VictorJuiz/thesis huggingface dataset:
Systems Consolidation in the Context of Schemas, Sleep, and Medial Temporal Lobe Damage

In recent years, models of systems consolidation have become more complex as we consider the different factors that influence the establishment of long-lasting memories. This dissertation outlines a series of experiments that examines systems consolidation in two contexts: 1) in patients with temporal lobe epilepsy who evince a relatively selective long-term memory disorder, termed accelerated long-term forgetting (ALF), and 2) in the context of schematic congruency of new information with prior knowledge in the healthy brain, which has been shown to accelerate consolidation in rodents. In study 1, we present evidence that ALF is not a disorder of hippocampal binding and is instead associated with diminished hippocampal coupling with neocortical regions important for ultimately supporting the memory trace over time. In study 2, we report evidence that in the same patients, sleep-related consolidation mechanisms are disrupted. We found that time spent in slow wave sleep overnight was detrimental to subsequent memory, and present evidence that forgetting may be due to more numerous epileptic discharges during this sleep stage. In study 3, we investigated the influence of schematic congruency on memory in the healthy brain over time. Relative to incongruent information, content that was schema-congruent was remembered more coarsely over time, which was associated with increased post-encoding functional coupling between the hippocampus and medial prefrontal cortex (mPFC). There was also greater integration according to the congruent schematic context in the mPFC over time, as assessed via multivoxel pattern-similarity analyses. These findings are consistent with the idea that schemas act as a scaffold for the accelerated consolidation of congruent information. Finally, in study 4, we describe a schema benefit to long-term memory in patients with ALF, although that benefit is not as great as that which was observed for controls. While schematic congruency improved long-term retention in patients, there was some indication that these benefits may not be long-lasting. Together, these studies present evidence for altered timelines of systems consolidation, depending on hippocampal-neocortical interaction, sleep, and schema-congruency.

Keywords: accelerated long-term forgetting
fMRI
memory
schema
systems consolidation
temporal lobe epilepsy
Advisor: McAndrews, Mary Pat
The Choral-Orchestral Works of Stephen Chatman

Canadian composer Stephen Chatman has composed noteworthy works within multiple musical genres, thus achieving international stature. Included among his compositions are several choral-orchestral works, which comprise the focus of this study. In my research, I determined the musical characteristics of Chatman’s choral-orchestral works, described how those works may be effectively prepared for performance by conductors, and assessed Chatman’s contributions to the choral-orchestral genre in Canada. A review of a wide assortment of literature and resources concerning Stephen Chatman’s works in the context of Canadian choral-orchestral repertoire produced fruitful results. I examined numerous and varied accomplishments of the composer using information found in dissertations and writings devoted specifically to Chatman and his music. Further research using materials located in the Chatman fonds at Library and Archives Canada yielded a comprehensive documentation of Chatman’s professional career and musical output. In addition, I achieved substantial insight through personal interviews with Chatman and seven other associated individuals who provided unique and informative data about his music. In this thesis, I discuss distinctive musical and textual characteristics of seven of Chatman’s choral-orchestral works: four major works composed for symphonic choir and full orchestra, and three shorter, single-movement works. I completed detailed analyses for two of these major works, Proud Music of the Storm (2001) and A Song of Joys (2013-14). During the analysis process, I discovered common threads, as well as advancements in Chatman’s compositional style over time. In order to facilitate successful performances of Chatman’s music, I prepared a conductor’s guide with detailed rehearsal suggestions for these two works specifically. To assist with score preparation, conductors will find informative data in the appendices: facts and features for all seven Chatman works studied and charts comprising bar-by-bar flow chart analyses for Proud Music of the Storm and A Song of Joys. It is my hope that this research will help promote these fine contributions within the contemporary choral-orchestral genre of music in Canada.

