GABAA receptors in visual and auditory cortex and neural activity changes during basic visual stimulation

Abstract

Recent imaging studies have demonstrated that levels of resting γ-aminobutyric acid (GABA) in the visual cortex predict the degree of stimulus-induced activity in the same region. These studies have used the presentation of discrete visual stimulus; the change from closed eyes to open also represents a simple visual stimulus, however, and has been shown to induce changes in local brain activity and in functional connectivity between regions. We thus aimed to investigate the role of the GABA system, specifically GABAA receptors, in the changes in brain activity between the eyes closed (EC) and eyes open (EO) state in order to provide detail at the receptor level to complement previous studies of GABA concentrations. We conducted an fMRI study involving two different modes of the change from EC to EO: an EO and EC block design, allowing the modeling of the haemodynamic response, followed by longer periods of EC and EO to allow the measuring of functional connectivity. The same subjects also underwent [18F]Flumazenil PET to measure GABAA receptor binding potentials. It was demonstrated that the local-to-global ratio of GABAA receptor binding potential in the visual cortex predicted the degree of changes in neural activity from EC to EO. This same relationship was also shown in the auditory cortex. Furthermore, the local-to-global ratio of GABAA receptor binding potential in the visual cortex also predicted the change in functional connectivity between the visual and auditory cortex from EC to EO. These findings contribute to our understanding of the role of GABAA receptors in stimulus-induced neural activity in local regions and in inter-regional functional connectivity.

Abnormal GABAergic Function and Negative Affect in Schizophrenia

“…Although the psychosis patients showed significantly less reduction than the comparison subjects in the left mid-occipital gyrus, consistent with postmortem findings described above, the patients also showed signal reduction with LRZ, particularly in right occipital cortex. Reduced BOLD signal in occipital cortex is consistent with inhibitory effects of LRZ on aggregate neuronal activity, as GABAergic mechanisms have been implicated in control of the aggregate BOLD signal in visual cortex (Qin et al, 2012). Inhibition of occipital cortex has been previously reported after GABAR potentiation (Menzies et al, 2007).…”

Occipital GABA correlates with cognitive failures in daily life

“…Further studies combining GABA MRS and paired pulse transcranial magnetic stimulation (TMS) (Kujirai et al, 1993) or flumazenil PET (Qin et al, 2012) could help clarify the underlying physiology through which occipital GABA may impact causally on cognitive failures, as both techniques are sensitive to GABA-a receptor changes.…”

The Whole-Brain “Global” Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism

“…However, unlike this study, those studies were interested in local differences so justifiably discarded the mean of each R-fMRI metric with each conditions through performing statistical parametric mapping using the general linear model (Bianciardi et al, 2009;Brandt, 2006;Gonzalez-Hernandez et al, 2005;Marx et al, 2004;Qin et al, 2012;Riedl et al, 2014;Wicker et al, 2003), performing global signal regression to find local significance (Xu et al, 2014;Yuan et al, 2014;Zou et al, 2009), or using paired T-tests on a per voxel basis (which can hypothetically detect a global change if region-to-region variation is small, but will not necessarily as it only compares per-voxel changes and global means are never calculated) (Patriat et al, 2013). All of these methods will amplify local region to region, voxel to voxel variation, but obscure the relations to the global change observed in FDG (Fig.…”