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 generall y concluded that migraine (particularly migraine with aura) is associated w ith a state of functional cortical hyperexcitability. The mechanisms giving rise to this hyperexcitability have hitherto been unclear. This paper repo rts two studies that used a novel investigative technique, derived from bas ic research in vision science, to examine specific deficits of inhibitory p rocessing in primary visual cortex. The technique is termed the metacontras t test, and it examines visual masking under highly specified conditions. I n Study 1, 12 migraine with aura patients (MA), 12 age-matched migraine wit hout aura patients (MO) and 12 age- and sex-matched headache-free control s ubjects (C) were compared using the metacontrast test. MA patients were sig nificantly less susceptible to visual masking in the metacontrast test than both MO and C groups: this result is highly consistent with a deficit in c ortical inhibitory processing in MA patients. Study 2 examined MA patients taking a variety of migraine prophylactics, again using the metacontrast te st. Test results normalized in those MA patients taking sodium valproate, b ut not in those taking other prophylactics. Sodium valproate is a GABA-A ag onist that is known to cross the blood-brain barrier: GABA-ergic networks a ct as the primary inhibitory mechanism in visual cortex. Taken together, th e results of these studies argue that cortical hyperexcitability, at least in MA patients, is likely to be a result of deficient intracortical inhibit ory processes.