Neurosciences Commons^™

Data-Driven Staging Of Neurodegenerative Pathology Related To Alzheimer’S Disease, Thomas Earnest

McKelvey School of Engineering Graduate Student Theses & Dissertations

Alzheimer’s Disease (AD), the most common cause of dementia, is a dual proteinopathy exhibiting deposits of extracellular amyloid-beta (Aβ) and intracellular tau in brain tissue. Models which describe the spatial and temporal trajectories of these pathologies have been invaluable for understanding AD and have the potential to support diagnosis, disease monitoring, and treatment development. Disease staging systems, which provide protocols for assessing individual disease severity based on their extent of brain pathology, have been crucial for explaining and diagnosing AD. However, these systems have been primarily informed by post-mortem histological assessments and are not directly applicable to disease assessment in …

Transient Activation Of Potent Progenitor Cells Is Required For Spinal Cord Regeneration, Chase Alexander Weinholtz

Arts & Sciences Graduate Student Theses and Dissertations

Mammalian spinal cord injury is an intractable biomedical problem driven by interlocking maladaptive cellular responses that prioritize acute stabilization over long-term recovery. However, this deficient regenerative capacity is not an inherent limitation. The zebrafish, for example, capably regenerates and regains motor function with 2 months of a full transection injury. This ability is thought to rely on the transient expansion of stem cell-like progenitors marked by sox2 expression. Yet our understanding of the identities and contributions of this crucial population remains limited. Here, we determine the molecular identities and cellular contributions of sox2+ progenitors during innate spinal cord repair in …

Dissecting Ms4a4a Function In Microglia And Its Role In Alzheimer’S Disease Pathogenesis, Emma Pascal Danhash

Arts & Sciences Graduate Student Theses and Dissertations

Genome-wide association studies have begun to uncover the complex genetic architecture of Alzheimer's disease (AD). Expression of many AD risk loci is enriched in microglia, the resident immune cells of the brain. Common variants near the MS4A gene family have been associated with AD risk and altered soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF). MS4A4A is a microglial gene that encodes a tetraspan membrane protein that regulates anti-inflammatory responses in macrophages. However, the mechanism by which MS4A4A contributes to microglial function and AD pathogenesis remains unknown. In this dissertation, I leveraged a …

The Effect Of Cerebellar Transcranial Direct Current Stimulation On Anxiety, Shivangi Bhardwaj

All-Inclusive List of Electronic Theses and Dissertations

Anxiety is one of the most prevalent mental health disorders in the U.S. Individuals of all ages are affected by anxiety. Therefore, research into anxiety and its potential treatment has constantly been an area of interest. Newer approaches to managing anxiety include non-invasive stimulation techniques, such as Transcranial Direct Current Stimulation (tDCS), because of its accessibility and effectiveness. Past tDCS work typically focused on regions in the frontal lobe. However, tDCS over the cerebellum has not received as much attention compared to the cerebrum, despite recent work demonstrating cerebellar involvement in emotion processing. Thus, a better understanding of how cerebellar …

Naturalistic Classroom And Home Practices To Support Executive Function And Self-Regulation Of Typically Developing Preschool Children Between The Ages Of 3-5 Years Old: A Mixed Method Study, Michelle Ann Burek

Rehabilitation Sciences Theses & Dissertations

Executive function (EF) and self-regulation (SR) are foundational developmental processes supporting young children’s participation in play, learning, social relationships, and everyday occupations. Although important to school readiness, social competence, health, and well-being, these skills are often examined in structured settings rather than the natural environments in which children develop. Guided by ecological, developmental, and occupational therapy perspectives, this dissertation examined EF and SR within children’s everyday participation and explored caregiver and teacher roles in supporting these processes.

