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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 (IPI ) or 30 (IPI ) mins. For each IPI, the first (priming) PAS block was either PAS (N20 latency + 2 ms) or PAS (N20 latency - 10 ms), while the second (test) PAS block was always PAS . 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 -primed PAS was significantly greater than the response produced by PAS -primed PAS . Furthermore, the effects of PAS priming on PAS were significantly greater for IPI . 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.

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The study aimed to examine the effect of a priming cathodal transcranial direct current stimulation (ctDCS) before subsequent anodal-tDCS (atDCS) was applied during low workload cycling exercise on the corticospinal responses in young healthy individuals. Eleven young subjects participated in two sessions receiving either priming ctDCS or sham stimulation, followed by atDCS while cycling (i.e. ctDCS-atDCS, sham-atDCS) at 1.2 times their body weight (84 ± 20 W) in a counterbalanced double-blind design. Corticospinal excitability was measured with motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation with the intensity set to produce an MEP amplitude of 1 mV in a resting hand muscle at baseline (PRE), following priming tDCS (POST-PRIMING) and post atDCS combined with cycling exercise (POST-TEST). There was a significant interaction between time and intervention (P < 0.01) on MEPs. MEPs increased from PRE (1.0 ± 0.06 mV) to POST-TEST (1.3 ± 0.06 mV) during ctDCS-atDCS (P < 0.001) but did not change across time during sham-atDCS (1.0 ± 0.06 mV, P > 0.7). Furthermore, MEPs were higher in ctDCS-atDCS compared to sham-atDCS (P < 0.01) at both POST-PRIMING (ctDCS-atDCS: 1.1 ± 0.06, sham-atDCS: 1.0 ± 0.06) and POST-TEST (ctDCS-atDCS: 1.3 ± 0.06, sham-atDCS: 1.0 ± 0.06). These outcomes demonstrate that cathodal tDCS priming can enhance corticospinal excitability following anodal tDCS applied in combination with cycling exercise. The findings have implications for the application of tDCS in combination with cycling exercise in rehabilitation and sporting contexts.