Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item Analyzing the Dynamics of Biological and Artificial Neural Networks with Applications to Machine Learning(2024) Srinivasan, Keshav; Girvan, Michelle; Biophysics (BIPH); Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The study of the brain has profoundly shaped the evolution of computational learning models and the history of neural networks. This journey began in the 1940s with Warren McCulloch and Walter Pitts’ groundbreaking work on the first mathematical model of a neuron, laying the foundation for artificial neural networks. The 1950s and 60s witnessed a significant milestone with Frank Rosenblatt’s development of the perceptron, showcasing the potential of neural networks for complex computational tasks. Since then, the field of neural networks has witnessed explosive growth, and terms like “Artificial Intelligence” and “Machine Learning” have become commonplace across diverse fields, including finance,medicine, and science. This dissertation explores the symbiotic parallels between neuroscience and machine learning, focusing on the dynamics of biological and artificial neural networks. We begin by examining artificial neural networks, particularly in predicting the dynamics of large, complex networks—a paradigm where traditional machine learning algorithms often struggle. To address this, we propose a novel approach utilizing a parallel architecture that mimics the network’s structure, achieving scalable and accurate predictions. Shifting our focus to biological neuronal networks, we delve into the theory of critical systems. This theory posits that the brain, when viewed as a complex dynamical system, operates near a critical point, a state ideal for efficient information processing. A key experimental observation of this type of criticality is neuronal avalanches—scale-free cascades of neuronal activity—which have been documented both in vitro (in neuronal cultures and acute brain slices) and in vivo (in the brains of awake animals). Recent advancements in experimental techniques, such as multi-photon imaging and genetically encoded fluorescent markers, allow for the measurement of activity in living organisms with unparalleled single-cell resolution. Despite these advances, significant challenges remain when only a fraction of neurons can be recorded with sufficient resolution, leading to inaccurate estimations of power-law relationships in size, duration, and scaling of neuronal avalanches. We demonstrate that by analyzing simulated critical neuronal networks alongside real 2-photon imaging data, temporal coarse-graining can recover the critical value of the mean size vs. duration scaling of neuronal avalanches, allowing for more accurate estimations of critical brain dynamics even from subsampled data. Finally, we bridge the gap between machine learning and neuroscience by exploring the concept of excitatory-inhibitory balance, a crucial feature of neuronal networks in the brain, within the framework of reservoir computing. We emphasize the stabilizing role of inhibition in reservoir computers (RCs), mirroring its function in the brain. We propose a novel inhibitory adaptation mechanism that allows RCs to autonomously adjust inhibitory connections to achieve a specific firing rate target, motivated by the firing rate homeostasis observed in biological neurons. Overall, this dissertation strives to deepen the ongoing collaboration between neuroscience and machine learning, fostering advancements that will benefit both fields.Item NEURAL BASIS OF VIBRATION DETECTION IN LEPIDOSAURIAN REPTILES(2024) Han, Dawei; Carr, Catherine E.; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)There are three potential pathways for detection of substrate vibration: cochlear, otolithic and somatosensory, reviewed in chapter one. How different lepidosaurian reptiles detect substrate vibration from these three pathways was explored from neuroanatomical and physiological perspectives. In chapter two, I described vibration sensitivity and the organization of the brainstem cochlear nuclei in the western snake (Pantherophis obsoletus). The western ratsnake is sensitive to low-frequency vibrations, comparable to other snakes. It has two first-order cochlear nuclei, nucleus magnocellularis (NM) and nucleus angularis (NA), similar to other reptiles. NM is small, while NA is relatively robust. In chapter three, I examined the connections and response properties of nucleus vestibularis ovalis (VeO) in the hindbrain of the tokay gecko (Gekko gecko). VeO receives input from the saccule, and connections of VeO mirror those of the cochlear nuclei, including an ascending projection to the central nucleus of the torus semicircularis. VeO neurons are sensitive to low-frequency vibration. In chapter four, I revisited a classic study to determine the connections and response properties of the snake torus semicircularis. In the western ratsnake, the torus can be divided into a central nucleus and a paratorus, the latter receiving input from the spinal cord, nucleus myelencephali dorsalis in the spinomedullary junction, as well as auditory nuclei. Toral neurons are sensitive to low frequency vibration and have heterogenous response characteristics. In chapter five, I discuss future directions based on findings in