Neuroscience and Neurobiology Commons^™

Clinical, Neuroimaging, And Molecular Spectrum Of Tecpr2-Associated Hereditary Sensory And Autonomic Neuropathy With Intellectual Disability, Sonja Neuser, Barbara Brechmann, Gali Heimer, Ines Brösse, Susanna Schubert, Lauren O'Grady, Michael Zech, Siddharth Srivastava, Shahnaz Ibrahim, Fatima Khan

Department of Paediatrics and Child Health

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms. A cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea as core manifestations. A review of brain magnetic resonance imaging scans demonstrated a …

Selective Neural Stimulation By Leveraging Electrophysiological Diversity And Using Alternative Stimulus Waveforms, Bemin Ghobreal

Dissertations

Efforts on finding the principle mechanism for selective neural stimulation have concentrated on segregating the neurons based on their size and other geometric factors. However, neuronal subtypes found in different parts of the nervous system also differ in their electrophysiological properties. The primary objective of this study is to investigate the feasibility of selective activation of neurons by leveraging the diversity seen in passive and active membrane properties.

Using both a local membrane model and an axon model based on the CRRSS, the diversity of electrophysiological properties is simulated by varying four model parameters (membrane leakage-Gleak and capacitance-Cm, temperature coefficient-Ktemp, …

Mechanisms Of Oscillations And Polyglot Entrainment In Neuronal And Circadian Models, Emel Khan

Dissertations

Entrainment is a type of synchronization in which the period of an endogenous oscillator matches the period of an external forcing signal and a stable phase relationship is maintained between them. Entrainment patterns are described in terms of the number of input oscillations (N) that are phase-locked to a number of output oscillations (M), referred to as N:M patterns. Arnold tongue diagrams are used to depict the regions of N:M entrainment patterns in the input period-amplitude parameter space. Although the entrainment of self-sustained oscillators by periodic forcing are well investigated is a well-studied problem, entrainment of damped oscillators has been …

Psychological Impact Of Novel Coronavirus Covid-19 Across The Globe-A Review, Sadaf Shaheen, Iram Asim, Rida Zainab, Humaira Yasmeen

Journal of Bioresource Management

The recent outbreaks of novel coronavirus disease have unprecedent impact on mental health of patients, front-line healthcare workers and local population. However, the impact is not fully documented. This review explores stress-driven factors, stress-vulnerable groups and stress management interventions. Repetitive exposure to mass media and inappropriate health protective measures has heightened stress responses. Fear of not getting recovered from COVID-19 and disaffection has profound impact of infected individuals and their families. They may experience fear, anxiety, anger, sleep deprives and anorexia which may weakens their immune system thus making them vulnerable to COVID-19. The COVID-19 pandemic has underscored potential gaps …

The Disproportionate Impact Of Covid-19 On Women, Ava Stallone

Honors Scholar Theses

The impact of COVID-19 is placing a large strain on women. This can be seen through reports of mental health and financial concerns. Women are more vulnerable to COVID-19 related economic effects due to existing gender inequalities, which in turn may also have a negative effect on mental health. Through this study gender disproportion is looked at between mental health and COVID-19 financial concerns among women and men. The aim is to asses how COVID-19 financial concerns may be contributing to stress, anxiety, and depression. It is hypothesized that; women will report worse mental health and greater economic concerns than …

Alzheimer’S Disease Drug Development Pipeline: 2021, Jeffrey Cummings, Garam Lee, Kate Zhong, Jorge Fonseca, Kazem Taghva

Brain Health Faculty Research

Introduction The number of individuals worldwide with Alzheimer's disease (AD) is growing at a rapid rate. New treatments are urgently needed. We review the current pipeline of drugs in clinical trials for the treatment of AD. Methods We interrogated ClinicalTrials.gov, the federal registry of clinical trials to identify drugs in trials. Results There are 126 agents in 152 trials assessing new therapies for AD: 28 treatments in Phase 3 trials, 74 in Phase 2, and 24 in Phase 1. The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification; 10.3% are …

