3,049 research outputs found

    Computational techniques to interpret the neural code underlying complex cognitive processes

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    Advances in large-scale neural recording technology have significantly improved the capacity to further elucidate the neural code underlying complex cognitive processes. This thesis aimed to investigate two research questions in rodent models. First, what is the role of the hippocampus in memory and specifically what is the underlying neural code that contributes to spatial memory and navigational decision-making. Second, how is social cognition represented in the medial prefrontal cortex at the level of individual neurons. To start, the thesis begins by investigating memory and social cognition in the context of healthy and diseased states that use non-invasive methods (i.e. fMRI and animal behavioural studies). The main body of the thesis then shifts to developing our fundamental understanding of the neural mechanisms underpinning these cognitive processes by applying computational techniques to ana lyse stable large-scale neural recordings. To achieve this, tailored calcium imaging and behaviour preprocessing computational pipelines were developed and optimised for use in social interaction and spatial navigation experimental analysis. In parallel, a review was conducted on methods for multivariate/neural population analysis. A comparison of multiple neural manifold learning (NML) algorithms identified that non linear algorithms such as UMAP are more adaptable across datasets of varying noise and behavioural complexity. Furthermore, the review visualises how NML can be applied to disease states in the brain and introduces the secondary analyses that can be used to enhance or characterise a neural manifold. Lastly, the preprocessing and analytical pipelines were combined to investigate the neural mechanisms in volved in social cognition and spatial memory. The social cognition study explored how neural firing in the medial Prefrontal cortex changed as a function of the social dominance paradigm, the "Tube Test". The univariate analysis identified an ensemble of behavioural-tuned neurons that fire preferentially during specific behaviours such as "pushing" or "retreating" for the animal’s own behaviour and/or the competitor’s behaviour. Furthermore, in dominant animals, the neural population exhibited greater average firing than that of subordinate animals. Next, to investigate spatial memory, a spatial recency task was used, where rats learnt to navigate towards one of three reward locations and then recall the rewarded location of the session. During the task, over 1000 neurons were recorded from the hippocampal CA1 region for five rats over multiple sessions. Multivariate analysis revealed that the sequence of neurons encoding an animal’s spatial position leading up to a rewarded location was also active in the decision period before the animal navigates to the rewarded location. The result posits that prospective replay of neural sequences in the hippocampal CA1 region could provide a mechanism by which decision-making is supported

    Meta-learning algorithms and applications

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    Meta-learning in the broader context concerns how an agent learns about their own learning, allowing them to improve their learning process. Learning how to learn is not only beneficial for humans, but it has also shown vast benefits for improving how machines learn. In the context of machine learning, meta-learning enables models to improve their learning process by selecting suitable meta-parameters that influence the learning. For deep learning specifically, the meta-parameters typically describe details of the training of the model but can also include description of the model itself - the architecture. Meta-learning is usually done with specific goals in mind, for example trying to improve ability to generalize or learn new concepts from only a few examples. Meta-learning can be powerful, but it comes with a key downside: it is often computationally costly. If the costs would be alleviated, meta-learning could be more accessible to developers of new artificial intelligence models, allowing them to achieve greater goals or save resources. As a result, one key focus of our research is on significantly improving the efficiency of meta-learning. We develop two approaches: EvoGrad and PASHA, both of which significantly improve meta-learning efficiency in two common scenarios. EvoGrad allows us to efficiently optimize the value of a large number of differentiable meta-parameters, while PASHA enables us to efficiently optimize any type of meta-parameters but fewer in number. Meta-learning is a tool that can be applied to solve various problems. Most commonly it is applied for learning new concepts from only a small number of examples (few-shot learning), but other applications exist too. To showcase the practical impact that meta-learning can make in the context of neural networks, we use meta-learning as a novel solution for two selected problems: more accurate uncertainty quantification (calibration) and general-purpose few-shot learning. Both are practically important problems and using meta-learning approaches we can obtain better solutions than the ones obtained using existing approaches. Calibration is important for safety-critical applications of neural networks, while general-purpose few-shot learning tests model's ability to generalize few-shot learning abilities across diverse tasks such as recognition, segmentation and keypoint estimation. More efficient algorithms as well as novel applications enable the field of meta-learning to make more significant impact on the broader area of deep learning and potentially solve problems that were too challenging before. Ultimately both of them allow us to better utilize the opportunities that artificial intelligence presents

