Neurochemical Imaging and Mapping of Excitatory and Inhibitory Neurometabolites in Adults with Autism Spectrum Disorder

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In recent years there has been a dramatic increase in the awareness of autism spectrum disorders (ASD) in adults. New evidence shows that the prevalence may be higher than 2%, with 0.75% in low functioning subjects attending special educational schools and ~1.89% of high functioning subjects receiving regular schooling. According to ICD-10, ASD is classified as a neurodevelopmental disorder. The precise etiology and pathogenesis of ASD is not clear. Important pathogenetic concepts focus on the role of a relation between excitatory and inhibitory neurotransmitters like glutamate and GABA, and are based on post-mortem, animal and genetic studies. Magnet resonance spectroscopy is a unique tool to non-invasively assess these metabolites in vivo in the human brain. So far, very few spectroscopic studies were performed in ASD, especially in adults with high functioning ASD, and no studies report simultaneous detection of excitatory glutamate and inhibitory GABA signals. The overall aim of our project is twofold. In a first subproject we want to investigate GABA-ergic and glutamatergic neurotransmission in adult high functioning ASD employing the newly established and validated method of GABA-determination with single voxel magnetic resonance spectroscopy (MRS) in dorsal ACC, DLPFC and parietal cortex. In the second subproject we want to further improve the MRS acquisition and post-processing algorithms to proceed from single voxel MRS imaging to spectroscopic imaging of the GABA signal. Consequently, we want to develop a clinically feasible method to map excitatory and inhibitory transmitter signals in larger brain areas of ASD patients, to establish the significance of these findings for ASD, and determine the feasibility as a biomarker for diagnostic purpose, severity assessment or treatment response in this disorder.