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The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.

The estimation of functional connectivity structure from functional neuroimaging data is an important step toward understanding the mechanisms of various brain diseases and building relevant biomarkers. Yet, such inferences have to deal with the low signal-to-noise ratio and the paucity of the data. With at our disposal a steadily growing olume of publicly available neuroimaging data, it is however possible to improve the estimation procedures involved in connectome mapping. In this work, we propose a novel learning scheme for functional connectivity based on sparse Gaussian graphical models that aims at minimizing the bias induced by the regularization used in the estimation, by carefully separating the estimation of the model support from the coefficients. Moreover, our strategy makes it possible to include new data with a limited computational cost. We illustrate the physiological relevance of he learned prior, that can be identified as a functional connectivity atlas, based on an experiment on 46 subjects of the Human Connectome Dataset.

We present a Riemannian approach for classifying fMRI connectivity patterns before and after intervention in longitudinal studies. A fundamental difficulty with using connectivity as features is that covariance matrices live on the positive semi-definite cone, which renders their elements inter-related. The implicit independent feature assumption in most classifier learning algorithms is thus violated. In this paper, we propose a matrix whitening transport for projecting the covariance estimates onto a common tangent space to reduce the statistical dependencies between their elements. We show on real data that our approach provides significantly higher classification accuracy than directly using Pearson's correlation. We further propose a non-parametric scheme for identifying significantly discriminative connections from classifier weights. Using this scheme, a number of neuroanatomically meaningful connections are found, whereas no significant connections are detected with pure permutation testing.

Inter-subject variability is a major hurdle for neuroimaging group-level inference, as it creates complex image patterns that are not captured by standard analysis models and jeopardizes the sensitivity of statistical procedures. A solution to this problem is to model random subjects effects by using the redundant information conveyed by multiple imaging contrasts. In this paper, we introduce a novel analysis framework, where we estimate the amount of variance that is fit by a random effects subspace learned on other images; we show that a principal component regression estimator outperforms other regression models and that it fits a significant proportion (10% to 25%) of the between-subject variability. This proves for the first time that the accumulation of contrasts in each individual can provide the basis for more sensitive neuroimaging group analyzes.

Functional Magnetic Resonance Imaging (fMRI) studies map the human brain by testing the response of groups of individuals to carefully-crafted and contrasted tasks in order to delineate specialized brain regions and networks. The number of functional networks extracted is limited by the number of subject-level contrasts and does not grow with the cohort. Here, we introduce a new group-level brain mapping strategy to differentiate many regions reflecting the variety of brain network configurations observed in the population. Based on the principle of functional segregation, our approach singles out functionally-specialized brain regions by learning group-level functional profiles on which the response of brain regions can be represented sparsely. We use a dictionary-learning formulation that can be solved efficiently with on-line algorithms, scaling to arbitrary large datasets. Importantly, we model inter-subject correspondence as structure imposed in the estimated functional profiles, integrating a structure-inducing regularization with no additional computational cost. On a large multi-subject study, our approach extracts a large number of brain networks with meaningful functional profiles.

Neuroimaging group analyses are used to compare the intersubject variability observed in brain organization with behavioural or genetic variables and to assess risks factors of brain diseases. The lack of stability and of sensitivity of current voxel-based analysis schemes may however lead to non-reproducible results. A new approach is introduced to overcome the limitations of standard methods, in which active voxels are detected according to a consensus on several random parcellations of the brain images, while a permutation test controls the false positive risk. Both on syntetic and real data, this approach shows higher sensitivity, better recovery and higher reproducibility than standard methods and succeeds in detecting a significant association in an imaging-genetic study between a genetic variant next to the COMT gene and a region in the left thalamus on a functional magnetic resonance imaging contrast.

The estimation of intra-subject functional connectivity is greatly complicated by the small sample size and complex noise structure in functional magnetic resonance imaging (fMRI) data. Pooling samples across subjects improves the conditioning of the estimation, but loses subject-specific connectivity information. In this paper, we propose a new sparse group Gaussian graphical model (SGGGM) that facilitates joint estimation of intra-subject and group-level connectivity. This is achieved by casting functional connectivity estimation as a regularized consensus optimization problem, in which information across subjects is aggregated in learning group-level connectivity and group information is propagated back in estimating intra-subject connectivity. On synthetic data, we show that incorporating group information using SGGGM significantly enhances intra-subject connectivity estimation over existing techniques. More accurate group-level connectivity is also obtained. On real data from a cohort of 60 subjects, we show that integrating intra-subject connectivity estimated with SGGGM significantly improves brain activation detection over connectivity priors derived from other graphical modeling approaches.

