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Related Experiment Video

Updated: Feb 13, 2026

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
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Investigating White Matter Functional Network Connectivity Across the Alzheimer's Disease Spectrum Using

Vaibhavi S Itkyal1,2,3, Theodore J LaGrow4,5,6, Kyle Mark Jensen2

  • 1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, GA.

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Summary

Alzheimer's disease (AD) shows altered white matter (WM) functional connectivity even in mild cognitive impairment (MCI). This study reveals WM functional network connectivity changes across the AD spectrum, suggesting it as a potential biomarker.

Keywords:
ADNIAlzheimer’s diseasefunctional connectivityindependent component analysisresting-state fMRIwhite matter

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Area of Science:

  • Neuroimaging
  • Neuroscience
  • Biomarker Discovery

Background:

  • White matter (WM) was historically viewed as functionally inert in fMRI research.
  • Emerging evidence highlights WM's role in BOLD fluctuations and functional connectivity.
  • Understanding WM's functional alterations is crucial for neurodegenerative disease research.

Purpose of the Study:

  • To investigate changes in WM functional network connectivity (FNC) across the Alzheimer's disease (AD) spectrum.
  • To assess WMWM, gray matter (GM)GM, and WMGM connectivity alterations in cognitively normal (CN), mild cognitive impairment (MCI), and AD groups.
  • To explore WM sFNC as a potential biomarker for AD staging and monitoring.

Main Methods:

  • Utilized resting-state fMRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (CN, MCI, AD).
  • Applied guided independent component analysis (ICA) with a multiscale template of 202 intrinsic connectivity networks (ICNs).
  • Computed static functional network connectivity (sFNC) and performed group comparisons with statistical correction.

Main Results:

  • Significant alterations in WMWM and WMGM connectivity were observed in AD, involving frontal, sensorimotor, and occipitotemporal networks.
  • WMGM connectivity disruptions were evident even in MCI patients compared to CN individuals.
  • Specific disruptions included reduced GMcerebellar:WMfrontal coupling and increased GMhippocampal to WMfrontal connectivity.

Conclusions:

  • WM functional connectivity is measurable and selectively altered across the AD continuum.
  • Functional disruption of WM circuits appears before overt dementia onset.
  • WM sFNC offers a complementary biomarker to GM-based measures for AD management.