Scholarlink

Background <p>The differences between episodic and chronic migraine phenotypes imply a system-level network reorganization often obscured by traditional discrete analyses. We employed multidimensional functional gradient analysis to characterize these distinct topological patterns and anchor them to microscale mechanisms.</p> Method <p>This study utilized resting-state fMRI in 111 participants with migraine without aura (MWoA) to map functional connectome gradients. To rigorously dissect disease-state-specific features from aging effects, we compared age-matched episodic and chronic cohorts. Beyond standard gradient axes, we systematically evaluated topological reorganization using manifold eccentricity and differentiation metrics. Furthermore, macroscopic alterations were biologically decoded by analyzing spatial correlations with cerebral blood flow, neurotransmitter receptors, transcriptomic profiles, and functional enrichment analysis.</p> Results <p>We identified divergent network profiles where EM was characterized by transmodal network shifts, whereas CM exhibited a distinct principal gradient shift coupled with sensory-cognitive axis compression. Alterations in low-dimensional gradient scores, alongside increased manifold eccentricity and segregation, effectively distinguished patients from controls and were significantly associated with clinical disability. These macroscopic alterations spatially converged with cerebral blood flow and serotonin transporter density, while decoding analysis revealed enrichment in synaptic-metabolic pathways, glial populations, and neuropsychiatric genetic risks.</p> Conclusion <p>This study identifies a novel multi-scale link between macroscopic topological architecture and microscale synaptic-metabolic patterns associated with the chronic migraine phenotype without aura. Moving beyond descriptive topology, these findings implicate “neuro-metabolic fragility” as a potential biological substrate of the disease, suggesting specific molecular targets for therapeutic interventions.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Topological signatures differentiating episodic and chronic phenotypes in migraine without aura: a multi-scale analysis revealing divergent network profiles

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月13日

查看全文
  • Chenyu Lin,
  • Chenyu Dai,
  • Yixuan Hu,
  • Xiaojie Zhang,
  • Zi Tao,
  • Xiaoqing Liu,
  • Xinhao Li,
  • Tong Xu,
  • Mengqian Ye,
  • Yungang Cao,
  • Keyang Chen,
  • Kun Liu,
  • Xiaozheng Liu,
  • Fangwang Fu,
  • Yan Li

摘要

Background

The differences between episodic and chronic migraine phenotypes imply a system-level network reorganization often obscured by traditional discrete analyses. We employed multidimensional functional gradient analysis to characterize these distinct topological patterns and anchor them to microscale mechanisms.

Method

This study utilized resting-state fMRI in 111 participants with migraine without aura (MWoA) to map functional connectome gradients. To rigorously dissect disease-state-specific features from aging effects, we compared age-matched episodic and chronic cohorts. Beyond standard gradient axes, we systematically evaluated topological reorganization using manifold eccentricity and differentiation metrics. Furthermore, macroscopic alterations were biologically decoded by analyzing spatial correlations with cerebral blood flow, neurotransmitter receptors, transcriptomic profiles, and functional enrichment analysis.

Results

We identified divergent network profiles where EM was characterized by transmodal network shifts, whereas CM exhibited a distinct principal gradient shift coupled with sensory-cognitive axis compression. Alterations in low-dimensional gradient scores, alongside increased manifold eccentricity and segregation, effectively distinguished patients from controls and were significantly associated with clinical disability. These macroscopic alterations spatially converged with cerebral blood flow and serotonin transporter density, while decoding analysis revealed enrichment in synaptic-metabolic pathways, glial populations, and neuropsychiatric genetic risks.

Conclusion

This study identifies a novel multi-scale link between macroscopic topological architecture and microscale synaptic-metabolic patterns associated with the chronic migraine phenotype without aura. Moving beyond descriptive topology, these findings implicate “neuro-metabolic fragility” as a potential biological substrate of the disease, suggesting specific molecular targets for therapeutic interventions.