Neuroscience and Neurobiology Commons^™

Sex Differences In The Risk Of Developing Alzheimer Disease, Cognitive Trajectories, And Relationships Between Cognition And Pathological Burden, Carling G. Robinson

Arts & Sciences Graduate Student Theses and Dissertations

Prior work suggests females may develop Alzheimer disease (AD) dementia at a higher rate than males, and that this effect may interact with apolipoprotein (APOE) ε4 genotype. However, this work has often been limited by imprecise clinical diagnoses and a lack of AD biomarkers. In addition to the frequency of dementia, there are mixed reports on whether sex impacts rates of cognitive decline. Further, females consistently exhibit greater accumulation of AD pathological biomarkers, particularly tau, than males. It has been theorized that females initially demonstrate resilience to AD pathology, maintaining cognitive functioning longer than males, but experiencing a steeper cognitive …

A Neuroimmune Circuit Mediates Chemo Brain Pathology, Daniel Ahmadi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chemotherapeutic agents, while effective in targeting malignant tumors, often reduce the patients’ quality of life by inducing fatigue, pain, and motivational deficits. These symptoms are collectively referred to as “chemo brain.” The mechanisms underlying these adverse effects, and specifically whether fatigue and motivational impairments share a common etiology, remain poorly understood. The neural–immune substrates of these symptoms remain obscure, in part because standard preclinical regimens either bypass key systemic signals or introduce local toxicity confounds. Here, I establish and validate a three‑day, low‑dose intravenous cisplatin protocol that avoids peritoneal inflammation and severe renal injury yet produces robust, reversible fatigue and …

What Is Trauma?: From Science To Social Justice, Judith Fleetwood Carlisle

Arts & Sciences Graduate Student Theses and Dissertations

In recent years, the term “trauma” has become increasingly controversial. Many of these controversies revolve around the definition of trauma, and the way that this definition varies across contexts. What kinds of experience can plausibly be considered “traumatic”? In some contexts, the standards are incredibly permissive, while others are much more restrictive. These different ways of understanding “trauma” prompts an important question: Who has the authority to define trauma? In other words, who decides which conception of trauma is the most “legitimate” – who decides when an experience is or is not traumatic? My project attempts to answer these questions …

Role Of Glia In Diurnal Rhythms In Neuroinflammation And Blood-Brain Barrier Breakdown, Jennifer Hoi-Ping Lawrence

Arts & Sciences Graduate Student Theses and Dissertations

While inflammation is an important mechanism for the return to homeostasis post insult or injury, inflammation in the central nervous system (CNS) can lead to irreparable damage. To mitigate this process, the brain is protected from circulating neurotoxic molecules as well as peripheral immune cells through the tightly regulated blood-brain barrier (BBB). The balance between pro- and anti- inflammation in the CNS rapidly shifts towards a neurotoxic proinflammatory state during acute bacterial or viral infections or chronic neuroinflammatory diseases. Excessive inflammatory responses are also coupled with extensive BBB leakage and breakdown, allowing rampant entry of peripheral inflammatory cells and mediators …

The Vices Of Virtues: Making Room For Moral Testimony In The Life Of The Virtuous Person, Maria Waggoner

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation sheds light on new and unacknowledged difficulties that we face in striving to be (more) virtuous. By making use of empirical literature from moral, affective, and perceptual learning, I explore the potential cognitive and psychological relationships between having a virtue in one context and the tendency to exhibit vices in another. I do this by showing how morally good behavioral habits can also lead to morally inappropriate actions, when a virtuous moral perceptual system can give rise to moral illusions, and when our basic evaluative affective responses differ in their degree of sensitivity, leading to having some virtues …

Manage Your Money Wisely: How Consumers And Marketers Can Effectively Communicate Money Issues, Alexander Park

Olin Business School Graduate Student Theses and Dissertations

Consumers and marketers find it challenging to communicate money matters. For example, consumers experience discomfort and uneasiness when discussing financial issues with their social relationships. Firms often receive backlash when sharing their good financial deeds (e.g., charitable efforts) with consumers. Because financial matters can be a sensitive topic, in my research, I explore the difficulties consumers and marketers experience when communicating money issues and how they can better navigate these problems.In Chapter One, I investigate a particularly uneasy interaction that consumers often face with their friends and acquaintances: the need to ask for money back. Seven fully preregistered studies (N …

Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik

McKelvey School of Engineering Graduate Student Theses & Dissertations

ABSTRACT OF THE THESIS Preparing Non-Human Primates to Study Hand-Eye Coordination in Frontal Eye Fields (FEF) During Delayed Movement Task by Juliusz Cydzik Master of Science in Biomedical Engineering Washington University in St. Louis, 2023 Professor Lawrence Snyder, Chair Hand-eye coordination enables humans and non-human primates to use their hands and eyes to perform various tasks. We are interested in coordination at the systems level, where saccades and reaches are encoded. The parietal reach region (PRR), situated at the posterior end of the intraparietal sulcus (IPS) and overlapping portions of the medial intraparietal area (MIP) and V6a, is commonly attributed …

Making Emotions Trustworthy, Xiaoyu Ke

Arts & Sciences Graduate Student Theses and Dissertations

I investigate ways by which agents can make their emotions more trustworthy from a perspective that’s informed by recent psychological research on the nature of emotion regulation. This dissertation is a collection of three articles, each addressing one type of cases of untrustworthy emotions in a particular context. Chapter one (Developing Appropriate Emotions) concerns emotions that are untrustworthy because they are irrelevant to the moral or epistemic judgements at hand. By situating the problem in the context of a situationist challenge to neo-Aristotelian virtue ethics, I argue that we can address this problem by developing ameliorative abilities such as emotion …

Noninvasive Neuromodulation Via Ultrasonic Activation Of Endogenous And Exogenous Ion Channels, Yaoheng Yang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Neuromodulation technology is key to understanding brain function and treating brain diseases. Conventional neuromodulation technologies, such as direct current stimulation, transcranial magnetic stimulation, and optogenetics, predominately rely on electromagnetic waves. However, the fundamental physical law  the tradeoff-relationship between penetration and spatial resolution, limits their transcranial penetration within the superficial cortex layer. To overcome this challenge, electrodes or optical fibers need to be surgically implanted into the brain to modulate specific brain regions. Different from electromagnetic waves, ultrasound, as a mechanical wave, can non-invasively penetrate through the intact skull to reach deep brain regions with millimeter spatial focus. Ultrasound has …

Mechanisms Of Primate Working Memory, Charles Damian Holmes

McKelvey School of Engineering Graduate Student Theses & Dissertations

One of the defining features of the behavior of many animal species is the ability to retain and utilize information from the environment even after it is gone. The encoding and utilization of information on short time scales is referred to as working memory. It is not yet fully understood how the brain accomplishes working memory.

This dissertation presents three studies that help to characterize the working memory system of primates. All three studies involve primates performing saccades during a spatial memory task. The first study demonstrates that while the local field potential power is contralaterally tuned (i.e., power is …

Development Of Noninvasive Biomarkers For Cervical Spondylotic Myelopathy, Dinal Jayasekera

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cervical spondylotic myelopathy (CSM) represents the most common cause of chronic spinal cord injury (SCI) in adults. Many patients with symptomatic CSM will experience a decline in neurological function and consequently undergo surgical decompression. Unfortunately, surgeons are unable to adequately counsel patients about the benefits of surgery because the natural history of disease and outcome after decompression vary widely among patients. This can hinder the decision-making capacity of patients and physicians. Therefore, we require additional tools to help guide therapy and counsel patients with CSM. Noninvasive biomarkers present valuable potential as predictors of a patient’s recovery in the long term. …

Anti-Amyloid Chimeric Antigen Receptor Macrophages For Alzheimer's Disease Immunotherapy, Qiuyun Pan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Alzheimer’s disease is the most common cause of dementia. None of the available drugs can cure the disease. Chimeric Antigen Receptor (CAR) macrophages, because of their phagocytic activity, have potential as a cellular treatment for amyloid aggregation. In this study, we generated an anti-amyloid CAR hematopoietic progenitor cell line. By inducing the progenitor cell line to differentiate into macrophages, we show that the anti-amyloid CAR-Macrophage has enhanced specific phagocytic activity towards amyloid in in vitro experiments. In addition, in ex vivo experiments, anti-amyloid CAR significantly reduces the plaque load on brain slice from APP/PS1 mice when compared to a non-targeted …

