Reduced gyral window and corpus callosum size in autism: possible macroscopic correlates of a minicolumnopathy

Abstract

Minicolumnar changes that generalize throughout a significant portion of the cortex have macroscopic structural correlates that may be visualized with modern structural neuroimaging techniques. In magnetic resonance images (MRIs) of fourteen autistic patients and 28 controls, the present study found macroscopic morphological correlates to recent neuropathological findings suggesting a minicolumnopathy in autism. Autistic patients manifested a significant reduction in the aperture for afferent/efferent cortical connections, i.e., gyral window. Furthermore, the size of the gyral window directly correlated to the size of the corpus callosum. 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 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.

Fig. 1

An MRI scan re-sliced in the sagittal plane, before (left) and after (right) noise reduction

Fig. 2

Left: Phantom cerebral hemispheres with lesser (a) and greater (b) gyrification. Contours inside the white matter indicate those points at a distance of 4, 8, or 12 arbitrary units from the exterior white matter boundary. Right: The cumulative distribution of white matter F(d) is the proportion of white matter a distance d or less from the boundary. With greater gyrification, boundary surface area increases without a concomitant increase in white matter volume. Proportionally more white matter is found nearer the boundary. This is reflected in a steeper cumulative distribution function

Fig. 3

Computation of corpus callosum displacement. Segmented corpora callosa (left) from two different individuals are shown in the same coordinate system prior to alignment (second panel). The two are registered as closely as possible using only translation, rotation, and uniform scaling (third panel). Then one is deformed to match the shape of the other precisely (right). Displacement CC is the distance by which points on one corpus callosum surface are moved toward the other surface by the deformation step

Fig. 4

Measurement of the gyrification index (GI). The outline of the cortical surface of one hemisphere is traced in a coronal section (left). The profile’s convex hull, the smallest convex set containing the outline, is computed automatically (right). Let s be the arc length of the outline, and let p be the perimeter of its convex hull; then GI = s/p. Thus, GI ≥ 1 by definition, and larger values correspond to a greater degree of nonconvexity. Repeating this process in a number of coronal sections along the rostral-caudal axis and again in the other hemisphere provides a mean GI for the brain

Fig. 5

Visualization of differences in white matter distribution. Narrower gyri (small w) in autism correspond to shallower white matter. Left: The cumulative distribution functions (CDFs) of white matter for each of the diagnostic categories show the proportional volume of white matter within a given distance of the white matter surface. These are the pointwise means of the CDFs for all brains within each category. Right: Density functions, computed from the CDFs by numerical approximation of their derivatives, provide another view of the same

Fig. 6

With increased gyrification (constriction of the gyral window) there is a correlated diminution in the number of long corticocortical connections, reflected in the shape of the corpus callosum

Fig. 7

Correcting GI for age. Using the model of Armstrong et al. (1995), GI measurements (open points) were adjusted downward to their expected value in adulthood (filled points) prior to statistical analysis. Following this correction, no systematic variation of GI with age is evident