Inhibition and action in the aging brain: role of GABA in brain function and network interactions

Studying the neural mechanisms underlying age deficits in movement control is of utmost socioeconomic relevance. Here, we will study inhibitory control mechanisms that shape motor behavior. Using magnetic resonance spectroscopy, we will determine the concentration of gammaaminobutyric acid (GABA), the chief inhibitory neurotransmitter in the brain. In Phase 1, multimodal imaging is used to study interactions between GABA concentration, brain structural and functional connectivity, and motor performance. Then, we will study task-related modulation of GABAergic inhibition during action selection and inhibition, using brain stimulation, either in isolation or combined with electro-encephalography. This will reveal age-related changes in GABAergic neurotransmission related to GABA-A and GABA-B receptor mechanisms. In Phase 2, using PET-MR, we will measure GABA concentration and GABA-A receptor density as well as task-related GABAergic modulation to reveal their interaction in older adults. In Phase 3, modulation of GABA concentration during the early and late phase of motor learning is studied to determine whether a metric of GABA modulation predicts learning and long-term memory as well as learning-induced changes in brain activity and task-related connectivity. Overall, this project aims at a deeper understanding of age-related changes in GABAergic mechanisms, their effect on functional brain networks and their reorganization through intervention.