Abnormal facilitatory mechanisms in motor cortex of migraine with aura

Experimental evidence suggests impairment of inhibitory intracortical circuits in migraine, while not much is known about activity of facilitatory intracortical circuits. In the present work we evaluated the effects of high frequency-repetitive transcranial magnetic stimulation (hf-rTMS) on the activity of facilitatory circuits of motor cortex in 18 patients affected by migraine with aura and 18 healthy subjects. Trains of 10 stimuli were applied to the motor cortex at 5-Hz frequency with recording of the EMG traces from the contralateral abductor pollicis brevis muscle (APB). Two intensities of stimulation (110% and 130% of resting motor threshold) were used in order to explore whether motor cortex excitability was differently modulated. Twelve patients underwent hf-rTMS both before and during prophylactic treatment with levetiracetam. Results showed that rTMS delivered at 110% intensity of stimulation at rest had a facilitatory effect on MEP size in untreated patients, while left MEP unchanged in controls. Conversely, when rTMS was applied at 130%, we observed MEP potentiation in healthy subjects and paradoxical MEP inhibition in migraineurs. In treated patients, levetiracetam inhibited MEP size at both 110% and 130% intensity of stimulation. Our findings reveal an opposite response of migraine motor cortex to 5-Hz rTMS when it is delivered at different stimulation intensities, providing evidence of both hyper-responsivity and self-limiting hyperexcitability capacity, in line with studies supporting the concept that under conditions of cortical hyperexcitability inhibitory mechanisms of homeostatic plasticity could be activated.