Increasing motor cortex plasticity with spaced paired associative stimulation at different intervals in older adults

The ability of priming non‐invasive brain stimulation (NIBS) to modulate neuroplasticity induction (i.e. metaplasticity) within primary motor cortex (M1) may be altered in older adults. Previous studies in young subjects suggest that consecutive NIBS protocols interact in a time‐dependent manner and involve homoeostatic metaplasticity mechanisms. This was investigated in older adults by assessing the response to consecutive blocks of paired‐associative stimulation (PAS) separated by different inter‐PAS intervals (IPIs). Fifteen older (62–82 years) subjects participated in four sessions, with each session involving two PAS blocks separated by IPIs of 10 (IPI₁₀) or 30 (IPI₃₀) mins. For each IPI, the first (priming) PAS block was either PAS_LTP (N20 latency + 2 ms) or PAS_LTD (N20 latency ? 10 ms), while the second (test) PAS block was always PAS_LTP. Changes in M1 excitability were assessed by recording motor evoked potentials from a muscle of the right hand. For both IPIs, the response produced by PAS_LTD‐primed PAS_LTP was significantly greater than the response produced by PAS_LTP‐primed PAS_LTP. Furthermore, the effects of PAS_LTD priming on PAS_LTP were significantly greater for IPI₃₀. These findings suggest that priming PAS can increase plasticity induction in older adults, and this occurs through mechanisms involving homoeostatic metaplasticity. They also demonstrate that the timing between priming and test NIBS is a crucial determinant of this effect, with a 30‐min interval being most effective. Providing a 30‐min delay between priming NIBS and motor training may improve the efficacy of NIBS in augmenting motor performance and learning in the elderly.