Low-frequency oscillatory correlates of auditory predictive processing in cortical-subcortical networks: a MEG-study

Emerging evidence supports the role of neural oscillations as a mechanism for predictive information processing across large-scale networks. However, the oscillatory signatures underlying auditory mismatch detection and information flow between brain regions remain unclear. To address this issue, we examined the contribution of oscillatory activity at theta/alpha-bands (4–8/8–13 Hz) and assessed directed connectivity in magnetoencephalographic data while 17 human participants were presented with sound sequences containing predictable repetitions and order manipulations that elicited prediction-error responses. We characterized the spectro-temporal properties of neural generators using a minimum-norm approach and assessed directed connectivity using Granger Causality analysis. Mismatching sequences elicited increased theta power and phase-locking in auditory, hippocampal and prefrontal cortices, suggesting that theta-band oscillations underlie prediction-error generation in cortical-subcortical networks. Furthermore, enhanced feedforward theta/alpha-band connectivity was observed in auditory-prefrontal networks during mismatching sequences, while increased feedback connectivity in the alpha-band was observed between hippocampus and auditory regions during predictable sounds. Our findings highlight the involvement of hippocampal theta/alpha-band oscillations towards auditory prediction-error generation and suggest a spectral dissociation between inter-areal feedforward vs. feedback signalling, thus providing novel insights into the oscillatory mechanisms underlying auditory predictive processing

BrainPrint: A discriminative characterization of brain morphology

We introduce BrainPrint, a compact and discriminative representation of brain morphology. BrainPrint captures shape information of an ensemble of cortical and subcortical structures by solving the eigenvalue problem of the 2D and 3D Laplace–Beltrami operator on triangular (boundary) and tetrahedral (volumetric) meshes. This discriminative characterization enables new ways to study the similarity between brains; the focus can either be on a specific brain structure of interest or on the overall brain similarity. We highlight four applications for BrainPrint in this article: (i) subject identification, (ii) age and sex prediction, (iii) brain asymmetry analysis, and (iv) potential genetic influences on brain morphology. The properties of BrainPrint require the derivation of new algorithms to account for the heterogeneous mix of brain structures with varying discriminative power. We conduct experiments on three datasets, including over 3000 MRI scans from the ADNI database, 436 MRI scans from the OASIS dataset, and 236 MRI scans from the VETSA twin study. All processing steps for obtaining the compact representation are fully automated, making this processing framework particularly attractive for handling large datasets.National Cancer Institute (U.S.) (1K25-CA181632-01)Athinoula A. Martinos Center for Biomedical Imaging (P41-RR014075)Athinoula A. Martinos Center for Biomedical Imaging (P41-EB015896)National Alliance for Medical Image Computing (U.S.) (U54-EB005149)Neuroimaging Analysis Center (U.S.) (P41-EB015902)National Center for Research Resources (U.S.) (U24 RR021382)National Institute of Biomedical Imaging and Bioengineering (U.S.) (5P41EB015896-15)National Institute of Biomedical Imaging and Bioengineering (U.S.) (R01EB006758)National Institute on Aging (AG022381)National Institute on Aging (5R01AG008122-22)National Institute on Aging (AG018344)National Institute on Aging (AG018386)National Center for Complementary and Alternative Medicine (U.S.) (RC1 AT005728-01)National Institute of Neurological Diseases and Stroke (U.S.) (R01 NS052585-01)National Institute of Neurological Diseases and Stroke (U.S.) (1R21NS072652-01)National Institute of Neurological Diseases and Stroke (U.S.) (1R01NS070963)National Institute of Neurological Diseases and Stroke (U.S.) (R01NS083534)National Institutes of Health (U.S.) ((5U01-MH093765

