This research investigated the concept of a sparsity method inspired by the principles of structural plasticity in the brain in order to create a sparse model of the Bayesian Confidence Propagation Neural Networks (BCPNN) during the training phase. This was done by extending the structural plasticity in the implementation of the BCPNN. While the initial algorithm presented two synaptic states (Active and Silent), this research extended it to three synaptic states (Active, Silent and Absent) with the aim to enhance sparsity configurability and emulate a more brain-like algorithm, drawing parallels with synaptic states observed in the brain. Benchmarking was conducted using the MNIST and Fashion-MNIST dataset, where the proposed threestate model was compared against the previous two-state model in terms of representational learning. The findings suggest that the three-state model not only provides added configurability but also, in certain low-sparsity settings, showcases similar representational learning abilities as the two-state model. Moreover, in high-sparsity settings, the three-state model demonstrates a commendable balance between accuracy and sparsity trade-off. / Denna forskning undersökte en konceptuell metod för gleshet inspirerad av principerna för strukturell plasticitet i hjärnan för att skapa glesa BCPNN. Forskningen utvidgade strukturell plasticitet i en implementering av BCPNN. Medan den ursprungliga algoritmen presenterade två synaptiska tillstånd (Aktiv och Tyst), utvidgade denna forskning den till tre synaptiska tillstånd (Aktiv, Tyst och Frånvarande) med målet att öka konfigurerbarheten av sparsitet och efterlikna en mer hjärnliknande algoritm, med paralleller till synaptiska tillstånd observerade i hjärnan. Jämförelse gjordes med hjälp av MNIST och Fashion-MNIST datasetet, där det föreslagna tre-tillståndsmodellen jämfördes med den tidigare tvåtillståndsmodellen med avseende på representationslärande. Resultaten tyder på att tre-tillståndsmodellen inte bara ger ökad konfigurerbarhet utan också, i vissa lågt glesa inställningar, visar samma inlärningsförmåga som två-tillståndsmodellen. Dessutom visar den tre-tillståndsmodellen i högsparsamma inställningar en anmärkningsvärd balans mellan noggrannhet och avvägningen mellan sparsitet.

No description available.

<p dir="ltr">Multi-omic studies ranging from genomics, transcriptomics (e.g., gene expression) to proteomics data exploration have been widely applied to interpret findings from genome wide association studies (GWAS) of Alzheimer's disease (AD). However, previous studies examine each -omics data type individually and the functional interactions between genetic variations, genes and proteins are only used after discovery to interpret the findings, but not beforehand. In this case, multi-omic findings are likely not functionally related and therefore it is challenging for result interpretation. To handle this challenge, we present new modularity constrained least absolute shrinkage and selection operator (M-LASSO), new modularity constrained logistic regression (M-Logistic), new interpretable multi-omic graph fusion neural network model (MoFNet) and new transfer learning framework integrated graph fusion neural network model (TransFuse) to integrate prior biological knowledge to model the functional interactions of multi-omic data. These approaches aim to identify functional connected sub-networks predictive of AD. In this thesis, the intrepretable model MoFNet and TransFuse incorporate prior biological connected multi-omics network, and for the first time model the dynamic information flow from deoxyribonucleic acid (DNA) to ribonucleic acid (RNA) and proteins. While applying the proposed models on multi-omic data from the religious orders study/memory and aging project (ROS/MAP) cohort, MoFNet and TransFuse outperformed all other state-of-art classifiers. Instead of targeting individual markers, the proposed methods identified multi-omic sub-networks associated with AD. MoFNet and TransFuse, produced sub-network and pathway findings that were robustly validated in another independent cohort. These identified gene/protein networks highlight potential pathways involved in AD pathogenesis and could offer systematic overview for understanding the molecular mechanisms of the disease. Investigating these identified pathways in more detail could help uncover the mechanisms causing synaptic dysfunction in AD and guide future research into potential therapeutic targets.</p>

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Visual attention is an important cognitive concept for the daily life of humans, but still not fully understood. Due to this, it is also rarely utilized in computer vision systems. However, understanding visual attention is challenging as it has many and seemingly-different aspects, both at neuronal and behavioral level. Thus, it is very hard to give a uniform explanation of visual attention that can account for all aspects. To tackle this problem, this thesis has the goal to identify a common set of neuronal mechanisms, which underlie both neuronal and behavioral aspects. The mechanisms are simulated by neuro-computational models, thus, resulting in a single modeling approach to explain a wide range of phenomena at once. In the thesis, the chosen aspects are multiple neurophysiological effects, real-world object localization, and a visual masking paradigm (OSM). In each of the considered fields, the work also advances the current state-of-the-art to better understand this aspect of attention itself. The three chosen aspects highlight that the approach can account for crucial neurophysiological, functional, and