The facilitatory effects of intermittent theta burst stimulation on corticospinal excitability are enhanced by nicotine

ObjectiveIntermittent theta burst stimulation (iTBS) is increasingly widely used as a means of facilitating corticospinal excitability in the human primary motor cortex. This form of facilitatory plasticity within the stimulated cortex may occur by induction of long term potentiation (LTP). In animal models, agonists of nicotinic acetylcholine receptors have been shown to modulate or induce LTP; we thus sought to test whether nicotine may modulate the effects of iTBS on corticospinal excitability in humans.MethodsA double-blind placebo-controlled cross-over design study was conducted with 10 healthy subjects. iTBS was delivered 60 min after subjects took either 4 mg nicotine or placebo lozenges, and motor-evoked potentials (MEPs) were then recorded for 40 min after the end of stimulation.ResultsIn the placebo arm, iTBS produced an increase in the amplitudes of MEPs which lasted for 5 min. In the nicotine arm, iTBS produced a more pronounced facilitation of MEPs that was still present at 40 min. In a control experiment, nicotine alone had no effect on MEP amplitudes when given in the absence of iTBS.ConclusionsThese data indicate that the effects of iTBS can be enhanced and prolonged by nicotine.SignificanceThese results are consistent with animal models demonstrating nicotinic modulation of facilitatory plasticity, and will be of interest to investigators seeking to enhance artificially induced changes in cortical excitability.