Electrophysiological correlates of episodic migraine chronification: evidence for thalamic involvement

Episodic migraine is characterized by decreased high-frequency somatosensory oscillations (HFOs), reflecting thalamo-cortical activity, and deficient habituation of low-frequency (LF-) somatosensory evoked potentials (SSEPs) to repetitive sensory stimulation between attacks. Here, we study conventional LF-SSEPs and HFOs in episodic migraineurs who developed chronic migraine (CM). Thirty-four episodic (15 interictally [MOii], 19 ictally [MOi]) and 19 CM patients underwent right median nerve SSEPs. The patient groups were compared to a group of 20 healthy volunteers (HV) of comparable age and gender distribution. We measured the N20-P25 LF-SSEP 1st amplitude block and habituation, and, after applying a band-pass filter (450-750 Hz), maximal peak-to-peak latency and the amplitudes of the early and late HFOs. Reduced early HFOs, lower 1st block LF-SSEPs and deficient habituation characterize MOii. Initially higher SSEP amplitudes and late normal habituation characterize both CM and MOi patients. After the digital filtration, both patient groups showed shortened latency peaks and normalization of early HFO amplitudes with increased late HFOs. When data of MO and CM patients were combined, the monthly number of days with headache negatively correlated with the LF-SSEP slope (r = -0.385, p = 0.006), which in turn negatively correlated with the 1st amplitude block (r = 0.568, p < 0.001). Our results show abnormalities in chronic migraine that are also reported during attacks in episodic migraineurs, namely early response sensitization and late habituation. The HFO analysis suggests that this sensory sensitization may be explained by an increase in the strength of the connections between the thalamus and cortex compared to episodic migraine between attacks. Whether this electro-functional behaviour is primary or secondary to daily headache, thus reflecting an electrophysiological fingerprint of the somatosensory system central sensitization process, remains to be determined.