Thomas Vincent

A fully Bayesian approach to the parcel-based detection-estimation of brain activity in fMRI

Within-subject analysis in fMRI essentially addresses two problems, i.e., the detection of activated brain regions in response to an experimental task and the estimation of the underlying dynamics, also known as the characterisation of Hemodynamic response function (HRF). So far, both issues have been treated sequentially while it is known that the HRF model has a dramatic impact on the localisation of activations and that the HRF shape may vary from one region to another. In this paper, we conciliate both issues in a region-based joint detection-estimation framework that we develop in the Bayesian formalism. Instead of considering function basis to account for spatial variability, spatially adaptive General Linear Models are built upon region-based non-parametric estimation of brain dynamics. Regions are first identified as functionally homogeneous parcels in the mask of the grey matter using a specific procedure [Thirion, B., Flandin, G., Pinel, P., Roche, A., Ciuciu, P., Poline, J.-B., August 2006. Dealing with the shortcomings of spatial normalization: Multi-subject parcellation of fMRI datasets. Hum. Brain Mapp. 27 (8), 678-693.]. Then, in each parcel, prior information is embedded to constrain this estimation. Detection is achieved by modelling activating, deactivating and non-activating voxels through mixture models within each parcel. From the posterior distribution, we infer upon the model parameters using Markov Chain Monte Carlo (MCMC) techniques. Bayesian model comparison allows us to emphasize on artificial datasets first that inhomogeneous gamma-Gaussian mixture models outperform Gaussian mixtures in terms of sensitivity/specificity trade-off and second that it is worthwhile modelling serial correlation through an AR(1) noise process at low signal-to-noise (SNR) ratio. Our approach is then validated on an fMRI experiment that studies habituation to auditory sentence repetition. This phenomenon is clearly recovered as well as the hierarchical temporal organisation of the superior temporal sulcus, which is directly derived from the parcel-based HRF estimates.

Spatially Adaptive Mixture Modeling for Analysis of fMRI Time Series

Within-subject analysis in fMRI essentially addresses two problems, the detection of brain regions eliciting evoked activity and the estimation of the underlying dynamics. In Makni et aL, 2005 and Makni et aL, 2008, a detection-estimation framework has been proposed to tackle these problems jointly, since they are connected to one another. In the Bayesian formalism, detection is achieved by modeling activating and nonactivating voxels through independent mixture models (IMM) within each region while hemodynamic response estimation is performed at a regional scale in a nonparametric way. Instead of IMMs, in this paper we take advantage of spatial mixture models (SMM) for their nonlinear spatial regularizing properties. The proposed method is unsupervised and spatially adaptive in the sense that the amount of spatial correlation is automatically tuned from the data and this setting automatically varies across brain regions. In addition, the level of regularization is specific to each experimental condition since both the signal-to-noise ratio and the activation pattern may vary across stimulus types in a given brain region. These aspects require the precise estimation of multiple partition functions of underlying Ising fields. This is addressed efficiently using first path sampling for a small subset of fields and then using a recently developed fast extrapolation technique for the large remaining set. Simulation results emphasize that detection relying on supervised SMM outperforms its IMM counterpart and that unsupervised spatial mixture models achieve similar results without any hand-tuning of the correlation parameter. On real datasets, the gain is illustrated in a localizer fMRI experiment: brain activations appear more spatially resolved using SMM in comparison with classical general linear model (GLM)-based approaches, while estimating a specific parcel-based HRF shape. Our approach therefore validates the treatment of unsmoothed fMRI data without fixed GLM definition at the subject level and makes also the classical strategy of spatial Gaussian filtering deprecated.

