Neuromodulation for evaluating the pathophysiology of migraine

The two most frequently used techniques for the non-invasive modulation of brain activity are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). These techniques have repeatedly been used to modulate the activity of a given area within a neuronal network to study pathophysiological changes in migraine. The most freqeuntly stimulated areas are visual and sensorimotor areas. We discuss here what kinds of paradoxical effects have been described in response to inhibitory and excitatory modulation in patients with episodic and chronic migraine and how neuromodulation can help distinguish patients with chronic migraine from those with medication overuse headache. Furthermore, we elaborate how these methods can normalize the habituation deficit in response to visual and somatosensory stimuli, frequently detected between migraine attacks. From the studies reviewed in this chapter, it emerges that the brain of the migraine patient is characterized by alterations of synaptic activity-dependent plasticity, i.e., the phenomena of long-term potentiation and depression

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