Towards The Discovery Of Prognostic Biomarkers For Glioblastoma Using Resting-State Functional Connectivity, Andy G. S. Daniel

McKelvey School of Engineering Graduate Student Theses & Dissertations

Gliomas are highly diffusive, primary brain tumors. The most malignant form, glioblastoma, has a dismal survival rate: 14-17 months following the current standard of care, which consists of surgery, radiation, and chemotherapy. Insights into the molecular, cellular, and microenvironmental components of glioblastoma have revealed a vast array of factors utilized to support its proliferation, infiltration, and resistance to treatment. Recent advancements have also identified diagnostic and prognostic biomarkers that are now being used to guide treatment planning. However, survival has improved only marginally, thus emphasizing the continued need for novel biomarkers and treatment strategies. Given its delicate location in the …

Positron Emission Tomography From 1930 To 1990: The Epistemology And Process Of Scientific Instrumentation, Rick Shang

Arts & Sciences Graduate Student Theses and Dissertations

Positron Emission Tomography (PET) is a groundbreaking detection system that, among many other applications, enabled neuroscience researchers to detect and image physiological changes in the brain associated with cognitive operations as subjects perform a task. This technology helped researchers learn to explore the physiological basis of human cognition in new ways and was the immediate forerunner of functional Magnetic Resonance Imaging (fMRI), a technology that continues to dominate the neurosciences. PET was also the founding invention of a new field of cognitive science: human functional neuroimaging. Indeed, some would say that PET encouraged a particular way of understanding the brain …

The Disunity Of Perception, Benjamin Austin Henke

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation argues for disunity in perceptual processing: rather than outputting to a single ‘centralized’ cognitive system, separate perceptual processing pathways produce different person-level representations for different purposes. I argue that this disunity has important implications for abstract theorizing in the philosophy and cognitive science of perception, for experimental methodology, and for our understanding of the normative role of perception itself. The first three chapters explore models in cognitive neuroscience which support perceptual disunity. In Chapter 1, I argue that a version of Milner and Goodale’s (2006) influential ‘two visual streams hypothesis’ survives its recent empirical challenges. In Chapter 2, …

Positron Emission Tomography From 1930 To 1990: The Epistemology And Process Of Scientific Instrumentation, Rick Shang

Arts & Sciences Graduate Student Theses and Dissertations

Positron Emission Tomography (PET) is a groundbreaking detection system that, among many other applications, enabled neuroscience researchers to detect and image physiological changes in the brain associated with cognitive operations as subjects perform a task. This technology helped researchers learn to explore the physiological basis of human cognition in new ways and was the immediate forerunner of functional Magnetic Resonance Imaging (fMRI), a technology that continues to dominate the neurosciences. PET was also the founding invention of a new field of cognitive science: human functional neuroimaging. Indeed, some would say that PET encouraged a particular way of understanding the brain …

Elucidating And Leveraging Dynamics-Function Relationships In Neural Circuits Through Modeling And Optimal Control, Sruti Mallik

McKelvey School of Engineering Graduate Student Theses & Dissertations

A fundamental research question in neuroscience pertains to understanding how neural networks through their activity encode and decode information. In this research, we build on methods from theoretical domains such as control theory, dynamical systems analysis and reinforcement learning to investigate such questions. Our objective is two-fold: first, to use methods from engineering to identify specific objectives that neural circuits might be optimizing through their spatiotemporal activity patterns, and second, to draw motivation from neuroscience to formulate new engineering principles such as synthesis of dynamical networks for decentralized control applications. We specifically take a top-down, optimization driven approach in our …

Long-Term Neural Activity Recorders Using Energy-Based Sensing, Compressive Computation And Data Logging, Darshit Mehta

McKelvey School of Engineering Graduate Student Theses & Dissertations

Insects are ideal candidates for developing bio-robotic systems owing to their ability to thrive in almost any environment. For example, neurons in their exquisite olfactory sensory systems can be tapped to create a sensing platform for standoff chemical monitoring. However, for enabling such cyborg systems, it is vital that the neural activity of a freely behaving organism can be measured for long periods of time. The current state-of-the-art neural recording techniques are power-intensive and they either need batteries, which make them too bulky for insects, or they have to maintain a continuous telemetry link to an external power source which …

