0.9966). CCx was reduced in patients with autism (5.3 cm²) relative to controls (6.6 cm²). There was no significant diagnosis dependence in t or GI_adj, and the latter did not correlate significantly with w.

Conclusions: A reduced gyral window constrains the possible size of projection fibers and biases connectivity towards shorter corticocortical fibers at the expense of longer association/commisural fibers. The normal maturation processes of enlarging cell somata, myelination, synaptogenesis, and increased dendritic branching manifest themselves as exuberant brain growth early in life only to be followed by the loss of those less efficient connections (long association fibers) that are constrained by the reduced aperture of the gyral window. These retractive events fall within a spectrum spanning normal individuals and autistic patients. The findings may help explain abnormalities in motor skill development, differences in postnatal brain growth, and the regression of acquired functions observed in some autistic patients.