Structural analysis of fMRI data revisited: improving the sensitivity and reliability of fMRI group studies.

International audienceGroup studies of functional magnetic resonance imaging datasets are usually based on the computation of the mean signal across subjects at each voxel (random effects analyses), assuming that all subjects have been set in the same anatomical space (normalization). Although this approach allows for a correct specificity (rate of false detections), it is not very efficient for three reasons: i) its underlying hypotheses, perfect coregistration of the individual datasets and normality of the measured signal at the group level are frequently violated; ii) the group size is small in general, so that asymptotic approximations on the parameters distributions do not hold; iii) the large size of the images requires some conservative strategies to control the false detection rate, at the risk of increasing the number of false negatives. Given that it is still very challenging to build generative or parametric models of intersubject variability, we rely on a rule based, bottom-up approach: we present a set of procedures that detect structures of interest from each subject's data, then search for correspondences across subjects and outline the most reproducible activation regions in the group studied. This framework enables a strict control on the number of false detections. It is shown here that this analysis demonstrates increased validity and improves both the sensitivity and reliability of group analyses compared with standard methods. Moreover, it directly provides information on the spatial position correspondence or variability of the activated regions across subjects, which is difficult to obtain in standard voxel-based analyses

Domain-general Stroop Performance and Hemispheric Asymmetries: A Resting-state EEG Study

The ability to suppress irrelevant information while executing a task or interference resistance is a function of pFC that is critical for successful goal-directed human behavior. In the study of interference resistance and, more generally, executive functions, two key questions are still open: Does pFC contribute to cognitive control abilities through lateralized but domain-general mechanisms or through hemispheric specialization of domain-specific processes? And what are the underlying causes of interindividual differences in executive control performance? To shed light on these issues, here we employed an interindividual difference approach to investigate whether participants' hemispheric asymmetry in resting-state electrophysiological brain dynamics may reflect their variability in domain-general interference resistance. We recorded participants' resting-state electroencephalographic activity and performed spectral power analyses on the estimated cortical source activity. To measure participants' lateralized brain dynamics at rest, we computed the right-left hemispheric asymmetry score for the \u3b2/\u3b1 power ratio. To measure their domain-general interference resistance ability, verbal and spatial Stroop tasks were used. Robust correlations followed by intersection analyses showed that participants with stronger resting-state-related left-lateralized activity in different pFC regions, namely the mid-posterior superior frontal gyrus, middle and posterior middle frontal gyrus, and inferior frontal junction, were more able to inhibit irrelevant information in both domains. The present results confirm and extend previous findings showing that neurophysiological difference factors may explain interindividual differences in executive functioning. They also provide support for the hypothesis of a left pFC hemispheric specialization for domain-independent phasic cognitive control processes mediating Stroop performance

Advances in Spectral Learning with Applications to Text Analysis and Brain Imaging