This dissertation consists of three interconnected studies. The first was a systematic review of peer-based interventions to improve social participation among children and …

Extracellular Vesicle-Mediated Transfer Of Gsdme-Nt Pores As A Mechanism Of Inflammation Propagation, Bifeng Xiao

Master's Theses

Inflammasomes are multiprotein complexes that initiate inflammatory signaling through activation of caspase-1, cytokine maturation, and cleavage of Gasdermin D (GSDMD). Cleaved GSDMD forms membrane pores that contribute to cytokine release and pyroptotic cell death. Recent evidence suggests that extracellular vesicles (EVs) may facilitate the intercellular transfer of inflammatory mediators. This study investigated whether GSDMD N-terminal fragment (GSDMD-NT) associates with EV-enriched fractions and contributes to inflammation propagation. Doxycycline-inducible HeLa cells expressing FLAG-tagged GSDMD-NT were used to generate EV-enriched fractions. Western blot analysis detected GSDMD-NT-associated material within EV fractions, while EV marker analysis supported successful enrichment of EV-associated material. Exposure of recipient …

The Role Of 14-3-3 Proteins In The Pro-Inflammatory Response Of Microglia And The Neuronal Stress Response To Trichloroethylene Exposure, William Stone

ETDs from 2020-2029

ABSTRACT This dissertation examines how 14-3-3 proteins, with a focus on the 14-3-3θ iso-form, regulate signaling pathways relevant to neurodegeneration. While tradition-ally described as molecular hubs that organize protein–protein interactions, our work reveals how 14-3-3 function is shaped by environmental insults, namely bac-terial and neurotoxicant exposures, and how its disruption contributes to disease-associated processes. Two complementary approaches were used, focusing on microglial inflammatory signaling and neuronal responses to an environmental neurotoxicant, to define a broader role for 14-3-3 proteins in disease associated pathways in the brain. Chapter I identifies 14-3-3 proteins as modulators of microglial activation. Disrup-tion of 14-3-3 interactions …

Anatomy And Function Of Vasopressin Receptor 1a-Expressing Neurons In The Limbic Thalamus, David Joseph Kahn

Theses and Dissertations

The vasopressin (Avp) system modulates social behavior through region-specific and sex-dependent mechanisms, yet the role of Avp receptor 1a (Avpr1a) signaling in the thalamus has remained largely unexplored. This dissertation examined the distribution and functional contributions of Avpr1a-expressing neurons across the mouse thalamus using a combination of genetic labeling, anatomical quantification, and chemogenetic manipulation. Mapping of Avpr1a-expressing neurons revealed a presence in most thalamic nuclei, with highest densities in the anterior thalamic nuclei and midline nuclei. Notably, Avpr1a-expressing neuron densities did not mirror previously described patterns of Avp innervation, and no sex differences in Avpr1a-expressing neuron density were observed. Chemogenetic …

The Role Of Mitochondrial And Lysosomal Damage In Neurotoxicity From Parkinson 'S-Related Environmental Exposures, Neda Ilieva

ETDs from 2020-2029

Parkinson's disease (PD) is a progressive motor neurodegenerative disorder with a predominantly idiopathic etiology. More recently, however, the contribution of exogenous risk factors such as environmental contaminants has become of interest. Some endogenous genetic risk factors have been well characterized, but the mechanisms by which exogenous insults, such as environmental contaminants, drive dopaminergic neurodegeneration remain incompletely understood. This dissertation will address how environmental contaminants converge on mitochondrial and lysosomal dysfunction to activate parallel neurotoxic signaling pathways, with a focus on the LRRK2 kinase and the cGAS-STING innate immune pathway. Chapter 2 demonstrates that pharmacological inhibition of LRRK2 kinase activity protects …

Understanding Whole-Brain Dynamics Through Generative Modeling, Ruiqi Chen

Arts & Sciences Graduate Student Theses and Dissertations

A central goal in cognitive neuroscience is to map mental processes onto their physical substrates. Traditionally, this goal is pursued by associating different mental processes with spatially-based anatomic localization. On the contrary, much less is known about the temporal dynamics of neural activity, particularly at the scale of the whole brain. Research into whole-brain dynamics has been challenging primarily due to the lack of an analytic framework that can summarize such dynamics, expose the underlying mechanisms, and associate the mechanisms with cognitive processes. In this dissertation, I describe my doctorate research aimed at building such a framework and deploying it …

