Visual paired-pulse stimulation reveals enhanced visual cortex excitability in migraineurs

Migraine is a common ictal disorder with an interindividual heterogeneous characteristic, whose underlying mechanisms remain elusive. On the one hand migraine is associated with abnormal cortical hyperexcitability. On the other hand, studies reported lower amplitudes of visual-evoked potentials (VEPs) and concluded that low preactivation levels imply decreased excitability. Here we measured visual cortex excitability and paired-pulse suppression in subjects suffering from migraine without aura and in a group of aged- and gender-matched healthy subjects to address the relation between activation levels and excitability. To that aim, we analysed amplitudes of VEPs and paired-pulse suppression evoked by a paired-pulse stimulation paradigm using stimulus onset asynchronies (SOAs) between 80 and 133 ms. We found that in migraineurs in the interictal state the amplitudes of the first VEP were reduced as compared with healthy subjects by approximately 20%. In the case of paired-pulse suppression comparable to healthy controls, the second response amplitude should be reduced as well, which was not the case. Instead, the ratio between the first and second VEP was higher than in healthy controls and did not depend on SOA in the range tested, which demonstrates reduced paired-pulse suppression and therefore implicates increased cortical excitability. Our data show that in migraineurs VEPs were reduced presumably due to reduced activation levels. However, paired-pulse suppression using short SOAs in the range of 100 ms or less was even higher than in normal subjects. Thus, our data show that signatures of both hyper- and hypoexcitability can be found depending on stimulation condition.