behavioral properties, thus the mechanisms might constitute the general neuronal substrate of visual attention in the cortex. As outlook, our work provides for computer vision a deeper understanding and a concrete prototype of attention to incorporate this crucial aspect of human perception in future systems.:1. General introduction 2. The state-of-the-art in modeling visual attention 3. Microcircuit model of attention 4. Object localization with a model of visual attention 5. Object substitution masking 6. General conclusion / Visuelle Aufmerksamkeit ist ein wichtiges kognitives Konzept für das tägliche Leben des Menschen. Es ist aber immer noch nicht komplett verstanden, so dass es ein langjähriges Ziel der Neurowissenschaften ist, das Phänomen grundlegend zu durchdringen. Gleichzeitig wird es aufgrund des mangelnden Verständnisses nur selten in maschinellen Sehsystemen in der Informatik eingesetzt. Das Verständnis von visueller Aufmerksamkeit ist jedoch eine komplexe Herausforderung, da Aufmerksamkeit äußerst vielfältige und scheinbar unterschiedliche Aspekte besitzt. Sie verändert multipel sowohl die neuronalen Feuerraten als auch das menschliche Verhalten. Daher ist es sehr schwierig, eine einheitliche Erklärung von visueller Aufmerksamkeit zu finden, welche für alle Aspekte gleichermaßen gilt. Um dieses Problem anzugehen, hat diese Arbeit das Ziel, einen gemeinsamen Satz neuronaler Mechanismen zu identifizieren, welche sowohl den neuronalen als auch den verhaltenstechnischen Aspekten zugrunde liegen. Die Mechanismen werden in neuro-computationalen Modellen simuliert, wodurch ein einzelnes Modellierungsframework entsteht, welches zum ersten Mal viele und verschiedenste Phänomene von visueller Aufmerksamkeit auf einmal erklären kann. Als Aspekte wurden in dieser Dissertation multiple neurophysiologische Effekte, Realwelt Objektlokalisation und ein visuelles Maskierungsparadigma (OSM) gewählt. In jedem dieser betrachteten Felder wird gleichzeitig der State-of-the-Art verbessert, um auch diesen Teilbereich von Aufmerksamkeit selbst besser zu verstehen. Die drei gewählten Gebiete zeigen, dass der Ansatz grundlegende neurophysiologische, funktionale und verhaltensbezogene Eigenschaften von visueller Aufmerksamkeit erklären kann. Da die gefundenen Mechanismen somit ausreichend sind, das Phänomen so umfassend zu erklären, könnten die Mechanismen vielleicht sogar das essentielle neuronale Substrat von visueller Aufmerksamkeit im Cortex darstellen. Für die Informatik stellt die Arbeit damit ein tiefergehendes Verständnis von visueller Aufmerksamkeit dar. Darüber hinaus liefert das Framework mit seinen neuronalen Mechanismen sogar eine Referenzimplementierung um Aufmerksamkeit in zukünftige Systeme integrieren zu können. Aufmerksamkeit könnte laut der vorliegenden Forschung sehr nützlich für diese sein, da es im Gehirn eine Aufgabenspezifische Optimierung des visuellen Systems bereitstellt. Dieser Aspekt menschlicher Wahrnehmung fehlt meist in den aktuellen, starken Computervisionssystemen, so dass eine Integration in aktuelle Systeme deren Leistung sprunghaft erhöhen und eine neue Klasse definieren dürfte.:1. General introduction 2. The state-of-the-art in modeling visual attention 3. Microcircuit model of attention 4. Object localization with a model of visual attention 5. Object substitution masking 6. General conclusion

A statistical meta-analysis combines the results of several studies that address a set of related research hypotheses, thus increasing the power and reliability of the inference. Meta-analytic methods are over 50 years old and play an important role in science; pooling evidence from many trials to provide answers that any one trial would have insufficient samples to address. On the other hand, the number of neuroimaging studies is growing dramatically, with many of these publications containing conflicting results, or being based on only a small number of subjects. Hence there has been increasing interest in using meta-analysis methods to find consistent results for a specific functional task, or for predicting the results of a study that has not been performed directly. Current state of neuroimaging meta-analysis is limited to coordinate-based meta-analysis (CBMA), i.e., using only the coordinates of activation peaks that are reported by a group of studies, in order to "localize" the brain regions that respond to a certain type of stimulus. This class of meta-analysis suffers from a series of problems and hence cannot result in as accurate results as desired. In this research, we describe the problems that existing CBMA methods are suffering from and introduce a hierarchical mixed-effects image-based metaanalysis (IBMA) solution that incorporates the sufficient statistics (i.e., voxel-wise effect size and its associated uncertainty) from each study. In order to improve the statistical-inference stage of our proposed IBMA method, we introduce a nonparametric technique that is capable of adjusting such an inference for spatial nonstationarity. Given that in common practice, neuroimaging studies rarely provide the full image data, in an attempt to improve the existing CBMA techniques we introduce a fully automatic model-based approach that employs Gaussian-process regression (GPR) for estimating the meta-analytic statistic image from its corresponding sparse and noisy observations (i.e., the collected foci). To conclude, we introduce a new way to approach neuroimaging meta-analysis that enables the analysis to result in information such as “functional connectivity” and networks of the brain regions’ interactions, rather than just localizing the functions.