my dissertation and highlight the importance of vibration detection for lepidosaurs.Item INTERACTIONS OF SOCIAL EXPERIENCE, ALCOHOL SENSITIVITY, AND THE SEROTONERGIC SYSTEM(2024) Ho, Ta-wen; Herberholz, Jens; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Social isolation has been shown to correlate with increased alcohol consumption in various animal species. In humans, a decreased sensitivity to acute alcohol is correlated with future alcohol dependence and addiction. A plausible explanation for this correlation is that alcohol sensitivity decreases after isolation; however, our understanding of the mechanistic interaction between social isolation and sensitivity to acute alcohol is still in its infancy. The serotonergic system is one promising candidate that could be involved in this interaction because of its wide range of behavioral and physiological effects, especially those related to social experiences. In my dissertation, I investigated the roles of the serotonergic (5-HT) system with three separate aims: In the first aim, I measured the effects of several 5-HT agents (neurotoxin, reuptake blocker, and receptor agonist/antagonists) in freely-behaving crayfish that were communally housed (COMs) or individually isolated (ISOs) prior to ethanol (EtOH) exposure. I found that 5-HT is important in regulating the social differences in EtOH sensitivity, and 5-HT2βPRO receptors emerged as candidates to produce this interaction between 5-HT and EtOH. My results from this aim suggest that these receptors are downregulated in isolated crayfish, leading to reduced behavioral EtOH sensitivity. The second aim employed single-cell neurophysiology and pharmacology in the lateral giant (LG) circuit of reduced ex vivo crayfish preparations to investigate the cellular-molecular mechanisms that underlie the interaction between 5-HT and specific EtOH receptor targets. I found that the LG neurons are stimulated by EtOH, and social differences in EtOH sensitivity between COMs and ISOs are paralleled at the level of these single neurons. Specifically, my results suggest that social isolation causes downregulation of 5-HT2βPRO receptors and 5-HT1αPRO receptors on the LG neurons and upregulation of these receptors subtypes in GABAergic neurons that send feed-forward inhibition onto the LG neurons. In my third aim, I developed a wearable, miniature, cyclic voltammetry device that is capable of detecting (injected) monoamine neurotransmitters (including 5-HT) in freely-behaving crayfish. With improved sensor sensitivity in the future, this will allow measurements of 5-HT release patterns in crayfish with different social histories, including during EtOH exposure. Together, the results from my dissertation will inform work in other model systems and improve our understanding of the interactions between social experience, the 5-HT system, and alcohol use.Item Sculpting Sounds: INTRINSIC PHYSIOLOGY AND INHIBITORY ANATOMY OF THE AVIAN AUDITORY BRAINSTEM(2024) Baldassano, James; MacLeod, Katrina; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Soundwaves are rapidly modulated, multi-dimensional stimuli. The cochlea decomposes these signals into frequency and intensity information which is conveyed via the auditory nerve into the brain. How does the brain manage to extract these multidimensional signals from auditory nerve activity? How does it sculpt this input so that both the microsecond precision of “where?” and the spectrotemporal modulations of “what?” are encoded with high fidelity? Birds are powerful models for studying early auditory processing because they interact with sounds similarly to mammals but have a simpler neuronal architecture. We describe the intrinsic physiology and anatomy and auditory brainstem neurons involved in spectrotemporal processing. In birds, the auditory nerve synapses onto two anatomically distinct cochlear nuclei, cochlear nucleus magnocellularis (NM) which encodes frequency/timing information, and the more heterogeneous cochlear nucleus angularis (NA) which encodes intensity information. NA has been shown to encode the acoustic envelope, likely through a subset of neurons that respond preferentially to modulations in their inputs via an adaptive spike threshold. We first examined the intrinsic basis of this adaptive threshold and found that a dendrotoxin-sensitive low threshold potassium conductance is responsible for it. In addition to the intrinsic properties of neurons, inhibition sculpts a number of auditory processes. The majority of inhibition in the avian auditory brainstem originates in the superior olivary nucleus (SON), which has multiple response types & projects either to multiple lower order ipsilateral nuclei, including NA & NM, or to the contralateral SON. Retrograde labeling experiments have demonstrated that these projections originate from distinct populations of SON neurons, however it is not clear if there is a relationship between response types and postsynaptic target. We used in vitro electrophysiology and neuronal reconstruction to establish a relationship between response types and targets. While the function of inhibition is well documented in timing circuits, its role in intensity processing is less clear. We used dynamic clamp to model inhibitory conductances while recording from NA neurons in vitro