# Association between white matter microstructural and functional abnormalities and clinical characteristics in migraine without aura: a mediation analysis

## TL;DR

This study explores how changes in brain white matter structure and function relate to clinical features in migraine without aura patients.

## Contribution

The study identifies specific white matter regions and their functional links that mediate clinical characteristics in migraine without aura.

## Key findings

- MWoA patients showed altered white matter microstructure and function in specific brain regions compared to healthy controls.
- Functional and microstructural changes in the corpus callosum and frontopontine regions correlated with disease duration and pain intensity.
- Mediation analysis suggests these brain abnormalities may explain the relationship between network integration and disease progression.

## Abstract

Migraine without aura (MWoA) is a neurological disorder associated with structural and functional abnormalities in white matter (WM). However, interactions between clinical characteristics and WM abnormalities of microstructure and function in MWoA have remained underexplored. In this study, we aimed to investigate these associations and broaden the understanding of the pathophysiology of MWoA.

A total of 51 MWoA patients and 51 healthy controls (HCs) underwent magnetic resonance imaging (MRI). Microstructural WM abnormalities were assessed using tract-based spatial statistics (TBSS). Functional alterations were evaluated by measuring the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC). Spearman’s rank correlation was used to assess the association between these abnormalities and clinical characteristics such as frequency, intensity, and disease progression of MWoA. We also conducted a region-level functional connectivity analysis, followed by mediation analysis to explore potential pathways linking WM abnormalities to clinical characteristics.

This study showed that, compared to HCs, MWoA patients showed decreased fractional anisotropy (FA), axial dispersion (AD), and DC and increased ALFF in the left frontopontine (FPT_L), decreased FA and AD in the forceps major (CC_ForcepsMajor), and decreased ALFF in the forceps minor (CC_ForcepsMinor). Among them, ALFF in the CC_ForcepsMinor and DC, FA, and AD in the FPT_L were inversely correlated with disease duration (p < 0.05). FA and AD in the CC_ForcepsMajor were inversely correlated with visual analog scale (VAS) scores (p < 0.05). Exploratory mediation analysis suggested that functional and microstructural abnormalities in the corpus callosum (CC) subregions may mediate the relationship between the DC value in the FPT-L and disease duration among MWoA patients.

This study reveals concomitant alterations in the function and microstructure of WM in the CC subregions and the FPT_L among MWoA patients. These alterations are significantly correlated with clinical characteristics and suggest that these abnormalities in functional fluctuations and WM integrity may serve as mediators between reduced network integration and disease duration in MWoA. These findings support the WM abnormality hypothesis and deepen our understanding of the pathophysiological mechanisms underlying MWoA.