The effect of gamma oscillations in boosting primary motor cortex plasticity is greater in young than older adults

Objective: In healthy subjects, the long-term potentiation (LTP)-like plasticity of the primary motor cortex (M1) induced by intermittent theta-burst stimulation (iTBS) can be boosted by modulating gamma (γ) oscillations through transcranial alternating current stimulation (tACS). γ-tACS also reduces short-interval intracortical inhibition (SICI). We tested whether the effects of γ-tACS differ between young (YA) and older adults (OA). Methods: Twenty YA (27.2 ± 2.7 years) and twenty OA (65.3 ± 9.5 years) underwent iTBS-γ tACS and iTBS-sham tACS in randomized sessions. In a separate session, we delivered γ-tACS alone and recorded SICI during stimulation. Results: iTBS-sham tACS produced comparable motor evoked potential (MEP) facilitation between groups. While iTBS-γ tACS boosted MEP facilitation in both the YA and OA groups, the magnitude of its effect was significantly lower in OA. Similarly, γ-tACS-induced modulation of GABA-A-ergic neurotransmission, as tested by SICI, was reduced in OA. The effect of iTBS-γ tACS negatively correlated with the age of OA subjects. Conclusions: Mechanisms underlying the effects of γ oscillations on LTP-like plasticity become less efficient in older adults. This could reflect age-related changes in neural elements of M1 resonant to γ oscillations, including GABA-A-ergic interneurons. Significance: The beneficial effect of γ-tACS on iTBS-induced plasticity is reduced in older adults.