Keywords: Choral Conducting
Advisor: Apfelstadt, Hilary J
Estimating Psychosis Risk in Individuals at Clinical High Risk using Event–related Brain Potential Indices of Cognitive Processing

Background: The N400 event-related brain potential waveform occurs in response to potentially meaningful stimuli and this effect is thought to reflect greater activation of related versus unrelated concepts in long-term semantic memory. In normal participants, related targets elicit smaller (less negative) N400 amplitudes than do unrelated items. These N400 semantic priming effects are found to be attenuated in schizophrenia patients, suggesting impaired activation of related concepts. Individuals at clinical high risk (CHR) for schizophrenia experience subthreshold symptoms of the disorder, including decreased functioning. The event-related potential Mismatch Negativity (MMN), P3a and gamma ASSR measures have been found to be abnormal in CHR patients compared to controls.Aim: We aimed to examine whether N400 semantic priming deficits are a biomarker of the CHR state, whether decreased N400 semantic priming predicts conversion to psychosis in this population over two years, and whether N400 effects predict high-risk symptomatology and impaired functioning over time. Methods: We examined the N400 ERP semantic priming effect, the MMN, P3a and gamma ASSR in a sample of CHR participants and healthy controls. We then re-assessed the CHR group at one and two years to measure global functioning, positive psychotic symptoms, and conversion status. Results: We found a deficient N400 effect in the CHR group compared to controls. In this group, the N400 was related to role functioning and cognitive defects at baseline, social functioning at one-year follow-up, and improvement of positive symptoms and functioning over two years’ follow-up. Conclusion: This study indicates that the N400 priming effect is deficient at the CHR state and may contribute to the worsening of positive symptoms and functioning over time. Given that only a minority of CHR individuals will go on to develop schizophrenia, efforts to refine our ability to identify those at highest risk are critical. These findings may help to target limited resources to those individuals at risk who need it the most and minimize unnecessary treatment and side effects.

Keywords: Clinically High Risk
Electroencephalogram
Event Related Potentials
Gamma Auditory Steady State
N400
Psychosis
Advisor: Kiang, Michael
Mizrahi, Romina
Greenhouse Gas Emission Mitigation Pathways for Light-duty Vehicle Fleets under Ambitious Climate Targets

Mitigating greenhouse gas (GHG) emissions from light-duty passenger vehicles (LDVs) will be necessary to maintain global warming below 2 °C, and ideally below 1.5 °C. In this dissertation, methods to estimate the life cycle GHG emission implications of LDV-focused mitigation strategies and to outline mitigation pathways under ambitious climate targets are developed at national and urban scales. First, a fleet-based life cycle model, the FLAME (Fleet Life cycle Assessment and Material-flow Estimation) is developed to examine the life cycle GHG emission implications of mitigation strategies, such as lightweighting the U.S. LDV fleet or deploying mid-level ethanol blends (15-30% ethanol by volume) in Canada's LDV fleet. The model combines the high technological resolution of life cycle assessment (LCA) with the temporal and dynamic perspectives of LDV fleet models. Recommendations are provided on the most effective timing of the mitigation strategies, and on their contributions to national GHG emission reduction pledges. Then, the FLAME model is augmented with a backcasting procedure to outline GHG emission mitigation pathways for LDV fleets to maintain global warming below 2 °C, and the electrification of the U.S. LDV fleet is used as a case study. The backcasting procedure relies on an innovative approach based on Integrated Assessment Models (IAMs) to quantify national and sectoral GHG emission budgets. Finally, the CURTAIL model (Climate change constrained URban passenger TrAnsport Integrated Life cycle assessment) is developed and applied in Singapore to integrate all passenger land transport modes at an urban level and to seek associated combinations of mitigation strategies that are consistent with maintaining global warming below 2 °C or 1.5 °C. The methods developed in this dissertation bridge gaps between the refined perspectives of LCA and the global perspectives of IAMs to support the development of national and urban policies for LDVs to respect ambitious climate targets. The findings suggest that there is no technological silver-bullet, there is an urgency to act, and all mitigation efforts should be pursued.

