White Matter-Associated Functional Connectivity in the Human Brain
| dc.contributor.committeeChair | Ding, Zhaohua | |
| dc.creator | Xu, Lyuan | |
| dc.creator.orcid | 0000-0002-9791-0806 | |
| dc.date.accessioned | 2025-09-26T11:09:52Z | |
| dc.date.created | 2025-08 | |
| dc.date.issued | 2025-06-11 | |
| dc.date.submitted | August 2025 | |
| dc.description.abstract | Functional magnetic resonance imaging (fMRI) has traditionally focused on gray matter (GM), while blood-oxygen-level-dependent (BOLD) signals in white matter (WM) were often dismissed as physiologically irrelevant. However, growing evidence indicates that WM exhibits coherent and meaningful neural activity. This dissertation systematically explores the spatiotemporal organization, modulation, and clinical relevance of WM-associated functional connectivity (FC) and proposes a novel framework to characterize the WM-GM connectome. We begin by examining the anisotropic structure of spontaneous BOLD correlations in WM, characterized through the construction of functional correlation tensors (FCTs). Leveraging a large normal aging cohort, we identify region-specific aging effects on FCT-derived indices, providing detailed maps of age-related alterations in local FCT metrics. We further examine seasonal modulations of WM-GM FC in a healthy population. By modeling sinusoidal trends across seasons, we detect significant periodic variations in low-frequency fluctuations, global and network-level FC strength, and topological properties of brain networks. These variations correlate with environmental factors like daylength and temperature, highlighting the dynamic influence of external cycles on intrinsic brain organization. Extending to clinical context, we analyze WM-GM FC and network properties in individuals with preclinical Alzheimer’s disease (AD) or AD dementia, compared to controls. Our findings reveal that the WM-GM functional connectome undergoes regional and systemic dysfunctions as early as in the preclinical stage, correlating with amyloid deposition and cognitive impairment. Finally, we introduce a hypergraph-based model to capture high-order WM-GM interactions, revealing group-level differences in clustering coefficients and centralities that may serve as novel AD biomarkers. Overall, this work establishes WM functional connectivity as a systematic and clinically informative feature, expanding our understanding of the functional role of WM in the human brain. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/1803/19888 | |
| dc.language.iso | en | |
| dc.subject | white matter | |
| dc.subject | fMRI | |
| dc.title | White Matter-Associated Functional Connectivity in the Human Brain | |
| dc.type | Thesis | |
| dc.type.material | text | |
| local.embargo.lift | 2026-08-01 | |
| local.embargo.terms | 2026-08-01 | |
| thesis.degree.discipline | Electrical and Computer Engineering | |
| thesis.degree.grantor | Vanderbilt University Graduate School | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | PhD |
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