Is the cerebral cortex hyperexcitable or hyperresponsive in migraine?

Although migraineurs appear in general to be hypersensitive to external stimuli, they maybe also have increased daytime sleepiness and complain of fatigue. Neurophysiological studies between attacks have shown that for a number of different sensory modalities the migrainous brain is characterised by a lack of habituation of evoked responses. Whether this is due to increased cortical hyperexcitability, possibly due to decreased inhibition, or to an abnormal responsivity of the cortex due a decreased preactivation level remains disputed. Studies using transcranial magnetic stimulation in particular have yielded contradictory results. We will review here the available data on cortical excitability obtained with different methodological approaches in patients over the migraine cycle. We will show that these data congruently indicate that the sensory cortices of migraineurs react excessively to repetitive, but not to single, stimuli and that the controversy above hyper- versus hypo-excitability is merely a semantic misunderstanding. Describing the migrainous brain as 'hyperresponsive' would fit most of the available data. Deciphering the precise cellular and molecular underpinnings of this hyperresponsivity remains a challenge for future research. We propose, as a working hypothesis, that a thalamo-cortical dysrhythmia might be the culprit.