BrainPrint: A discriminative characterization of brain morphology

We introduce BrainPrint, a compact and discriminative representation of brain morphology. BrainPrint captures shape information of an ensemble of cortical and subcortical structures by solving the eigenvalue problem of the 2D and 3D Laplace–Beltrami operator on triangular (boundary) and tetrahedral (volumetric) meshes. This discriminative characterization enables new ways to study the similarity between brains; the focus can either be on a specific brain structure of interest or on the overall brain similarity. We highlight four applications for BrainPrint in this article: (i) subject identification, (ii) age and sex prediction, (iii) brain asymmetry analysis, and (iv) potential genetic influences on brain morphology. The properties of BrainPrint require the derivation of new algorithms to account for the heterogeneous mix of brain structures with varying discriminative power. We conduct experiments on three datasets, including over 3000 MRI scans from the ADNI database, 436 MRI scans from the OASIS dataset, and 236 MRI scans from the VETSA twin study. All processing steps for obtaining the compact representation are fully automated, making this processing framework particularly attractive for handling large datasets.National Cancer Institute (U.S.) (1K25-CA181632-01)Athinoula A. Martinos Center for Biomedical Imaging (P41-RR014075)Athinoula A. Martinos Center for Biomedical Imaging (P41-EB015896)National Alliance for Medical Image Computing (U.S.) (U54-EB005149)Neuroimaging Analysis Center (U.S.) (P41-EB015902)National Center for Research Resources (U.S.) (U24 RR021382)National Institute of Biomedical Imaging and Bioengineering (U.S.) (5P41EB015896-15)National Institute of Biomedical Imaging and Bioengineering (U.S.) (R01EB006758)National Institute on Aging (AG022381)National Institute on Aging (5R01AG008122-22)National Institute on Aging (AG018344)National Institute on Aging (AG018386)National Center for Complementary and Alternative Medicine (U.S.) (RC1 AT005728-01)National Institute of Neurological Diseases and Stroke (U.S.) (R01 NS052585-01)National Institute of Neurological Diseases and Stroke (U.S.) (1R21NS072652-01)National Institute of Neurological Diseases and Stroke (U.S.) (1R01NS070963)National Institute of Neurological Diseases and Stroke (U.S.) (R01NS083534)National Institutes of Health (U.S.) ((5U01-MH093765

Distance Metric Learning using Graph Convolutional Networks: Application to Functional Brain Networks

Evaluating similarity between graphs is of major importance in several computer vision and pattern recognition problems, where graph representations are often used to model objects or interactions between elements. The choice of a distance or similarity metric is, however, not trivial and can be highly dependent on the application at hand. In this work, we propose a novel metric learning method to evaluate distance between graphs that leverages the power of convolutional neural networks, while exploiting concepts from spectral graph theory to allow these operations on irregular graphs. We demonstrate the potential of our method in the field of connectomics, where neuronal pathways or functional connections between brain regions are commonly modelled as graphs. In this problem, the definition of an appropriate graph similarity function is critical to unveil patterns of disruptions associated with certain brain disorders. Experimental results on the ABIDE dataset show that our method can learn a graph similarity metric tailored for a clinical application, improving the performance of a simple k-nn classifier by 11.9% compared to a traditional distance metric.Comment: International Conference on Medical Image Computing and Computer-Assisted Interventions (MICCAI) 201

The hippocampus and cerebellum in adaptively timed learning, recognition, and movement

The concepts of declarative memory and procedural memory have been used to distinguish two basic types of learning. A neural network model suggests how such memory processes work together as recognition learning, reinforcement learning, and sensory-motor learning take place during adaptive behaviors. To coordinate these processes, the hippocampal formation and cerebellum each contain circuits that learn to adaptively time their outputs. Within the model, hippocampal timing helps to maintain attention on motivationally salient goal objects during variable task-related delays, and cerebellar timing controls the release of conditioned responses. This property is part of the model's description of how cognitive-emotional interactions focus attention on motivationally valued cues, and how this process breaks down due to hippocampal ablation. The model suggests that the hippocampal mechanisms that help to rapidly draw attention to salient cues could prematurely release motor commands were not the release of these commands adaptively timed by the cerebellum. The model hippocampal system modulates cortical recognition learning without actually encoding the representational information that the cortex encodes. These properties avoid the difficulties faced by several models that propose a direct hippocampal role in recognition learning. Learning within the model hippocampal system controls adaptive timing and spatial orientation. Model properties hereby clarify how hippocampal ablations cause amnesic symptoms and difficulties with tasks which combine task delays, novelty detection, and attention towards goal objects amid distractions. When these model recognition, reinforcement, sensory-motor, and timing processes work together, they suggest how the brain can accomplish conditioning of multiple sensory events to delayed rewards, as during serial compound conditioning.Air Force Office of Scientific Research (F49620-92-J-0225, F49620-86-C-0037, 90-0128); Advanced Research Projects Agency (ONR N00014-92-J-4015); Office of Naval Research (N00014-91-J-4100, N00014-92-J-1309, N00014-92-J-1904); National Institute of Mental Health (MH-42900

Analysis of Sub-Cortical Morphology in Benign Epilepsy with Centrotemporal Spikes

