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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 detachability. 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. Funding: McDonnell Center for Systems Neuroscience at Washington University; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2017-04889, 2018-06689]; Royal Physiographic Society of Lund; Thorsten and Elsa Segerfalk Foundation; Hans Werthen Foundation; ITEA3/VINNOVA; Center for Industrial Information Technology (CENIIT) at Linkoping University; BrightFocus FoundationBrightFocus Foundation [A2016172S]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; National Institute of Diabetes and Digestive and Kidney DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [K01DK101631]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R56AG068261]; [1U54MH091657]

In this work, we leverage the Laplacian eigenbasis of voxelwise white matter (WM) graphs derived from diffusionweighted MRI data, dubbed WM harmonics, to characterize the spatial structure of WM fMRI data. Our motivation for such a characterization is based on studies that show WM fMRI data exhibit a spatial correlational anisotropy that coincides with underlying fiber patterns. By quantifying the energy content of WM fMRI data associated with subsets of WM harmonics across multiple spectral bands, we show that the data exhibits notable subtle spatial modulations under functional load that are not manifested during rest. WM harmonics provide a novel means to study the spatial dynamics of WM fMRI data, in such way that the analysis is informed by the underlying anatomical structure. Funding: Swedish Research CouncilSwedish Research CouncilEuropean Commission [2017-04889]; Royal Physiographic Society of Lund; Thorsten and Elsa Segerfalk Foundation; BrightFocus FoundationBrightFocus Foundation [A2016172S]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K01DK101631, R56AG068261, P41EB015902, R01MH074794]; ITEA3/VINNOVA funded project Intelligence based iMprovement of Personalized treatment And Clinical workflow supporT (IMPACT); Center for Industrial Information Technology (CENIIT) at Linkoping University; Hans Werth en Foundation; SwedenAmerica Foundation

The human brain cortical layer has a convoluted morphology that is unique to each individual. Characterization of the cortical morphology is necessary in longitudinal studies of structural brain change, as well as in discriminating individuals in health and disease. A method for encoding the cortical morphology in the form of a graph is presented. The design of graphs that encode the global cerebral hemisphere cortices as well as localized cortical regions is proposed. Spectral metrics derived from these graphs are then studied and proposed as descriptors of cortical morphology. As proof-of-concept of their applicability in characterizing cortical morphology, the metrics are studied in the context of hemispheric asymmetry as well as gender dependent discrimination of cortical morphology., Comment: arXiv admin note: substantial text overlap with arXiv:1810.10339