Reversal rate and check-size differences do not seem to explain the discrepant visual evoked potential habituation results in the migraine literature. Furthermore, no differences in first block amplitudes or N70, P100, and N145 latencies between healthy controls and migraineurs were found. We recommend blinded evaluation designs in future habituation studies in migraine.

Please cite this article as: Omland, P.M., Uglem, M., Hagen, K., Linde, M., Tronvik, E., Sand, T., Visual evoked potentials in migraine: Is the "neurophysiological hallmark" concept still valid ?, Clinical Neurophysiology (2015), doi: http://dx.doi.org/10. 1016/j.clinph.2014.12.035 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. • Lack of VEP habituation is not a reliable "neurophysiological hallmark" in interictal migraine• Strict focus on methodology, including blinding during the recording and assessment of VEP, is important to avoid overestimation of effect sizes in future studies.2 Abstract Objective Lack of habituation is considered a neurophysiological hallmark of migraine. However, the results of visual evoked potential (VEP) studies have been discrepant, possibly because of different stimulation parameters and lack of blinding. Hence, there is a need for independent confirmation of lack of VEP habituation in migraine. In this blinded study we applied 16' checks to supplement our previous findings with 8', 31', 62' and 65' checks. MethodsVEPs in 41 interictal migraineurs and 30 controls were compared. VEPs were recorded in six blocks of 100 single responses. Linear N70-P100 amplitude change over blocks (habituation slope) was compared with an independent samples Student's t-test. ResultsAmplitude decline over blocks was observed in both groups. Habituation slope was not significantly different between controls (-0.43 ± 0.54 μV/block) and migraineurs (-0.29 ± 0.35 μV/block) (p = 0.33). ConclusionVEP habituation with 16' checks did not differ in migraineurs and controls. This is in agreement with previous findings with other stimulation parameters. It is therefore unlikely that use of different stimulation parameters could explain the discrepant results of previous studies. No studies that applied blinding during recording of VEP have found lack of habituation in migraineurs. SignificanceLack of VEP habituation cannot be considered a reliable neurophysiological hallmark in migraine.

Objective Studies suggest that pain thresholds may be altered before and during migraine headaches, but it is still debated if a central or peripheral dysfunction is responsible for the onset of pain in migraine. The present blinded longitudinal study explores alterations in thermal pain thresholds and suprathreshold heat pain scores before, during, and after headache. Methods We measured pain thresholds to cold and heat, and pain scores to 30 seconds of suprathreshold heat four times in 49 migraineurs and once in 31 controls. Sessions in migraineurs were categorized by migraine diaries as interictal, preictal (≤one day before attack), ictal or postictal (≤one day after attack). Results Trigeminal cold pain thresholds were decreased ( p = 0.014) and pain scores increased ( p = 0.031) in the ictal compared to the interictal phase. Initial pain scores were decreased ( p < 0.029), and the temporal profile showed less adaptation ( p < 0.020) in the preictal compared to the interictal phase. Hand cold pain thresholds were decreased in interictal migraineurs compared to controls ( p < 0.019). Conclusion Preictal heat hypoalgesia and reduced adaptation was followed by ictal trigeminal cold suballodynia and heat hyperalgesia. Our results support that cyclic alterations of pain perception occur late in the prodromal phase before headache. Further longitudinal investigation of how pain physiology changes within the migraine cycle is important to gain a more complete understanding of the pathogenic mechanisms behind the migraine attack.

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