RÉSUMÉ Au Canada, l’épilepsie affecte environ 5 à 8 enfants par 3222 âgés de 2 à 37 ans dans la population globale. Quinze à 47 % de ces enfants ont une épilepsie bénigne avec des pointes centrotemporelles (BECTS), ce qui fait de BECTS le syndrome épileptique focal de l’enfant bénin le plus fréquent. Initialement, BECTS était considéré comme bénin parmi les autres épilepsies car il était généralement rapporté que les capacités cognitives ont été préservées ou ramenées à la normale pendant la rémission. Cependant, certaines études ont trouvé des déficits cognitifs et comportementaux, qui peuvent bien persister même après la rémission. Compte tenu des différences neurocognitives chez les enfants atteints de BECTS et de témoins normaux, la question est de savoir si des variations morphométriques subtiles dans les structures cérébrales sont également présentes chez ces patients et si elles expliquent des variations dans les performence cognitifs. En fait, malgré les preuves accumulées d’une étiologie neurodéveloppementale dans le BECTS, peu est connu sur les altérations structurelles sous-jacentes. À cet égard, la proposition de méthodes avancées en neuroimagerie permettrait d’évaluer quantitativement les variations de la morphologie cérébrale associées à ce trouble neurologique. En outre, l’étude du développement morphologique du cerveau et sa relation avec la cognition peut aider à élucider la base neuroanatomique des déficits cognitifs. Le but de cette thèse est donc de fournir un ensemble d’outils pour analyser les variations morphologiques sous-corticales subtiles provoquées par différentes maladies, telles que l’épilepsie bénigne avec des pointes centrotemporelles. La méthodologie adoptée dans cette thèse a conduit à trois objectifs de recherche spécifiques. La première étape vise à développer un nouveau cadre automatisé pour segmenter les structures sous-corticales sur les images à resonance magnètique (IRM). La deuxième étape vise à concevoir une nouvelle approche basée sur la correspondance spectrale pour capturer précisément la variabilité de forme chez les sujets épileptiques. La troisième étape conduit à une analyse de la relation entre les changements morphologiques du cerveau et les indices cognitifs. La première contribution vise plus spécifiquement la segmentation automatique des structures sous-corticales dans un processus de co-recalage et de co-segmentation multi-atlas. Contrairement aux approches standards de segmentation multi-atlas, la méthode proposée obtient la segmentation finale en utilisant un recalage en fonction de la population, tandis que les connaissances à prior basés sur les réseaux neuronaux par convolution (CNNs) sont incorporées dans la formulation d’énergie en tant que représentation d’image discriminative. Ainsi, cette méthode exploite des représentations apprises plus sophistiquées pour conduire le processus de co-recalage. De plus, étant donné un ensemble de volumes cibles, la méthode proposée calcule les probabilités de segmentation individuellement, puis segmente tous les volumes simultanément. Par conséquent, le fardeau de fournir un sous-ensemble de vérité connue approprié pour effectuer la segmentation multi-atlas est évité. Des résultats prometteurs démontrent le potentiel de notre méthode sur deux ensembles de données, contenant des annotations de structures sous-corticales. L’importance des estimations fiables des annotations est également mise en évidence, ce qui motive l’utilisation de réseaux neuronaux profonds pour remplacer les annotations de vérité connue en co-recalage avec une perte de performance minimale. La deuxième contribution vise à saisir la variabilité de forme entre deux populations de surfaces en utilisant une analyse morphologique multijoints. La méthode proposée exploite la représentation spectrale pour établir des correspondances de surface, puisque l’appariement est plus simple dans le domaine spectral plutôt que dans l’espace euclidien conventionnel. Le cadre proposé intègre la concordance spectrale à courbure moyenne dans un plateforme d’analyse de formes sous-corticales multijoints. L’analyse expérimentale sur des données cliniques a montré que les différences de groupe extraites étaient similaires avec les résultats dans d’autres études cliniques, tandis que les sorties d’analyse de forme ont été créées d’une manière à réduire le temps de calcul. Enfin, la troisième contribution établit l’association entre les altérations morphologiques souscorticales chez les enfants atteints d’épilepsie bénigne et les indices cognitifs. Cette étude permet de détecter les changements du putamen et du noyau caudé chez les enfants atteints de BECTS gauche, droit ou bilatéral. De plus, l ’association des différences volumétriques structurelles et des différences de forme avec la cognition a été étudiée. Les résultats confirment les altérations de la forme du putamen et du noyau caudé chez les enfants atteints de BECTS. De plus, nos résultats suggèrent que la variation de la forme sous-corticale affecte les fonctions cognitives. Cette étude démontre que les altérations de la forme et leur relation avec la cognition dépendent du côté de la focalisation de l’épilepsie. Ce projet nous a permis d’étudier si de nouvelles méthodes permettraient de traiter automatiquement les informations de neuro-imagerie chez les enfants atteints de BECTS et de détecter des variations morphologiques subtiles dans leurs structures sous-corticales. De plus, les résultats obtenus dans le cadre de cette thèse nous ont permis de conclure qu’il existe une association entre les variations morphologiques et la cognition par rapport au côté de la focalisation de la crise épileptique.