Fixel-based structure-function coupling in Alzheimer’s disease and Mild Cognitive Impairment
Poster No:
1279
Submission Type:
Abstract Submission
Authors:
Charly Billaud1, Junhong Yu1
Institutions:
1Nanyang Technological University, Singapore, NA
First Author:
Co-Author:
Introduction:
Functional MRI (fMRI) and diffusion tensor imaging (DTI) allowed researchers to explore correlations between structural connectivity (SC) and functional connectivity (FC) (SC-FC coupling). Studies on Mild cognitive impairment (MCI) and Alzheimer's disease (AD) observed disruptions in coupling, co-occurring with cognitive decline. Advanced "fixel-based" analyses improved DTI's accuracy in assessing microstructural and macrostructural features of white matter (WM) fibres (Dhollander et al., 2021; Raffelt et al., 2017), but were not used in ageing coupling studies. Previous studies commonly defined SC via tensor-based voxel averages and streamline counts, thereby losing fibre-specific information. We investigated different types of fixel-FC coupling across the neurocognitive ageing spectrum and their relation to cognition.
Methods:
Data from 392 participants (Age mean=73; 207F) from the ADNI, 225 cognitively normal, 142 MCI, and 25 AD who completed diffusion-weighted and resting-state fMRI scans, were analysed. Structural connectomes were constructed using average fixel-metrics (fibre density (FD), fibre-bundle cross-section Log(FbC), or their combined measure (FDC)) as edges. Various types of subject- and group-wise SC-FC coupling for each SC metric were calculated at edge and node levels.
Results:
Whole-connectome SC-FC coupling derived from various SC metrics did not differ significantly between groups, and was low to medium in magnitude, not exceeding previously reported instances of DTI-based SC-FC coupling. However, distinct node- and edge-specific alterations were found across SC measures and diagnosis groups. Only a fraction of coupling differences overlapped across different fixel SC metrics and none overlapped between fixel-based coupling and streamline count. Relative to CN, coupling alterations included the left lateral prefrontal cortex, the bilateral middle temporal gyrus (MTG), and the precuneus/posterior cingulate cortex in AD, and the bilateral MTG and right precuneus in MCI, but MCI and AD alterations were not affecting the same specific nodes and edges. Nodal FD-FC and FDC-FC coupling of DMN nodal strength predicted memory performance and cognitive decline within the full sample.
Conclusions:
The partial overlap in group differences across fixel-metrics-FC coupling (and absence of overlap with streamline count-FC coupling) suggests fixel-based microscopic and macroscopic features of white matter provide distinct information about structure-function coupling. Streamline SC nodal coupling did not differ, which suggests the number of streamlines may not be a good indicator of regional FC. The fact that coupling alterations did not occur in a consistent direction across MCI and AD is in line with a previous report of FC showing counterintuitive increases in MCI and decreases in AD and vice versa in the DMN. The fact that only FD and FDC coupling metrics were robustly associated with cognition suggests node coupling is more relevant to cognition at the microstructural level of WM, while SC metrics characterising macrostructural features such as Log(FbC) and "raw" streamline SC may not be as relevant.
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 1
fMRI Connectivity and Network Modeling 2
Keywords:
Aging
Cognition
FUNCTIONAL MRI
MRI
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - fixel; multimodal; coupling; Alzheimer's; Mild Cognitive Impairment
1|2Indicates the priority used for review
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Raffelt, D. A., Tournier, J.-D., Smith, R. E., Vaughan, D. N., Jackson, G., Ridgway, G. R., & Connelly, A. (2017). Investigating white matter fibre density and morphology using fixel-based analysis. Neuroimage, 144, 58–73. https://doi.org/10.1016/j.neuroimage.2016.09.029