3,645 research outputs found

    Computational techniques to interpret the neural code underlying complex cognitive processes

    Get PDF
    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

    Development of variable and robust brain wiring patterns in the fly visual system

    Get PDF
    Precise generation of synapse-specific neuronal connections are crucial for establishing a robust and functional brain. Neuronal wiring patterns emerge from proper spatiotemporal regulation of axon branching and synapse formation during development. Several neuropsychiatric and neurodevelopmental disorders exhibit defects in neuronal wiring owing to synapse loss and/or dys-regulated axon branching. Despite decades of research, how the two inter-dependent cellular processes: axon branching and synaptogenesis are coupled locally in the presynaptic arborizations is still unclear. In my doctoral work, I investigated the possible role of EGF receptor (EGFR) activity in coregulating axon branching and synapse formation in a spatiotemporally restricted fashion, locally in the medulla innervating Dorsal Cluster Neuron (M- DCN)/LC14 axon terminals. In this work I have explored how genetically encoded EGFR randomly recycles in the axon branch terminals, thus creating an asymmetric, non-deterministic distribution pattern. Asymmetric EGFR activity in the branches acts as a permissive signal for axon branch pruning. I observed that the M-DCN branches which stochastically becomes EGFR ‘+’ during development are synaptogenic, which means they can recruit synaptic machineries like Syd1 and Bruchpilot (Brp). My work showed that EGFR activity has a dual role in establishing proper M-DCN wiring; first in regulating primary branch consolidation possibly via actin regulation prior to synaptogenesis. Later in maintaining/protecting the levels of late Active Zone (AZ) protein Brp in the presynaptic branches by suppressing basal autophagy level during synaptogenesis. When M-DCNs lack optimal EGFR activity, the basal autophagy level increases resulting in loss of Brp marked synapses which is causal to increased exploratory branches and post-synaptic target loss. Lack of EGFR activity affects the M-DCN wiring pattern that makes adult flies more active and behave like obsessive compulsive in object fixation assay. In the second part of my doctoral work, I have asked how non-genetic factors like developmental temperature affects adult brain wiring. To test that, I increased or decreased rearing temperature which is known to inversely affect pupal developmental rate. We asked if all the noisy cellular processes of neuronal assembly: filopodial dynamics, axon branching, synapse formation and postsynaptic connections scale up or down accordingly. I observed that indeed all the cellular processes slow down at lower developmental temperature and vice versa, which changes the DCN wiring pattern accordingly. Interestingly, behavior of flies adapts to their developmental temperature, performing best at the temperature they have been raised at. This shows that optimal brain function is an adaptation of robust brain wiring patterns which are specified by noisy developmental processes. In conclusion, my doctoral work helps us better understand the developmental regulation of axon branching and synapse formation for establishing precise brain wiring pattern. We need all the cell intrinsic developmental processes to be highly regulated in space and time. It is infact a combinatorial effect of such stochastic processes and external factors that contribute to the final outcome, a functional and robust adult brain

    Multimodal MRI analysis using deep learning methods

    Get PDF
    Magnetic resonance imaging (MRI) has been widely used in scientific and clinical research. It is a non-invasive medical imaging technique that reveals anatomical structures and provides useful information for investigators to explore aging and pathological processes. Different MR modalities offer different useful properties. Automatic MRI analysis algorithms have been developed to address problems in many applications such as classification, segmentation, and disease diagnosis. Segmentation and labeling algorithms applied to brain MRIs enable evaluations of the volumetric changes of specific structures in neurodegenerative diseases. Reconstruction of fiber orientations using diffusion MRI is beneficial to obtain better understanding of the underlying structures. In this thesis, we focused on development of deep learning methods for MRI analysis using different image modalities. Specifically, we applied deep learning techniques on different applications, including segmentation of brain structures and reconstruction of tongue muscle fiber orientations. For segmentation of brain structures, we developed an end-to-end deep learning algorithm for ventricle parcellation of brains with ventriculomegaly using T1-w MR images. The deep network provides robust and accurate segmentation results in subjects with high variability in ventricle shapes and sizes. We developed another deep learning method to automatically parcellate the thalamus into a set of thalamic nuclei using T1-w MRI and features from diffusion MRI. The algorithm incorporates a harmonization step to make the network adapt to input images with different contrasts. We also studied the strains associated with tongue muscles during speech production using multiple MRI modalities. To enable this study, we first developed a deep network to reconstruct crossing tongue muscle fiber orientations using diffusion MRI. The network was specifically designed for the human tongue and accounted for the orthogonality property of the tongue muscles. Next, we proposed a comprehensive pipeline to analyze the strains associated with tongue muscle fiber orientations during speech using diffusion MRI, and tagged and cine MRI. The proposed pipeline provides a solution to analyze the cooperation between muscle groups during speech production

