Effect of Levetiracetam on Brain Excitability

Overview

This study will examine the effect of the newly developed anti-epileptic drug, levetiracetam, on excitability of the cortex (surface layer) of the brain. Levetiracetam works differently from other anti-seizure drugs, but its mechanism is not well understood. This study may provide insight into a new protection mechanism against seizures as well as the effect of the drug on cortical excitability. Healthy normal volunteers 18 years of age and older may be eligible for this study. Candidates will have a medical history taken and undergo physical and neurological examinations. Participants will undergo two different procedures in four separate sessions. One procedure (cortical excitability) involves taking either levetiracetam or placebo (a look-alike inactive substance) and having transcranial magnetic stimulation (TMS). The other procedure (pinch-training related changes) involves taking levetiracetam or placebo, doing a motor exercise called pinch training, and having transcranial magnetic stimulation. For TMS, a very brief electrical current is passed through an insulated coil wire placed on the scalp. The magnetic pulse travels through the scalp and skull, causing small electrical currents in the cortex that may cause muscle, hand, or arm twitching or it may affect movements or reflexes. During the study, subjects may be asked to make movements, do simple tasks or tense muscles. Electrical activity of the muscles will be recorded using electrodes taped to the skin over the muscle. For the pinch training, the subject makes a brief, brisk pinch after each beat of a metronome every two seconds and then completely relaxes the hand until the next beat. Subjects will be tested on four different days at least 72 hours apart. Each session will last about 3 to 4 hours. Approximate schedule for cortical excitability testing: TMS (study 1) Take levetiracetam or placebo TMS (study 2) \< 60 minutes after drug or placebo TMS (study 3) \< 120 minutes after drug or placebo Approximate schedule for pinch-training related changes: Take levetiracetam or placebo TMS and pinch power measurement \< 60 minutes after drug or placebo Pinch training for 30 minutes TMS and pinch power measurement Sample schedule: Session 1 \< LTC and cortical excitability testing Session 2 \< Placebo and cortical excitability testing Session 3 \< LTC and pinch-training related changes Session 4 \< Placebo and pinch-training related changes

The purpose of this study is to investigate the effect of newly developed antiepileptic drug, levetiracetam, on cortical excitability in humans. This drug may be useful in patients with myoclonus, and its mode of action is not well understood. We plan to determine if oral administration of levetiracetam in therapeutic dosage alters cortical excitability measured by transcranial magnetic stimulation as well as long-term potentiation measured by pinching practice in humans.