The Impact of the Brain Overgrowth in Autism on Inter-Hemispheric Connectivity

Background: Ringo et al (1991) hypothesized that, due to the larger metabolic costs and conduction delays associated with long-distance fibers, species with larger brains would show decreased long-distance connectivity.  That hypothesis is supported by computational modeling (Ringo et al, 1991) and cross-species MRI findings (Rilling and Insel, 1999).  A negative relation between brain size and connectivity has also been shown in humans (Jancke et al, 1997, Lewis et al, 2008).  This scaling relation has been found in adults in all regions of the callosum except the isthmus, but is only present in children in the two sub-regions of the callosum which have the longest interhemispheric connections (Lewis et al, 2007; 2008).  The contrast suggests an impact of connection length on axonal remodeling (Lewis et al, 2004; 2007; 2008).  This motivates the hypothesis that the abnormal early brain overgrowth seen in autism (Courchesne et al, 2001; Hazlett et al, 2005) will lead to a lesser degree of long-distance connectivity (Lewis et al, 2005; 2008) — consistent with findings of underconnectivity in autism (Just et al, 2004; 2005; 2007).  The frontal lobes are the locus of the early brain overgrowth in autism (Carper et al, 2005), and so degree of long-distance connectivity should be most reduced in anterior regions of the callosum.

Objectives: The goal of this research was to test the prediction that individuals with autism will show a negative relation between callosal fiber length and degree of interhemispheric connectivity, as do controls, but with a lesser degree of interhemispheric connectivity between the frontal lobes.

Methods: Using diffusion tensor imaging (DTI) and tractography to detail the patterns of connectivity of the corpus callosum, and to estimate the length of interhemispheric fibers in each of five sub-regions, we investigated the relation between callosal fiber-tract length and degree of interhemispheric connectivity in 20 young adult males with autism and 22 controls.  Regression analyses were used to assess the scaling relation in each of the five sub-regions in both groups, and between group differences were assessed with analysis of variance tests.

Results: Regressions of callosal fiber-tract length on degree of interhemispheric connectivity were significant in anterior, mid, and posterior sub-regions in both individuals with autism and in controls.  Anterior regions showed a significantly reduced degree of connectivity in the autistic group.

Conclusions: The results support the hypothesis that the early brain overgrowth in autism leads to reduced connectivity.