Cyclical changes of cortical excitability and metaplasticity in migraine: Evidence from a repetitive transcranial magnetic stimulation study.

The primary brain dysfunctions leading to the onset of a migraine attack remain largely unknown. Other important open questions concern the mechanisms of initiation, continuation, and termination of migraine pain, and the changes in brain function underlying migraine transformation. Brief trains of high-frequency repetitive transcranial magnetic stimulation (rTMS), when applied to the primary motor cortex at suprathreshold intensity (≥120% of resting motor threshold [RMT]), elicit in healthy subjects a progressive, glutamate-dependent facilitation of the motor evoked potentials (MEP). Conversely, in conditions of increased cortical excitability, the rTMS trains induce inhibitory MEP responses likely mediated by cortical homeostatic mechanisms. We enrolled 66 migraine-without-aura patients, 48 migraine-with-aura patients, 14 patients affected by chronic migraine (CM), and 20 healthy controls. We assessed motor cortical response to 5-Hz rTMS trains of 10 stimuli given at 120% RMT. Patien...