Evidence for Cortical Dysfunction in Autism: A Proton Magnetic Resonance Spectroscopic Imaging Study

Abstract

Although brain imaging studies have reported neurobiological abnormalities in autism, the nature and distribution of the underlying neurochemical irregularities are unknown. The purpose of this study was to examine cerebral gray and white matter cellular neurochemistry in autism with proton magnetic resonance spectroscopic imaging (MRSI). Proton MRSI examinations were conducted in 26 males with autism (age 9.8 +/- 3.2 years) and 29 male comparison subjects (age 11.1 +/- 2.4 years). Estimates of cerebral gray and white matter concentrations of N-acetylaspartate (NAA), creatine + phosphocreatine, choline-containing compounds, myo-inositol, and glutamate + glutamine (Glx) were made by linear regression analysis of multi-slice MRSI data and compared between groups. Regional estimates of metabolite concentration were also made with multivariate linear regression, allowing for comparisons of frontal, temporal, and occipital gray matter, cerebral white matter, and the cerebellum. Patients with autism exhibited significantly lower levels of gray matter NAA and Glx than control subjects. Deficits were widespread, affecting most cerebral lobes and the cerebellum. No significant differences were detected in cerebral white matter or cerebellar metabolite levels. These results suggest widespread reductions in gray matter neuronal integrity and dysfunction of cortical and cerebellar glutamatergic neurons in patients with autism.