Abstract
The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) has uncovered underlying mechanisms of two anti-epileptic medications: levetiracetam and lamotrigine. Despite their different mechanism of action, both drugs modulated TMS-evoked EEG potentials (TEPs) in a similar way. Since both medications increase resting motor threshold (RMT), the current aim was to examine the similarities and differences in post-drug TEPs, depending on whether stimulation intensity was adjusted to take account of post-drug RMT increase. The experiment followed a placebo controlled, double blind, crossover design, involving a single dose of either lamotrigine or levetiracetam. When a drug-induced increase of RMT occurred, post-drug measurements involved two blocks of stimulations, using unadjusted and adjusted stimulation intensity. A cluster based permutation analysis of differences in TEP amplitude between adjusted and unadjusted stimulation intensity showed that lamotrigine induced a stronger modulation of the N45 TEP component compared to levetiracetam. Results highlight the impact of adjusting stimulation intensity.
Highlights
Levetiracetam and lamotrigine are two commonly prescribed anti-epileptic drugs (AEDs) (Nicholas et al, 2012)
Cluster-based permutation analysis was applied between post-RMT2 and pre-drug conditions to test the effect of AEDs on TMS-evoked EEG potentials (TEPs) recorded with adjusted stimulation intensity
We have recently demonstrated that, despite the different mechanism of action that lamotrigine and levetiracetam exert at the molecular level, both AEDs impact the TMS with electroencephalography (TMS-EEG) response in a similar way
Summary
Levetiracetam and lamotrigine are two commonly prescribed anti-epileptic drugs (AEDs) (Nicholas et al, 2012). Electromyographic (EMG) responses to TMS indicate that lamotrigine and levetiracetam increase the resting motor threshold (RMT) (Ziemann et al, 1996), a TMS-EMG parameter which reflects neural membrane excitability and ion channel conductance (Ziemann et al, 1996; Solinas et al, 2008). Single-pulses delivered over the motor area at threshold intensity (100% RMT) result in positive and negative deflections named TMS-evoked EEG potentials (TEP) which may provide insights into brain connectivity (Ilmoniemi et al, 1997) and neurotransmission (Premoli et al, 2014a). We used TMS-EEG to characterize the effects of single oral doses of Adjusting Stimulation Intensity in Pharmaco-TMS-EEG lamotrigine and levetiracetam. Both AEDs increased the N45 and suppressed the P180. This study showed the expected finding that these AEDs both increase RMT (Premoli et al, 2016)
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