Abstract

Brain activation mapping using functional magnetic resonance imaging (fMRI) has been extensively studied in brain gray matter (GM), whereas in large disregarded for probing white matter (WM). This unbalanced treatment has been in part due to controversies in relation to the nature of the blood oxygenation level-dependent (BOLD) contrast in WM and its detectability. However, an accumulating body of studies has provided solid evidence of the functional significance of the BOLD signal in WM and has revealed that it exhibits anisotropic spatio-temporal correlations and structure-specific fluctuations concomitant with those of the cortical BOLD signal. In this work, we present an anisotropic spatial filtering scheme for smoothing fMRI data in WM that accounts for known spatial constraints on the BOLD signal in WM. In particular, the spatial correlation structure of the BOLD signal in WM is highly anisotropic and closely linked to local axonal structure in terms of shape and orientation, suggesting that isotropic Gaussian filters conventionally used for smoothing fMRI data are inadequate for denoising the BOLD signal in WM. The fundamental element in the proposed method is a graph-based description of WM that encodes the underlying anisotropy observed across WM, derived from diffusion-weighted MRI data. Based on this representation, and leveraging graph signal processing principles, we design subject-specific spatial filters that adapt to a subject’s unique WM structure at each position in the WM that they are applied at. We use the proposed filters to spatially smooth fMRI data in WM, as an alternative to the conventional practice of using isotropic Gaussian filters. We test the proposed filtering approach on two sets of simulated phantoms, showcasing its greater sensitivity and specificity for the detection of slender anisotropic activations, compared to that achieved with isotropic Gaussian filters. We also present WM activation mapping results on the Human Connectome Project’s 100-unrelated subject dataset, across seven functional tasks, showing that the proposed method enables the detection of streamline-like activations within axonal bundles.

Highlights

  • To date, reports on task-based functional magnetic resonance imaging activation mapping and resting-state functional connectivity have been overwhelmingly restricted to the gray matter (GM), whereas white matter (WM) functional data have been largely ignored or treated as a nuisance regressor

  • We validated the performance of the proposed diffusion-informed spatial smoothing (DSS) method relative to isotropic Gaussian spatial smoothing (GSS) through a series of tests on synthetic phantoms—circular and streamline-based—and produced proof-of-concept results on real data from the HCP100 subject set

  • While the former controls the spatial extent of the filter in a manner akin to the full width at half maximum (FWHM) of isotropic Gaussian filters, the latter controls the

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Summary

Introduction

Reports on task-based functional magnetic resonance imaging (fMRI) activation mapping and resting-state functional connectivity have been overwhelmingly restricted to the gray matter (GM), whereas white matter (WM) functional data have been largely ignored or treated as a nuisance regressor. Such unbalanced treatment of fMRI data within GM and WM, due in part to controversies in relation to the source of the BOLD signal in WM, has led to a systematic underreporting of BOLDrelated activity in WM (Gawryluk et al, 2014; Mazerolle et al, 2019). A growing number of recent studies have shown that low frequency BOLD fluctuations can be used to estimate the dynamic functioning of fiber tracts (Gore et al, 2019), in both health (Huang et al, 2018b; Li et al, 2020b; Marussich et al, 2017) and disease (Gao et al, 2020; Ji et al, 2019; Jiang et al, 2019), providing a powerful means to study how information is transferred and integrated between functionally specialized cortices

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