For decades, fMRI data have been used to search for biomarkers for patients with schizophrenia. Still, firm conclusions are yet to be made, which is often attributed to the high internal heterogeneity of the disorder. A promising way to disentangle the heterogeneity is to search for subgroups of patients with more homogeneous biological profiles. We applied an unsupervised multiple co-clustering (MCC) method to identify subtypes using functional connectivity data from a multisite resting-state data set. We merged data from two publicly available databases and split the data into a discovery data set (143 patients and 143 healthy controls (HC)) and an external test data set (63 patients and 63 HC) from independent sites. On the discovery data, we investigated the stability of the clustering toward data splits and initializations. Subsequently we searched for cluster solutions, also called "views," with a significant diagnosis association and evaluated these based on their subject and feature cluster separability, and correlation to clinical manifestations as measured with the positive and negative syndrome scale (PANSS). Finally, we validated our findings by testing the diagnosis association on the external test data. A major finding of our study was that the stability of the clustering was highly dependent on variations in the data set, and even across initializations, we found only a moderate subject clustering stability. Nevertheless, we still discovered one view with a significant diagnosis association. This view reproducibly showed an overrepresentation of schizophrenia patients in three subject clusters, and one feature cluster showed a continuous trend, ranging from positive to negative connectivity values, when sorted according to the proportions of patients with schizophrenia. When investigating all patients, none of the feature clusters in the view were associated with severity of positive, negative, and generalized symptoms, indicating that the cluster solutions reflect other disease related mechanisms.

Spatial Transformer Networks (STNs) estimate image transformations that can improve downstream tasks by ‘zooming in’ on relevant regions in an image. However, STNs are hard to train and sensitive to mis-predictions of transformations. To circumvent these limitations, we propose a probabilistic extension that estimates a stochastic transformation rather than a deterministic one. Marginalizing transformations allows us to consider each image at multiple poses, which makes the localization task easier and the training more robust. As an additional benefit, the stochastic transformations act as a localized, learned data augmentation that improves the downstream tasks. We show across standard imaging benchmarks and on a challenging real-world dataset that these two properties lead to improved classification performance, robustness and model calibration. We further demonstrate that the approach generalizes to non-visual domains by improving model performance on time-series data.

Ergodicity describes an equivalence between the expectation value and the time average of observables. Applied to human behaviour, ergodic theories of decision-making reveal how individuals should tolerate risk in different environments. To optimize wealth over time, agents should adapt their utility function according to the dynamical setting they face. Linear utility is optimal for additive dynamics, whereas logarithmic utility is optimal for multiplicative dynamics. Whether humans approximate time optimal behavior across different dynamics is unknown. Here we compare the effects of additive versus multiplicative gamble dynamics on risky choice. We show that utility functions are modulated by gamble dynamics in ways not explained by prevailing decision theories. Instead, as predicted by time optimality, risk aversion increases under multiplicative dynamics, distributing close to the values that maximize the time average growth of in-game wealth. We suggest that our findings motivate a need for explicitly grounding theories of decision-making on ergodic considerations.

Dynamic functional connectivity has become a prominent approach for tracking the changes of macroscale statistical dependencies between regions in the brain. Effective parametrization of these statistical dependencies, referred to as brain states, is however still an open problem. We investigate different emission models in the hidden Markov model framework, each representing certain assumptions about dynamic changes in the brain. We evaluate each model by how well they can discriminate between schizophrenic patients and healthy controls based on a group independent component analysis of resting-state functional magnetic resonance imaging data. We find that simple emission models without full covariance matrices can achieve similar classification results as the models with more parameters. This raises questions about the predictability of dynamic functional connectivity in comparison to simpler dynamic features when used as biomarkers. However, we must stress that there is a distinction between characterization and classification, which has to be investigated further.

Many data-driven approaches exist to extract neural representations of functional magnetic resonance imaging (fMRI) data, but most of them lack a proper probabilistic formulation. We propose a scalable group level probabilistic sparse factor analysis (psFA) allowing spatially sparse maps, component pruning using automatic relevance determination (ARD) and subject specific heteroscedastic spatial noise modeling. For task-based and resting state fMRI, we show that the sparsity constraint gives rise to components similar to those obtained by group independent component analysis. The noise modeling shows that noise is reduced in areas typically associated with activation by the experimental design. The psFA model identifies sparse components and the probabilistic setting provides a natural way to handle parameter uncertainties. The variational Bayesian framework easily extends to more complex noise models than the presently considered.

