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Disrupted Brain Structure-Function Coupling and Its Mediating Effects on the Associations Between Cerebral Small

Na Wang1, Lingfei Guo1, Yian Gao2

  • 1Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

CNS Neuroscience & Therapeutics
|September 18, 2025
PubMed

Insights

Cerebral small vessel disease (CSVD) burden disrupts brain structure-function coupling, specifically in the right putamen, which mediates cognitive dysfunction. This imaging indicator offers new insights into CSVD

Area of Science:

  • Neuroimaging
  • Neurology
  • Brain Structure and Function

Background:

  • Cerebral small vessel disease (CSVD) is associated with cognitive decline.
  • Understanding the neural mechanisms linking CSVD burden to cognitive dysfunction is crucial.

Purpose of the Study:

  • To investigate the relationship between CSVD burden, cognitive impairment, and brain structure-function coupling.
  • To identify specific brain regions and coupling metrics involved in this association.

Main Methods:

  • Included 108 mild CSVD (CSVD-m), 53 severe CSVD (CSVD-s) patients, and 76 healthy controls (HC).
  • Calculated regional homogeneity (ReHo)-gray matter volume (GMV) and amplitude of low-frequency fluctuation (ALFF)-GMV ratios as voxel-wise structure-function coupling indicators.

Main Results:

  • Severe CSVD burden showed altered ReHo-GMV and ALFF-GMV coupling in specific brain regions.
  • Disrupted structure-function coupling in the right putamen mediated the link between CSVD burden and cognitive dysfunction.

Conclusions:

  • Brain structure-function coupling (ReHo-GMV, ALFF-GMV) mediates CSVD-related cognitive dysfunction.
  • This coupling serves as an innovative imaging biomarker for studying CSVD burden and cognitive impairment.
Abstract

Keywords:
ALFF–GMV couplingReHo–GMV couplingcerebral small vessel diseasemediation analysisstructure–function coupling

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