title: Cyclical changes of cortical excitability and metaplasticity in migraine: evidence from a repetitive transcranial magnetic stimulation study.
abstract: 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. Patients with episodic migraine were studied in different phases of the migraine cycle: interictal, preictal, ictal, and postictal states. Results showed a facilitatory MEP response during the trains in patients evaluated in the preictal phase, whereas inhibitory responses were observed during and after a migraine attack, as well as in CM patients. In the interictal phase, different responses were observed, depending on attack frequency: facilitation in patients with low and inhibition in those with high attack recurrence. Our findings suggest that changes in cortical excitability and fluctuations in the threshold for inhibitory metaplasticity underlie the migraine attack recurrence, and could be involved in the process of migraine transformation.
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo 90219, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cosentino
authors.forename: Brigida
authors.initials: B
authors.lastname: Fierro
authors.forename: Simone
authors.initials: S
authors.lastname: Vigneri
authors.forename: Simona
authors.initials: S
authors.lastname: Talamanca
authors.forename: Piera
authors.initials: P
authors.lastname: Paladino
authors.forename: Roberta
authors.initials: R
authors.lastname: Baschi
authors.forename: Serena
authors.initials: S
authors.lastname: Indovino
authors.forename: Simona
authors.initials: S
authors.lastname: Maccora
authors.forename: Francesca
authors.initials: F
authors.lastname: Valentino
authors.forename: Enrico
authors.initials: E
authors.lastname: Fileccia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giglia
authors.forename: Filippo
authors.initials: F
authors.lastname: Brighina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004576:Electromyography / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D009044:Motor Cortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
keywords: Headache; Homeostatic plasticity; Magnetic stimulation; Migraine pathogenesis; Migraine with aura; Motor cortex