Multi-compartment diffusion magnetic resonance imaging models link tract-related characteristics with working memory performance in healthy older adults

Christopher E. Bauer, Valentinos Zachariou, Pauline Maillard, Arvind Caprihan, Brian T. Gold

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Multi-compartment diffusion MRI metrics [such as metrics from free water elimination diffusion tensor imaging (FWE-DTI) and neurite orientation dispersion and density imaging (NODDI)] may reflect more specific underlying white-matter tract characteristics than traditional, single-compartment metrics [i.e., metrics from Diffusion Tensor Imaging (DTI)]. However, it remains unclear if multi-compartment metrics are more closely associated with age and/or cognitive performance than single-compartment metrics. Here we compared the associations of single-compartment [Fractional Anisotropy (FA)] and multi-compartment diffusion MRI metrics [FWE-DTI metrics: Free Water Eliminated Fractional Anisotropy (FWE-FA) and Free Water (FW); NODDI metrics: Intracellular Volume Fraction (ICVF), Orientation Dispersion Index (ODI), and CSF-Fraction] with both age and working memory performance. A functional magnetic resonance imaging (fMRI) guided, white matter tractography approach was employed to compute diffusion metrics within a network of tracts connecting functional regions involved in working memory. Ninety-nine healthy older adults (aged 60–85) performed an in-scanner working memory task while fMRI was performed and also underwent multi-shell diffusion acquisition. The network of white matter tracts connecting functionally-activated regions was identified using probabilistic tractography. Diffusion metrics were extracted from skeletonized white matter tracts connecting fMRI activation peaks. Diffusion metrics derived from both single and multi-compartment models were associated with age (ps ≤ 0.011 for FA, FWE-FA, ICVF and ODI). However, only multi-compartment metrics, specifically FWE-FA (p = 0.045) and ICVF (p = 0.020), were associated with working memory performance. Our results suggest that while most current diffusion metrics are sensitive to age, several multi-compartment metrics (i.e., FWE-FA and ICVF) appear more sensitive to cognitive performance in healthy older adults.

Original languageEnglish
Article number995425
JournalFrontiers in Aging Neuroscience
StatePublished - Oct 5 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (grant numbers: NIA R01 AG055449, NIA R01 AG068055, NINDS RF1 NS122028, NIA P30 AG072946, and NIGMS S10 OD023573).

Publisher Copyright:
Copyright © 2022 Bauer, Zachariou, Maillard, Caprihan and Gold.


  • aging
  • brain
  • diffusion tensor imaging (DTI)
  • free water
  • functional networks
  • neurite orientation dispersion and density imaging (NODDI)
  • white matter
  • working memory

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience


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