to determine how inhibition impacts the range of inputs that a NA neuron can encode before its firing rate saturates.Item SEROTONIN REGULATES AN OLFACTORY CRITICAL PERIOD IN DROSOPHILA(2024) Mallick, Ahana; Araneda, Ricardo; Gaudry, Quentin; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Serotonin (5-HT) is known to modulate early development during critical periods when experience drives heightened levels of plasticity in sensory systems. Studies in the somatosensory and visual cortices implicate multiple target points of serotonergic modulation, yet the underlying cellular and molecular mechanisms of 5-HT modulation of critical period plasticity remain elusive. Here, we take advantage of the genetically tractable olfactory system of Drosophila to investigate how 5-HT modulates critical period plasticity (CPP) in the CO2 sensing circuit of fruit flies. During the critical period, chronic exposure to CO2 has been shown to increase the volume of the CO2 sensing V glomerulus. We found that 5-HT release by serotonergic neurons in the antennal lobe (AL) is required for increase in the volume of the V glomerulus. Furthermore, signaling via the 5-HT1B, 5-HT2B and 5-HT7 receptors in different neuronal populations is also required during the critical period. Olfactory CPP is known to involve local inhibitory networks and consistent with this we found that knocking down 5-HT7 receptors in a subset of GABAergic local interneurons was sufficient to block CPP, as was knocking down GABA receptors expressed by olfactory sensory neurons (OSNs). Additionally, 5-HT2B expression in the cognate OSNs sensing CO2 is also essential for CPP indicating that direct modulation of OSNs also contributes to the olfactory CPP. Furthermore, 5-HT1B expression by serotonergic neurons in the olfactory system is also required during the critical period. Our study reveals that 5HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit. Finally, we wanted to isolate the neuromodulatory effects of individual serotonergic neurons. To achieve this, we combined a state-of-the-art technique to sparsely label serotonergic neurons and a computer algorithm to search against 10,000 Gal4 promoter lines and identify candidate lines that would allow individual manipulation of the 110 serotonergic neurons.Item Predictors of Peer Interaction Success for Autistic and Non-Autistic Youth(2024) McNaughton, Kathryn; Redcay, Elizabeth; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Successful peer interactions are a crucial component of mental health and well-being for autistic and non-autistic youth. Factors that influence successful peer interactions are particularly relevant to investigate in middle childhood and adolescence, a developmental period in which peer interactions take on increased importance for mental health. Research into social interactions can involve both individual-level and interindividual-level understanding of interaction outcomes. Individual-level predictors can yield insight into the way one’s own characteristics predict social interaction outcomes, for example, informing theories about how an individual’s social motivation may predict their social enjoyment. However, because research into social interaction challenges and success in autism has historically focused on individual-level contributions of autistic individuals to social interaction outcomes, it is also important to understand interindividual-level mechanisms, such as the similarity or synchrony between individuals, to understand the role both non-autistic and autistic individuals play in shaping social interactions and their outcomes. Therefore, the overarching goal of this dissertation is to evaluate potential neural and behavioral predictors of peer interaction success in autistic and non-autistic youth during middle childhood and adolescence at the individual and interindividual level. First, I demonstrate that neural sensitivity to social-interactive reward is an individual-level predictor of peer interaction enjoyment. Next, I move beyond individual-level neural predictors to interindividual-level neural predictors, providing evidence for how neural similarity to peers may differentially relate to day-to-day interaction success across different interaction types, such as interactions with peers. Finally, I establish smiling synchronization as an interindividual predictor of peer interaction enjoyment. These studies span the neural and behavioral levels of analysis, providing insight into how these levels of analysis can be investigated from both an individual and interindividual perspective. The findings advance understanding of factors that predict peer interaction success, leading to better understanding of opportunities to support successful peer interactions through individual and interindividual interventions with autistic and non-autistic youth.Item HIPPOCAMPAL GLUCOSE TRANSPORT AND OXIDATION IN RESPONSE TO DISRUPTED BLOOD FLOW IN AN AGING RAT MODEL OF HEART FAILURE(2023) Pena, Gabriel Santiago; Smith, J. Carson; Kuzmiak-Glancy, Sarah; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The primary objective of this dissertation was to investigate, in a rodent model of cardiovascular disease promoted by transverse aortic constriction (TAC), whether cerebral hypoperfusion stemming from chronic high