Tout au long de la vie, le cerveau développe des représentations de son environnement permettant à l’individu d’en tirer meilleur profit. Comment ces représentations se développent-elles pendant la quête de récompenses demeure un mystère. Il est raisonnable de penser que le cortex est le siège de ces représentations et que les ganglions de la base jouent un rôle important dans la maximisation des récompenses. En particulier, les neurones dopaminergiques semblent coder un signal d’erreur de prédiction de récompense. Cette thèse étudie le problème en construisant, à l’aide de l’apprentissage machine, un modèle informatique intégrant de nombreuses évidences neurologiques. Après une introduction au cadre mathématique et à quelques algorithmes de l’apprentissage machine, un survol de l’apprentissage en psychologie et en neuroscience et une revue des modèles de l’apprentissage dans les ganglions de la base, la thèse comporte trois articles. Le premier montre qu’il est possible d’apprendre à maximiser ses récompenses tout en développant de meilleures représentations des entrées. Le second article porte sur l'important problème toujours non résolu de la représentation du temps. Il démontre qu’une représentation du temps peut être acquise automatiquement dans un réseau de neurones artificiels faisant office de mémoire de travail. La représentation développée par le modèle ressemble beaucoup à l’activité de neurones corticaux dans des tâches similaires. De plus, le modèle montre que l’utilisation du signal d’erreur de récompense peut accélérer la construction de ces représentations temporelles. Finalement, il montre qu’une telle représentation acquise automatiquement dans le cortex peut fournir l’information nécessaire aux ganglions de la base pour expliquer le signal dopaminergique. Enfin, le troisième article évalue le pouvoir explicatif et prédictif du modèle sur différentes situations comme la présence ou l’absence d’un stimulus (conditionnement classique ou de trace) pendant l’attente de la récompense. En plus de faire des prédictions très intéressantes en lien avec la littérature sur les intervalles de temps, l’article révèle certaines lacunes du modèle qui devront être améliorées. Bref, cette thèse étend les modèles actuels de l’apprentissage des ganglions de la base et du système dopaminergique au développement concurrent de représentations temporelles dans le cortex et aux interactions de ces deux structures. / Throughout lifetime, the brain develops abstract representations of its environment that allow the individual to maximize his benefits. How these representations are developed while trying to acquire rewards remains a mystery. It is reasonable to assume that these representations arise in the cortex and that the basal ganglia are playing an important role in reward maximization. In particular, dopaminergic neurons appear to code a reward prediction error signal. This thesis studies the problem by constructing, using machine learning tools, a computational model that incorporates a number of relevant neurophysiological findings. After an introduction to the machine learning framework and to some of its algorithms, an overview of learning in psychology and neuroscience, and a review of models of learning in the basal ganglia, the thesis comprises three papers. The first article shows that it is possible to learn a better representation of the inputs while learning to maximize reward. The second paper addresses the important and still unresolved problem of the representation of time in the brain. The paper shows that a time representation can be acquired automatically in an artificial neural network acting like a working memory. The representation learned by the model closely resembles the activity of cortical neurons in similar tasks. Moreover, the model shows that the reward prediction error signal could accelerate the development of the temporal representation. Finally, it shows that if such a learned representation exists in the cortex, it could provide the necessary information to the basal ganglia to explain the dopaminergic signal. The third article evaluates the explanatory and predictive power of the model on the effects of differences in task conditions such as the presence or absence of a stimulus (classical versus trace conditioning) while waiting for the reward. Beyond making interesting predictions relevant to the timing literature, the paper reveals some shortcomings of the model that will need to be resolved. In summary, this thesis extends current models of reinforcement learning of the basal ganglia and the dopaminergic system to the concurrent development of representation in the cortex and to the interactions between these two regions.