Spectral learning algorithms are becoming increasingly popular in data-rich domains, driven in part by recent advances in large scale randomized SVD, and in spectral estimation of Hidden Markov Models. Extensions of these methods lead to statistical estimation algorithms which are not only fast, scalable, and useful on real data sets, but are also provably correct. Following this line of research, we make two contributions. First, we propose a set of spectral algorithms for text analysis and natural language processing. In particular, we propose fast and scalable spectral algorithms for learning word embeddings -- low dimensional real vectors (called Eigenwords) that capture the “meaning” of words from their context. Second, we show how similar spectral methods can be applied to analyzing brain images. State-of-the-art approaches to learning word embeddings are slow to train or lack theoretical grounding; We propose three spectral algorithms that overcome these limitations. All three algorithms harness the multi-view nature of text data i.e. the left and right context of each word, and share three characteristics: 1). They are fast to train and are scalable. 2). They have strong theoretical properties. 3). They can induce context-specific embeddings i.e. different embedding for “river bank” or “Bank of America”. \end{enumerate} They also have lower sample complexity and hence higher statistical power for rare words. We provide theory which establishes relationships between these algorithms and optimality criteria for the estimates they provide. We also perform thorough qualitative and quantitative evaluation of Eigenwords and demonstrate their superior performance over state-of-the-art approaches. Next, we turn to the task of using spectral learning methods for brain imaging data. Methods like Sparse Principal Component Analysis (SPCA), Non-negative Matrix Factorization (NMF) and Independent Component Analysis (ICA) have been used to obtain state-of-the-art accuracies in a variety of problems in machine learning. However, their usage in brain imaging, though increasing, is limited by the fact that they are used as out-of-the-box techniques and are seldom tailored to the domain specific constraints and knowledge pertaining to medical imaging, which leads to difficulties in interpretation of results. In order to address the above shortcomings, we propose Eigenanatomy (EANAT), a general framework for sparse matrix factorization. Its goal is to statistically learn the boundaries of and connections between brain regions by weighing both the data and prior neuroanatomical knowledge. Although EANAT incorporates some neuroanatomical prior knowledge in the form of connectedness and smoothness constraints, it can still be difficult for clinicians to interpret the results in specific domains where network-specific hypotheses exist. We thus extend EANAT and present a novel framework for prior-constrained sparse decomposition of matrices derived from brain imaging data, called Prior Based Eigenanatomy (p-Eigen). We formulate our solution in terms of a prior-constrained l1 penalized (sparse) principal component analysis. Experimental evaluation confirms that p-Eigen extracts biologically-relevant, patient-specific functional parcels and that it significantly aids classification of Mild Cognitive Impairment when compared to state-of-the-art competing approaches

Neural evidence of motivational conflict between social values

Motivational interdependence is an organizing principle in Schwartz’s circumplex model of social values, which has received abundant cross-cultural support. We used fMRI to test whether motivational relations between social values predict different brain responses in a situation of choice between values. We hypothesized that differences in brain responses would become evident when the more important value had to be selected in pairs of congruent (e.g., wealth and success) as opposed to incongruent (e.g., curiosity and stability) values as they are described in Schwartz’s model, because the former serve mutually facilitating motives, whereas the latter serve mutually inhibiting motives. Consistent with the model, choosing between congruent values led to longer response times and more activation in conflict-related brain regions (e.g., the supplementary motor area, dorsolateral prefrontal cortex) than selecting between incongruent values. These results provide novel neural evidence supporting the circumplex model’s predictions about motivational interdependence between social values. In particular, our results show that the neural networks underlying social values are organized in a way that allows activation patterns related to motivational similarity between congruent values to be dissociated from those related to incongruent values

The smoothness constraint in spatially informed minimum norm approaches for the reconstruction of neuroelectromagnetic sources

