Neurochemical Concentration, White Matter Integrity, and Brain Functioning in Autism Spectrum Disorder

Background:  Widespread functional and anatomical alterations have been the main features of the brain in autism spectrum disorders (ASD). Despite previous findings of abnormalities in the brain in ASD, results have been fairly inconsistent and the affected brain areas and connections varied. Therefore, a firm neurobiological etiology of ASD has been rather elusive, and the need to find reliable neural signatures for the disorder has been paramount. Multimodal neuroimaging approach may provide a novel and valuable window of opportunity in this regard as such investigations may provide a global characterization of the brain in ASD. The current study utilizes proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), and functional MRI (fMRI) to examine the brain in high-functioning adults with ASD.

Objectives:  To determine brain metabolite levels and white matter integrity, and their relationship to brain functioning in high-functioning adults with ASD.

Methods:  Eighteen high-functioning adults with ASD and 18 typically developing (TD) control participants took part in this study.1H-MRS, DTI, and fMRI data were acquired using a 3T Siemens Allegra scanner. Spectra for N-acetylaspartate (NAA), choline (Ch), glutamate/glutamine (Glx) and creatine (Cr) were acquired from two regions of interest, the dorsal anterior cingulate cortex (dACC) and the posterior cingulate cortex/precuneus (PCC). DTI data were collected using a single shot, spin echo sequence in 46 orthogonal directions. fMRI data were acquired during a task that assess the processing of emotional body language.

Results:  The main results are as follows: (1) Significantly reduced NAA/Cr in ASD participants compared to TD peers in the dACC [t(34)=3.09, p=0.004]. A marginally significant lower level of Glx/Cr in ASD relative to TD participants in the dACC [t(34)=1.91, p=0.06]. There were no significant differences in any of the neurochemicals for the PCC voxel; (2) A significant positive relationship was found between NAA/Cr level in dACC and brain activity in dACC during emotional body language processing, with greater metabolite concentration predicting greater activation in that region; and (3) The DTI data showed significantly lower fractional anisotropy (FA) in right cingulum bundle, especially along several anterior nodes, in ASD adults compared to TD peers. Other tracts that showed reduced FA in ASD include the bilateral inferior frontal occipital fasciculus, left superior longitudinal fasciculus, right inferior longitudinal fasciculus, and right uncinate fasciculus. 

Conclusions:  Differences in NAA/Cr level in the dACC are in line with the findings of a recent study (Fujii et al., 2010), and indicative of possible alterations in neuronal and axonal health in this region in ASD adults. The correlation between 1H-MRS findings and fMRI based brain activity during a social cognition task suggest and the importance of neuronal health in brain functioning. Affected white matter tracts in ASD adults point to potential problems of brain connectivity and myelination in ASD. Converging findings from this multimodal neuroimaging study provide evidence for the pathobiology of ASD brain at multiple (neurochemical, functional, and structural) levels.