Keywords: Biofuel
Climate Change Mitigation
Electric Vehicle
Life Cycle Assessment
Light-duty Vehicle
Lightweighting
Advisor: MacLean, Heather L. H.L.
Posen, I. Daniel I.D.
The Feedback between Core Heat Flux, Compositional Heterogeneity, and the Dynamics of a Rheologically Obtained Plate-like Surface in Numerical Mantle Convection Model

The present day Earth features a surface characterized by broad regions of low strain rate and narrow bands of high deformation, comprising the plates and their boundaries, respectively. Moreover, a distinction exists between the divergent boundaries which include frequent transform-like offsets and the convergent boundaries, which are smooth continuous features. Above the Core Mantle Boundary (CMB), seismic tomography has revealed the presence of two Large Low Shear-wave Velocity Provinces (LLSVPs) below the African and Pacific Plates. This thesis presents mantle convection simulations focused on the feedback between a rheologically obtained plate-like surface and the characteristics of the lower mantle including the core mantle boundary heat flux and the presence of a Compositionally Anomalous Intrinsically Dense (CAID) component, speculated to be the origin of the LLSVPs. Over 200 two-dimensional and 13 three-dimensional numerical simulations were conducted in this study. Two-dimensional calculations illustrate the general impact of model parameters on the mantle's thermal state while it is found that three-dimensional calculations are necessary to properly investigate the feedback between the surface velocity field and the distribution of CAID material. The presence of a dense component near the core mantle boundary can act to inhibit heat flow into the mantle, effectively cooling the system. Previous studies have investigated the parameters affecting the distribution of a dense component above the CMB, however, some lack the presence of a dynamically evolving surface or a three-dimensional geometry. The rheologically obtained plate-like surfaces in this study feature evolving regions of convergence, where cold downwelling surface material sinks into the deep mantle, and divergence, at boundaries punctuated with transform-like offsets. Downwelling material sinks to the CMB driving CAID material into a variety of different distributions. Given the insulating nature of the CAID material, its distribution effects the basal heat flux and the thermal state of the mantle. The physical requirements necessary to generate a plate-like surface velocity field do not allow for the development of diametrically opposed CAID material provinces, however, the presence of the CAID material impacts the surface dynamics.

Advisor: Lowman, Julian P
Adaptive myelination and its synchronous dynamics in the Kuramoto network model with state-dependent delays

White matter pathways form a complex network of myelinated axons that play a critical role in brain function by facilitating the timely transmission of neural signals. Recent evidence reveals that white matter networks are adaptive and that myelin undergoes continuous reformation through behaviour and learning during both developmental stages and adulthood in the mammalian life cycle. Consequently, this allows axonal conduction delays to adjust in order to regulate the timing of neuron signals propagating between different brain regions. Despite its newly founded relevance, the network distribution of conduction delays have yet to be widely incorporated in computational models, as the delays are typically assumed to be either constant or ignored altogether. From its clear influence towards temporal dynamics, we are interested in how adaptive myelination affects oscillatory synchrony in the brain. We introduce a plasticity rule into the delays of a weakly coupled oscillator network, whose positions relative to its natural limit cycle oscillations is described through a coupled phase model. From this, the addition of slowly adaptive network delays can potentially lead coupled oscillators to a more phase synchronous limit cycle. To see how adaptive white matter remodelling can shape synchronous dynamics, we modify the canonical Kuramoto model by enabling all connections with phase-dependent delays that change over time. We directly compare the synchronous behaviours of the Kuramoto model equipped with static delays and adaptive delays by analyzing the synchronized equilibria and stability of the system's phases. Our mathematical analysis of the model with Dirac and exponentially distributed connection delays, supported by numerical simulations, demonstrates that larger, more widely varying distributions of delays generally impede synchronization in the Kuramoto network. Adaptive delays act as a stabilizing mechanism for the synchrony of the network by adjusting towards a more optimal distribution of delays. Adaptive delays also make global synchronization more resilient to perturbations and injury towards network architecture. Our results provide insights about the potential significance of activity-dependent myelination. We hope that these results lay out the groundwork to computationally study the influence of adaptative myelination towards large-scale brain synchrony.

