The cognitive symptoms of autism spectrum disorder (ASD) may be due to changes in neuronal microstructures in the brain, according to a review in the October 2013 issue of Frontiers in Human Neuroscience.

Kathryn McFadden, MD, assistant professor of pathology in the department of neurobiology at the University of Pittsburgh, and colleagues reviewed current functional and diffusion tensor imaging and high-definition fiber tracking studies and suggests that the culprit behind ASD symptoms is in microstructure alterations of axonal tracts connecting cortical areas. This understanding is growing in the literature.

Rather than focusing on brain dysfunction, the research shows that people with ASD have different trajectories of brain growth. As much as 70 percent of ASD babies have brains that grow at an accelerated rate in their first year. In one reported study, there was a 67 percent increase in neurons in the prefrontal cortex for seven ASD children relative to healthy controls. Areas showing the most enlargement are frontal cortical gray and white matter, and secondly are the temporal and parietal lobes, whereas occipital gray and white matter and parietal gray matter don’t seem to be altered significantly. The result seems to be normal or heightened simple information and perceptual processing but problems with complex information processing.

“Rather than implicating dysfunction in a particular brain area/structure, this cognitive profile is most consistent with altered functioning of the distributed cortical neural network, i.e., how and how well cortical functional areas, particularly association areas, communicate with each other and their subcortical targets,” wrote McFadden. “This model of aberrant connectivity in ASD is now widely accepted, although the details vary.”

Functional MRI and microscopy have provided clear visual representations of altered connectivity and lower synchronization of important cortical areas of ASD-affected brains, but genomics offers more clues for the 10-15 percent of ASD children considered to have a syndromic form. These seem to be anchored in several documented genetic mutations, namely in the mammalian target of rapamycin (mTOR) signaling pathway, including tuberous sclerosis (TSC1/2), fragile X mental retardation 1 (FMR1), neurofibromatosis type 1 (NF1), PTEN mutation syndrome and Rett’s syndrome (MECP2). Still other genetic mutations center on synaptic connections in the brain. The newest research focuses on axon targeting, guidance and outgrowth. Functional MRI as well as genetic modeling are expected to further expand knowledge of the pathogenesis of ASD.

“Current interpretations of the genetic and neuropathologic data are more a matter of emphasis than mutual exclusion, however, the concept of a significant axonal component to the pathogenesis of ASD should be considered in constructing a model that encompasses all of the clinical, structural, and functional observations,” wrote the authors.