Structure-function coupling as a correlate and potential biomarker of cognitive impairment in multiple sclerosis

Shanna D. Kulik*, Ilse M. Nauta, Prejaas Tewarie, Ismail Koubiyr, Edwin van Dellen, Aurelie Ruet, Kim A. Meijer, Brigit A. de Jong, Cornelis J. Stam, Arjan Hillebrand, Jeroen J.G. Geurts, Linda Douw, Menno M. Schoonheim

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Multiple sclerosis (MS) features extensive connectivity changes, but how structural and functional connectivity relate, and whether this relation could be a useful biomarker for cognitive impairment in MS is unclear. This study included 79 MS patients and 40 healthy controls (HCs). Patients were classified as cognitively impaired (CI) or cognitively preserved (CP). Structural connectivity was determined using diffusion MRI and functional connectivity using resting-state magnetoencephalography (MEG) data (theta, alpha1, and alpha2 bands). Structure-function coupling was assessed by correlating modalities, and further explored in frequency bands that significantly correlated with whole-brain structural connectivity. Functional correlates of short-and long-range structural connections (based on tract length) were then specifically assessed. Receiving operating curve analyses were performed on coupling values to identify biomarker potential. Only the theta band showed significant correlations between whole-brain structural and functional connectivity (rho = −0.26, p = 0.023, only in MS). Long-range structure-function coupling was stronger in CI patients compared to HCs ( p = 0.005). Short-range coupling showed no group differences. Structure-function coupling was not a significant classifier of cognitive impairment for any tract length (short-range area under the curve (AUC) = 0.498, p = 0.976, long-range AUC = 0.611, p = 0.095). Long-range structure-function coupling was stronger in CI MS compared to HCs, but more research is needed to further explore this measure as biomarkers in MS.

Original languageEnglish
Pages (from-to)339-356
Number of pages18
JournalNetwork Neuroscience
Issue number2
Publication statusPublished - 1 Jun 2022
Externally publishedYes


  • Cognition
  • Diffusion tensor imaging
  • Functional connectivity
  • Magnetoencephalography
  • Multiple sclerosis
  • Structural connectivity


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