Tout au long de la vie, le cerveau développe des représentations de son environnement permettant à l’individu d’en tirer meilleur profit. Comment ces représentations se développent-elles pendant la quête de récompenses demeure un mystère. Il est raisonnable de penser que le cortex est le siège de ces représentations et que les ganglions de la base jouent un rôle important dans la maximisation des récompenses. En particulier, les neurones dopaminergiques semblent coder un signal d’erreur de prédiction de récompense. Cette thèse étudie le problème en construisant, à l’aide de l’apprentissage machine, un modèle informatique intégrant de nombreuses évidences neurologiques. Après une introduction au cadre mathématique et à quelques algorithmes de l’apprentissage machine, un survol de l’apprentissage en psychologie et en neuroscience et une revue des modèles de l’apprentissage dans les ganglions de la base, la thèse comporte trois articles. Le premier montre qu’il est possible d’apprendre à maximiser ses récompenses tout en développant de meilleures représentations des entrées. Le second article porte sur l'important problème toujours non résolu de la représentation du temps. Il démontre qu’une représentation du temps peut être acquise automatiquement dans un réseau de neurones artificiels faisant office de mémoire de travail. La représentation développée par le modèle ressemble beaucoup à l’activité de neurones corticaux dans des tâches similaires. De plus, le modèle montre que l’utilisation du signal d’erreur de récompense peut accélérer la construction de ces représentations temporelles. Finalement, il montre qu’une telle représentation acquise automatiquement dans le cortex peut fournir l’information nécessaire aux ganglions de la base pour expliquer le signal dopaminergique. Enfin, le troisième article évalue le pouvoir explicatif et prédictif du modèle sur différentes situations comme la présence ou l’absence d’un stimulus (conditionnement classique ou de trace) pendant l’attente de la récompense. En plus de faire des prédictions très intéressantes en lien avec la littérature sur les intervalles de temps, l’article révèle certaines lacunes du modèle qui devront être améliorées. Bref, cette thèse étend les modèles actuels de l’apprentissage des ganglions de la base et du système dopaminergique au développement concurrent de représentations temporelles dans le cortex et aux interactions de ces deux structures. / Throughout lifetime, the brain develops abstract representations of its environment that allow the individual to maximize his benefits. How these representations are developed while trying to acquire rewards remains a mystery. It is reasonable to assume that these representations arise in the cortex and that the basal ganglia are playing an important role in reward maximization. In particular, dopaminergic neurons appear to code a reward prediction error signal. This thesis studies the problem by constructing, using machine learning tools, a computational model that incorporates a number of relevant neurophysiological findings. After an introduction to the machine learning framework and to some of its algorithms, an overview of learning in psychology and neuroscience, and a review of models of learning in the basal ganglia, the thesis comprises three papers. The first article shows that it is possible to learn a better representation of the inputs while learning to maximize reward. The second paper addresses the important and still unresolved problem of the representation of time in the brain. The paper shows that a time representation can be acquired automatically in an artificial neural network acting like a working memory. The representation learned by the model closely resembles the activity of cortical neurons in similar tasks. Moreover, the model shows that the reward prediction error signal could accelerate the development of the temporal representation. Finally, it shows that if such a learned representation exists in the cortex, it could provide the necessary information to the basal ganglia to explain the dopaminergic signal. The third article evaluates the explanatory and predictive power of the model on the effects of differences in task conditions such as the presence or absence of a stimulus (classical versus trace conditioning) while waiting for the reward. Beyond making interesting predictions relevant to the timing literature, the paper reveals some shortcomings of the model that will need to be resolved. In summary, this thesis extends current models of reinforcement learning of the basal ganglia and the dopaminergic system to the concurrent development of representation in the cortex and to the interactions between these two regions.