Age-related decline in cortical inhibitory tone strengthens motor memory

Ageing disrupts the finely tuned excitation/inhibition balance (E:I) across cortex, driven by a natural decline in inhibitory tone ({gamma}-amino butyric acid, GABA). This causes functional decrements. However, in young adults, experimentally lowering GABA in sensorimotor cortex enhances adaptation memory. Therefore, using a cross-sectional design, here we tested the hypothesis that as sensorimotor cortical GABA declines naturally with age, adaptation memory would increase, and the former would explain the latter. Results confirmed this prediction. To probe causality, we used brain stimulation to further lower sensorimotor cortical GABA during adaptation. Across individuals, how stimulation changed memory depended on sensorimotor cortical E:I. In those with low E:I, stimulation increased memory; in those with high E:I stimulation reduced memory. Thus, we identify a form of motor memory that improves naturally with age, depends causally on sensorimotor cortex neurochemistry, and may be a potent target for motor skill preservation strategies in healthy ageing and neurore-habilitation.