Mapping The Neuroexposome: Integrative Analysis Of Dementia Risk Factors Through Multi-Omics And Environmental Profiling In The Egyptian Population., Mai Ahmed Saadzaghloul Othman

Theses and Dissertations

Background: Dementia represents one of the most pressing public health challenges of the twenty-first century, with the global burden projected to reach 153 million cases by 2050. Egypt, as the most populous Arab nation, faces a corresponding rise in age-related diseases, yet comprehensive data from low- and middle-income countries remain severely limited. The neuroexposome framework, integrating genetic susceptibility, environmental exposures, and metabolic alterations, offers a powerful strategy to characterize the complex interplay between internal and external risk factors for Alzheimer's disease (AD) and Alzheimer's disease Related Dementias (ADRD).

Objectives: This thesis aimed to: (1) examine the distribution of APOE alleles …

Molecular And Histologic Studies Of The Amygdala And Reward Circuits In Rhesus Macaques (Macaca Mulatta) With Self-Injurious Behavior (Sib), Jackie Barua

Doctoral Dissertations

Self-injurious behavior (SIB), also known as non-suicidal self-injury (NSSI), is characterized by deliberate infliction of harming one’s own body tissues without committing suicide, and persists in a group of captive rhesus macaques despite an enhanced enrichment program and pharmacological intervention with diazepam. The aim of this dissertation was to identify the neurobiological underpinnings of SIB by combining RNA-seq guided transcriptomic discovery and targeted candidate gene validation with unbiased histological and imaging analysis. The secondary aim was to employ a complementary mouse model to investigate the endogenous opioid system in response to diazepam. The amygdala transcriptome of primates with SIB (n …

Activated Dorsomedial Hypothalamic Astrocytes Regulate Feeding Behavior, Bella M. Lisenby

Honors Projects

The dorsomedial hypothalamus (DMH) region of the brain has been shown to be important for anticipatory feeding activity and play a role in restricting excessive food intake. In obese animals that overconsume calories, astrocytes within the DMH exhibit intracellular signaling changes indicative of cellular activation. Because astrocytes are known to influence neuronal function, we hypothesize that activated astrocytes regulate behavior. In the current study, we use chemogenetics combined with stereotaxic surgery to assess the contribution of astrocyte activity in the DMH towards metabolic behaviors.

Fentanyl Mediated Distortions Of Phasic Dopamine Release Dynamics Encoding Natural Reward And Aversive Processing In The Mammalian Mesolimbic Circuit, Oliver P. Culver Iv

MUSC Theses and Dissertations

Mu opioid receptor (MOR) agonists are recognized to disinhibit tonic dopamine (DA) in the ventral striatum (VS), contributing to opioid addiction and euphoria. However, MOR agonists can also inhibit non-drug reward-seeking, and disrupt conditioned responding to aversive stimuli, a phenomenon not readily explained by tonic DA disinhibition. We hypothesized that this effect could be due in part to disruption of phasic DA responses to conditioned stimuli (CS) which critically shape and maintain behaviors during naturalistic reward and aversive processing. Because MOR effects on CS-evoked phasic DA are largely unexamined, we conducted in vivo fiber photometric recordings in water-deprived male and …

Neuroinflammation And Neuropathology In A Novel Tau, Amyloid-Beta And Alpha-Synuclein Co-Pathology Model, Jhodi Mickayla Webster

ETDs from 2020-2029

Neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson disease (PD) often present with overlapping proteinopathies rather than aggregated proteins in isolation. Amyloid-β (Aβ) and phosphorylated tau are found in a substantial proportion of idiopathic PD cases, while α-synuclein (α-syn) pathology is present in over half of AD cases. The presence of these co-pathologies is associated with accelerated cognitive decline and increase mortality in these patients. In parallel, neurodegenerative diseases are increasingly recognized as being shaped by interactions between central nervous system (CNS) pathology and the immune system. Despite this, most experimental animal models of neurodegenerative disease examine single pathologies in …

From Transcriptome To Function: Multimodal Characterization Of Transcriptionally Defined Ventral Tegmental Area Dopamine Neurons, Natalie Dalton Fitzgerald

