Effect of levetiracetam on rapid motor learning in humans

Abstract

Background The human motor cortex (M1) has a role in motor learning. Antiepileptic drugs that suppress M1 excitability may affect learning, presumably by inhibiting long-term potentiation. Levetiracetam, a new antiepileptic drug with a unique preclinical profile, also suppresses M1 excitability, but in a way that is different from other antiepileptic drugs. The effect of levetiracetam on motor learning has yet to be addressed.

Objective To investigate whether levetiracetam alters rapid motor learning in humans.

Methods We measured pinch force and acceleration and motor excitability before and after 30 minutes of pinch practice at 0.5 Hz in 10 healthy volunteers. Either 3000 mg of levetiracetam or placebo was administered 1 hour before the experiment.

Results After practice, pinch acceleration was significantly increased with placebo, but not with levetiracetam. All other measures showed no significant change.

Conclusion Levetiracetam interferes with rapid motor learning; this is consistent with a negative influence on long-term potentiation.

THE HUMAN MOTOR cortex (M1) has a role not only in executing voluntary movement but also in performing more intricate processes such as motor learning.1 Motor output maps are enlarged during acquisition of new skills.2,3 In addition to its involvement in motor skill learning that occurs over several days to weeks, M1 can show changes in excitability with relatively short-term training for an hour or less.4 Rapid motor learning is presumably related to reorganization of M1 that encodes the kinematic details of the practiced movement.5 In rat brain, repetition of certain movements modifies synaptic efficacy,6 resulting in long-term potentiation (LTP) that has also been demonstrated in M1.7 Thus, rapid motor learning may require short-term alterations in synaptic dynamics, such as LTP or a similar process, that contribute to change in M1 excitability.