Keywords: Delay differential equations
Kuramoto model
Synchronization
White matter plasticity
Advisor: Lefebvre, Jéremie
Towards Biologically Plausible Gradient Descent

Synaptic plasticity is the primary physiological mechanism underlying learning in the brain. It is dependent on pre- and post-synaptic neuronal activities, and can be mediated by neuromodulatory signals. However, to date, computational models of learning that are based on pre- and post-synaptic activity and/or global neuromodulatory reward signals for plasticity have not been able to learn complex tasks that animals are capable of. In the machine learning field, neural network models with many layers of computations trained using gradient descent have been highly successful in learning difficult tasks with near-human level performance. To date, it remains unclear how gradient descent could be implemented in neural circuits with many layers of synaptic connections. The overarching goal of this thesis is to develop theories for how the unique properties of neurons can be leveraged to enable gradient descent in deep circuits and allow them to learn complex tasks. The work in this thesis is divided into three projects. The first project demonstrates that networks of cortical pyramidal neurons, which have segregated apical dendrites and exhibit bursting behavior driven by dendritic plateau potentials, can in theory leverage these physiological properties to approximate gradient descent through multiple layers of synaptic connections. The second project presents a theory for how ensembles of pyramidal neurons can multiplex sensory and learning signals using bursting and short-term plasticity, in order to approximate gradient descent and learn complex visual recognition tasks that previous biologically inspired models have struggled with. The final project focuses on the fact that machine learning models implementing gradient descent assume symmetric feedforward and feedback weights, and presents a theory for how the spiking properties of neurons can enable them to align feedforward and feedback weights in a network. As a whole, this work aims to bridge the gap between powerful algorithms developed in the machine learning field and our current understanding of learning in the brain. To this end, we develop novel theories into how neuronal circuits in the brain can coordinate the learning of complex tasks, and present a number of experimental predictions that are fruitful avenues for future experimental research.

Keywords: Credit assignment
Deep learning
Gradient descent
Neural networks
Pyramidal neurons
Advisor: Richards, Blake A
Investigating the Involvement of the Sulfotransferase Pathway in Drug-induced Skin Rash

Circumstantial evidence suggests that most idiosyncratic drug reactions are caused by chemically reactive metabolites of the drug that covalently binds to proteins. The skin is a major target of idiosyncratic reactions; however, drug metabolism in the skin is limited. One exception is the presence of relatively high sulfotransferase activity in human skin. For example, nevirapine-induced skin rash is caused by a reactive benzylic sulfate formed in the skin. The working hypothesis is that the serious skin rashes caused by other drugs involve reactive sulfate metabolites formed in the skin. Trimethoprim, lamotrigine, valdecoxib, and sertraline have the potential to produce reactive sulfate metabolites that may be responsible for drug-induced skin rash. Anti-drug antibodies against trimethoprim, lamotrigine, and valdecoxib were made to study covalent binding of the drug to proteins. Brown Norway rats were treated with these drugs, and their liver and skin proteins were immunoblotted to look for covalent binding. No covalent binding of any of these drugs was detected in the skin, but covalent binding of trimethoprim was detected in the liver. The immunoassay may not be sufficiently sensitive to detect covalent binding in the skin, or binding may be limited to human skin. The sulfates of hydroxy-trimethoprim and lamotrigine-N-oxide, which are metabolites of these drugs, were chemically synthesized, and both were found to be chemically reactive. Surprisingly, even hydroxy-trimethoprim itself had sufficient reactivity to covalently bind to proteins in vitro. Dr. Liu, our collaborator at the University of Toledo, tested whether hydroxy-trimethoprim, lamotrigine-N-oxide, hydroxy-valdecoxib or hydroxy-sertraline were substrates of human sulfotransferases. He found that lamotrigine-N-oxide was a substrate for several human sulfotransferases, while hydroxy-trimethoprim was only a substrate for the fetal sulfotransferase SULT1C4, and hydroxy-valdecoxib and hydroxy-sertraline were not substrates for human sulfotransferases. That implies that the rashes caused by valdecoxib and sertraline are not due to a sulfate metabolite. Given that hydroxy-trimethoprim is only a substrate for a fetal sulfotransferase but is weakly reactive, it may be responsible for trimethoprim rashes. The rash caused by lamotrigine is likely due to the N-O-sulfate; however, detection of covalent binding in skin would have strengthened the evidence for this hypothesis.

