Neuroscience and Neurobiology Commons^™

Sex Differences In Circadian Rhythmicity Arise Outside The Hypothalamus, Sneha M. Chaturvedi

Senior Honors Papers / Undergraduate Theses

Most biological processes are regulated by an internal circadian rhythm. This body clock synchronizes daily rhythms in physiology with the environment. Circadian outputs can differ between females and males, but the underlying mechanisms for these differences are unknown. Glucocorticoids, a class of circadian stress hormones in vertebrates, provide a model for studying sexual dimorphisms in circadian timing. Female rodents show a higher mean and peak-to-trough amplitude of corticosterone than males. This is most prevalent during proestrus when estrogen levels are high. To test the hypothesis that male-female differences in daily corticosterone secretion arise within circadian cells in the brain, we …

Approaches To Understanding The Function Of Intrinsic Activity And Its Relationship To Task-Evoked Activity In The Human Brain, Dohyun Kim

McKelvey School of Engineering Graduate Student Theses & Dissertations

Traditionally neuroscience research has focused on characterizing the topography and patterns of brain activation evoked by specific cognitive or behavioral tasks to understand human brain functions. This activation-based paradigm treated underlying spontaneous brain activity, a.k.a. intrinsic activity, as noise hence irrelevant to cognitive or behavioral functions. This view, however, has been profoundly modified by the discovery that intrinsic activity is not random, but temporally correlated at rest in widely distributed spatiotemporal patterns, so called resting state networks (RSN). Studies of temporal correlation of spontaneous activity among brain regions, or functional connectivity (FC), have yielded important insights into the network organization …

Coupled Correlates Of Attention And Consciousness, Ravi Varkki Chacko

McKelvey School of Engineering Graduate Student Theses & Dissertations

Introduction: Brain Computer Interfaces (BCIs) have been shown to restore lost motor function that occurs in stroke using electrophysiological signals. However, little evidence exists for the use of BCIs to restore non-motor stroke deficits, such as the attention deficits seen in hemineglect. Attention is a cognitive function that selects objects or ideas for further neural processing, presumably to facilitate optimal behavior. Developing BCIs for attention is different from developing motor BCIs because attention networks in the brain are more distributed and associative than motor networks. For example, hemineglect patients have reduced levels of arousal, which exacerbates their attentional deficits. More …

Moral Pathology, Katie Rapier

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation explores the relationship between morality and mental illness. Mental illness is often thought to impair moral functioning but careful examination reveals that mental illness offers its own insight into moral functioning. While we learn a great deal about moral responsibility and exempting conditions (psychopathy and addiction), we also discover that there a multiple ways to be moral and that many individuals act morally despite ongoing conditions (high-functioning autism spectrum disorder and recovered borderline personality disorder). I conclude that these insights ought to shape our ethical theories.

Elucidating The Roles Of Astrocyte-Derived Factors In Recovery And Regeneration Following Spinal Cord Injury, Russell E. Thompson

McKelvey School of Engineering Graduate Student Theses & Dissertations

Central nervous system (CNS) injury often causes some level of long-term functional deficit, due to the limited regenerative potential of the CNS, that results in a decreased quality of life for patients. CNS regeneration is inhibited partly by the development of a glial scar following insult that is inhibitory to axonal growth. The major cell population responsible for the formation this glial scar are astrocytes, which has led to the belief that astrocytes are primarily inhibitory following injury. Recent work has challenged this conclusion, finding that astrocyte reactivity is heterogeneous and that some astrocytes are pro-regenerative following injury. Astrocyte transplantation …

Epistemic Justice And Epistemic Participation, Kate C.S. Schmidt

Arts & Sciences Graduate Student Theses and Dissertations

I advance a new theory of epistemic injustice, with important implications for pursuing epistemic justice. This project develops a positive account of epistemic justice, broadens the scope of the phenomenon, and motivates new interventions. This dissertations works towards a better understanding of what it means to be an epistemic subject and to be treated as such.I argue that epistemic injustice can be understood through a lens of participation in inquiry, rather than using the received view that focuses on testimony. On my account, victims are marginalized when disrespected and devalued as potential participants in inquiry due to prejudice. This account …