Neuronal processes in the brain give rise to electromagnetic signals that can be measured by means of EEG/MEG. However, the ambiguity of the bioelectromagnetic inverse problem limits the localizability of the underlying generators. The solution of the inverse problem requires additional assumptions. A very common method is to model brain activity using distributed sources. In that case, a large number of equivalent current dipoles covers the volume in which activity is expected (usually the cortex). Reconstruction methods on the basis of distributed sources allow the incorporation of additional information on the functional similarity between sources (i.e. information on the spatial structure of brain activity). This kind of information can be derived from prior knowledge, for instance from the subdivision of the cortex into distinct functional areas (i.e. parcellations) or from fMRI. The work presented here is based on a previously published method that combines a general smoothness constraint with priori knowledge on the (binary) similarity between neighboring sources by means of a 2nd order spatial derivative operator (PatchLORETA). The first part of this work addressed the systematic evaluation on how the integration of prior knowledge into the derivative operator affects the estimation of a priori assumed source covariances. It turned out that the method introduced incorrect prior assumptions. Consequently, some extensions were proposed to generalize the approach. These are an additional normalization operator and an additional parameter to encode arbitrary mutual similarity between neighbors. Moreover, a technique was developed to adjust the correlation structure according to a desired smoothness level. The final method (called informed LORETA) is particularly suited for the use of functio-anatomical boundaries. The second part addressed the systematic evaluation of the question whether the use of prior knowledge (derived from parcellations) can improve source localization. This was done using Monte-Carlo simulations. A main focus was the evaluation on how potential errors / uncertainties in the prior knowledge influence the reconstruction performance. Finally, informed LORETA was used for the localization of auditory evoked potentials from experimental data. It turned out that spatially informed methods provide very plausible reconstruction results.EEG/MEG ermöglicht die Messung elektrischer Gehirnaktivität, die durch neuronale Prozesse im Gehirn hervorgerufen wird. Die Lokalisierbarkeit der Aktivität ist aufgrund der fehlenden Eindeutigkeit des bioelektromagnetischen inversen Problems allerdings eingeschränkt. Zur Lösung sind Zusatzannahmen erforderlich. Eine Klasse von Lösungsverfahren basiert auf der Verwendung verteilter Quellenmodelle. Dabei werden im gesamten wahrscheinlichen Quellraum (typischerweise im Cortex) Stromdipole modelliert, um schließlich eine räumliche Verteilung der Dipolstärken zu bestimmen. Dieser Ansatz erlaubt es, Zusatzannahmen über die funktionelle Ähnlichkeit zwischen den Dipolen (d.h. über die räumliche Strukturierung von Gehirnaktivität) zu formulieren. Derartiges Wissen kann zum Beispiel aus der Unterteilung des Cortex in funktional unterschiedliche Areale (Parzellierungen) oder mittels fMRI gewonnen werden. Diese Arbeit befasst sich mit einer bereits zuvor publizierten Technik, bei der Zusatzwissen über die funktionelle Ähnlichkeit benachbarter Quellen in einen Differentialoperator integriert und mit einer allgemeinen Glattheitsannahme kombiniert wird (PatchLORETA). Im ersten Teil dieser Arbeit wurde systematisch untersucht, wie sich eine derartige Integration auf die tatsächliche Korrelationsstruktur auswirkt. Dabei wurden verschiedene Probleme identifiziert, die zu fehlerhaften a priori Annahmen führen. Aus diesem Grund wurde die Methode um einen Normalisierungsoperator, lokale Ähnlichkeitsparameter, und ein Verfahren zur Einstellung einer definierten Glattheitsannahme erweitert. Im Ergebnis liegt ein als informed LORETA bezeichnetes Verfahren vor, in das grundsätzlich beliebige Ähnlichkeitsinformation eingebunden werden kann. Es ist besonders zur Integration funktio-anatomischer Grenzen geeignet. Im zweiten Teil dieser Arbeit wurde die Nutzbarkeit informierter linearer inverser Verfahren mithilfe von Monte-Carlo-Simulationen und unter Verwendung von Parzellierungen systematisch untersucht. Im Fokus stand dabei vor allem der Einfluss möglicher Fehler im Zusatzwissen auf die Rekonstruktionsqualität. Abschließend wurde informed LORETA zur Lokalisierung auditorisch evozierter Aktivität aus EEG/MEG-Daten eingesetzt. Dabei konnte gezeigt werden, dass die Plausibilität der rekonstruierten Quellenverteilung durch die Integration von Zusatzwissen deutlich gesteigert werden kann

