Imaging Evidence for Pathological Brain Development in Autism Spectrum Disorders

Abstract

Though much has been learned about autism spectrum disorders (ASD) during the past decade, the mechanisms underlying ASD remain an enigma. One of the more consistent brain anatomical findings associated with ASD has been larger brains, on average 10–15% enlargement by magnetic resonance imaging (MRI), in preschool-aged children evaluated soon after clinical diagnosis. It is the premise of this chapter that research investigating cellular composition in ASD in vivo can elucidate aspects of the underlying pathophysiology, such as the phenomenon of early brain enlargement in ASD, and help guide ongoing theoretical model development. This chapter will review applications of magnetic resonance spectroscopy (MRS) and magnetic resonance transverse relaxation techniques (T2r) used in an attempt to elucidate developmental mechanisms underlying brain structural alterations in ASD. For example, one hypothesis put forth to explain findings of brain enlargement in ASD has implicated alterations in the complicated biochemistry governing apoptosis and/ or synaptic pruning, with resultant neuronal ‘‘overgrowth.’’ However, studies from our laboratory of brain chemical alterations in preschool-aged ASD children instead have found evidence for decreased neuronal compactness or density, contradictory to such theories. Another theory to explain observations of early but not later brain enlargement in ASD suggests accelerated ‘‘normal’’ brain growth, which then decelerates or plateaus before the time course of brain growth for typically developing children. Contrary to this theory, our recent quantitative T2r study, designed to characterize the temporal progression of brain maturation, implicates mechanism(s) other thanmore rapid growth to account for larger brains in ASD. Although these research findings cannot be considered diagnostic, they do provide new insights for pursuing mechanisms underlying ASD.