Mapping the Synchronization Effect of Gamma-Aminobutyric Acid Inhibition on the Cerebral Cortex Using Magnetic Resonance Imaging

Abstract

Background:

Functional magnetic resonance imaging (fMRI) of spontaneous brain activity permits the identification of functional networks on the basis of region synchrony. The functional coupling between the elements of a neural system increases during brain activation. However, neural synchronization may also be the effect of inhibitory gamma-aminobutyric acid (GABA) neurons in states of brain inhibition such as sleep or pharmacological sedation. We investigated the effects of an oral dose of alprazolam, a classical benzodiazepine known to enhance inhibitory neurotransmission, using recently developed measures of local functional connectivity.

Methods:

In a randomized, double-blind, placebo-controlled, crossover design, 32 non-treatment-seeking individuals with social anxiety underwent two identical resting-state fMRI sessions on separate days after receiving 0.75 mg of alprazolam and placebo. Functional connectivity maps of the cerebral cortex were generated by using multidistance functional connectivity measures defined within iso-distant local areas.

Results:

Relative to placebo, increased intracortical functional connectivity was observed in the alprazolam condition in visual, auditory, and sensorimotor cortices, and in areas of sensory integration such as the posterior insula and orbitofrontal cortex (OFC). Alprazolam significantly reduced subjective arousal compared with placebo, and the change was associated with variations in multidistance functional connectivity measures in the OFC.

Discussion:

In conclusion, we report evidence that alprazolam significantly modifies neural activity coupling at rest in the form of functional connectivity enhancement within the cerebral cortex. The effect of alprazolam was particularly evident in the cortical sensory system, which would further suggest a differentiated effect of GABA inhibition on sensory processing.

Impact statement

Magnetic resonance imaging (MRI) signal synchronization between brain regions is regularly used as a measure of functional connectivity denoting activity of a network or co-activation of its elements. Less studied in the functional MRI field, however, is neural synchronization in states of brain inhibition. We mapped the effect of a pharmacological agent known to enhance gamma-aminobutyric acid inhibitory neurotransmission on the local functional structure of the cerebral cortex. We observed that alprazolam significantly increased intracortical activity coupling at rest, particularly in the cortical sensory system. The results emphasize that changes in functional connectivity measures may also reflect the synchronization effect of inhibitory neurons.