MRS-assessed brain GABA modulation in response to task performance and learning

Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the human brain, has long been considered essential in human behavior in general and learning in particular. GABA concentration can be quantified using magnetic resonance spectroscopy (MRS). Using this technique, numerous studies have reported associations between baseline GABA levels and various human behaviors. However, regional GABA concentration is not fixed and may exhibit rapid modulation as a function of environmental factors. Hence, quantification of GABA levels at several time points during the performance of tasks can provide insights into the dynamics of GABA levels in distinct brain regions. This review reports on findings from studies using repeated measures (n = 41) examining the dynamic modulation of GABA levels in humans in response to various interventions in the perceptual, motor, and cognitive domains to explore associations between GABA modulation and human behavior. GABA levels in a specific brain area may increase or decrease during task performance or as a function of learning, depending on its precise involvement in the process under investigation. Here, we summarize the available evidence and derive two overarching hypotheses regarding the role of GABA modulation in performance and learning. Firstly, training-induced increases in GABA levels appear to be associated with an improved ability to differentiate minor perceptual differences during perceptual learning. This observation gives rise to the 'GABA increase for better neural distinctiveness hypothesis'. Secondly, converging evidence suggests that reducing GABA levels may play a beneficial role in effectively filtering perceptual noise, enhancing motor learning, and improving performance in visuomotor tasks. Additionally, some studies suggest that the reduction of GABA levels is related to better working memory and successful reinforcement learning. These observations inspire the 'GABA decrease to boost learning hypothesis', which states that decreasing neural inhibition through a reduction of GABA in dedicated brain areas facilitates human learning. Additionally, modulation of GABA levels is also observed after short-term physical exercise. Future work should elucidate which specific circumstances induce robust GABA modulation to enhance neuroplasticity and boost performance.