Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study

The effect of a single oral dose of various antiepileptic drugs on the excitability of the motor system was studied in healthy volunteers by means of transcranial magnetic stimulation. Motor threshold, duration of the cortical silent period, and intracortical excitability after double-shock transcranial stimulation were tested before and at defined intervals after drug intake. Antiepileptic drugs that support the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the neocortex (vigabatrin, baclofen) reduced intracortical excitability but had no effect on motor threshold. Gabapentin, whose mechanism of action has not yet been unequivocally identified, showed a similar profile. By contrast, sodium and calcium channel blockers without considerable neurotransmitter properties (carbamazepine, lamotrigine, losigamone) elevated motor threshold but did not change intracortical excitability. The cortical silent period was lengthened by gabapentin and carbamazepine. Changes in peripheral motor excitability (maximum M wave, peripheral silent period) were not observed. We conclude that the changes in intracortical excitability are caused by GABA-controlled interneuronal circuits in the motor cortex while changes in motor threshold are dependent on ion channel conductivity and may reflect membrane excitability. Transcranial magnetic stimulation may be a promising noninvasive approach to study the selective effects of antiepileptic drugs on brain function.