Migraine is a very common disorder occurring in 20% of women and 6% of men. Central neuronal hyperexcitability is proposed to be the putative basis for the physiological disturbances in migraine. Since there are no consistent structural disturbances in migraine, physiological and psychophysical studies have provided insight into the underlying mechanisms. This is a review of the neurophysiological studies which have provided an insight to migraine pathogenesis supporting the theory of hyperexcitability.

The brain is hyperexcitable in migraine.

We have studied habituation of the pattern-reversal visual evoked potential (VEP) in healthy volunteers (n = 16) and in patients suffering from migraine without (n = 27) or with aura (n = 9). Five blocks of 50 responses at a stimulation rate of 3.1 Hz were sequentially averaged and analyzed separately for latencies, peak-to-peak amplitudes of N1-P1 and P1-N2, and the area under the N2 component Latencies of N1, P1, or N2 components were not significantly different between the sequential trial blocks, or between groups. Mean amplitudes of N1-P1 and P1-N2 in the first and subsequent blocks of SO responses were not statistically different among groups. In healthy subjects, there was a decrement of N1-P1 and P1-N2 amplitudes and N2 area on successive averagings. This habituation was maximal in the third and fourth blocks, but tended to disappear in the fifth block. In marked contrast to healthy subjects, migraine patients were characterized by a transient amplitude increment (i.e. potentiation) of VEP components which reached its maximum in the second to fourth blocks. Amplitude changes in sequential blocks were not dependent on attention and differed significantly between healthy subjects and migraineurs, but not between migraine with and without aura. Taken together with previous studies showing deficient habituation of contingent negative variation in migraine, these results indicate a dysfunction of central information processing which might have behavioral and pathogenic correlates.

Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attacks.

Migraine is associated with stimulus hypersensitivity, increased evoked cortical responses, and abnormal 5-HT levels in peripheral blood. We studied cortical auditory evoked potentials (AEPs) between attacks in 35 patients suffering from migraine without aura (MO, n = 25) or with aura (MA, n = 10) and in 25 healthy volunteers. Binaural tones were delivered at 40, 50, 60, and 70 dB sensation level (SL) in a pseudorandomized order. The intensity dependence of the auditory Nl-P2 component was significantly greater in MO ( p = 0.003) and MA ( p = 0.02) patients than in healthy controls, resulting in a much steeper amplitudeistimulus intensity function slope. When three sequential blocks of 40 averaged responses were analyzed at the 40- and 70-dB SL intensities, N1–P2 amplitude decreased in second and third blocks at both intensities in controls, but increased in migraineurs, a difference that was significant in both blocks for the 70-dB SL stimulus. The strong interictal dependence of AEPs on stimulus intensity may thus be due to potentiation (instead of habituation) of the response during repetition of the high-intensity stimulation. In concordance with previous studies of visual evoked potentials, these results confirm that migraine is characterized between attacks by an abnormality of cortical information processing, which might be a consequence of low 5-HT transmission and favor cortical energy demands.

Intensity dependence of auditory evoked potentials is pronounced in migraine An indication of cortical potentiation and low serotonergic neurotransmission

Evoked potentials and transcranial magnetic stimulation in migraine: published data and viewpoint on their pathophysiologic significance.

Electrophysiological methods may help to unravel some of the pathophysiological mechanisms of migraine. Lack of habituation is the principal and most reproducible interictal abnormality in sensory processing in migraineurs. It is found in evoked potential (EP) studies for every stimulation modality including nociceptive stimuli, and it is likely to be responsible for the increased intensity dependence of EP. We have hypothesized that deficient EP habituation in migraine could be due to a reduced preactivation level of sensory cortices because of hypofunctioning subcortico-cortical aminergic pathways. This is not in keeping with simple hyperexcitability of the cortex, which has been suggested by some, but not all, studies of transcranial magnetic stimulation (TMS). A recent study of the effects of repetitive TMS on visual EP strongly supports the hypothesis that migraine is characterized by interictal cortical hypoexcitability. With regard to pain mechanisms in migraine, electrophysiological studies of trigeminal pathways using nociceptive blink and corneal reflexes have confirmed that sensitization of central trigeminal nociceptors occurs during migraine attacks.

T Nyrke

Papers

Spectral analysis of visual potentials evoked by sine wave modulated light in migraine