Sulfide Catabolism Ameliorates Hypoxic Brain Injury, Eizo Marutani, Masanobu Morita, Shuichi Hirai, Shinichi Kai, Robert M.H. Grange, Yusuke Miyazaki, Fumiaki Nagashima, Lisa Traeger, Aurora Magliocca, Tomoaki Ida, Tetsuro Matsunaga, Daniel R. Flicker, Benjamin Corman, Naohiro Mori, Yumiko Yamazaki, Annabelle Batten, Rebecca Li, Tomohiro Tanaka, Takamitsu Ikeda, Akito Nakagawa, Dmitriy N. Atochin, Hideshi Ihara, Benjamin A. Olenchock, Xinggui Shen, Motohiro Nishida, Kenjiro Hanaoka, Christopher G. Kevil, Ming Xian, Donald B. Bloch, Takaaki Akaike, Allyson G. Hindle

Life Sciences Faculty Research

The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia …

Scaling Up Information Sharing On Hiv-Associated Neurocognitive Disorder: Raising Awareness And Knowledge Among Key Stakeholders, Renato M. Liboro, Paul A. Shuper, Lori E. Ross

Psychology Faculty Research

Although the majority of specialists and researchers in the field of HIV/AIDS are aware and knowledgeable about HIV-associated neurocognitive disorder (HAND) as a condition that affects as much as 50% of people living with HIV/AIDS (PLWH), research has documented that many health care and service providers who work directly with PLWH are either unaware of HAND or believe they do not know enough information about HAND to effectively support their clients experiencing neurocognitive challenges. Based on the findings of a qualitative study that interviewed 33 health care and service providers in HIV/AIDS services to identify and examine their awareness and …

Characterizing The Gene Regulatory Network Required To Specify The Excitatory Neurotransmitter Phenotype Of V0v Spinal Interneurons, Amber Kellie Woodard

Theses - ALL

The majority of neurons within the spinal cord are interneurons. Interneurons make important connections with other cells that allow signals to be relayed between the brain and the rest of the body, and aid in functions such as locomotion. One key functional characteristic of interneurons is the neurotransmitter that they use to communicate with other cells. Interneurons that use GABA or glycine neurotransmitters to communicate have an inhibitory phenotype, while interneurons that use glutamate neurotransmitters have an excitatory neurotransmitter phenotype. Without the correct neurotransmitter phenotype, connections within the central nervous system will malfunction. It is therefore important to understand how …

Exploring Tactile Art-Making With Deafblind Students And Their Families: An Opportunity For Creative Play, Alice Rodgers

Expressive Therapies Capstone Theses

The impact of a deafblind diagnosis on an individual’s mental health and the well-being of the family involved can be profound. However, current research and available literature for the mental health treatment and therapy practices of deafblind persons and their families is limited (Kyzar et al., 2016; “WFDB Global Report 2018,” n.d.). This thesis used the Leeds Family Psychology and Therapy Service principles (Leeds FPTS) and the Expressive Therapies Continuum with established deafblind teaching strategies to facilitate an original arts-based community project entitled: “Things We Like.” This project provided an opportunity for deafblind students (ages three to 22) and their …

Inflammatory Regulation Of Cns Barriers After Traumatic Brain Injury: A Tale Directed By Interleukin-1, Colleen N. Bodnar, James B. Watson, Emma K. Higgins, Ning Quan, Adam D. Bachstetter

Neuroscience Faculty Publications

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during …

Cnd-1/Neurod Is Required For Rme Head Neuron Cell Fate Specification In The Nematode Caenorhabditis Elegans., Genevieve Doxakis

Symposium of Student Scholars

cnd-1/NeuroD is required for RME head neuron cell fate specification in the nematode Caenorhabditis elegans.

Genevieve Doxakis (1), Illyana Weitzel (2), Amber Baldwin (1), Davron Hanley (1), and Martin L. Hudson (1)

(1) Department of Molecular and Cellular Biology, Kennesaw State University

(2) STEM Magnet Program, Wheeler High School

Transcription factors are proteins that control gene transcription. NeuroD is a deeply conserved transcription factor that regulates neuronal differentiation and pancreatic development. Mutations in this gene correlate with several neurological disorders, creating an imperative for further study. The nematode Caenorhabditis elegans has a NeuroD ortholog, cnd-1, which means we can use …

Igf1-Stimulated Posttraumatic Hippocampal Remodeling Is Not Dependent On Mtor, Erica L. Littlejohn, Anthony J. Desana, Hannah C. Williams, Rudy T. Chapman, Binoy Joseph, Jelena A. Juras, Kathryn E. Saatman

