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Objectives <p>This study investigated whether the coupling between cortical blood-oxygen-level-dependent (BOLD) signals and cerebrospinal fluid (CSF) flow, a physiologically motivated but indirect proxy related to glymphatic-associated dynamics, moderates the relationship between migraine disability (MIDAS) and brain age gap (BAG).</p> Methods <p>Patients with episodic migraine (EM), chronic migraine (CM), and healthy controls were recruited. BAG was estimated using a deep learning-based framework, and glymphatic-related hemodynamic-CSF dynamics were assessed using BOLD-CSF coupling. A moderation model, adjusted for sleep quality (PSQI) and biological covariates using HC3 robust standard errors, evaluated the statistical moderating role of BOLD-CSF coupling on the MIDAS-BAG association.</p> Results <p>A network-specific pattern of altered BOLD-CSF coupling was identified, with higher-order network abnormalities observed specifically in CM (<i>p</i> = 0.037). CM patients exhibited a significantly greater BAG than EM patients and healthy controls (<i>p</i> = 0.007). BOLD-CSF coupling significantly moderated the association between MIDAS and BAG (interaction <i>β</i> = -0.104, <i>p</i> = 0.035; Wald test <i>p</i> = 0.036). In individuals with relatively stronger coupling, MIDAS was more strongly associated with BAG (<i>β</i> = 0.066, <i>p</i> &lt; 0.001), whereas this association was attenuated in those with weaker coupling (<i>β</i> = 0.035, <i>p</i> = 0.005).</p> Conclusions <p>Altered higher-order network BOLD-CSF coupling may represent a relevant imaging feature of migraine chronification. BOLD-CSF coupling was associated with interindividual differences in the relationship between migraine-related disability and BAG, independent of sleep quality. These findings support the potential relevance of glymphatic-related physiological processes in chronic migraine.</p>

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Impaired glymphatic function and advanced brain age gap in chronic migraine: a multimodal MRI study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月13日

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  • Chenyu Dai,
  • Fangwang Fu,
  • Yu Guo,
  • Xiaoqing Liu,
  • Zi Tao,
  • Xiaojie Zhang,
  • Xinhao Li,
  • Chenyu Lin,
  • Mengqian Ye,
  • Mei Huang,
  • Yixuan Hu,
  • Kun Liu,
  • Yungang Cao,
  • Keyang Chen,
  • Beilei Hu,
  • Xiaozheng Liu,
  • Yan Li

摘要

Objectives

This study investigated whether the coupling between cortical blood-oxygen-level-dependent (BOLD) signals and cerebrospinal fluid (CSF) flow, a physiologically motivated but indirect proxy related to glymphatic-associated dynamics, moderates the relationship between migraine disability (MIDAS) and brain age gap (BAG).

Methods

Patients with episodic migraine (EM), chronic migraine (CM), and healthy controls were recruited. BAG was estimated using a deep learning-based framework, and glymphatic-related hemodynamic-CSF dynamics were assessed using BOLD-CSF coupling. A moderation model, adjusted for sleep quality (PSQI) and biological covariates using HC3 robust standard errors, evaluated the statistical moderating role of BOLD-CSF coupling on the MIDAS-BAG association.

Results

A network-specific pattern of altered BOLD-CSF coupling was identified, with higher-order network abnormalities observed specifically in CM (p = 0.037). CM patients exhibited a significantly greater BAG than EM patients and healthy controls (p = 0.007). BOLD-CSF coupling significantly moderated the association between MIDAS and BAG (interaction β = -0.104, p = 0.035; Wald test p = 0.036). In individuals with relatively stronger coupling, MIDAS was more strongly associated with BAG (β = 0.066, p < 0.001), whereas this association was attenuated in those with weaker coupling (β = 0.035, p = 0.005).

Conclusions

Altered higher-order network BOLD-CSF coupling may represent a relevant imaging feature of migraine chronification. BOLD-CSF coupling was associated with interindividual differences in the relationship between migraine-related disability and BAG, independent of sleep quality. These findings support the potential relevance of glymphatic-related physiological processes in chronic migraine.