title: N-acetyl aspartate in autism spectrum disorders: regional effects and relationship to fMRI activation.
abstract: Rapid progress in our understanding of macrostructural abnormalities in autism spectrum disorders (ASD) has occurred in recent years. However, the relationship between the integrity of neural tissue and neural function has not been previously investigated. Single-voxel proton magnetic resonance spectroscopy and functional magnetic resonance imaging of an executive functioning task was obtained in 13 high functioning adolescents and adults with ASD and 13 age-matched controls. The ASD group showed significant reductions in N-acetyl aspartate (NAA) in all brain regions combined and a specific reduction in left frontal cortex compared to controls. Regression analyses revealed a significant group interaction effect between frontal and cerebellar NAA. In addition, a significant positive semi-partial correlation between left frontal lobe NAA and frontal lobe functional activation was found in the ASD group. These findings suggest that widespread neuronal dysfunction is present in high functioning individuals with ASD. Hypothesized developmental links between frontal and cerebellar vermis neural abnormalities were supported, in that impaired neuronal functioning in the vermis was associated with impaired neuronal functioning in the frontal lobes in the ASD group. Furthermore, this study provided the first direct evidence of the relationship between abnormal functional activation in prefrontal cortex and neuronal dysfunction in ASD.
authors.affiliation: Department of Radiology, University of Washington, Box 357115, Seattle, WA 98195, USA. nkleinha@u.washington.edu
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Kleinhans
authors.forename: Brian C
authors.initials: BC
authors.lastname: Schweinsburg
authors.forename: David N
authors.initials: DN
authors.lastname: Cohen
authors.forename: Ralph-Axel
authors.initials: RA
authors.lastname: Müller
authors.forename: Eric
authors.initials: E
authors.lastname: Courchesne
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001321:Autistic Disorder / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D001931:Brain Mapping; D016022:Case-Control Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D010100:Oxygen