Auditory Gamma-Band Power Is Related to GABA Concentration in Autism

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.