Physiology Faculty Publications

Adult hippocampal neurogenesis is stimulated acutely following traumatic brain injury (TBI). However, many hippocampal neurons born after injury develop abnormally and the number that survive long-term is debated. In experimental TBI, insulin-like growth factor-1 (IGF1) promotes hippocampal neuronal differentiation, improves immature neuron dendritic arbor morphology, increases long-term survival of neurons born after TBI, and improves cognitive function. One potential downstream mediator of the neurogenic effects of IGF1 is mammalian target of rapamycin (mTOR), which regulates proliferation as well as axonal and dendritic growth in the CNS. Excessive mTOR activation is posited to contribute to aberrant plasticity related to posttraumatic epilepsy, …

Monolingual And Bilingual Language Networks In Healthy Subjects Using Functional Mri And Graph Theory, Qiongge Li, Luca Pasquini, Gino Del Ferraro, Madeleine Gene, Kyung K. Peck, Hernán A. Makse, Andrei I. Holodny

Publications and Research

Bilingualism requires control of multiple language systems, and may lead to architectural differences in language networks obtained from clinical fMRI tasks. Emerging connectivity metrics such as k-core may capture these differences, highlighting crucial network components based on resiliency. We investigated the influence of bilingualism on clinical fMRI language tasks and characterized bilingual networks using connectivity metrics to provide a patient care benchmark. Sixteen right-handed subjects (mean age 42-years; nine males) without neurological history were included: eight native English-speaking monolinguals and eight native Spanish-speaking (L1) bilinguals with acquired English (L2). All subjects underwent fMRI with gold-standard clinical language tasks. Starting from …

Dopamine Neurons That Cotransmit Glutamate, From Synapses To Circuits To Behavior, Daniel Eskenazi, Lauren Malave, Susana Mingote, Leora Yetnikoff, Samira Ztaou, Vlad Velicu, Nao Chuhma

Publications and Research

Discovered just over 20 years ago, dopamine neurons have the ability to cotransmit both dopamine and glutamate. Yet, the functional roles of dopamine neuron glutamate cotransmission and their implications for therapeutic use are just emerging. This review article encompasses the current body of evidence investigating the functions of dopamine neurons of the ventral midbrain that cotransmit glutamate. Since its discovery in dopamine neuron cultures, further work in vivo confirmed dopamine neuron glutamate cotransmission across species. From there, growing interest has led to research related to neural functioning including roles in synaptic signaling, development, and behavior. Functional connectome mapping reveals robust …

Value-Generating Exploratory Trials In Neurodegenerative Dementias, Lauren G. Friedman, Nicholas Mckeehan, Yuko Hara, Jeffrey L. Cummings, Dawn C. Matthews, Jian Zhu, Richard C. Mohs, Deli Wang, Suzanne B. Hendrix, Melanie Quintana, Lon S. Schneider, Michael Grundman, Samuel P. Dickson, Howard H. Feldman, Judith Jaeger, Elizabeth C. Finger, J. Michael Ryan, Debra Niehoff, Susan L.J. Dickinson, Jessica T. Markowitz, Meriel Owen, Alessio Travaglia, Howard M. Fillit

School of Medicine Faculty Research

Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3 clinical trials that failed to show efficacy of investigational drugs. Despite differences in clinical and behavioral characteristics, these disorders have shared pathologies and face common challenges in designing early-phase trials that are predictive of late-stage success. Here, we discuss exploratory clinical trials in neurodegenerative dementias. These are generally phase 1b or phase 2a trials that are designed to assess pharmacologic effects and rely on biomarker outcomes, with shorter treatment durations and fewer patients than traditional phase 2 …

Determining The Role Of Methylglyoxal (Mgo) And The Trpa1 Channel In Inducing Astrocyte Senescence And Neurodegeneration, Natalie Hill

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Aging is the largest risk factor for the development of Alzheimer’s disease (AD) and related dementias. A recently proposed driver of age-related pathologies is cellular senescence, a phenotype that consists of cell-cycle arrest and an inflammatory response known as the senescence-associated secretory phenotype (SASP). Although there is a link between the accumulation of senescent cells and neurodegeneration, much remains unknown about how senescent cells arise in the brain. Astrocytes are the most abundant cell type in the brain that serve important roles like supporting neurons and proliferating in response to stress. Methylglyoxal (MGO) is a glycolytic byproduct that can react …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing …

