Dynamic Changes of Cognitive Habituation and Serotonin Metabolism During the Migraine Interval

Abstract

Migraine patients show a specific cognitive processing with a loss of habituation in the interval and a normal habituation in the attack as measured by event-related potentials (ERPs). It is unknown whether the loss of habituation changes during the migraine interval or is a stable state. Serotonin (5HT) metabolism is involved in the pathophysiology of migraine and also in the generation of ERPs. We enrolled 14 patients with regular migraine attacks in order to measure visually evoked ERPs repetitively during the migraine interval and in the migraine attack. Cognitive habituation was evaluated by analysis of P3 latency. Platelet serotonin content and free serotonin plasma level were measured at the same time points. The loss of habituation increased continuously during the migraine interval and abruptly normalized in the migraine attack (p < 0.05, time series analysis). The platelet 5HT content decreased significantly in the migraine attack (p < 0.03) and was at its maximum in the middle of the interval. The P3 latency was significantly increased in the attack (p < 0.01) and was significantly inversely correlated with the platelet 5HT content (r = -0.44, p < 0.001). Free 5HT plasma levels did not show any significant change. Our findings suggest that loss of cognitive habituation continuously increases during the migraine interval until its normalization in the migraine attack. This phenomenon cannot be attributed to serotonergic transmission. In patients with regular changes of cognitive habituation before the migraine attack, it might be possible to predict the attack by analysing ERPs.

Cortical Excitability in Chronic Migraine

“…By contrast, during the attack (ie, ictally), habituation and 1st block amplitude increase and normalize, while during the days immediately preceding the attack (ie, preictally), the habituation deficit further worsens. We have postulated that these cortical electrophysiological patterns are related to changes in serotonin transmission, which is low interictally [26], and may further decrease preictally but increase ictally, as suggested by several biochemical studies [27,28] and numerous imaging studies [29,30] showing activation of pontomesencephalic areas comprising monoaminergic nuclei during migraine attacks (see [6] for a review).…”

Altered processing of sensory stimuli in patients with migraine

“…This pattern has been shown for CNV, 36,70,71 VEP, 57,72 and SSEP 61 amplitudes, and for visual P300 latency. 73 The R2 component recorded during blink reflexes-evoked by an electrical stimulus delivered with a classic non nociceptive surface electrode-showed a habituation deficit in patients before a migraine attack, 76 although in another study only slight habituation abnormalities were found interictally. 77 In a longitudinal study of brainstem AEPs, habituation of wave IV-V amplitude was deficient in patients with migraine, but did not change over the migraine cycle.…”

“…For instance, cortical responsivity is cyclic in individuals with migraine, 71 and varies in parallel with changes in platelet serotonin content. 73 The period icity of neurophysiological brain activity might also be related to psychophysical, genetic 66,79 or metabolic factors, 80 or to the biorhythms of hypothalamic activity. 81 Migraine periodicity might thus be the result of several inter acting biological cycles.…”

Migraine and motion sickness: What is the link?

“…However, the precise role of 5-HT is not clear (Evers, Quibeldey, Grotemeyer, Suhr and Husstedt, 1999;Ferrari and Saxena, 1993;Fontes Ribeiro, Cotrim, Morgadinho, Ramos, Seabra Santos and Macedo, 1990). During a migraine attack the trigeminal sensory system presumably activates second-order nociceptive neurons within the brainstem, which relay signals to autonomic brainstem nuclei and higher cortical pain processing centres.…”