Spontaneous brain activity reveals mechanisms of brain function and dysfunction. Its population-level statistical analysis based on functional images often relies on the definition of brain regions that must summarize efficiently the covariance structure between the multiple brain networks. In this paper, we extend a network-discovery approach, namely dictionary learning, to readily extract brain regions. To do so, we introduce a new tool drawing from clustering and linear decomposition methods by carefully crafting a penalty. Our approach automatically extracts regions from rest fMRI that better explain the data and are more stable across subjects than reference decomposition or clustering methods.

Medical imaging datasets often contain deviant observations, the so-called outliers, due to acquisition or preprocessing artifacts or resulting from large intrinsic inter-subject variability. These can undermine the statistical procedures used in group studies as the latter assume that the cohorts are composed of homogeneous samples with anatomical or functional features clustered around a central mode. The effects of outlying subjects can be mitigated by detecting and removing them with explicit statistical control. With the emergence of large medical imaging databases, exhaustive data screening is no longer possible, and automated outlier detection methods are currently gaining interest. The datasets used in medical imaging are often high-dimensional and strongly correlated. The outlier detection procedure should therefore rely on high-dimensional statistical multivariate models. However, state-of-the-art procedures, based on the Minimum Covariance Determinant (MCD) estimator, are not well-suited for such high-dimensional settings. In this work, we introduce regularization in the MCD framework and investigate different regularization schemes. We carry out extensive simulations to provide backing for practical choices in absence of ground truth knowledge. We demonstrate on functional neuroimaging datasets that outlier detection can be performed with small sample sizes and improves group studies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We present a novel probabilistic framework to learn across several subjects a mapping from brain anatomical connectivity to functional connectivity, i.e. the covariance structure of brain activity. This prediction problem must be formulated as a structured-output learning task, as the predicted parameters are strongly correlated. We introduce a model selection framework based on cross-validation with a parametrization-independent loss function suitable to the manifold of covariance matrices. Our model is based on constraining the conditional independence structure of functional activity by the anatomical connectivity. Subsequently, we learn a linear predictor of a stationary multivariate autoregressive model. This natural parameterization of functional connectivity also enforces the positive-definiteness of the predicted covariance and thus matches the structure of the output space. Our results show that functional connectivity can be explained by anatomical connectivity on a rigorous statistical basis, and that a proper model of functional connectivity is essential to assess this link.

Fluctuations in brain on-going activity can be used to reveal its intrinsic functional organization. To mine this information, we give a new hierarchical probabilistic model for brain activity patterns that does not require an experimental design to be specified. We estimate this model in the dictionary learning framework, learning simultaneously latent spatial maps and the corresponding brain activity time-series. Unlike previous dictionary learning frameworks, we introduce an explicit difference between subject-level spatial maps and their corresponding population-level maps, forming an atlas. We give a novel algorithm using convex optimization techniques to solve efficiently this problem with non-smooth penalties well-suited to image denoising. We show on simulated data that it can recover population-level maps as well as subject specificities. On resting-state fMRI data, we extract the first atlas of spontaneous brain activity and show how it defines a subject-specific functional parcellation of the brain in localized regions.

In many application of functional Magnetic Resonance Imaging (fMRI), including clinical or pharmacological studies, the definition of the location of the functional activity between subjects is crucial. While current acquisition and normalization procedures improve the accuracy of the functional signal localization, it is also important to ensure that functional foci detection yields accurate results, and reflects between-subject variability. Here we introduce a fast functional landmark detection procedure, that explicitly models the spatial variability of activation foci in the observed population. We compare this detection approach to standard statistical maps peak extraction procedures: we show that it yields more accurate results on simulations, and more reproducible results on a large cohort of subjects. These results demonstrate that explicit functional landmark modeling approaches are more effective than standard statistical mapping for brain functional focus detection.

Functional brain connectivity, as revealed through distant correlations in the signals measured by functional Magnetic Resonance Imaging (fMRI), is a promising source of biomarkers of brain pathologies. However, establishing and using diagnostic markers requires probabilistic inter-subject comparisons. Principled comparison of functional-connectivity structures is still a challenging issue. We give a new matrix-variate probabilistic model suitable for inter-subject comparison of functional connectivity matrices on the manifold of Symmetric Positive Definite (SPD) matrices. We show that this model leads to a new algorithm for principled comparison of connectivity coefficients between pairs of regions. We apply this model to comparing separately post-stroke patients to a group of healthy controls. We find neurologically-relevant connection differences and show that our model is more sensitive that the standard procedure. To the best of our knowledge, these results are the first report of functional connectivity differences between a single-patient and a group and thus establish an important step toward using functional connectivity as a diagnostic tool.