Group-level impacts of within- and between-subject hemodynamic variability in fMRI

Inter-subject fMRI analyses have specific issues regarding the reliability of the results concerning both the detection of brain activation patterns and the estimation of the underlying dynamics. Among these issues lies the variability of the hemodynamic response function (HRF), that is usually accounted for using functional basis sets in the general linear model context. Here, we use the joint detection-estimation approach (JDE) (Makni et al., 2008; Vincent et al., 2010) which combines regional nonparametric HRF inference with spatially adaptive regularization of activation clusters to avoid global smoothing of fMRI images. We show that the JDE-based inference brings a significant improvement in statistical sensitivity for detecting evoked activity in parietal regions. In contrast, the canonical HRF associated with spatially adaptive regularization is more sensitive in other regions, such as motor cortex. This different regional behavior is shown to reflect a larger discrepancy of HRF with the canonical model. By varying parallel imaging acceleration factor, SNR-specific region-based hemodynamic parameters (activation delay and duration) were extracted from the JDE inference. Complementary analyses highlighted their significant departure from the canonical parameters and the strongest between-subject variability that occurs in the parietal region, irrespective of the SNR value. Finally, statistical evidence that the fluctuation of the HRF shape is responsible for the significant change in activation detection performance is demonstrated using paired t-tests between hemodynamic parameters inferred by GLM and JDE.

Spatial Mixture Modelling for the Joint Detection-Estimation of Brain Activity in fMRI

Within-subject analysis in event-related functional magnetic resonance imaging (fMRI) first relies on (i) a detection step to localize which parts of the brain are activated by a given stimulus type, and then on (ii) an estimation step to recover the temporal dynamics of the brain response. Recently, we have proposed a Bayesian detection-estimation approach that jointly addresses (i)-(ii). This approach provides both a spatial activity map and an estimate of brain dynamics. Here, we consider an extension that accounts for spatial correlation using a spatial mixture model (SMM) based on a binary Markov random field. It allows us to avoid any spatial smoothing of the data prior to the statistical analysis. Our simulation results support that SMM gives a better control of false positive (specificity) and false negative (sensitivity) rates than independent mixtures.

Min-max Extrapolation Scheme for Fast Estimation of 3D Potts Field Partition Functions. Application to the Joint Detection-Estimation of Brain Activity in fMRI

In this paper, we propose a fast numerical scheme to estimate Partition Functions (PF) of symmetric Potts fields. Our strategy is first validated on 2D two-color Potts fields and then on 3D two- and three-color Potts fields. It is then applied to the joint detection-estimation of brain activity from functional Magnetic Resonance Imaging (fMRI) data, where the goal is to automatically recover activated, deactivated and inactivated brain regions and to estimate region-dependent hemodynamic filters. For any brain region, a specific 3D Potts field indeed embodies the spatial correlation over the hidden states of the voxels by modeling whether they are activated, deactivated or inactive. To make spatial regularization adaptive, the PFs of the Potts fields over all brain regions are computed prior to the brain activity estimation. Our approach is first based upon a classical path-sampling method to approximate a small subset of reference PFs corresponding to prespecified regions. Then, we propose an extrapolation method that allows us to approximate the PFs associated to the Potts fields defined over the remaining brain regions. In comparison with preexisting methods either based on a path-sampling strategy or mean-field approximations, our contribution strongly alleviates the computational cost and makes spatially adaptive regularization of whole brain fMRI datasets feasible. It is also robust against grid inhomogeneities and efficient irrespective of the topological configurations of the brain regions.

Robust Extrapolation Scheme for Fast Estimation of 3D Ising Field Partition Functions: Application to Within-Subject fMRI Data Analysis

In this paper, we present a fast numerical scheme to estimate Partition Functions (PF) of 3D Ising fields. Our strategy is applied to the context of the joint detection-estimation of brain activity from functional Magnetic Resonance Imaging (fMRI) data, where the goal is to automatically recover activated regions and estimate region-dependent hemodynamic filters. For any region, a specific binary Markov random field may embody spatial correlation over the hidden states of the voxels by modeling whether they are activated or not. To make this spatial regularization fully adaptive, our approach is first based upon a classical path-sampling method to approximate a small subset of reference PFs corresponding to prespecified regions. Then, the proposed extrapolation method allows us to approximate the PFs associated with the Ising fields defined over the remaining brain regions. In comparison with preexisting approaches, our method is robust to topological inhomogeneities in the definition of the reference regions. As a result, it strongly alleviates the computational burden and makes spatially adaptive regularization of whole brain fMRI datasets feasible.