ETDs from 2020-2029

Substance use disorder is a complex neurobiological disease characterized by impaired control over drug taking and drug seeking. Drugs of abuse exert their reinforcing effects largely through dopaminergic (DAergic) projections from the ventral tegmental area (VTA) to the nucleus accumbens, where all drugs of abuse increase DA transmission. Beyond reward processing and reward learning, the VTA contributes to a range of psychiatric conditions, including schizophrenia and attention-related disorders. Although DA signaling has long been a major focus of addiction research, recent transcriptomic studies have revealed substantial heterogeneity of cell types within the VTA. Previous work from our lab identified two …

Investigating The Effects Of Increased O-Glcnaylation On Pathology In Alzheimer’S Disease, Melissa Louise Garcia

ETDs from 2020-2029

Alzheimer’s disease (AD) is currently the 7th leading cause of death, with few treatment options. It is known that AD pathology begins 20-30 years before clinical symptoms manifest. Some of the earliest pathological changes occur in glial cells of the hippocampus, causing them to become chronically reactive, as well as the accumulation of Amyloid-β (Aβ) in the hippocampus and hyperphosphorylated Tau (pTau) in the locus coeruleus, resulting in dysfunction of the noradrenergic (NA) system. Preclinical studies have shown promise in the abilities of the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc). O-GlcNAc is a tightly regulated reversible enzymatic modification controlled by the …

Characterizing The Role Of The Paraventricular Nucleus Of The Thalamus D2r+ Neurons In Interoceptive Predictions, Briana Machen

ETDs from 2020-2029

Interoceptive predictions are internal models through which the brain anticipates future bodily states based on past experiences and environmental cues. Under healthy conditions, these predictions allow organisms to anticipate physiological needs and proactively adjust behavior to maintain homeostasis. When these processes become dysregulated, however, environmental cues can trigger maladaptive physiological responses. Although interoceptive prediction is increasingly recognized as a key mechanism underlying adaptive behavior, the neuronal circuits responsible for generating these predictions remain poorly understood. The paraventricular nucleus of the thalamus (PVT) receives convergent inputs from brain regions involved in processing both interoceptive signals and exteroceptive cues, positioning it to …

Environmental And Pharmacological Modulation Of Opioid-Mediated Behavioral Effects In Rats, Corinne Ann Gallagher

Theses and Dissertations

Opioid Use Disorder (OUD) and opioid-associated overdoses continue to pose significant burden to US healthcare systems—both financially and in lives lost. It is imperative to identify risk factors which may predispose vulnerability to OUD development, which could aid in discovery of new therapeutic strategies for susceptible populations. This dissertation investigated the impacts of two such risk factors which modulate opioid-induced reward and behavioral effects: adolescent stress and the adulteration of illicit opioids by xylazine. In Chapter 2, we examined the effects of acute adolescent stress on oxycodone self-administration in rats, and the potential involvement of the locus coeruleus in these …

Foveate, Dahlia Aggarwal

Masters Theses

This thesis investigates how textiles can unsettle visual assumptions, encouraging a perceptual shift. Through weaving, upholstery, and spatial installation, the work stages a tension between what a surface appears to be and how it is encountered by the body. Through woven pattern, tactile texture, and trompe l’oeil textile surfaces, perception is something negotiated rather than fixed: the eye anticipates one reality while the hand discovers another.

Drawing on a range of sensations gathered from observing landscape formations and textures, it translates enduring scale and material qualities into an interior landscape of woven surfaces and textile-based furniture. Rather than serving as …

Rhythms Of Hippocampal Function And Memory After Moderate Prenatal Alcohol Exposure, Lilliana May Sanchez

Psychology ETDs

Fetal Alcohol Spectrum Disorders involve morphologic and neurobiological abnormalities in offspring subjected to prenatal alcohol exposure. Although not as well studied as high exposure, moderate prenatal alcohol exposure represents the most common and undetected form in humans. While learning and memory deficits have been well characterized at the behavioral level in humans with Fetal Alcohol Spectrum Disorders and in animal models of moderate prenatal alcohol exposure, few studies have determined the circuit or systems level mechanisms of the behavioral deficits. A complete understanding of the neural bases of memory deficits after moderate prenatal alcohol exposure is needed to ultimately identify …