pulsatile blood flow, and cerebral hypoperfusion stemming from low cerebral blood flow differentially affected hippocampal glucose transport and hippocampal mitochondrial function. We first, characterized the changes in right and left carotid hemodynamics and diameter in response to TAC and in a SHAM control group at three different time points (20-, 30-, and 40 weeks) post-surgery. Then, right, and left hippocampal mitochondrial content and substrate oxidation were investigated, and protein expression of glucose transporters and mitochondrial quality control markers were quantified. In this study, both the SHAM and TAC conditions included male and female rats to address possible sex differences. We report that all time points within TAC, right carotid blood flow velocities and pulsatility were greater than the left, but did not worsen over time. No differences in mitochondrial content were found within TAC nor between TAC and SHAM, but within TAC animals there were impairments in right hippocampal coupled and uncoupled respiration when compared to the left. When compared to the SHAM controls, right and left hippocampi of TAC animals had higher protein expression of mitochondrial quality control markers, but no differences in glucose transporter expression were found. Thus, while both high blood flow and/or pulsatility as well as low cerebral blood flow may lead to brain hypoperfusion, the metabolic consequences of the two may not be the same. The results from this dissertation contribute to the expanding literature characterizing the intersection between cardiovascular disease and neurodegeneration.Item HOW BILINGUALS' COMPREHENSION OF CODE-SWITCHES INFLUENCES ATTENTION AND MEMORY(2024) Salig, Lauren; Novick, Jared; Slevc, L. Robert; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Bilinguals sometimes code-switch between their shared languages. While psycholinguistics research has focused on the challenges of comprehending code-switches compared to single-language utterances, bilinguals seem unhindered by code-switching in communication, suggesting benefits that offset the costs. I hypothesize that bilinguals orient their attention to speech content after hearing a code-switch because they draw a pragmatic inference about its meaning. This hypothesis is based on the pragmatic meaningfulness of code-switches, which speakers may use to emphasize information, signal their identity, or ease production difficulties, inter alia. By considering how code-switches may benefit listeners, this research attempts to better align our psycholinguistic understanding of code-switch processing with actual bilingual language use, while also inspiring future work to investigate how diverse language contexts may facilitate learning in educational settings. In this dissertation, I share the results of three pre-registered experiments with Spanish-English bilinguals that evaluate how hearing a code-switch affects attention and memory. Experiment 1a shows that code-switches increase bilinguals’ self-reported attention to speech content and improve memory for that information, compared to single-language equivalents. Experiment 1b demonstrates that this effect requires bilingual experience, as English-speaking monolinguals did not demonstrate increased attention upon hearing a code-switch. Experiment 2 attempts to replicate these results and establish the time course of the attentional effect using an EEG measure previously associated with attentional engagement (alpha power). However, I conclude that alpha power was not a valid measure of attention to speech content in this experiment. In Experiment 3, bilinguals again showed better memory for information heard in a code-switched context, with a larger benefit for those with more code-switching experience and when listeners believed the code-switches were natural (as opposed to inserted randomly, removing the element of speaker choice). This suggests that the memory benefit comes from drawing a pragmatic inference, which likely requires prior code-switching experience and a belief in code-switches’ communicative purpose. These experiments establish that bilingual listeners derive attentional and memory benefits from ecologically valid code-switches—challenging a simplistic interpretation of the traditional finding of “costs.” Further, these findings motivate future applied work assessing if/how code-switches might benefit learning in educational contexts.Item MODULATION OF SIGNALING IN THE ANTERIOR CINGULATE CORTEX AND ITS IMPACT ON DECISION-MAKING(2024) Vazquez, Daniela; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Attentional deficits are defining hallmarks of some of the most prevalent and disruptive neuropsychiatric disorders—including attention deficit hyperactivity disorder (ADHD) and substance abuse disorders. The anterior cingulate cortex (ACC) is a brain region that is highly implicated in shifting attention allocation towards relevant stimuli after unexpected events or outcomes occur. Importantly, increases in attention facilitate flexible learning, as attention allows you to dynamically filter relevant and necessary information during decision-making. My dissertation work seeks to identify the ACC as a novel point of intervention for the treatment of neuropsychiatric and addiction disorders by providing