Variational solution to the joint detection estimation of brain activity in fMRI

We address the issue of jointly detecting brain activity and estimating underlying brain hemodynamics from functional MRI data. We adopt the so-called Joint Detection Estimation (JDE) framework that takes spatial dependencies between voxels into account. We recast the JDE into a missing data framework and derive a Variational Expectation-Maximization (VEM) algorithm for its inference. It follows a new algorithm that has interesting advantages over the previously used intensive simulation methods (Markov Chain Monte Carlo, MCMC): tests on artificial data show that the VEM-JDE is more robust to model mis-specification while additional tests on real data confirm that it achieves similar performance in much less computation time.

Flexible multivariate hemodynamics fMRI data analyses and simulations with PyHRF

As part of fMRI data analysis, the pyhrf package provides a set of tools for addressing the two main issues involved in intra-subject fMRI data analysis: (1) the localization of cerebral regions that elicit evoked activity and (2) the estimation of activation dynamics also known as Hemodynamic Response Function (HRF) recovery. To tackle these two problems, pyhrf implements the Joint Detection-Estimation framework (JDE) which recovers parcel-level HRFs and embeds an adaptive spatio-temporal regularization scheme of activation maps. With respect to the sole detection issue (1), the classical voxelwise GLM procedure is also available through nipy, whereas Finite Impulse Response (FIR) and temporally regularized FIR models are concerned with HRF estimation (2) and are specifically implemented in pyhrf. Several parcellation tools are also integrated such as spatial and functional clustering. Parcellations may be used for spatial averaging prior to FIR/RFIR analysis or to specify the spatial support of the HRF estimates in the JDE approach. These analysis procedures can be applied either to volume-based data sets or to data projected onto the cortical surface. For validation purpose, this package is shipped with artificial and real fMRI data sets, which are used in this paper to compare the outcome of the different available approaches. The artificial fMRI data generator is also described to illustrate how to simulate different activation configurations, HRF shapes or nuisance components. To cope with the high computational needs for inference, pyhrf handles distributing computing by exploiting cluster units as well as multi-core machines. Finally, a dedicated viewer is presented, which handles n-dimensional images and provides suitable features to explore whole brain hemodynamics (time series, maps, ROI mask overlay).

Modelling the neurovascular habituation effect on fMRI time series

In this paper, a novel non-stationary model of functional Magnetic Resonance Imaging (fMRI) time series is proposed. It allows us to account for some putative habituation effect arising in event-related fMRI paradigms that involves the so-called repetition-suppression phenomenon [1] and induces decreasing magnitude responses over successive trials. Akin to [2], this model is defined over functionnally homogeneous regions-of-interest (ROIs) and embedded in a joint detection-estimation approach of brain activity. Importantly, its non-stationarity character is embodied in the trial-varying nature of the BOLD response magnitude. Habituation and activation maps are then estimated within the Bayesian framework in a fully unsupervised MCMC procedure. On artificial fMRI datasets, we show that habituation effects can be accurately recovered in activating voxels.

Impact of the joint detection-estimation approach on random effects group studies in FMRI

Inter-subject analysis of functional Magnetic Resonance Imaging (fMRI) data relies on single intra-subject studies, which are usually conducted using a massively univariate approach. In this paper, we investigate the impact of an improved intra-subject analysis on group studies. basically the joint detection-estimation (JDE) framework [1–3] where an explicit characterization of the Hemodynamic Response Function (HRF) is performed at a regional scale and a stimulus-specific adaptive spatial correlation model enables the detection of activation clusters at voxel level. For the group statistics, we conducted several Random effect analyses (RFX) which relied either on the General Linear Model (GLM), or on the JDE analyses, or even on an intermediate approach named Spatially Adaptive GLM (SAGLM). Our comparative study perfomed during a fast-event related paradigm involves 18 subjects and illustrates the regionspecific differences between the GLM, SAGLM and JDE analyses in terms of statistical sensitivity. On different contrasts of interest, spatial regularization is shown to have a beneficial impact on the statistical sensitivity. Also, by studying the spatial variability of the HRF, we demonstrate that the JDE framework provides more robust detection performance in cognitive regions due to the higher hemodynamic variability in these areas.