The interaction between endogenous GABA, functional connectivity and behavioral flexibility is critically altered with advanced age

Abstract

Previous links endogenous gamma-aminobutyric acid (GABA) with behavioral efficiency across perceptual and cognitive domains but with potentially strongest impact on those types of behavior that require a high level of dynamic control. Using a Bayesian moderated mediation analysis, we modeled the age-associated interactions between electroencephalography- and electromyography-derived connectivity metrics and behavior and investigated the specificity of the indirect effect of GABA concentration as measured with magnetic resonance spectroscopy. Only the integrated analysis of all three modalities revealed marked differences between the two age groups. Specifically, relatively lower GABA was more beneficial for the connectivity-behavior association in the young, whereas the older showed a beneficial behavioral effect in the presence of higher GABA given their generally elevated task-related connectivity. Age-related alteration of the preferred state of endogenous GABA concentration may reflect a generic compensatory mechanism allowing for higher temporal precision in neural tuning and maintaining a higher behavioral functioning level.