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

Pengmin Qin,Niall W Duncan,Jeroen Verhaeghe,Christine Wiebking,Georg Northoff,Oliver Lyttelton,Ralf Schirrmacher,Alexey Kostikov,Paul Gravel,Dave J Hayes,Andrew J Reader

doi:10.3389/fnhum.2012.00337

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.

Highlights

Preliminary work in humans has suggested that the neurotransmitter γ-aminobutyric acid (GABA) plays a role in the brain’s response to external stimuli
We report for the first time in humans on the relationship between GABAA receptor BPND and neural activity change between the eyes closed (EC) and eyes open (EO) conditions
Our findings show that the local-to-global ratio of GABAA receptor BPND in the visual cortex positively predicts the degree of change in neural activity in the same region between EC and EO

Summary

Introduction

Preliminary work in humans has suggested that the neurotransmitter γ-aminobutyric acid (GABA) plays a role in the brain’s response to external stimuli. The magnitude of the BOLD response elicited by a visual stimulus has been shown to be negatively correlated with baseline GABA concentrations in the same region, as measured using magnetic resonance spectroscopy (MRS) (Donahue et al, 2010). Further evidence for the involvement of GABA in stimulus induced neural activity comes from non-human primates, where BOLD responses in the visual cortex, as induced by discrete visual stimuli, have been shown to be modulated by local injections of a GABAA receptor antagonist (Logothetis et al, 2010). Evidence for this in humans has not been shown to date, though, leaving open the question as to what mechanisms may underlie the correlations between GABA concentrations and human visual cortex activity

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