Brain-Based Mechanisms Of Behavioral Impairment In Fetal Alcohol Spectrum Disorder (Fasd): The Neuroimaging Biomarkers Of Inhibitory Control, Zinia Pervin

Biomedical Engineering ETDs

The developing brain is highly susceptible to alcohol-induced toxicity, often resulting in long-term deficits in executive function and behavioral regulation. Inhibitory control impairments are among the most prominent deficits observed in Fetal Alcohol Spectrum Disorder (FASD). This study investigated the neural mechanisms of inhibitory dysfunction using a multimodal MEG–DTI approach in 67 children aged 6–8 years (34 with FASD, 33 controls) who performed a Go/No-Go task. Source-level MEG analyses revealed reduced stimulus-locked cortical activation in the anterior cingulate cortex and significant group-by-hemisphere interactions in the superior parietal cortex and cuneus. Time–frequency analyses showed diminished response-locked beta power in the sensory-motor …

Exploring The Biological Basis For Exercise Neuroprotection In Parkinson’S Disease: A Cross-Sectional Study Of Exercise And Physical Activity On Inflammatory Cytokines And Neurotrophins, Leah Isabelle P. Alegre, Jacob M. Brewer, Adeline Florschutz, Kate E. Hamiltonthompson

UNLV Theses, Dissertations, Professional Papers, and Capstones

Regular exercise and physical therapy are known to increase production of neurotrophins, including brain-derived neurotrophic factor (BDNF), and anti-inflammatory cytokines. These changes combine to theoretically protect and slow the progressive loss of neurons in Parkinson’s disease (PD). The purpose of this study was to examine the effect of exercise and physical activity on various anti-inflammatory and pro-inflammatory cytokines and neurotrophins in people with PD (PwP). This was a cross-sectional design involving PwP (n=37), aged 43-85 years, who participated in two 30-minute bouts of exercise (with brief rest breaks during and pre/post blood draws) separated by a week. Measures collected prior …

Effectiveness Of Cognitive Stimulation Therapy On The Quality Of Life Of Adults With Dementia: A Secondary Analysis, Evelyn Airam

UNLV Theses, Dissertations, Professional Papers, and Capstones

This secondary analysis study evaluated the effectiveness of Cognitive Stimulation Therapy (CST) on quality of life (QoL), depressive symptoms, and cognitive function in 108 community-dwelling older adults with cognitive impairments, including dementia. Outcomes involved Quality of Life (QoL) measured by the Quality of Life in Alzheimer’s Disease (QoL-AD), symptoms of depression by the Cornell Scale for Depression in Dementia (CSDD), and cognitive function using the Saint Louis University Mental Status (SLUMS). After the CST, significant improvements were observed in QoL (p = .004), depressive symptoms (p = .002), and cognitive function (p < .001), with small effect sizes. Additionally, a significant interaction between sex and dementia diagnosis status was found in predicting cognitive changes, suggesting that the relationship between dementia diagnosis and cognitive improvement differs by sex. No between-group differences were found for QoL or depression. Findings support CST as a multidimensional, non-pharmacological intervention that improves cognitive, psychological, and social outcomes. Although effects were small, consistent improvements are clinically meaningful given the progressive nature of dementia. This study extends existing literature by demonstrating CST’s effectiveness in a community-based setting and reinforces its alignment with occupational therapy’s emphasis on participation and holistic care. Results highlight the need for early intervention and expanded access to CST programs to enhance quality of life in this population.

