SHORT-TERM SYNAPTIC PLASTICITY IN MIGRAINE MOTOR CORTEX: EVIDENCE BY PRECONDITIONING OF HIGH-FREQUENCY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (rTMS) WITH TRANSCRANIAL DIRECT CURRENT STIMULATION (tDCS).

Abstract

Background: Brief 5Hz repetitive transcranial magnetic stimulation (rTMS) trains at 120% of the resting- motorthreshold (RMT) intensity determine in healthy subjects a potentiation of motor evoked potentials (MEPs), likely due to short-term presynaptic plasticity facilitation. We recently showed paradoxical intensity-dependent MEP changes to 5Hz rTMS in migraine with MEP facilitation at 110% and inhibition at 130% RMT. This provides evidence of both hyper-responsivity and self-limiting hyperexcitability capacity in migraine, likely due to earlier activation of inhibitory homeostatic plasticity mechanisms. To explore this, we applied in migraineurs cathodal transcranial Direct Current Stimulation (tDCS) to reduce motor-cortical excitability and subsequently reassess motor-cortical response to 5Hz rTMS trains at 130% RMT- intensity. Methods: 10 migraine with aura patients received 5Hz rTMS of motor cortex at 130% RMT intensity (10 pulses), recording MEP from contralateral abductor pollicis brevis (APB). This protocol was preconditioned by cathodal tDCS (10 min, 1mA intensity). Sham cathodal tDCS was used as control. Results: As expected MEP amplitude decreased significantly during trains of 5Hz before tDCS preconditioning or with sham tDCS. Conversely, after inhibitory preconditioning with cathodal tDCS, 5Hz rTMS trains determined a reduction in the first MEP size and a trend toward MEP facilation during the trains. Conclusions: Inhibitory cathodal tDCS preconditioning is able to normalize the response of migraine motor-cortex to rTMS trains at 130% of RMT. This supports the hypothesis that in migraine motor cortex the mechanisms of short-term presynaptic plasticity evaluated by 5Hz rTMS trains could be affected intericatally by an abnormal increased cortical excitability level.