Psychological Construct Validity, Caroline Marie Stone

Arts & Sciences Graduate Student Theses and Dissertations

A primary concern for any psychological research project is determining how to measure unobservable mental entities, such as "implicit memory", or "intelligence". Psychologists say that a measure has construct validity when they believe that a measurement method measures the construct they intend it to measure, where a construct is any theoretical term that refers to a mental entity. Construct validity, then, is the process of justifying one's belief that a measure has construct validity. My dissertation seeks to answer three related questions, 1. What is construct validity?, 2. What is the best epistemic theory of justification for construct validation?, and …

Oppression And The Limits Of Individual Moral Progress, Cameron Charles Evans

Arts & Sciences Graduate Student Theses and Dissertations

Systemic social problems are the product of complex interactions among institutions, policies, biases, stereotypes, and false beliefs. While we may be pessimistic about our abilities to combat social change, we may remain optimistic about our abilities as individuals to achieve moral growth. However, in societies organized by socially unjust practices, our individual capacities for improvement may be stunted. My primary concern is to identify key obstacles to our moral development. I argue that "self-help" methods for reducing our social biases and prejudices are ineffective. Our biases interact in complex ways with each other, and with the environment, in ways that …

The Feeling Mind, Maria Doulatova

Arts & Sciences Graduate Student Theses and Dissertations

According to standard conceptions of agency, our reasons and intentions guide our actions. That is, goal-directed intentions play a key role in practical deliberation, planning, and execution of action. Furthermore, purposeful, goal-directed behavior warrants attributions of responsibility or “reactive attitudes” like resentment, anger, gratitude and forgiveness. However, recent developments of the dual-process theory of mind cast doubt on the empirical adequacy of this picture. While people take themselves to be responding to relevant reasons, they are often bypassed by irrelevant affective or automatic reactions. In this work I go beyond the dual-process theory of mind to offer a mechanistic account …

Event Perception, Emily Prychitko

Arts & Sciences Graduate Student Theses and Dissertations

We seem to perceive events, like songs playing, thunderstorms, and people having conversations. Extensive empirical research suggests that we indeed perceive events. Yet the philosophy of perception has not addressed event perception much at all. I lay out goals and methods for a fruitful philosophical investigation of event perception, then pursue that investigation. Primarily on the basis of the empirical evidence, I argue that we perceive events across the senses, and that event representations are a unique type of perceptual representation. In doing so, I address concerns about event perception as such, relative to object and property perception. I argue, …

Cortical Organization In Humans And Nonhuman Primates: The Evolution Of Cognitive Areas And Circuits, Chad Joseph Donahue

McKelvey School of Engineering Graduate Student Theses & Dissertations

Similarities in organization of cerebral cortex in humans and nonhuman primates offer the promise of leveraging data from invasive animal studies to better understand the complexities of the human brain, particularly those related to higher cognitive function (e.g. attention, working memory, language). Such comparisons necessitate the identification of convincing cortical homologues (areas or regions presumed to have derived from a common ancestor), requiring an accurate interspecies mapping of cortical areas and features. To this end, I describe (i) a survey of connectivity and its measures across primate species, particularly retrograde tracing and diffusion tractography, (ii) a morphometric analysis of cognitive …

Neural Dynamics, Adaptive Computations, And Sensory Invariance In An Olfactory System, Srinath Nizampatnam

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sensory stimuli evoke spiking activities that are patterned across neurons and time in the early processing stages of olfactory systems. What features of these spatiotemporal neural response patterns encode stimulus-specific information (i.e. ‘neural code’), and how they are translated to generate behavioral output are fundamental questions in systems neuroscience. The objective of this dissertation is to examine this issue in the locust olfactory system. In the locust antennal lobe (analogous to the vertebrate olfactory bulb), a neural circuit directly downstream to the olfactory sensory neurons, even simple stimuli evoke neural responses that are complex and dynamic. We found each odorant …

Constructing And Analyzing Neural Network Dynamics For Information Objectives And Working Memory, Elham Ghazizadeh Ahsaei