----------ABSTRACT In Canada, epilepsy affects approximately 5 to 8 children per 3222 aged from 2 to 37 years in the overall population. Fifteen to 47% of these children have benign epilepsy with centrotemporal spikes (BECTS), making BECTS the most common benign childhood focal epileptic syndrome. Initially, BECTS was considered as benign among other epilepsies since it was generally reported that cognitive abilities were preserved or brought back to normal during remission. However, some studies have found cognitive and behavioral deficits, which may well persist even after remission. Given neurocognitive differences among children with BECTS and normal controls, the question is whether subtle morphometric variations in brain structures are also present in these patients, and whether they explain variations in cognitive indices. In fact, despite the accumulating evidence of a neurodevelopmental etiology in BECTS, little is known about underlying structural alterations. In this respect, proposing advanced neuroimaging methods will allow for quantitative assessment of variations in brain morphology associated with this neurological disorder. In addition, studying the brain morphological development and its relationship with cognition may help elucidate the neuroanatomical basis of cognitive deficits. Therefore, the focus of this thesis is to provide a set of tools for analyzing the subtle sub-cortical morphological alterations in different diseases, such as benign epilepsy with centrotemporal spikes. The methodology adopted in this thesis led to addressing three specific research objectives. The first step develops a new automated framework for segmenting subcortical structures on MR images. The second step designs a new approach based on spectral correspondence to precisely capture shape variability in epileptic individuals. The third step finds the association between brain morphological changes and cognitive indices. The first contribution aims more specifically at automatic segmentation of sub-cortical structures in a groupwise multi-atlas coregistration and cosegmentation process. Contrary to the standard multi-atlas segmentation approaches, the proposed method obtains the final segmentation using a population-wise registration, while Convolutional Neural Network (CNN)- based priors are incorporated in the energy formulation as a discriminative image representation. Thus, this method exploits more sophisticated learned representations to drive the coregistration process. Furthermore, given a set of target volumes the developed method computes the segmentation probabilities individually, and then segments all the volumes simultaneously. Therefore, the burden of providing an appropriate ground truth subset to perform multi-atlas segmentation is removed. Promising results demonstrate the potential of our method on two different datasets, containing annotations of sub-cortical structures. The importance of reliable label estimations is also highlighted, motivating the use of deep neural nets to replace ground truth annotations in coregistration with minimal loss in performance. The second contribution intends to capture shape variability between two population of surfaces using groupwise morphological analysis. The proposed method exploits spectral representation for establishing surface correspondences, since matching is simpler in the spectral domain rather than in the conventional Euclidean space. The designed framework integrates mean curvature-based spectral matching in to a groupwise subcortical shape analysis pipeline. Experimental analysis on real clinical dataset showed that the extracted group differences were in parallel with the findings in other clinical studies, while the shape analysis outputs were created in a computational efficient manner. Finally, the third contribution establishes the association between sub-cortical morphological alterations in children with benign epilepsy and cognitive indices. This study detects putamen and caudate changes in children with left, right, or bilateral BECTS to age and gender matched healthy individuals. In addition, the association of structural volumetric and shape differences with cognition is investigated. The findings confirm putamen and caudate shape alterations in children with BECTS. Also, our results suggest that variation in sub-cortical shape affects cognitive functions. More importantly, this study demonstrates that shape alterations and their relation with cognition depend on the side of epilepsy focus. This project enabled us to investigate whether new methods would allow to automatically process neuroimaging information from children afflicted with BECTS and detect subtle morphological variations in their sub-cortical structures. In addition, the results obtained in this thesis allowed us to conclude the existence of the association between morphological variations and cognition with respect to the side of seizure focus