    Fictocritical Cyberfeminism: A Paralogical Model for Post-Internet Communication

    Get PDF
    This dissertation positions the understudied and experimental writing practice of fictocriticism as an analog for the convergent and indeterminate nature of “post-Internet” communication as well a cyberfeminist technology for interfering and in-tervening in metanarratives of technoscience and technocapitalism that structure contemporary media. Significant theoretical valences are established between twen-tieth century literary works of fictocriticism and the hybrid and ephemeral modes of writing endemic to emergent, twenty-first century forms of networked communica-tion such as social media. Through a critical theoretical understanding of paralogy, or that countercultural logic of deploying language outside legitimate discourses, in-volving various tactics of multivocity, mimesis and metagraphy, fictocriticism is ex-plored as a self-referencing linguistic machine which exists intentionally to occupy those liminal territories “somewhere in among/between criticism, autobiography and fiction” (Hunter qtd. in Kerr 1996). Additionally, as a writing practice that orig-inated in Canada and yet remains marginal to national and international literary scholarship, this dissertation elevates the origins and ongoing relevance of fictocriti-cism by mapping its shared aims and concerns onto proximal discourses of post-structuralism, cyberfeminism, network ecology, media art, the avant-garde, glitch feminism, and radical self-authorship in online environments. Theorized in such a matrix, I argue that fictocriticism represents a capacious framework for writing and reading media that embodies the self-reflexive politics of second-order cybernetic theory while disrupting the rhetoric of technoscientific and neoliberal economic forc-es with speech acts of calculated incoherence. Additionally, through the inclusion of my own fictocritical writing as works of research-creation that interpolate the more traditional chapters and subchapters, I theorize and demonstrate praxis of this dis-tinctively indeterminate form of criticism to empirically and meaningfully juxtapose different modes of knowing and speaking about entangled matters of language, bod-ies, and technologies. In its conclusion, this dissertation contends that the “creative paranoia” engendered by fictocritical cyberfeminism in both print and digital media environments offers a pathway towards a more paralogical media literacy that can transform the terms and expectations of our future media ecology

    Simultaneous Multiparametric and Multidimensional Cardiovascular Magnetic Resonance Imaging

    Get PDF
    No abstract available

    On the Utility of Representation Learning Algorithms for Myoelectric Interfacing

    Get PDF
    Electrical activity produced by muscles during voluntary movement is a reflection of the firing patterns of relevant motor neurons and, by extension, the latent motor intent driving the movement. Once transduced via electromyography (EMG) and converted into digital form, this activity can be processed to provide an estimate of the original motor intent and is as such a feasible basis for non-invasive efferent neural interfacing. EMG-based motor intent decoding has so far received the most attention in the field of upper-limb prosthetics, where alternative means of interfacing are scarce and the utility of better control apparent. Whereas myoelectric prostheses have been available since the 1960s, available EMG control interfaces still lag behind the mechanical capabilities of the artificial limbs they are intended to steer—a gap at least partially due to limitations in current methods for translating EMG into appropriate motion commands. As the relationship between EMG signals and concurrent effector kinematics is highly non-linear and apparently stochastic, finding ways to accurately extract and combine relevant information from across electrode sites is still an active area of inquiry.This dissertation comprises an introduction and eight papers that explore issues afflicting the status quo of myoelectric decoding and possible solutions, all related through their use of learning algorithms and deep Artificial Neural Network (ANN) models. Paper I presents a Convolutional Neural Network (CNN) for multi-label movement decoding of high-density surface EMG (HD-sEMG) signals. Inspired by the successful use of CNNs in Paper I and the work of others, Paper II presents a method for automatic design of CNN architectures for use in myocontrol. Paper III introduces an ANN architecture with an appertaining training framework from which simultaneous and proportional control emerges. Paper Iv introduce a dataset of HD-sEMG signals for use with learning algorithms. Paper v applies a Recurrent Neural Network (RNN) model to decode finger forces from intramuscular EMG. Paper vI introduces a Transformer model for myoelectric interfacing that do not need additional training data to function with previously unseen users. Paper vII compares the performance of a Long Short-Term Memory (LSTM) network to that of classical pattern recognition algorithms. Lastly, paper vIII describes a framework for synthesizing EMG from multi-articulate gestures intended to reduce training burden

    Serial sectioning PSOCT and 2PM for imaging post-mortem human brain and neurodegeneration

    Full text link
    The study of aging and neurodegenerative processes in the human brain necessitates a comprehensive understanding of its myeloarchitectonic, cytoarchitectonic, and vascular structures. While recent computational advances have enabled volumetric reconstruction of the human brain using stained slices, the standard histological processing methods have often led to tissue distortions and loss, making deformation-free reconstruction challenging. Therefore, the development of a multi-scale and volumetric imaging technique that can accurately measure multiple structures within the intact brain would be a significant technical breakthrough. In this work, we present the development of an integrated approach that combines serial sectioning Polarization Sensitive Optical Coherence Tomography (PSOCT) and Two Photon Microscopy (2PM) to provide label-free multi-contrast imaging of human brain tissue. Our method allows for the simultaneous visualization of scattering, birefringence, and autofluorescence properties of the post-mortem human brain. By utilizing high-throughput reconstruction of 4x4x2cm3 sample blocks and simple registration of PSOCT and 2PM images, we enable comprehensive analysis of myelin content, cellular information, and vascular structure. PSOCT provides mesoscopic images and enables quantitative measurement of those brain structures, while 2PM provide complementary microscopic validation and enrichment of cellular and capillary information. This combined approach reveals myelin density and structure maps of the whole brain block and supplies intricate vessel and capillary networks as well as lipofuscin-filled cell soma across cortical regions, providing insights into the myeloarchitectural, cellular and vascular changes associated with neurodegenerative diseases such as Alzheimer's disease (AD) and Chronic Traumatic Encephalopathy (CTE)
    corecore