Age-related decline in cortical inhibitory tone strengthens motor memory

Abstract

Ageing causes a natural decline in cortical inhibitory tone and associated functional decrements. However, in young adults, experimentally lowering cortical inhibition during adaptation enhances retention. Here we tested the hypothesis that as sensorimotor cortex inhibitory tone decreases naturally with age, adaptation memory would increase. As predicted, older age was associated with lower γ-amino butyric acid (GABA), the inhibitory neurotransmitter, and stronger adaptation memory. Mediation analyses confirmed that the former explained the latter. To probe causality, brain stimulation was used to further lower sensorimotor cortical inhibitory tone during adaptation. Across individuals, stimulation enhanced or impaired memory, as a function of sensorimotor cortical excitation:inhibition ratio (E:I = Glutamate:GABA). Stimulation increased retention in individuals with low E:I, but disrupted it in those with high E:I. Thus, we identify a form of memory that improves naturally with age, depends causally on sensorimotor neurochemistry, and may be a potent target for neurorehabilitation.