Medicine and Health Sciences Commons^™

Cortical Stimulation Mapping Of Heschl’S Gyrus In The Auditory Cortex For Tinnitus Treatment, Austin Huang

CMC Senior Theses

Tinnitus is the perception of sound in the absence of an actual sound stimulus. Recent developments have shifted the focus to the central nervous system and the neural correlate of tinnitus. Broadly, tinnitus involves cortical map rearrangement, pathological neural synchrony, and increased spontaneous firing rates. Various cortical regions, such as Heschl’s gyrus in the auditory cortex, have been found to be associated with different aspects of tinnitus, such as perception and loudness. I propose a cortical stimulation mapping study of Heschl’s gyrus using a depth and subdural electrode montage to conduct electrocorticography. This study would provide high-resolution data on abnormal …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

The Invisible Brain Injury Crisis, Michael E. Rosenthal

Capstones

According to the Center for Disease Control and Prevention’s 2013 data, over 282,000 hospitalizations and 2.5 million emergency department visits were at least in part attributable to TBI. In the same year, about 56,000 people died.

Emergency departments in 2012 treated about 329,290 kids under 20 for TBI following an injury taking place during physical activity.

This project explores the rise in traumatic brain injuries and examines the difficult path that some of the survivors have to go through during recovery. By telling the story through my own personal experiences, I guide the reader through what the initial trauma and …

Freezing Of Gait: Mechanisms, Mechanics, And Management, Peter S. Myers

Arts & Sciences Electronic Theses and Dissertations

Parkinson disease (PD) is a neurodegenerative disease with multiple motor and non-motor symptoms, including postural instability, gait impairments, and cognitive deficits. More than 50% of individuals with PD experience a symptom called freezing of gait (FOG), described as a transient inability to take another step forward. Individuals with PD who experience FOG (freezers) have further postural, gait, and cognitive impairments compared to individuals with PD without FOG (non-freezers). While degeneration of the dopaminergic neurons in the substantia nigra is accepted as the primary etiology of the disease, research shows that the disease has a global impact on the brain, accounting …

The Role Of Apolipoprotein E In Regulating Tau Pathogenesis And Neurodegeneration In A Tauopathy Mouse Model, Yang Shi

Arts & Sciences Electronic Theses and Dissertations

APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 increases brain amyloid-β (Aβ) pathology relative to other APOE isoforms. However, whether APOE independently influences tau pathology, the other pathological hallmark of AD and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human APOE knock in (KI) or APOE knockout (KO) background, we show that the presence of human APOE, regardless of APOE isoforms, leads to various degrees of brain atrophy in 9-month old P301S mice, whereas APOE ablation strongly protects against neurodegeneration. In particular, P301S/E4 mice develop …

Singing As A Therapeutic Technique To Improve Gait For People With Parkinson Disease, Elinor Harrison

Arts & Sciences Electronic Theses and Dissertations

Abstract of the Dissertation

Singing as a Therapeutic Technique to

Improve Gait for People with Parkinson Disease

by

Elinor Clare Harrison

Doctor of Philosophy in Movement Science

Neurosciences

Washington University in St. Louis, 2018

Professor Gammon Earhart, Chair

Gait impairment is common in older adults and even more prevalent for people with Parkinson disease (PD). Gait dysfunction is often characterized by reductions in speed, step frequency, and step length. In addition, decreased ability to regulate step length and step frequency may contribute to increased gait variability, making walking less stable and increasing risk for falls. As gait deficits are often …

Hypothalamic Circuits In The Control Of Feeding And Emotional Behaviors, Leandra Mangieri

Dissertations & Theses (Open Access)

Feeding results from the integration of both nutritional and affective states, and is guided by complex neural circuitry in the brain. The hypothalamus is a critical center controlling feeding and motivated behaviors. We found that targeted photostimulation of projections from the lateral hypothalamus (LH) to the paraventricular hypothalamus (PVH) in mice elicited voracious feeding and repetitive self-grooming behavior. GABA neurotransmission in the LH->PVH circuit mediated the evoked feeding behavior, and elicited behavioral approach, whereas glutamate release promoted repetitive self-grooming, which was stress-related in nature. Optogenetic inhibition of LH^GABA ->PVH circuit reduced feeding after fasting, whereas photostimulation abruptly …

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations & Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

A Role For Epac1 And Epac2 In Nociceptor Hyperexcitability And Chronic Pain After Spinal Cord Injury, Samantha Berkey

Dissertations & Theses (Open Access)

Chronic pain is a major complaint of those living with spinal cord injury (SCI), affecting 65-80% of the SCI population, but the treatment options remain limited or non-existent. The cAMP sensor EPAC has previously been shown to play a key role in chronic inflammatory and neuropathic pain, though the contribution from each of its two main isoforms, EPAC1 and EPAC2, is unclear. Here I test the hypothesis that both EPAC1 and EPAC2 play a key role in the maintenance of persistent nociceptor hyperexcitability and chronic pain after SCI.

