ContextFunctional Magnetic Resonance Imaging (fMRI) is a non-invasive imaging technique that provides an indirect view into brain activity via the blood oxygen level dependent (BOLD) response. In particular, resting-state fMRI poses challenges to the recovery of brain activity without prior knowledge on the experimental paradigm, as it is the case for task fMRI. Conventional methods to infer brain activity from the fMRI signals, for example, the general linear model (GLM), require the knowledge of the experimental paradigm to define regressors and estimate the contribution of each voxel's time course to the task. To overcome this limitation, approaches to deconvolve the BOLD response and recover the underlying neural activations without a priori information on the task have been proposed. State-of-the-art techniques, and in particular the total activation (TA), formulate the deconvolution as an optimization problem with decoupled spatial and temporal regularization and an optimization strategy that alternates between the constraints.ApproachIn this work, we propose a paradigm-free regularization algorithm named Anisotropic 4D-fMRI (A4D-fMRI) that is applied on the 4D fMRI image, acting simultaneously in the 3D space and 1D time dimensions. Based on the idea that large image variations should be preserved as they occur during brain activations, whereas small variations considered as noise should be removed, the A4D-fMRI applies an anisotropic regularization, thus recovering the location and the duration of brain activations.ResultsUsing the experimental paradigm as ground truth, the A4D-fMRI is validated on synthetic and real task-fMRI data from 51 subjects, and its performance is compared to the TA. Results show higher correlations of the recovered time courses with the ground truth compared to the TA and lower computational times. In addition, we show that the A4D-fMRI recovers activity that agrees with the GLM, without requiring or using any knowledge of the experimental paradigm.