# Influence of Sensory and Motor Dysfunctions on White - Gray Matters Functional Connectome in Preclinical AD

> **NIH NIH R21** · VANDERBILT UNIVERSITY · 2024 · $438,448

## Abstract

PROJECT SUMMARY
Sensory and motor dysfunctions are potential biomarkers of preclinical Alzheimer’s disease (AD) as they may
precede cognitive impairments. However, how the sensory and motor dysfunctions affect the brain functional
connectivity (FC) between white matter (WM) and gray matter (GM) remains uninvestigated. This is because
previous functional MRI analyses have overlooked WM due to weaker signal in WM. We recently demonstrated
that FC between WM and GM (i.e., WM-GM FC) is reliably detectable and sensitive to AD, confirming its potential
in capturing brain function and its changes. However, three major methodological obstacles hinder accurate
evaluations and analyses of WM-GM FC at multiple scales. First, the unique topology of WM-GM FC network
cannot be adequately modeled by a conventional graph model. Second, the most advanced WM spatial
smoothing method, which requires diffusion MRI data for guidance, is complex and impractical for standalone
fMRI data. Third, the elongated shape of WM functional architecture compromises traditional group-level voxel-
scale statistical analysis. Therefore, our overall goal is to develop and apply a novel family of methods to
investigate multi-scale alterations in the WM-GM functional connectome resulting from sensory and motor
dysfunctions in preclinical AD. This goal will be achieved through two aims. Aim 1 is to develop innovative
methods to characterize, detect and analyze WM-GM FC at multiple scales, including network-, region-
and voxel- scales. Specifically, we will develop a bipartite-graph model to characterize WM-GM FC networks
and quantify network properties, create a 4D atlas composed of diffusion-informed smoothing kernels for all WM
voxels to simplify WM smoothing for any fMRI images, and develop a functional tract-based spatial statistics
(fTBSS) method to optimize group-level voxel-scale analysis. Aim 2 is to apply the developed methods to
investigate changes in WM-GM FC at multiple scales resulting from motor dysfunctions in preclinical
AD. Exploiting our developed methods and existing databases, we will test three hypotheses. 1) specific WM-
GM FC network metrics, especially within the somatomotor-related networks, may alter in preclinical AD subjects
with MD relative to elderly controls and more altered WM-GM FC metrics may be associated with more severe
MD; 2) the relationship between MD and WM-GM FC metrics may be moderated by other biological factors (e.g.,
sex, APOE ε4 status and brain atrophy). 3) the WM-GM FC metrics may act as mediators in the relationship
between amyloid deposit and MD. The outcomes of this project will fill the gaps in our knowledge of how sensory
and motor dysfunctions influence WM-GM functional connectome in preclinical AD and enrich the set of
biomarkers for prediction of early AD, which will eventually enhance the well-being of both the aging population
and their caregivers. The released code and atlases will benefit a broad community of investigators in...

## Key facts

- **NIH application ID:** 10884723
- **Project number:** 1R21AG083915-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Yurui Gao
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $438,448
- **Award type:** 1
- **Project period:** 2024-06-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884723

## Citation

> US National Institutes of Health, RePORTER application 10884723, Influence of Sensory and Motor Dysfunctions on White - Gray Matters Functional Connectome in Preclinical AD (1R21AG083915-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10884723. Licensed CC0.

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