Quantification of γ-aminobutyric acid (GABA) in 1 H MRS volumes composed heterogeneously of grey and white matter.

The quantification of γ-aminobutyric acid (GABA) concentration using localised MRS suffers from partial volume effects related to differences in the intrinsic concentration of GABA in grey (GM) and white (WM) matter. These differences can be represented as a ratio between intrinsic GABA in GM and WM: rM . Individual differences in GM tissue volume can therefore potentially drive apparent concentration differences. Here, a quantification method that corrects for these effects is formulated and empirically validated. Quantification using tissue water as an internal concentration reference has been described previously. Partial volume effects attributed to rM can be accounted for by incorporating into this established method an additional multiplicative correction factor based on measured or literature values of rM weighted by the proportion of GM and WM within tissue-segmented MRS volumes. Simulations were performed to test the sensitivity of this correction using different assumptions of rM taken from previous studies. The tissue correction method was then validated by applying it to an independent dataset of in vivo GABA measurements using an empirically measured value of rM . It was shown that incorrect assumptions of rM can lead to overcorrection and inflation of GABA concentration measurements quantified in volumes composed predominantly of WM. For the independent dataset, GABA concentration was linearly related to GM tissue volume when only the water signal was corrected for partial volume effects. Performing a full correction that additionally accounts for partial volume effects ascribed to rM successfully removed this dependence. With an appropriate assumption of the ratio of intrinsic GABA concentration in GM and WM, GABA measurements can be corrected for partial volume effects, potentially leading to a reduction in between-participant variance, increased power in statistical tests and better discriminability of true effects.

Structural and neurochemical correlates of individual differences in gamma frequency oscillations in human visual cortex.

Neuronal oscillations in the gamma frequency range play an important role in stimulus processing in the brain. The frequency of these oscillations can vary widely between participants and is strongly genetically determined, but the cause of this variability is not understood. Previous studies have reported correlations between individual differences in gamma frequency and the concentration of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), as well as with age and primary visual cortex (V1) area and thickness. This study assessed the relationships between all of these variables in the same group of participants. There were no significant correlations between gamma frequency and GABA+ concentration, V1 area or V1 thickness, although the relationship with GABA+/Cr approached significance. Considering age as a covariate further reduced the strength of all correlations and, in an additional dataset with a larger age range, gamma frequency was strongly inversely correlated with age but not V1 thickness or area, suggesting that age modulates gamma frequency via an additional, as yet unknown, mechanism. Consistent with other recent studies, these findings do not demonstrate a clear relationship between gamma frequency and GABA+ concentration. Further investigation of additional variables and the interactions between them will be necessary in order to more accurately determine predictors of the frequency of gamma oscillations.

Marked reductions in visual evoked responses but not γ-aminobutyric acid concentrations or γ-band measures in remitted depression.

BACKGROUND: Magnetic resonance spectroscopy (MRS) studies have consistently demonstrated reduced cortical γ-aminobutyric acid (GABA) concentrations in individuals with major depression. However, evidence for a persistent deficit during remission, which would suggest that GABA dysfunction is a possible trait marker of depression, is equivocal. Although MRS measures total concentration of GABA, magneto-encephalography provides direct measures of neural activity, with cortical γ oscillations shaped by the activity of GABAergic inhibitory interneurons. In this study we investigated whether γ oscillations and GABA concentrations would differ in individuals with remitted depression (RD) compared with never depressed control subjects (ND). METHODS: Thirty-seven healthy, unmedicated female volunteers (n = 19 RD, and n = 18 ND) were recruited. The γ oscillation frequencies and amplitudes in the visual cortex, induced by simple grating stimuli, were quantified with time-frequency analyses. Distinct GABA/glutamate + glutamine MRS peaks were resolved from MEGA-PRESS difference spectra in prefrontal, occipital, and subcortical volumes. RESULTS: The RD and ND individuals did not differ in the frequency of subclinical depressive symptoms. The ND were slightly older (mean = 23 years vs. 21 years), but age did not correlate with dependent measures. There were no group differences in GABA levels or induced cortical γ measures, but RD individuals had markedly reduced M80 (C1) components of the pattern-onset evoked response (46% reduction, Cohen's d = 1.01, p = .006). CONCLUSIONS: Both MRS and magneto-encephalography measures of the GABA system are normal in RD. However, the early visual evoked response is a potential trait marker of the disorder.