Associative Motor Cortical Plasticity is Modulated by the Activation History of Motor Cortex

Pairing median nerve stimulation repetitively with transcranial magnetic stimulation over the contralateral motor cortex (paired associative stimulation, PAS) may increase, or decrease, human motor cortical excitability at interstimulus intervals of 25 ms (PAS25), or 10 ms (PAS10). The properties of this plasticity resemble associative long-term potentiation (LTP) and long-term depression (LTD) as established in vitro. We employed these protocols to examine possible physiological correlates of motor memory formation. Subjects performed brisk isometric abductions with their right thumb at a defined force window adjusted to their individual maximum force in a series of 10 training sessions consisting of 50 contractions each. The percentage increase of successful attempts was taken as a measure of motor learning. Motor cortex excitability changes induced by PAS25 and PAS10 were evaluated before and after motor training on day 1 and day 2 in two different groups A (N=11) and B (N=11). At baseline LTP-like plasticity and LTD-like plasticity were similar in both groups (% change of MEP amplitude; group A: PAS10: –22.1±3.5 mean, s.e.m.; PAS25: +41.1±9.6, group B: PAS10: –23.8±3.9; PAS25: +43.4±7.9). Similarly, training-induced percentage successful attempts (A: 14.6±3.2; B: 19.3±4.4%) did not differ between both groups. Immediately after training (day 3), the capacity of the motor cortex to undergo LTP-like plasticity in response to PAS25 was abolished (group A,% change: –9.1±6.2; different from baseline, p=0.001). When retested several days after motor training (day 4), PAS25-induced plasticity recovered to baseline levels. PAS10-induced plasticity remained unchanged by prior training. In a separate experiment evidence was obtained for continued improvement of motor performance at a time when PAS25 was ineffective in inducing LTP-like plasticity. PAS25-induced plasticity was restored when the induction protocol was applied immediately after motor learning and subsequent depotentiation of the previously enhanced synapses by induction of PAS10-induced plasticity (before +30.2±3.0%, after +79.5±16.2%) Immediately after training, normal PAS25-induced plasticity was observed in the untrained motor cortex (before +29.8±6.3%, after +46.6±17.6). These results are consistent with a concept of temporary (heterosynaptic) suppression of associative LTP by mechanisms involved in motor memory formation. Supported by Hertie foundation, Germany.