Investigating Brain Functional Networks in a Riemannian Framework

The brain is a complex system of several interconnected components which can be categorized at different Spatio-temporal levels, evaluate the physical connections and the corresponding functionalities. To study brain connectivity at the macroscale, Magnetic Resonance Imaging (MRI) technique in all the different modalities has been exemplified to be an important tool. In particular, functional MRI (fMRI) enables to record the brain activity either at rest or in different conditions of cognitive task and assist in mapping the functional connectivity of the brain. The information of brain functional connectivity extracted from fMRI images can be defined using a graph representation, i.e. a mathematical object consisting of nodes, the brain regions, and edges, the link between regions. With this representation, novel insights have emerged about understanding brain connectivity and providing evidence that the brain networks are not randomly linked. Indeed, the brain network represents a small-world structure, with several different properties of segregation and integration that are accountable for specific functions and mental conditions. Moreover, network analysis enables to recognize and analyze patterns of brain functional connectivity characterizing a group of subjects. In recent decades, many developments have been made to understand the functioning of the human brain and many issues, related to the biological and the methodological perspective, are still need to be addressed. For example, sub-modular brain organization is still under debate, since it is necessary to understand how the brain is functionally organized. At the same time a comprehensive organization of functional connectivity is mostly unknown and also the dynamical reorganization of functional connectivity is appearing as a new frontier for analyzing brain dynamics. Moreover, the recognition of functional connectivity patterns in patients affected by mental disorders is still a challenging task, making plausible the development of new tools to solve them. Indeed, in this dissertation, we proposed novel methodological approaches to answer some of these biological and neuroscientific questions. We have investigated methods for analyzing and detecting heritability in twin's task-induced functional connectivity profiles. in this approach we are proposing a geodesic metric-based method for the estimation of similarity between functional connectivity, taking into account the manifold related properties of symmetric and positive definite matrices. Moreover, we also proposed a computational framework for classification and discrimination of brain connectivity graphs between healthy and pathological subjects affected by mental disorder, using geodesic metric-based clustering of brain graphs on manifold space. Within the same framework, we also propose an approach based on the dictionary learning method to encode the high dimensional connectivity data into a vectorial representation which is useful for classification and determining regions of brain graphs responsible for this segregation. We also propose an effective way to analyze the dynamical functional connectivity, building a similarity representation of fMRI dynamic functional connectivity states, exploiting modular properties of graph laplacians, geodesic clustering, and manifold learning

Automated multi-subject fiber clustering of mouse brain using dominant sets

Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra- and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups.Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra-and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups

Data-driven fMRI data analysis based on parcellation

Functional Magnetic Resonance Imaging (fMRI) is one of the most popular neuroimaging methods for investigating the activity of the human brain during cognitive tasks. As with many other neuroiroaging tools, the group analysis of fMRI data often requires a transformation of the individual datasets to a common stereotaxic space, where the different brains have a similar global shape and size. However, the local inaccuracy of this procedure gives rise to a series of issues including a lack of true anatomical correspondence and a loss of subject specific activations. Inter-subject parcellation of fMRI data has been proposed as a means to alleviate these problems. Within this frame, the inter-subject correspondence is achieved by isolating homologous functional parcels across individuals, rather than by matching voxels coordinates within a stereotaxic space. However, the large majority of parcellation methods still suffer from a number of shortcomings owing to their dependence on a general linear model. Indeed, for all its appeal, a GLM-based parcellation approach introduces its own biases in the form of a priori knowledge about such matters as the shape of the Hemodynamic Response Function (HRF) and taskrelated signal changes. In this thesis, we propose a model-free data-driven parcellation approach to singleand multi-subject parcellation. By modelling brain activation without an relying on an a priori model, parcellation is optimized for each individual subject. In order to establish correspondences of parcels across different subjects, we cast this problem as a multipartite graph partitioning task. Parcels are considered as the vertices of a weighted complete multipartite graph. Cross subject parcel matching becomes equivalent to partitioning this graph into disjoint cliques with one and only one parcel from each subject in each clique. In order to solve this NP-hard problem, we present three methods: the OBSA algorithm, a method with quadratic programming and an intuitive approach. We also introduce two quantitative measures of the quality of parcellation results. We apply our framework to two fMRI data sets and show that both our single- and multi-subject parcellation techniques rival or outperform model-based methods in terms of parcellation accuracy