Keywords: covalent binding
idiosyncratic drug reactions
reactive metabolite
skin rash
sulfotransferase
Advisor: Uetrecht, Jack JU
Being as a Kind in Plato's Sophist

What is being for Plato? While in several dialogues ‘being’ (to on, ousia) typically designates the intelligible domain in general, in the Sophist Plato was led, through his engagement with the paradox of falsehood and the problem of not-being, to single out being as just one among the kinds (or forms) – notably, one of the so-called ‘greatest kinds’. Surprisingly little effort has been devoted by scholars to working out the motivations and implications of this move. I shall argue that the kind being, just like any other kind (or form), is first and foremost conceived of by Plato as a robust causal principle. It is not a most generic genus encompassing all other genera, but the entity metaphysically responsible for the property named after it, viz. being (simpliciter). Against the current orthodoxy, I therefore think that the famous slogan ‘to be is to be something’, often taken to capture a fundamental truth of Plato’s conception of being, does not fit the Sophist. Further, this also means that, unlike many modern philosophers, Plato conceives of being as a real property. What property? Although the Sophist is not fully explicit on this point, Plato probably suggests that it is the property of having ‘the power to act or to be acted upon’, which can be interpreted as the power to take part in a causal relation. Finally, I argue that the isolation of a kind being is a necessary condition for Plato’s account of not-being. Were there no kind being, Plato could not bring his ambitious project about not-being to completion.

Keywords: Being
Kind
metaphysics
ontology
Plato
Sophist
Advisor: Gerson, Lloyd P.
The Bidirectional Acquisition of Oral and Nasal Gestural Timing in L2 Brazilian Portuguese and Rioplatense Spanish Nasal Structures

Brazilian Portuguese (BP) nasal vowels (Ṽᴺ) and Rioplatense Spanish (RS) vowel + nasal sequences (VN) are realized with two oral (vowel and consonant) gestures and a nasal (velum) gesture, but they differ in the way these gestures are sequenced. Adult native speakers of RS and BP who aim to acquire the opposite language will thus need to learn this cross-linguistic difference. On the one hand, non-native speakers of BP will have to realize a longer overlap of the vowel and velum gestures and a shorter nasal coda. On the other hand, non-native speakers of RS will need to produce a shorter gestural overlap and a longer nasal coda. The main purpose of this dissertation is to investigate the relative difficulties that RS and BP speakers encounter at the phonetic and phonological levels when acquiring the gestural pattern of the other language’s nasal structure. To accomplish this goal, four studies were conducted. The findings from the studies on monolingual and bilingual production suggest that nasal structures in RS and BP are similar but differ in terms of their gestural timing and that their phonetic implementation and phonological representation may be affected by the dominant language of heritage speakers. Moreover, the studies on naïve and L2 perception and production indicate that, with experience in the L2, the timing of the oral-nasal gestural overlap can be acquired by non-native speakers. However, the gestural timing of a longer nasal coda seems more difficult to realize than that of a shorter nasal coda, not only at first exposure but also with more experience in the L2. This suggests that nasal coda weakening, a common phonological process in language variation and change, poses less articulatory difficulties to L2 learners than nasal coda strengthening. We propose that a gestural timing constraint on nasal coda strengthening should be integrated into L2 models of phonological acquisition to better predict and explain relative difficulties encountered by L2 learners.

Keywords: Articulatory Phonology
L2 Acquisition
Nasal structures
Phonetics
Portuguese
Spanish
Advisor: Colantoni, Laura