Alterations of white matter microstructure in migraine patients vary in the peri-ictal phases

Abstract

Alterations in white matter (WM) microstructure are commonly found in migraine patients. Here, we employ a longitudinal study of episodic migraine without aura using diffusion MRI (dMRI) to investigate whether such WM microstructure alterations vary through the different phases of the pain cycle. Fourteen patients with episodic migraine without aura related with menstruation were scanned through four phases of their (spontaneous) migraine cycle (interictal, preictal, ictal and postictal). Fifteen healthy controls were studied in the corresponding phases of the menstrual cycle. Multi-shell dMRI data was acquired and pre-processed to obtain maps of diffusion parameters reflecting WM microstructure. After a whole-brain analysis comparing patients with controls, a region-of-interest analysis was performed to determine whether the patients' microstructural changes varied across the migraine cycle in specific WM tracts. Compared with controls, patients showed reduced axial diffusivity (AD) in several WM tracts across the whole brain in the interictal phase, and increased fractional anisotropy (FA) in commissural fibers in the ictal phase. Interestingly, AD returned to baseline levels during peri-ictal phases in specific projection and association fibers. In contrast, FA values decreased in the ictal phase away from normal values in a few commissural and projection tracts. Widespread WM fiber tracts suffer structural variations across the migraine cycle, suggesting microstructural changes potentially associated with limbic and salience functional networks and highlighting the importance of the cycle phase in imaging studies of migraine.Significance Statement Our study reveals dynamic changes in white matter microstructure across different phases of the migraine cycle, using advanced diffusion MRI. By employing a case-control longitudinal design on patients with episodic menstrual migraine, we identified transient reductions in axial diffusivity and fractional anisotropy in specific white matter tracts, which varied with migraine phases independently of hormonal influences. This is the first study to document such phase-dependent microstructural changes, highlighting the brain's ability to adapt rapidly to pain. Our findings provide significant insights into neuroplasticity, enhancing the understanding of migraine and potentially informing broader neurological research on the brain's response to pathological states.