    Life on a scale:Deep brain stimulation in anorexia nervosa

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    Anorexia nervosa (AN) is a severe psychiatric disorder marked by low body weight, body image abnormalities, and anxiety and shows elevated rates of morbidity, comorbidity and mortality. Given the limited availability of evidence-based treatments, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. This thesis represents the first study in the Netherlands and one of a limited number globally to evaluate the efficacy, safety, and tolerability of deep brain stimulation (DBS) in the treatment of AN. DBS has the advantage of being both reversible and adjustable. Beyond assessing the primary impact of DBS on body weight, psychological parameters, and quality of life, this research is novel in its comprehensive approach. We integrated evaluations of efficacy with critical examinations of the functional impact of DBS in AN, including fMRI, electroencephalography EEG, as well as endocrinological and metabolic assessments. Furthermore, this work situates AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Finally, we reflect on the practical, ethical and philosophical aspects of conducting an experimental, invasive procedure in a vulnerable patient group. This thesis deepens our understanding of the neurobiological underpinnings of AN and paves the way for future research and potential clinical applications of DBS in the management of severe and enduring AN

    Single-cell time-series analysis of metabolic rhythms in yeast

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    The yeast metabolic cycle (YMC) is a biological rhythm in budding yeast (Saccharomyces cerevisiae). It entails oscillations in the concentrations and redox states of intracellular metabolites, oscillations in transcript levels, temporal partitioning of biosynthesis, and, in chemostats, oscillations in oxygen consumption. Most studies on the YMC have been based on chemostat experiments, and it is unclear whether YMCs arise from interactions between cells or are generated independently by each cell. This thesis aims at characterising the YMC in single cells and its response to nutrient and genetic perturbations. Specifically, I use microfluidics to trap and separate yeast cells, then record the time-dependent intensity of flavin autofluorescence, which is a component of the YMC. Single-cell microfluidics produces a large amount of time series data. Noisy and short time series produced from biological experiments restrict the computational tools that are useful for analysis. I developed a method to filter time series, a machine learning model to classify whether time series are oscillatory, and an autocorrelation method to examine the periodicity of time series data. My experimental results show that yeast cells show oscillations in the fluorescence of flavins. Specifically, I show that in high glucose conditions, cells generate flavin oscillations asynchronously within a population, and these flavin oscillations couple with the cell division cycle. I show that cells can individually reset the phase of their flavin oscillations in response to abrupt nutrient changes, independently of the cell division cycle. I also show that deletion strains generate flavin oscillations that exhibit different behaviour from dissolved oxygen oscillations from chemostat conditions. Finally, I use flux balance analysis to address whether proteomic constraints in cellular metabolism mean that temporal partitioning of biosynthesis is advantageous for the yeast cell, and whether such partitioning explains the timing of the metabolic cycle. My results show that under proteomic constraints, it is advantageous for the cell to sequentially synthesise biomass components because doing so shortens the timescale of biomass synthesis. However, the degree of advantage of sequential over parallel biosynthesis is lower when both carbon and nitrogen sources are limiting. This thesis thus confirms autonomous generation of flavin oscillations, and suggests a model in which the YMC responds to nutrient conditions and subsequently entrains the cell division cycle. It also emphasises the possibility that subpopulations in the culture explain chemostat-based observations of the YMC. Furthermore, this thesis paves the way for using computational methods to analyse large datasets of oscillatory time series, which is useful for various fields of study beyond the YMC

    INTEGRATED COMPUTER-AIDED DESIGN, EXPERIMENTATION, AND OPTIMIZATION APPROACH FOR PEROVSKITES AND PETROLEUM PACKAGING PROCESSES