Its Skin Is My Skin, Bryan Page

Graduate School of Art Theses

This text examines the complexity of attempting to empathize with bodies that are vastly othered from my own. This broad yet nuanced subject crosses epistemological boundaries and complicates the dualities between both the mind and body, and between the corporeal and the virtual. My desire to better understand the conditions of another’s experience originates from a painful traumatic loss which caused me to feel isolated and incomplete. In response to this suffering, I long to emotionally connect with other beings and create artwork that attempts to bridge the qualia of individual experience.

I am interested in the capacity (or lack …

Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation, Namratha Srinivas

McKelvey School of Engineering Graduate Student Theses & Dissertations

Alzheimer’s disease (AD) is a chronic neurodegenerative disease and is the sixth leading cause of death in the United States with approximately 5.5 million Americans diagnosed with it. The neuropathological hallmark includes extracellular senile plaques and intraneuronal neurofibrillary tangles. Recent GWAS studies have identified genes associated with AD, and have revealed several classes of genes implicated in disease pathogenesis. In particular, three general pathways associated with an increased risk of AD included: 1) cholesterol metabolism, innate immune system, and the membrane trafficking. Our lab has focused on intracellular trafficking as it relates to the processing of amyloid precursor protein (APP), …

Functional Electrical Stimulation Of Peripheral Nerve Tissue Via Regenerative Sieve Microelectrodes, Matthew Reagan Macewan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Functional electrical stimulation (FES) of peripheral nervous tissue offers a promising method for restoring motor function in patients suffering from complex neurological injuries. However, existing microelectrodes designed to stimulate peripheral nerve are unable to provide the type of stable, selective interface required to achieve near-physiologic control of peripheral motor axons and distal musculature. Regenerative sieve electrodes offer a unique alternative to such devices, achieving a highly stable, selective electrical interface with independent groups of regenerated nerve fibers integrated into the electrode. Yet, the capability of sieve electrodes to functionally recruit regenerated motor axons for the purpose of muscle activation remains …

Population Coding And Spectrotemporal Tuning In The Owl’S Optic Tectum, Olivia K. Murray, Roland Ferger, Michael V. Beckert, Keaunu Shadron, José L. Peña

Undergraduate Research Symposium Posters

Barn owls (Tyto furcata) are a model organism to study sound location and provide access to a neural population representing auditory space. They use interaural time differences (ITD) and interaural level differences (ILD) to localize sound. Neurons in the barn owl’s optic tectum (OT), a part of the midbrain, which respond to combinations of these binaural cues, form a neural map of auditory space which supports sound-orienting behavior. Understanding population responses in the auditory system involves identifying the frequency components of acoustic signals which evoke spikes. Together, these frequency components and the time between their occurrence in the stimulus and …

Extrinsic And Intrinsic Control Of Integrative Processes In Neural Systems, Anirban Nandi

McKelvey School of Engineering Graduate Student Theses & Dissertations

At the simplest dynamical level, neurons can be understood as integrators. That is, neurons accumulate excitation from afferent neurons until, eventually, a threshold is reached and they produce a spike. Here, we consider the control of integrative processes in neural circuits in two contexts. First, we consider the problem of extrinsic neurocontrol, or modulating the spiking activity of neural circuits using stimulation, as is desired in a wide range of neural engineering applications. From a control-theoretic standpoint, such a problem presents several interesting nuances, including discontinuity in the dynamics due to the spiking process, and the technological limitations associated with …

Mechanics Of The Developing Brain: From Smooth-Walled Tube To The Folded Cortex, Kara Ellspermann Garcia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development.

