Cortical hyperexcitability is cortical under-inhibition: evidence from a novel functional test of migraine patients

Recent studies of the visual cortex in patients with migraine have generally concluded that migraine (particularly migraine with aura) is associated with a state of functional cortical hyperexcitability. The mechanisms giving rise to this hyperexcitability have hitherto been unclear. This paper reports two studies that used a novel investigative technique, derived from basic research in vision science, to examine specific deficits of inhibitory processing in primary visual cortex. The technique is termed the metacontrast test, and it examines visual masking under highly specified conditions. In Study 1, 12 migraine with aura patients (MA), 12 age-matched migraine without aura patients (MO) and 12 age- and sex-matched headache-free control subjects (C) were compared using the metacontrast test. MA patients were significantly less susceptible to visual masking in the metacontrast test than both MO and C groups: this result is highly consistent with a deficit in cortical inhibitory processing in MA patients. Study 2 examined MA patients taking a variety of migraine prophylactics, again using the metacontrast test. Test results normalized in those MA patients taking sodium valproate, but not in those taking other prophylactics. Sodium valproate is a GABA-A agonist that is known to cross the blood-brain barrier: GABA-ergic networks act as the primary inhibitory mechanism in visual cortex. Taken together, the results of these studies argue that cortical hyperexcitability, at least in MA patients, is likely to be a result of deficient intracortical inhibitory processes.