Whole-brain multivariate hemodynamic deconvolution for functional MRI with stability selection.

Conventionally, analysis of functional MRI (fMRI) data relies on available information about the experimental paradigm to establish hypothesized models of brain activity. However, this information can be inaccurate, incomplete or unavailable in multiple scenarios such as resting-state, naturalistic paradigms or clinical conditions. In these cases, blind estimates of neuronal-related activity can be obtained with paradigm-free analysis methods such as hemodynamic deconvolution. Yet, current formulations of the hemodynamic deconvolution problem have three important limitations: (1) their efficacy strongly depends on the appropriate selection of regularization parameters, (2) being univariate, they do not take advantage of the information present across the brain, and (3) they do not provide any measure of statistical certainty associated with each detected event. Here we propose a novel approach that addresses all these limitations. Specifically, we introduce multivariate sparse paradigm free mapping (Mv-SPFM), a novel hemodynamic deconvolution algorithm that operates at the whole brain level and adds spatial information via a mixed-norm regularization term over all voxels. Additionally, Mv-SPFM employs a stability selection procedure that removes the need to select regularization parameters and also lets us obtain an estimate of the true probability of having a neuronal-related BOLD event at each voxel and time-point based on the area under the curve (AUC) of the stability paths. Besides, we present a formulation tailored for multi-echo fMRI acquisitions (MvME-SPFM), which allows us to better isolate fluctuations of BOLD origin on the basis of their linear dependence with the echo time (TE) and to assign physiologically interpretable units (i.e., changes in the apparent transverse relaxation ΔR2∗) to the resulting deconvolved events. Remarkably, we demonstrate that Mv-SPFM achieves comparable performance even when using a single-echo formulation. We demonstrate that this algorithm outperforms existing state-of-the-art deconvolution approaches, and shows higher spatial and temporal agreement with the activation maps and BOLD signals obtained with a standard model-based linear regression approach, even at the level of individual neuronal events. Furthermore, we show that by employing stability selection, the performance of the algorithm depends less on the selection of temporal and spatial regularization parameters λ and ρ. Consequently, the proposed algorithm provides more reliable estimates of neuronal-related activity, here in terms of ΔR2∗, for the study of the dynamics of brain activity when no information about the timings of the BOLD events is available. This algorithm will be made publicly available as part of the splora Python package.

ICA-based denoising strategies in breath-hold induced cerebrovascular reactivity mapping with multi echo BOLD fMRI.

Performing a BOLD functional MRI (fMRI) acquisition during breath-hold (BH) tasks is a non-invasive, robust method to estimate cerebrovascular reactivity (CVR). However, movement and breathing-related artefacts caused by the BH can substantially hinder CVR estimates due to their high temporal collinearity with the effect of interest, and attention has to be paid when choosing which analysis model should be applied to the data. In this study, we evaluate the performance of multiple analysis strategies based on lagged general linear models applied on multi-echo BOLD fMRI data, acquired in ten subjects performing a BH task during ten sessions, to obtain subject-specific CVR and haemodynamic lag estimates. The evaluated approaches range from conventional regression models, i.e. including drifts and motion timecourses as nuisance regressors, applied on single-echo or optimally-combined data, to more complex models including regressors obtained from multi-echo independent component analysis with different grades of orthogonalization in order to preserve the effect of interest, i.e. the CVR. We compare these models in terms of their ability to make signal intensity changes independent from motion, as well as the reliability as measured by voxelwise intraclass correlation coefficients of both CVR and lag maps over time. Our results reveal that a conservative independent component analysis model applied on the optimally-combined multi-echo fMRI signal offers the largest reduction of motion-related effects in the signal, while yielding reliable CVR amplitude and lag estimates, although a conventional regression model applied on the optimally-combined data results in similar estimates. This work demonstrates the usefulness of multi-echo based fMRI acquisitions and independent component analysis denoising for precision mapping of CVR in single subjects based on BH paradigms, fostering its potential as a clinically-viable neuroimaging tool for individual patients. It also proves that the way in which data-driven regressors should be incorporated in the analysis model is not straight-forward due to their complex interaction with the BH-induced BOLD response.

Stability-Based Sparse Paradigm Free Mapping Algorithm for Deconvolution of Functional MRI Data.

Neuronal-related activity can be estimated from functional magnetic resonance imaging (fMRI) data with no knowledge of the timings of blood oxygenation level-dependent (BOLD) events by means of deconvolution with regularized least-squares. This work proposes two improvements on the deconvolution algorithm of sparse paradigm free mapping (SPFM): a new formulation that enables the estimation of neuronal events with long, sustained activity; and the implementation of a subsampling approach based on stability selection that avoids the choice of any regularization parameter. The proposed method is evaluated on real fMRI data and compared with both the original SPFM algorithm and conventional analysis with a general linear model (GLM) that is aware of the temporal model of the neuronal-related activity. We demonstrate that the novel stability-based SPFM algorithm yields activation maps with higher resemblance to the maps obtained with GLM analyses and offers improved detection of neuronal-related events over SPFM, particularly in scenarios with low contrast-to-noise ratio.

Sparse coupled logistic regression to estimate co-activation and modulatory influences of brain regions.

Accurate mapping of the functional interactions between remote brain areas with resting-state functional magnetic resonance imaging requires the quantification of their underlying dynamics. In conventional methodological pipelines, a spatial scale of interest is first selected and dynamic analysis then proceeds at this hypothesised level of complexity. If large-scale functional networks or states are studied, more local regional rearrangements are then not described, potentially missing important neurobiological information. Here, we propose a novel mathematical framework that jointly estimates resting-state functional networks and spatially more localised cross-regional modulations. To do so, the changes in activity of each brain region are modelled by a logistic regression including co-activation coefficients (reflective of network assignment, as they highlight simultaneous activations across areas) and causal interplays (denoting finer regional cross-talks, when one region active at timetmodulates thettot + 1 transition likelihood of another area). A two-parameterℓ1regularisation scheme is used to make these two sets of coefficients sparse: one controls overall sparsity, while the other governs the trade-off between co-activations and causal interplays, enabling to properly fit the data despite the yet unknown balance between both types of couplings. Across a range of simulation settings, we show that the framework successfully retrieves the two types of cross-regional interactions at once. Performance across noise and sample size settings was globally on par with that of other existing methods, with the potential to reveal more precise information missed by alternative approaches. Preliminary application to experimental data revealed that in the resting brain, co-activations and causal modulations co-exist with a varying balance across regions. Our methodological pipeline offers a conceptually elegant alternative for the assessment of functional brain dynamics and can be downloaded athttps://c4science.ch/source/Sparse_logistic_regression.git.