First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for …

Multiscale Imaging Of The Mouse Cortex Using Two-Photon Microscopy And Wide-Field Illumination, Jonathan Richard Bumstead

McKelvey School of Engineering Graduate Student Theses & Dissertations

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing …

Characterization Of Structural Dynamics Of The Human Head Using Magnetic Resonance Elastography, Andrew Arun Badachhape

McKelvey School of Engineering Graduate Student Theses & Dissertations

In traumatic brain injury (TBI), the skull-brain interface, composed of three meningeal layers: the dura mater, arachnoid mater, and pia mater, along with cerebrospinal fluid (CSF) between the layers, plays a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is a noninvasive imaging modality capable of providing in vivo estimates of tissue motion and material properties. The objective of this work is to augment human and phantom MRE studies to better characterize the mechanical contributions of the skull-brain interface to improve the parameterization and validation of computational models of TBI. Three specific aims …

Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate detection and identification of gases pose a number of challenges for chemical sensory systems. The stimulus space is enormous; volatile compounds vary in size, charge, functional groups, and isomerization among others. Furthermore, variability arises from intrinsic (poisoning of the sensors or degradation due to aging) and extrinsic (environmental: humidity, temperature, flow patterns) sources. Nonetheless, biological olfactory systems have been refined over time to overcome these challenges. The main objective of this work is to understand how the biological olfactory system deals with these challenges, and translate them to artificial olfaction to achieve comparable capabilities. In particular, this thesis focuses …

Developing An In Vitro Assay For Detection And Characterization Of Functional Connectivity Within Transplantation Candidate Embryonic Stem Cell-Derived V2a Interneuron Networks, Jeffrey Robert Gamble

McKelvey School of Engineering Graduate Student Theses & Dissertations

Facilitating plasticity after spinal cord injury tends to be the focus of most modern interventions for this condition. In particular, stem cell therapies attempt to both modulate and mimic some of the native plasticity after injury through multiple mechanisms. One such mechanism, the creation of new exogenous relay circuits bridging the injury, has been explored extensively, revealing serious impediments to its optimization and adoption for clinical settings. Our collaborator, the Sakiyama-Elbert group, has spent years addressing the first limitation, the variability of cellular graft composition, by perfecting protocols to generate embryonic stem cell (ESC)-derived populations of neurons with pre-determined genetic …

Model And World: Generalizing The Ontic Conception Of Scientific Explanation, Mark Povich

Arts & Sciences Graduate Student Theses and Dissertations

Model and World defends a theory of scientific explanation that I call the “Generalized Ontic Conception” (GOC), according to which a model explains when and only when it provides (approximately) veridical information about the ontic structures on which the explanandum phenomenon depends. Causal and mechanistic explanations are species of GOC in which the ontic structures on which the explanandum phenomenon depends are causes and mechanisms, respectively, and the kinds of dependence involved are causal and constitutive/mechanistic, respectively. The kind of dependence relation about which information is provided determines the species of the explanation. This provides an intuitive typology of explanations …

Investigating Localization And Activity-Dependent Translation Of Astrocyte Mrna, Rohan Khazanchi

Senior Honors Papers / Undergraduate Theses

Over the past two and a half years, I have studied fundamental aspects of astrocyte biology by investigating the existence and mechanism of astrocyte local translation peripherally around tripartite synapses consisting of pre- and post-synaptic neuron terminals and an associated astrocyte. Astrocytes are critical components of central nervous system synapses (which are predominately tripartite in nature); thus, it is important to consider how astrocyte dysregulation and dysfunction could contribute to the pathogenesis of diseases of synaptic connectivity such as autism spectrum disorders, Alzheimer’s disease, seizure disorders, and more. Overall, my projects involved the development of novel methods to identify astrocyte-specific …

The Normative Problem Of Shame, Timothy James Oakberg

Arts & Sciences Graduate Student Theses and Dissertations

What role should shame play in our lives? This is the normative problem of shame, and it is the focus of this dissertation. Through an examination of empirical research on shame and shame-proneness, I argue that shame should have only a very limited role in our lives. More specifically, we ought not cultivate shame, because a substantial amount of empirical literature points to the conclusion that shame-proneness is counterproductive at both an individual and a societal level. Expanding on this general answer to the normative problem of shame, I discuss in detail three proposals regarding shame from the realms of …