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    According to the World Economic Forum report, the U.S. currently has an energy efficiency of just 30%, thus illustrating the potential scope and need for efficiency enhancement and waste minimization. In the U.S. energy sector, petroleum and solar energy are the two key pillars that have the potential to create research opportunities for transition to a cleaner, greener, and sustainable future. In this research endeavor, the focus is on two pivotal areas: (i) Computer-aided perovskite solar cell synthesis; and (ii) Optimization of flow processes through multiproduct petroleum pipelines. In the area of perovskite synthesis, the emphasis is on the enhancement of structural stability, lower costs, and sustainability. Utilizing modeling and optimization methods for computer-aided molecular design (CAMD), efficient, sustainable, less toxic, and economically viable alternatives to conventional lead-based perovskites are obtained. In the second area of optimization of flow processes through multiproduct petroleum pipelines, an actual industrial-scale operation for packaging multiple lube-oil blends is studied. Through an integrated approach of experimental characterization, process design, procedural improvements, testing protocols, control mechanisms, mathematical modeling, and optimization, the limitations of traditional packaging operations are identified, and innovative operational paradigms and strategies are developed by incorporating methods from process systems engineering and data-driven approaches

    Computational and experimental studies on the reaction mechanism of bio-oil components with additives for increased stability and fuel quality

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    As one of the world’s largest palm oil producers, Malaysia encountered a major disposal problem as vast amount of oil palm biomass wastes are produced. To overcome this problem, these biomass wastes can be liquefied into biofuel with fast pyrolysis technology. However, further upgradation of fast pyrolysis bio-oil via direct solvent addition was required to overcome it’s undesirable attributes. In addition, the high production cost of biofuels often hinders its commercialisation. Thus, the designed solvent-oil blend needs to achieve both fuel functionality and economic targets to be competitive with the conventional diesel fuel. In this thesis, a multi-stage computer-aided molecular design (CAMD) framework was employed for bio-oil solvent design. In the design problem, molecular signature descriptors were applied to accommodate different classes of property prediction models. However, the complexity of the CAMD problem increases as the height of signature increases due to the combinatorial nature of higher order signature. Thus, a consistency rule was developed reduce the size of the CAMD problem. The CAMD problem was then further extended to address the economic aspects via fuzzy multi-objective optimisation approach. Next, a rough-set based machine learning (RSML) model has been proposed to correlate the feedstock characterisation and pyrolysis condition with the pyrolysis bio-oil properties by generating decision rules. The generated decision rules were analysed from a scientific standpoint to identify the underlying patterns, while ensuring the rules were logical. The decision rules generated can be used to select optimal feedstock composition and pyrolysis condition to produce pyrolysis bio-oil of targeted fuel properties. Next, the results obtained from the computational approaches were verified through experimental study. The generated pyrolysis bio-oils were blended with the identified solvents at various mixing ratio. In addition, emulsification of the solvent-oil blend in diesel was also conducted with the help of surfactants. Lastly, potential extensions and prospective work for this study have been discuss in the later part of this thesis. To conclude, this thesis presented the combination of computational and experimental approaches in upgrading the fuel properties of pyrolysis bio-oil. As a result, high quality biofuel can be generated as a cleaner burning replacement for conventional diesel fuel

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    Factor Graph Neural Networks

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    In recent years, we have witnessed a surge of Graph Neural Networks (GNNs), most of which can learn powerful representations in an end-to-end fashion with great success in many real-world applications. They have resemblance to Probabilistic Graphical Models (PGMs), but break free from some limitations of PGMs. By aiming to provide expressive methods for representation learning instead of computing marginals or most likely configurations, GNNs provide flexibility in the choice of information flowing rules while maintaining good performance. Despite their success and inspirations, they lack efficient ways to represent and learn higher-order relations among variables/nodes. More expressive higher-order GNNs which operate on k-tuples of nodes need increased computational resources in order to process higher-order tensors. We propose Factor Graph Neural Networks (FGNNs) to effectively capture higher-order relations for inference and learning. To do so, we first derive an efficient approximate Sum-Product loopy belief propagation inference algorithm for discrete higher-order PGMs. We then neuralize the novel message passing scheme into a Factor Graph Neural Network (FGNN) module by allowing richer representations of the message update rules; this facilitates both efficient inference and powerful end-to-end learning. We further show that with a suitable choice of message aggregation operators, our FGNN is also able to represent Max-Product belief propagation, providing a single family of architecture that can represent both Max and Sum-Product loopy belief propagation. Our extensive experimental evaluation on synthetic as well as real datasets demonstrates the potential of the proposed model.Comment: Accepted by JML
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