Hyperexcitability of the primary somatosensory cortex in migraine--a magnetoencephalographic study

Abstract

The excitability of the cerebral cortex in the interictal state of migraine appears to be fundamental in the brain's susceptibility to migraine attacks. Subpopulations of cortical neurons are reported to have different physiological response properties to different interstimulus intervals (ISIs) and, hence, may be differentially altered or modulated in migraine. The aim of this study therefore was to evaluate response characteristics of temporally and spatially defined neuronal subpopulations in the cortex of migraineurs. To this end, we measured, by means of magnetoencephalography (37-channel neuromagnetometer), the response properties of the early components of the somatosensory evoked magnetic fields following electrical stimulation of the median nerve, the N20m and P35m, at ISIs ranging between 0.3 and 6 s. As a measure of the number of excited neurons underlying the N20m and P35m, we evaluated the root mean square (r.m.s.) of the deflections across all 37 channels at the corresponding latencies and the corresponding dipole moment of the equivalent current dipole (ECD strength). Twenty consecutive women with at least three migraine attacks/month (range 3-8/month) fulfilling the International Headache Society criteria and 20 age-matched healthy women were included in the study. In migraineurs, the r.m.s. and ECD strength of N20m was increased at all ISIs (r.m.s., P < 0.05; ECD strength, P < 0.01) and positively related to the mean attack frequency (r.m.s., R(s) = 0.6, P < 0.01; ECD strength, R(s) = 0.5, P < 0.05). In contrast, the r.m.s. and ECD strength of P35m did not differ significantly between migraineurs and control subjects and did not correlate significantly with the frequency of migraine attacks. Responses to different ISIs did not differ significantly between migraineurs and control subjects. The r.m.s. of N20m was stable for ISIs between 0.5 and 6 s and decreased significantly at an ISI of 0.3 s. In contrast, the r.m.s. of P35m decreased continuously as the ISI was decreased below 6 s and this reached significance for an ISI of < or =1 s. Habituation of N20m or P35m, i.e. a decrease in response magnitude following repetitive stimulation over time, was not found in either the control subjects or in the migraineurs. It is concluded that the population of neurons in the primary somatosensory cortex underlying the N20m are hyperexcitable and that this hyperexcitability is linked to the frequency of migraine attacks. This hyperexcitability appears not to be related to habituation since habituation was not found in the control subjects. In contrast, the magnitude of P35m is not pathophysiologically linked to the interictal state of migraine. Furthermore, the cellular mechanisms causing ISI-dependent depression of N20m and P35m are not altered in migraine.

Statistical group comparison of diffusion tensors via multivariate hypothesis testing

“…Since migraine is primarily referred cutaneous sensation, it is reasonable to conclude that the cluster identified by the multivariate tensor test appears to be inserting into area 3 of the postcentral gyrus. Furthermore, the finding of diffusion alterations in postcentral gyrus WM is consistent with the established involvement of somatosensory cortex in migraine pathophysiology (41,42). The significant clusters from the FA and tensor-based comparisons both localized to left postcentral gyrus, but the tensor-based cluster traversed the length of the gyrus consistent with the projections of the corona radiata.…”

Altered processing of sensory stimuli in patients with migraine

“…[53][54][55] Several other studies, however, were not able to reproduce these results and found no habitu ation deficit in individuals with migraine, possibly because of differences in the methods used or selection of patients. [56][57][58][59][60][61][62] The reasons for the discrepant results of habituation studies are not fully understood. Insufficient blinding of the investigator has been suggested as a possible culprit; 63 however, since the same researchers have found the same result (that is, normal habituation) in individuals with migraine in both blinded and nonblinded studies, 57 and lack of habituation has also been reported in a blinded study, this factor is unlikely to be the sole cause.…”

“…Interestingly, the habituation deficit reappears when patients evolve from chronic to episodic migraine. 83 Since the response pattern in chronic migraine is indistinguishable from that observed during migraine attacks, 43,[51][52][53][54][55][56][57][58][59][60][61][62][70][71][72] our research group has suggested that patients with chronic migraine are locked in an ictal like state. 84 The most prevalent factor associated with the tran sition from episodic to chronic migraine is acute medication overuse.…”

Electrophysiological response patterns of primary sensory cortices in migraine

“…The migraine response pattern of somatosensory cortex has also been investigated with magneto-encephalography [85]. In this study the equivalent current dipole of the first MEP cortical component, the N20m, was increased in migraine patients and positively related to their mean attack frequency, which led the Authors to suggest that the population of neurons in the primary somatosensory cortex underlying the N20m are hyperexcitable and that this hyperexcitability is linked to the frequency of migraine attacks.…”