Cluster analysis of functional magnetic resonance imaging (fMRI) data is often performed using gaussian mixture models, but when the time series are standardized such that the data reside on a hypersphere, this modeling assumption is questionable. The consequences of ignoring the underlying spherical manifold are rarely analyzed, in part due to the computational challenges imposed by directional statistics. In this letter, we discuss a Bayesian von Mises-Fisher (vMF) mixture model for data on the unit hypersphere and present an efficient inference procedure based on collapsed Markov chain Monte Carlo sampling. Comparing the vMF and gaussian mixture models on synthetic data, we demonstrate that the vMF model has a slight advantage inferring the true underlying clustering when compared to gaussian-based models on data generated from both a mixture of vMFs and a mixture of gaussians subsequently normalized. Thus, when performing model selection, the two models are not in agreement. Analyzing multisubject whole brain resting-state fMRI data from healthy adult subjects, we find that the vMF mixture model is considerably more reliable than the gaussian mixture model when comparing solutions across models trained on different groups of subjects, and again we find that the two models disagree on the optimal number of components. The analysis indicates that the fMRI data support more than a thousand clusters, and we confirm this is not a result of overfitting by demonstrating better prediction on data from held-out subjects. Our results highlight the utility of using directional statistics to model standardized fMRI data and demonstrate that whole brain segmentation of fMRI data requires a very large number of functional units in order to adequately account for the discernible statistical patterns in the data.

The brain consists of specialized cortical regions that exchange information between each other, reflecting a combination of segregated (local) and integrated (distributed) processes that define brain function. Functional magnetic resonance imaging (fMRI) is widely used to characterize these functional relationships, although it is an ongoing challenge to develop robust, interpretable models for high-dimensional fMRI data. Gaussian mixture models (GMMs) are a powerful tool for parcellating the brain, based on the similarity of voxel time series. However, conventional GMMs have limited parametric flexibility: they only estimate segregated structure and do not model interregional functional connectivity, nor do they account for network variability across voxels or between subjects. To address these issues, this letter develops the functional segregation and integration model (FSIM). This extension of the GMM framework simultaneously estimates spatial clustering and the most consistent group functional connectivity structure. It also explicitly models network variability, based on voxel- and subject-specific network scaling profiles. We compared the FSIM to standard GMM in a predictive cross-validation framework and examined the importance of different model parameters, using both simulated and experimental resting-state data. The reliability of parcellations is not significantly altered by flexibility of the FSIM, whereas voxel- and subject-specific network scaling profiles significantly improve the ability to predict functional connectivity in independent test data. Moreover, the FSIM provides a set of interpretable parameters to characterize both consistent and variable aspects functional connectivity structure. As an example of its utility, we use subject-specific network profiles to identify brain regions where network expression predicts subject age in the experimental data. Thus, the FSIM is effective at summarizing functional connectivity structure in group-level fMRI, with applications in modeling the relationships between network variability and behavioral/demographic variables.

Functional magnetic resonance imaging (fMRI) can be applied to study the functional connectivity of the neural elements which form complex network at a whole brain level. Most analyses of functional resting state networks (RSN) have been based on the analysis of correlation between the temporal dynamics of various regions of the brain. While these models can identify coherently behaving groups in terms of correlation they give little insight into how these groups interact. In this paper we take a different view on the analysis of functional resting state networks. Starting from the definition of resting state as functional coherent groups we search for functional units of the brain that communicate with other parts of the brain in a coherent manner as measured by mutual information. We use the infinite relational model (IRM) to quantify functional coherent groups of resting state networks and demonstrate how the extracted component interactions can be used to discriminate between functional resting state activity in multiple sclerosis and normal subjects.

Non-negative matrix factorization (NMF), i.e. V ap WH where both V, W and H are non-negative has become a widely used blind source separation technique due to its part based representation. The NMF decomposition is not in general unique and a part based representation not guaranteed. However, imposing sparseness both improves the uniqueness of the decomposition and favors part based representation. Sparseness in the form of attaining as many zero elements in the solution as possible is appealing from a conceptional point of view and corresponds to minimizing reconstruction error with an L0norm constraint. In general, solving for a given L0norm is an NP hard problem thus convex relaxation to regularization by the L1norm is often considered, i.e., minimizing (1/2||V - WH||F2+ lambda||H||1).An open problem is to control the degree of sparsity lambda imposed. We here demonstrate that a full regularization path for the L1norm regularized least squares NMF for fixed W can be calculated at the cost of an ordinary least squares solution based on a modification of the least angle regression and selection (LARS) algorithm forming a non-negativity constrained LARS (NLARS). With the full regularization path, the L1regularization strength lambda that best approximates a given L0can be directly accessed and in effect used to control the sparsity of H. The MATLAB code for the NLARS algorithm is available for download.

Nonlinear hemodynamic models express the BOLD (blood oxygenation level dependent) signal as a nonlinear, parametric functional of the temporal sequence of local neural activity. Several models have been proposed for both the neural activity and the hemodynamics. We compare two such combined models: the original balloon model with a square-pulse neural model (Friston, Mechelli, Turner, & Price, 2000) and an extended balloon model with a more sophisticated neural model (Buxton, Uludag, Dubowitz, & Liu, 2004). We learn the parameters of both models using a Bayesian approach, where the distribution of the parameters conditioned on the data is estimated using Markov chain Monte Carlo techniques. Using a split-half resampling procedure (Strother, Anderson, & Hansen, 2002), we compare the generalization abilities of the models as well as their reproducibility, for both synthetic and real data, recorded from two different visual stimulation paradigms. The results show that the simple model is the better one for these data.