an in-depth perspective on its involvement in cognitive control and attentional processes.My research explores the neural correlates of decision-making by using electrophysiology to record single unit activity while rats perform a complex reward-based decision-making task, and employing chemical, optogenetic, and epigenetic manipulations to modulate attentional correlates in the ACC. I explored the ACC’s role in attention—and how it is impacted by drug use—using electrophysiology to record from ACC neurons as both cocaine-exposed and drug-naïve rats performed a reward-guided decision-making task. Using this task, we found a dose-dependent attenuation of ACC signaling after cocaine self-administration, which was correlated with decreases in task performance and attention to the task. Rats that had self-administered large amounts of cocaine had diminished neural responsiveness to cues, which translated into reductions in behavioral measures of attention, disruptions in cognitive flexibility, and decision-making impairments. These results both supported previous findings establishing the ACC’s role in attentional allocation, and revealed an intake-dependent effect of drugs on decision-making and neural encoding. In aim 2, we wanted to be able to precisely modulate ACC activity in order to better interrogate the role of the ACC in the absence of confounding variables (e.g. cocaine use results in the dysregulation of various neural circuits), and conduct within-subject analyses. Thus, in our next experiment we used optogenetics to inactivate the ACC, and found that ACC inhibition severely impaired task engagement, as evinced by reductions in trial initiations, and trial and session completions—resulting in overall impaired session performance. In order to disambiguate whether these behavioral deficits resulted from ACC impairment dysregulating downstream action-outcome encoding, we performed chemical lesions of the ACC, and recorded neural activity from the dorsomedial striatum (DMS)—a downstream brain region that is importantly involved in goal-directed behavior—as rats performed the previously mentioned decision-making task. Again, we found that ACC lesions resulted in disrupted attention to the task, and similar behavioral deficits to the ones we observed following cocaine use. Interestingly, we found that DMS encoding was minimally impacted, reinforcing that the observed decision-making deficits stem from disruptions in attentional signaling and not dysregulations in downstream action-outcome encoding. In the aforementioned experiments, we employed an array of techniques to dissect how disrupting ACC signaling in a variety of manners impacted task performance and engagement, so for our final experiment we sought to explore a therapeutically relevant way to potentially repair signaling disruptions that lead to the breakdown in attentional signaling. Thus, we turned to epigenetics—specifically, decreasing the expression of HDAC5, an enzyme that is involved in negatively regulating gene expression—to explore whether epigenetic changes might map onto specific alterations of neural activity and behavior. Surprisingly, we found that HDAC5 knockdown in the ACC dysregulates attentional signals that are necessary for flexible and adaptive decision-making. Together, these studies established that signaling in the functional ACC is importantly involved in attention, and that dampening these signals leads to decision-making impairments and decreased task engagement, notably characterized by significant reductions in the proportion of initiated and completed trials, and prolonged periods of inattention.Item MULTIMODAL ANALYSIS OF NEURAL SIGNALS RELATED TO SOURCE MEMORY ENCODING IN YOUNG CHILDREN(2024) Lei, Yuqing; Riggins, Tracy; Psychology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The emergence of source memory is an important milestone during memory development. Decades of research has explored neural correlates of source memory using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). However, connections between findings from the two approaches, particularly within children, remain unclear. This dissertation identified fMRI-informed cortical sources of two EEG signals during memory encoding, the P2 and the late slow wave (LSW), that predicted subsequent source memory performance in a sample of children aged 4 to 8 years. Both P2 and LSW were source localized to cortical areas of the medial temporal lobe (MTL), reflecting MTL’s crucial role in both early-stage information processing and late-stage integration of memory, which also validated LSW’s suspected role in memory updating. The P2 effect was localized to all six tested subregions of cortical MTL in both left and right hemispheres, whereas the LSW effect was only present in the parahippocampal cortex and entorhinal cortex. P2 was additionally localized to multiple areas in the frontoparietal network, a cortical network known as the “attention network”, highlighting interactions between memory encoding and other cognitive functions. These results reflect the importance of considering both spatial and temporal aspects of neural activity to decode memory mechanism, and demonstrated the potential of combining multimodal measures in children, paving the way for future developmental research.