Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes

Evoked potentials

The quest toward a specific biomarker for migraine stands among the biggest challenges of the last 50 years. Electrophysiological techniques are particularly suitable to study the nervous system in human beings. They are noninvasive, riskless and quite easy to perform and have a temporal resolution that cannot be achieved with other methods. Among them, the visual-evoked modality is being widely studied for several decades. Higher amplitude of fundamental harmonic from steady-state visual stimulation is commonly found in episodic migraine. Many studies performed interictally in groups of episodic patients have shown a habituation deficit of visual evoked potentials, even if this finding has been a matter of controversy. An abnormal thalamic control of information reaching the cortex, which in turn causes an altered degree of lateral inhibition of the visual cortex, could be the key of this functional abnormality, which normalizes during or close to a migraine attack. Along the same line, a habituation deficit has been demonstrated using a somatosensory modality (SSEPs), the magnitude of the habituation deficit being significantly correlated to the evolution of migraine. Additional works highlighted a less-efficient subcortical inhibition of sensory cortices. As far as the auditory modality is concerned, a stronger stimulus intensity dependence of late, long-latency, auditory evoked cortical potentials (IDAP) was found between attacks in migraineurs compared with controls. It seems also worthwhile to notice that an interhemispheric asymmetry of responses has been described using most sensory stimulations. Using single-pulse transcranial magnetic stimulation (sTMS) over the visual cortex, a higher phosphene prevalence and a lower threshold were found in migraine with aura patients. Otherwise, resting-state motor or phosphene thresholds obtained with sTMS in episodic patients provided discrepant results. In chronic migraine (CM), neurophysiologic signs of sensitization have been reported while recording SSEPs. Interestingly, a simultaneous analysis of SSEP habituation and thalamocortical loop activation in chronic subjects showed a neurophysiological pattern similar to that of ictal episodic migraine. In medication overuse headache patients, SSEPs suggested a persistent cortical sensitization. The recorded habituation abnormalities appear to vary according to the overused drug. Akin to results of SSEP studies, VEP amplitudes habituate normally during stimulus repetition in CM and may change with the transition from CM to episodic migraine, switching from normal to deficient habituation. In conclusion, studies of evoked potentials in migraine show that the migraine brain processes sensory information differently from healthy subjects. The most frequently detected peculiarity during the migraine pain-free phase is an excessive cortical responsivity to almost any type of sensory stimulation. The cortical hyperresponsivity is not constant in migraine patients and may not be reproducible. The reasons for these between-studies discrepancies are multifaceted, and they reflect the complex pathophysiology of the disease

Neurophysiology of migraine with aura

In this chapter, we review the findings obtained by neurophysiological studies in migraine with aura (MA). Spontaneous electroencephalography activity in MA is characterized by abnormalities in alpha rhythm power and symmetry, and the presence of slowing, and increased, information flow in a wide range of frequency bands. Evoked potential (EP) studies indicate the occurrence of increased grand-average cortical response amplitudes, interhemispheric response asymmetry, as well as deficient habituation to any kind of repetitive sensory stimulation, in MA patients. Transcranial magnetic stimulation (TMS) methods applied in MA confirm abnormalities in cortical responsivity, such as greater motor evoked potential (MEP) amplitude, lower threshold for phosphene production, and paradoxical effects induced by depressing or enhancing repetitive TMS. Brainstem reflex studies indicate a deficit of blink reflex habituation in MA. Mild abnormalities of neuromuscular transmission shown by single-fibre electromyography were more pronounced in migraineurs with aura, and positively correlated to the complexity of their aura. The few studies performed in patients during the aura described suppression of evoked potentials, desynchronization in extrastriate areas and the temporal lobe, and large variations in direct current potentials using magnetoelectroencephalography. In contrast, patients affected by familial hemiplegic migraine had opposite neurophysiological patterns in comparison with patients suffering from the common forms of migraine