Heads Up! Designing A Nursing Assessment Tool For Early Recognition Of Intracranial Hypertension Post Head Injury, Sergio A. Dondiego

Honors Capstones

This meta-analysis identifies noninvasive clinical predictors of intracranial hypertension (IH) post head trauma to develop a multi-criteria IH screening tool designed for nurses to wear on their badge reels. High-sensitivity predictors were prioritized to assist in early IH suspicion. Findings suggest that radiographic-measured abnormalities including an optic nerve sheath diameter (ONSD) 5.6 mm and signs of significant head trauma via computed tomography (CT) were highly effective for predicting IH and were therefore defined as major criteria for the assessment tool. Other significant examination findings include a Glasgow Coma Scale (GCS) score 8 and atypical pupillary reactivity. While age showed conflicting …

Supporting An Inclusive Summer Camp For Children With Developmental Disabilities Who Use Aac And Their Neurotypical Peers: A Practice-Based Report, Jessica Hicks

Communication Disorders and Occupational Therapy Undergraduate Honors Theses

For my honors research, I completed an internship in an augmentative and alternative communication (AAC) lab at the University of Arkansas. For most of my internship work, I helped support an inclusive AAC summer camp for children with and without developmental disabilities, such as autism, for whom speech does not fully meet their communication needs. AAC includes high-tech tools such as communication apps on tablets that serve as speech-generating devices (SGDs). SGDs were used by many of the AAC summer camp participants with developmental disabilities. In this report, I will provide background information on AAC and developmental disabilities. I will …

Stromal Interaction Molecule (Stim) Proteins In Microglia And The Impact On Store-Operated Calcium Entry (Soce) And Spinal Cord Injury Recovery, Norah G. Hill

College of Arts & Sciences Senior Theses

In spinal cord injury (SCI), worsening functional outcomes are largely because of secondary injury processes and prolonged chronic inflammation. A major contributor of secondary injury is overload of intracellular calcium, causing neuronal overexcitation and persistent inflammatory responses. One of the primary mediators of calcium entry into the cell is store-operated calcium entry (SOCE). In SOCE, sensors detecting calcium depletion from the endoplasmic reticulum stores are called STIM proteins (1-2). When calcium is low in the cell, STIM proteins will activate Orai channels to open, allowing for the influx of calcium into the cell. The purpose of this study was to …

The Power Of Belief: Investigating The Intersection Of Religious Observance, Social Support, And Psychological Distress, Victoria R. Atwater

Undergraduate Honors Thesis Collection

Religion can act as a protective factor against stress and depression (Koenig et al., 2009; Krok, 2008) and can be examined through an individual’s relationship with religion or the efficacy of religious practices on mental health. In this study, 206 participants completed an online questionnaire that measured stress, depression, religious coping, religiosity (intrinsic religiosity, organized religious activities and non-organized religious activities), and social support using validated scales. The results indicate a positive correlation between stress, depression, and negative religious coping as predicted. While intrinsic religiosity and positive religious coping did not significantly influence stress or depression, organized religious activities were …

Targeting The Dorsolateral Prefrontal Cortex With Transcranial Direct Current Stimulation To Improve Depression And Anxiety In Parkinson's Disease, Brock Renicks

Honors Theses

The aim of this study is to observe the outcomes of transcranial direct current stimulation (tDCS) as a treatment for Parkinson’s Disease (PD). This study will primarily look at changes in depression and anxiety, as these symptoms are often comorbid with Parkinson’s Disease. Transcranial direct current stimulation is a non-invasive, very low-intensity form of electrical stimulation of the brain. It is being increasingly used as a form of treatment for Parkinson’s Disease and depression and anxiety, however the literature is ambiguous, showing mixed results throughout various studies, with no standardization of tDCS administration. To determine the effect of tDCS on …

Utilizing Brain Computer Interfaces That Interact With A Virtual Keyboard, Skye Lilienthal

Honors Theses

A brain-computer interface (BCI) can allow someone to utilize electrical signals in their brain to complete tasks using a computer. BCIs can help people take advantage of technology to type without the need for a traditional keyboard setup. This paper used the OpenBCI Mark IV to test the effectiveness of non-invasive BCIs with dry electrodes within the OpenViBE P300 Speller. This paper shows how to use the P300 speller through a setup pipeline. Results indicate that electrode placement affects P300 accuracy and that areas related to visual processing improve accuracy, suggesting that P300 signals can be detected within OpenBCI Mark …