McKelvey School of Engineering Graduate Student Theses & Dissertations

Creation of quantitative models of neural functions and discovery of underlying principles of how neural circuits learn and compute are long-standing challenges in the field of neuroscience. In this work, we blend ideas from computational neuroscience, information and control theories with machine learning to shed light on how certain key functions are encoded through the dynamics of neural circuits. In this regard, we pursue the ‘top-down’ modeling approach of engineering neuroscience to relate brain functions to basic generative dynamical mechanisms. Our approach encapsulates two distinct paradigms in which ‘function’ is understood. In the first part of this research, we explore …

Neural Coding And Organization Principles In The Drosophila Olfactory System, Haoyang Rong

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sensory systems receive and process external stimuli to allow an organism to perceive and react to the environment. How is sensory information subsequently represented, transformed, and interpreted in the neural system? In this dissertation, I have investigated this fundamental question using the fruit fly (Drosophila melanogaster) olfactory system.Chemical cues are transduced into neural signals in the insect antenna by the olfactory receptor neurons (ORNs). The ORNs send their axons to the antennal lobe (AL), with each ORN type innervating a specific neuropil (glomerulus), where they synapse onto excitatory and inhibitory projection neurons (ePNs and iPNs). The ePNs project their axons …

‘Nouns That Cut Slices’: The Ontology And Ethics Of Stereotypes And Implicit Bias, Christiane Merritt

Arts & Sciences Graduate Student Theses and Dissertations

Stereotypes and implicit bias have long been objects of psychological study. Recently, philosophers, too, have attempted to understand stereotypes and implicit bias: what kinds of mental states or objects are they? Are stereotypes epistemically deficient or ethically suspect? How do implicit biases affect behavior, and how might these biases be changed? This dissertation takes up these and related questions, advancing accounts of stereotyping and implicit bias informed by evidence from psychology.Chapter 1 sets the stage by conducting a critical survey of the history and development of today’s most widely used measures of implicit bias. Although the history of the different …

Transdiagnostic Multimodal Neural Correlates Of Psychosis Dimensions, Dov Bernard Lerman-Sinkoff

McKelvey School of Engineering Graduate Student Theses & Dissertations

Psychosis refers to a debilitating set of symptoms that impacts individuals, their communities, and society at large. Current psychiatric nosology treats psychosis as a categorical construct. However, recent evidence suggests that a dimensional approach that cuts across extant nosological boundaries may more accurately represent the underlying phenomena contributing to dysfunction in psychosis. One putative domain of transdiagnostic variation is cognitive control, a construct that refers to the set of functions that enable and support goal-directed behavior and regulation of one’s thoughts and actions. Previous analyses in both healthy individuals and individuals with psychosis have led to a number of findings …

Dynamics And Control In Spiking Neural Networks, Fuqiang Huang

McKelvey School of Engineering Graduate Student Theses & Dissertations

In the brain, neurons (brain cells) produce electrical impulses, or spikes, that are thought to be the substrate of information processing and computation. Through enigmatic processes, these spikes are ultimately decoded into perceptions and actions. The nature of this encoding and decoding is one of the most pervasive questions in theoretical neuroscience. In other words, what are the specific functions enacted by neural circuits, through their biophysics and dynamics? This thesis examines the dynamics of neural networks from the perspective of control theory and engineering. The pivotal concept is that of the normative synthesis of neural circuits, wherein neural dynamics …

A Microfluidic Platform To Investigate The Mechanism By Which Gdnf Overexpression In Schwann Cells Causes Neuronal Axon Entrapment, Ze Zhong Wang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Twenty million Americans suffer from peripheral nerve injury (PNI) caused by trauma and medical disorders, with approximately $150 billion spent in annual health-care dollars in the United States. Even with proper surgical reconstruction, less than 50% of the patients achieve satisfactory functional recovery. The gold standard surgical repair for long gaps (>3cm) is the autologous nerve graft, despite its disadvantages such as donor site morbidity, risk of infection, and increased cost. Alternative methods, such as acellular nerve grafts (ANA), are ineffective for large lesion gaps because of the lack of cells and regeneration factors. Recent efforts have been focused …