Stimulating studies of visual cortical function in migraine.

A variety of clinical and experimental evidence suggests that migraine involves changes in the excitability of the visual cortex. The recent study by Aurora and colleagues (1) adds to this evidence by confirming their previous finding that the response of the occipital cortex to transcranial magnetic stimulation (TMS) is different in migraine patients as compared with controls. In addition, this study shows that treatment with topiramate results in normalisation of the response to TMS in migraine patients such that it is similar to control subjects. These results are significant on multiple levels. First, they indicate that alterations in the response of the occipital cortex to TMS may be a consistent feature of migraine patients, and that this neurophysiological feature may have potential as a biomarker of the disorder. Second, they add further evidence in support of the concept that there is increased excitability in the occipital cortex of migraine patients. Finally, they show that a migraine preventive therapy reduces this excitability, suggesting that TMS paradigms may be useful for the investigation of the mechanisms by which different therapies prevent migraine. Aurora and colleagues used a method known as magnetic suppression of perceptual accuracy (MSPA) to study migraine patients before and after therapy with topiramate. A transcranial magnetic pulse delivered over the occipital cortex impairs the ability of subjects to perceive visual stimuli with a characteristic time course. The MSPA technique quantifies the accuracy with which a subject can identify a series of letters when a TMS pulse is delivered at different time intervals after the letters are presented (2). Normal subjects have a ‘U-shaped’ pattern of visual accuracy relative to the timing of the TMS pulse, i.e. they have accurate visual perception when the pulse is delivered at short (40ms) or longer (190ms) intervals after the characters are flashed, but impaired perception when the pulse is delivered at an intermediate interval (100ms). Migraine patients, by contrast, have been reported to show a reduced suppression of perceptual accuracy at the 100-ms time point, resulting in a ‘shallower’ curve of the MSPA temporal profile (2,3). Aurora and colleagues found that with increased frequency of migraine, there is even further reduction in the magnetic suppression of visual accuracy (3,4). They concluded that these findings are consistent with an increased excitability of the occipital cortex in migraine patients, possibly due to reduced cortical inhibition. In their current paper, they report that treatment with topiramate resulted in a dose-dependent restoration of the magnetic suppression of visual perception (1). The average profile of the MSPA response in patients on ‘optimal doses’ of topiramate was similar to those of controls, whereas the average MSPA profile of patients on smaller doses of topiramate was the same as that of untreated migraine patients. Overall, the extent of MSPA change did not show a significant correlation with the extent to which migraine frequency was reduced, although this correlation was present for some individual patients. One important implication of this study is that MSPA, and potentially other quantitative measures of cortical excitability based on TMS responses, could represent a ‘biomarker’ for migraine. At present, there are no laboratory, neurophysiological, or imaging studies that are consistent indicators for migraine (5). If differences in MSPA in migraine patients vs. controls can be consistently replicated in other laboratories, there is the potential for this and other approaches using TMS to become more widely used in the investigation of migraine. A key question is whether the variability of individual patient responses will be manageable enough to make more wide-spread use of this approach feasible. There may be significant variability in neurophysiological responses of migraine patients depending on when the measurements are obtained relative to the last migraine attack, or the one that is about to occur (6,7). Given this temporal