Using both a T9 SCI mouse model and a T10 SCI rat …

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the best …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

Magnetic Field Frequency-Response For Human Magnetophosphene Perception And Associated Eeg Modulations, Cadence M. Baker

Electronic Thesis and Dissertation Repository

Background: Magnetophosphenes are among the most reliably reported effects resulting from magnetic induction. The frequency dependence of the perception threshold is crucial, as guideline agencies use this information to set exposure limits whose purpose is to protect public and workers.

Objective:Establish the magnetophosphene perception thresholds throughout the extremely low frequency range (0-300 Hz) and evaluate the use of EEG as a biomarker.

Hypothesis:Perception thresholds will be lowest at ~30 Hz. EEG occipital alpha power will decrease upon perception.

Methods:60 participants were exposed to homogenous magnetic fields up to 300 Hz, and 70 mT. EEG alpha power …

Cannabinoid Transmission In The Basolateral Amygdala Modulates Prefrontal Cortex And Ventral Hippocampal Activity, Brian J. Pereira

Electronic Thesis and Dissertation Repository

The cannabinoid system is important for maintaining neuron-to-neuron communication within the mammalian brain. One of the most commonly used substances to alter the cannabinoid system is cannabis. Individuals who are exposed to cannabis report having dissociable effects; both positive and negative. High amounts of THC have been commonly associated with the negative effects of cannabis, whereas CBD can be used to counter these. Pre-clinical evidence suggests that the combination of the two compounds can produce a therapeutic benefit for individuals who are susceptible to the effects of THC. The present study investigates whether the combination of THC+CBD can prevent electrophysiological …

Operant Conditioning Of Human Upper-Limb Stretch Reflexes, Ehsan Abolhasani

Electronic Thesis and Dissertation Repository

Operant conditioning of short-latency reflex (SLR) and H-reflex have been investigated in animals and humans. We modified previously established protocols for conditioning lower limb H-reflexes to up-condition the SLR in brachioradialis muscle and to investigate the effect of such conditioning on the long-latency response (LLR) of synergistic muscles. Our study included 12 healthy participants. Each participant took part in 3 baseline and 27 conditioning sessions in 6 weeks, followed by two additional sessions one month and two months after the last conditioning session. We found an increase in SLR magnitude in 50% of participants (by 15%±2.50). However, there was no …

Underlying Contribution Of Executive Functioning To Cognition And Academic Achievement In Individuals With Dystrophinopathy, Robert Fee

Dissertations, Theses, and Capstone Projects

Dystrophinopathy is a genetic disorder that results in the lack of or abnormal expression of the protein dystrophin. It is a disorder that alters cell structure and function, impacts the developing brain and brain function, presents with multi-domain cognitive deficits, and influences both mood and behavior. Cognitive impairments appear to be more localized to specific areas of functioning rather than a global deficit; however, deficits have been identified across multiple cognitive domains including language and aspects of executive functioning. A careful examination of the cognitive phenotype and its association to mutations affecting CNS isoforms is necessary to clarify the neuropsychological …

Curcumin Inhibits The Ikk:Nf-Kappa B Pathway In Neural Fear Circuits, Miguel A. Briones

Dissertations, Theses, and Capstone Projects

The study of how the brain acquires fearful memories has attracted considerable experimental attention, due in part to the promise of discovering novel therapeutic approaches for psychiatric disorders that are characterized by unusually strong and persistent traumatic memories. In recent years, extensive research has focused on studying the neural and molecular mechanisms by which fear memories are acquired, stored, and retrieved in the brain. Once acquired, fear memories may be attenuated using one of 2 procedures: 1) fear extinction, which involves repeated presentation of the fear-arousing stimulus in the absence of an aversive consequence, or 2) interference with the reconsolidation …

Working Memory And Falls Risk In Older Adults: An Event-Related Potential Study, Yee (Michelle) S. Wong

Electronic Thesis and Dissertation Repository

BACKGROUND: The aging population is rapidly increasing, where currently in North America, the population of older adults (ages 60+) outnumbers the population of children. Falls are a major concern for older adults and their quality of life. Cognitive impairment has been shown to be declined in older adults at-risk for falls, but working memory has not been thoroughly investigated within this population. PURPOSE: To examine differences in Non-Fallers, Moderate Risk for Falls, and Fallers in a working memory task using electroencephalography (EEG). METHODS: Older adults (n=44, female=27) aged 60 – 80 years (m=68.8, SD=4.7) completed two sessions. The first session …

The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis, Jennifer S. Romer-Seibert

Graduate School of Biomedical Sciences Theses and Dissertations

Developmental timing is a key aspect of tissue and organ formation in which distinct cell types are generated through a series of steps from common progenitors. These progenitors undergo specific changes in gene expression that signifies both a distinct progenitor type and developmental time point that thereby specifies a particular cell fate at that stage of development. The nervous system is an important setting for understanding developmental timing because different cell types are produced in a certain order and the switch from stem cells to progenitors requires precise timing and regulation. Notable examples of such regulatory molecules include the RNA-binding …

Ischemic Stroke Damage Is Reduced By Inhibition Of Il-6 Signaling With Tocilizumab, Jacob Hudobenko

Dissertations & Theses (Open Access)

Introduction:

Stroke is the leading cause of serious long-term disability and is the 5^th leading cause of death causing approximately 130,000 deaths in the United States every year {1}. