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.
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ABSTRACT: Compulsivity and impulsivity are cross-disorder traits observed in Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD). Aberrant fronto-striatal glutamatergic signaling is core to the understanding of compulsive and impulsive disorders. In this review, the glutamate (Glu) neurochemistry of fronto-striatal circuits in paediatric and adult ASD, ADHD and OCD, as described in 59 studies, is outlined from the perspective of proton magnetic resonance spectroscopy ((1)H MRS). Despite the methodological inconsistencies between studies, two observations stand out that form possible hypotheses for future studies. Firstly, a possible increase in Glx (combination of Glu, glutamine and GABA) in the striatum across ADHD, OCD and ASD. Secondly, an increased Glx signal in the anterior cingulate cortex in paediatric ASD and ADHD but a lower Glx signal in adult ASD and ADHD. This suggests neurodevelopmental changes in fronto-striatal glutamatergic circuits across the lifespan. Future studies should incorporate more homogeneous samples, perform MRS at field strengths of at least 3 Tesla and provide much more precise and standardized information on methods to improve our understanding of fronto-striatal glutamatergic transmission in compulsive and impulsive syndromes. Copyright © 2015. Published by Elsevier Ltd.Neuroscience & Biobehavioral Reviews 02/2015; 52. DOI:10.1016/j.neubiorev.2015.02.009 · 10.28 Impact Factor
Conference Paper: Auditory Gamma-Band Power Is Related to GABA Concentration in Autism[Show abstract] [Hide abstract]
ABSTRACT: Background: Gamma band oscillatory activity, as measured using EEG and magnetoencephalography (MEG), has been associated with intrinsic GABA in animal models and in combined MR spectroscopy and MEG studies. We have previously published data demonstrating that auditory gamma-band responses are reduced in people with autism and their first-degree relatives, suggesting the utility of some of the findings as endophenotypes. Independently, prior work has suggested elevation of reduction of GABA in persons with autism. The relationship between GABA concentration and auditory gamma-band activity has not yet been studied in autism. Objectives: To assess the relationship between auditory GABA concentration and auditory gamma-band power in individuals with autism, unaffected siblings of persons with autism, and in control subjects. Methods: We examined auditory transient and steady-state gamma-band responsesand auditory cortical GABA concentration in 3 groups of children and adolescents: a) healthy controls (N=25), b) people with autism spectrum disorders (N=24) and c) unaffected siblings (N=19) of older children with ASD. Auditory response data were acquired using a 248-channel magnetoencephalography (MEG) system, and glutamate concentrations were obtained from proton magnetic resonance spectroscopy (1H-MRS) using a MEGA-PRESS sequence on a 3T MRI system. All measures were restricted to the left hemisphere due to time constraints of the spectroscopy sequence. Results: Transient gamma-band power was significantly higher in the control group compared to individuals with autism (p < .01) and the sibling group (p < .05). Auditory steady-state gamma-band power was also higher in controls than in the autism and sibling groups. GABA concentration was significantly lower in the autism (p < .05) and sibling groups (p < .05) compared with controls. GABA concentration was correlated with transient gamma-band power in the control group (r = .45, p < .002). In the autism group, the association between GABA and gamma-band power approached significance, r = .35, p = .08. The sibling group also exhibited a significant association between GABA concentration and gamma-band power, r = .51, p = .02. No correlations with steady-state response power and GABA were observed. Conclusions: This study suggests that reduced GABA concentration might be related to reductions in stimulus related gamma-band power that have frequently been reported in autism. The fact that only the obligatory transient auditory gamma response was associated with GABA levels implicates different mechanisms of generation for the transient and steady-state responses, consistent with earlier literature suggesting that the steady-state responses reflect superimposition of mid-latency auditory evoked responses. GABA concentration and gamma-band power may both be related endophenotypes in autism that are related to an underlying change inhibitory function.2014 International Meeting for Autism Research; 05/2014
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ABSTRACT: Autism spectrum disorders (ASDs) encompass a range of syndromes that are characterised by social interaction impairments, verbal and nonverbal communication difficulties, and stereotypic or repetitive behaviours. Although there has been considerable progress in understanding the mechanisms underlying the changes in the 'social' and 'communicative' aspects of ASD, the neurofunctional architecture of repetitive and stereotypic behaviours, as well as other cognitive domains related to response and action control, remain poorly understood. Based on the findings of neurobiological and neuroanatomical alterations in ASD and the functional neuroanatomy and neurobiology of different action control functions, we emphasise that changes in action control processes, including response inhibition, conflict and response monitoring, task switching, dual-tasking, motor timing, and error monitoring, are important facets of ASD. These processes must be examined further to understand the executive control deficits in ASD that are related to stereotypic or repetitive behaviours as a major facet of ASD. The review shows that not all domains of action control are strongly affected in ASD. Several factors seem to determine the consistency with which alterations in cognitive control are reported. These factors relate to the relevance of neurobiological changes in ASD for the cognitive domains examined and in how far action control relies upon the adjustment of prior experience. Future directions and hypotheses are outlined that may guide basic and clinical research on action control in ASD.Progress in Neurobiology 11/2014; DOI:10.1016/j.pneurobio.2014.11.002 · 10.30 Impact Factor