Hippocampal Functional Activity Following Prenatal Alcohol Exposure, Ryan E. Harvey

Psychology ETDs

Prenatal alcohol exposure (PAE) is among the most common developmental insults to the nervous system and is characterized by spatial memory disruption. There is a pressing need to identify physiological alterations that help explain this memory impairment. The hippocampal (HPC) formation and connected regions are a compelling candidate for this purpose as they are vital for navigation, spatial memory, and memory consolidation. This document is broken up into 3 main parts, a detailed review of the prior literature followed by several experiments. First, It starts out with a comprehensive review on spatial behavioral impairments following PAE and the synaptic & …

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 …

Molecular Characterization Of A Unique Population Of Human Cortical Interneurons; Implications For Primate-Specific Development, Crina Peterson

Biomedical Sciences ETDs

The human brain consists of 86 billion neurons compared to rodent brain, which consists of 75 million neurons, and the underlying mechanisms for the increased complexity of the primate cortex are not fully elucidated. However, an increase in specific cell populations, including calretinin-expressing (CALB2/CR) interneurons (INs), has been identified. In my thesis work, I demonstrate that human pluripotent stem cells (hPSCs) differentiated to neurons by default patterning give rise to this CR population in vitro, providing a method to study their development.

Chapter I reviews cortical development and hPSCs as an appropriate proxy for studying human cortical development. Chapter …

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 …

Proceedings From The Second Annual Society For Neurosports Conference, William R. Kochen

Journal for Sports Neuroscience

Proceedings from the Second Annual Society for NeuroSports Conference

Effects Of Bimodal Transcranial Direct Current Stimulation On Modulation Of Spinal Circuitry In People With Chronic Post-Stroke Hemiparesis, John Patrick Gan, Rafael Cabrera, Lana Laudermilch, Benjamin Wolkenhauer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: Stroke can lead to gait abnormalities such as foot drop. Foot drop can result from decreased corticospinal tract input to the ankle dorsiflexors and/or from exaggerated stretch reflexes on the soleus due to reduced reciprocal inhibition from spinal reflex pathways. Transcranial direct current stimulation (tDCS) attempts to modulate corticospinal tract input and spinal reflex pathways by delivering electrical signals to parts of the brain. The degree of neuromodulation from tDCS can be measured through the Hoffman Reflex (H-reflex)—a tool used to estimate alpha motor neuron excitability which is increased in individuals post-stroke. Purpose: The primary purpose of this study …

Mental Imagery In The Regulation Of Differential Fear Conditioning: A Multimodal Investigation Involving Self-Report, Psychophysiology, And Brain Imaging, Tyler Daniel Robinson

LSU Doctoral Dissertations

Mental imagery is a common component in a range of emotion regulation techniques. However, the effectiveness and neural mechanisms of regulation via mental imagery are underexplored due to a lack of studies targeting mental imagery specifically. This discrepancy results in uncertainty regarding the mechanism of regulation in existing paradigms. Biased competition for attentional resources presents a plausible model by which a mental imagery-based distracter can downregulate response to an emotional stimulus. If visualizing an imagined distracter effectively regulates emotional response, the inclusion of mental imagery components in other techniques represents a potential confound. To address this discrepancy, this dissertation investigates …

Predicting Propofol-Induced Burst Suppression Using An Individualized Model-Based Approach Over Repeated Treatments, Jason C. Huang

Utah Space Grant Consortium

Our group is investigating the antidepressant effects of high-dose propofol, but dosing propofol to induce standardized changes in EEG activity (“burst suppression”) is challenging due to limited knowledge of each subject’s pharmacokinetics (PK) and pharmacodynamics (PD). In this paper, we approximated PK-PD models for propofol-induced burst suppression (PIBS), based on multiple subjects over repeated treatments. We then applied these models to predict BSR in each subject’s repeated treatment, then evaluate their predictive performances. We hypothesized that predicting BSR from a greater number of previous treatments would improve performance, but our current results are not conclusive enough to validate the hypothesis. …