Transcranial cortico-cortical paired associative stimulation (ccPAS) over ventral premotor-motor pathways enhances action performance and corticomotor excitability in young adults more than in elderly adults

Transcranial magnetic stimulation (TMS) methods such as cortico-cortical paired associative stimulation (ccPAS) can increase the strength of functional connectivity between ventral premotor cortex (PMv) and primary motor cortex (M1) via spike timing-dependent plasticity (STDP), leading to enhanced motor functions in young adults. However, whether this STDP-inducing protocol is effective in the aging brain remains unclear. In two groups of young and elderly healthy adults, we evaluated manual dexterity with the 9-hole peg task before and after ccPAS of the left PMv-M1 circuit. We observed that ccPAS enhanced dexterity in young adults, and this effect was anticipated by a progressive increase in motor-evoked potentials (MEPs) during ccPAS administration. No similar effects were observed in elderly individuals or in a control task. Across age groups, we observed that the magnitude of MEP changes predicted larger behavioral improvements. These findings demonstrate that left PMv-to-M1 ccPAS induces functionally specific improvements in young adults’ manual dexterity and an increase in corticomotor excitability, but altered plasticity prevents the effectiveness of ccPAS in the elderly.