Development And Investigation Of Sparse Co-Adaptive Algorithms In Ecog Based Closed-Loop Brain Computer Interface, Piyush Karande

McKelvey School of Engineering Graduate Student Theses & Dissertations

Electrocorticography (ECoG) has gained a lot of momentum and has become a serious contender as a recording modality for the implementation of Brain-Computer Interface (BCI) systems in the last few years. ECoG signals provide the right balance between minimal invasiveness and robust spectral information to accomplish a BCI task. However, all the BCI studies until now have used signals recorded from a large number of implanted electrodes and a larger number of spectral features. The recording and processing of these signals uses a lot of electrical power and thus hinders its use outside the research setting. To translate this research …

Tau And Aβ Imaging, Csf Measures, And Cognition In Alzheimer's Disease, Matthew R. Brier, Brian Gordon, Karl Friedrichsen, John E. Mccarthy, Ari Stern, Jon Christensen, Christopher Owen, Patricia Aldea, Yi Su, Jason Hassenstab, Nigel J. Cairns, David M. Holtzman, Anne M. Fagan, John C. Morris, Tammie L.S. Benzinger, Beau M. Ances

Mathematics Faculty Research

Alzheimer’s disease (AD) is characterized by two molecular pathologies: cerebral β-amyloidosis in the form of β-amyloid (Aβ) plaques and tauopathy in the form of neurofibrillary tangles, neuritic plaques, and neuropil threads. Until recently, only Aβ could be studied in humans using positron emission tomography (PET) imaging owing to a lack of tau PET imaging agents. Clinical pathological studies have linked tau pathology closely to the onset and progression of cognitive symptoms in patients with AD. We report PET imaging of tau and Aβ in a cohort of cognitively normal older adults and those with mild AD. Multivariate analyses identified unique …

Lesion Identification And The Effect Of Lesion On Motor Mapping After Stroke, Ruixi Zhou

McKelvey School of Engineering Graduate Student Theses & Dissertations

Stroke is the most common cause of long-term severe disability and the motor system that is most commonly affected in stroke. One of the mechanisms that underlies recovery of motor deficits is reorganization or remapping of functional representations around the motor cortex. This mechanism has been shown in monkeys, but results in human subjects have been variable. In this thesis, I used a database that includes longitudinal behavioral and multimodal imaging data in both stroke patients and healthy controls for two research projects. Firstly, I improved an automatic lesion segmentation method to aid in the identification of the location and …

Partial Covariance Based Functional Connectivity Computation Using Ledoit-Wolf Covariance Regularization, Matthew R. Brier, Anish Mitra, John E. Mccarthy, Beau M. Ances, Abraham Z. Snyder

Mathematics Faculty Research

Highlights •We use the well characterized matrix regularization technique described by Ledoit and Wolf to calculate high dimensional partial correlations in fMRI data. •Using this approach we demonstrate that partial correlations reveal RSN structure suggesting that RSNs are defined by widely and uniquely shared variance. •Partial correlation functional connectivity is sensitive to changes in brain state indicating that they contain functional information. Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a …

Presence-At-Hand, Eric Lyle Schultz

Graduate School of Art Theses

Abstract

The writing that follows is intended to provide a theoretical framework for the motives behind my practice. The primary concerns addressed are the reception, transmission, and physical shape of knowledge. I will discuss a human condition that exists as a byproduct of both the legacy of representation as well as the innate biology of the brain. I will argue that as a society we are governed by the residue of an extreme logic, and that this condition places severe margins on our potential for creative solutions. I will propose that our ability to create meaning is stifled by the …

Integrating Cognitive Science With Innovative Teaching In Stem Disciplines, Mark A. Mcdaniel, Regina F. Frey, Susan M. Fitzpatrick, Henry L. Roediger Iii

Books and Monographs

This volume collects the ideas and insights discussed at a novel conference, the Integrating Cognitive Science with Innovative Teaching in STEM Disciplines Conference, which was held September 27-28, 2012 at Washington University in St. Louis. With funding from the James S. McDonnell Foundation, the conference was hosted by Washington University’s Center for Integrative Research on Cognition, Learning, and Education (CIRCLE), a center established in 2011. Available for download as a PDF. Titles of individual chapters can be found at http://openscholarship.wustl.edu/circle_book/.

