Association of white matter microstructural and functional abnormalities with clinical characteristics in migraine without aura: A mediation analysis

Qixuan Fu¹Chao-rong Xie¹Xu Ouyang¹Zhiyang Zhang¹Xuhong Yang²Xiangdong Luo³Qinyi Yan¹Tong Wang¹Xiao Wang^1,4*Ling Zhao^1,4*

• ¹Chengdu University of Traditional Chinese Medicine School of Acupuncture and Tuina, Chengdu, China
• ²Hospital of Chengdu University of Traditional Chinese Medicine Department of Neurology, Chengdu, China
• ³Sichuan Provincial People's Hospital Department of Neurology, Chengdu, China
• ⁴Acupoint Effect Key Laboratory of Sichuan Province, Chengdu, China

Background: 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. Methods: Fifty-one 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 fluctuations (ALFF) and degree centrality (DC). Spearman rank correlation was used to assess the association of these abnormalities with clinical characteristics such as frequency, intensity and disease progression of MWoA. We also conducted region-level functional connectivity analysis, followed by mediation analysis to explore potential pathways linking WM abnormalities to clinical characteristics. Results: This study showed that, compared with HCs, MWoA patients showed decreased fractional anisotropy (FA) and 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 CC_ForcepsMinor and DC, FA, and AD in FPT_L were inversely correlated with disease duration (p < 0.05). FA and AD in 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 in MWoA patients. Conclusion: This study reveals concomitant alterations in function and microstructure of WM in the CC subregions and the FPT_L in MWoA. These alterations are significantly correlated to clinical characteristics, and suggested that these abnormalities in functional fluctuations and WM integrity may serve as a mediator between reduced network integration and disease duration in MWoA. These findings support the WM abnormality hypothesis, deepen our understanding of the pathophysiological mechanisms underlying MWoA.