The Processing Of Amyloid Precursor Protein In The Central Nervous System Of Humans And Rhesus Macaques, Justyna Anna Dobrowolska

All Theses and Dissertations (ETDs)

Alzheimer's disease: AD) is the most common dementia, currently afflicting 30 million people worldwide, with prevalence steadily increasing. Over 99% of AD cases are classified as sporadic, in which the major risk factors are age: greater than 65 years) and the ApoE-ε4 allele: in a gene dose dependent manner). The minority of AD cases: less than 1%) are caused by autosomal dominant inheritance of a genetic mutation in one of three genes: Amyloid Precursor Protein: APP), Presenilin-1: PSEN1), or Presenilin-2: PSEN2). Mutation carriers will generally notice cognitive decline starting at a relatively young age, anytime between their 30s-50s, and eventually …

Intermediate Level Mechanisms Supporting Face Perception, Eric J. Feczko

All Theses and Dissertations (ETDs)

I propose that the intermediate neural mechanisms involved in face processing may be better understood by studying concentric form-from-structure integration. This dissertation involves behavioral adaptation and masking experiments that provide evidence regarding whether face perception and concentric form-from-structure perception engage a common processing mechanism.

Despite faces being complex visual stimuli, humans are able to perceive and identify faces rapidly. Studies of face perception strongly suggest that this ability involves processing the arrangement of the face features. Although high-level aspects of face perception have been studied extensively, less is known about the intermediate mechanisms involved in face processing. Converging evidence has …

Concentration Coding In The Accessory Olfactory System, Hannah Ada Arnson

All Theses and Dissertations (ETDs)

Understanding how sensory systems encode stimuli is a fundamental question of neuroscience. The role of every sensory system is to encode information about the identity and quantity of stimuli in the environment. Primary sensory neurons in the periphery are faced with the task of representing all relevant information for further processing by downstream circuits, ultimately leading to detection, classification and potential response. However, environmental variability potentially alters stimulus properties in non-relevant ways. Here, we address these problems using the mouse accessory olfactory system: AOS) as a model. The AOS is an independent olfactory system possessed by most terrestrial vertebrates, although …

Analyzing Reading Specialization Using Fmri, Rs-Fcmri, And Development, Alecia Cristen Vogel-Hammen

All Theses and Dissertations (ETDs)

Reading is an important, phylogenetically new skill. While neuroimaging studies have identified brain regions used in reading, it is unclear to what extent these regions become specialized for use predominantly in reading versus other tasks. The goal of this dissertation is to investigate the extent to which reading specialization exists at the region and network level, with a focus on orthography, the visual processing of words and letters.

I used task-based and resting state functional connectivity: rs-fcMRI) studies to investigate the specialization of orthographic processing, purportedly localized to a left occipito-temporal fusiform cortex region. In Chapter 2, we find no …

Monocytic Cells Mediate Granulocyte-Colony Stimulating Factor-Induced Mobilization Of Hematopoietic Stem And Progenitor Cells, Mahil Rao

All Theses and Dissertations (ETDs)

In the normal, healthy adult, hematopoiesis occurs primarily in the bone marrow. As such, at steady state, a majority of hematopoietic stem and progenitor cells: HSPCs) are tightly held within specialized areas of the bone marrow collectively referred to as the `hematopoietic stem cell niche.' In response to various forms of stress, such as infection or hemorrhage, or following administration of a variety of pharmacologic agents, niche function is altered and HSPCs are released into the peripheral circulation through a process known as mobilization. Granulocyte-colony stimulating factor: G-CSF), a hematopoietic growth factor, is the most widely-used mobilizing agent clinically. However, …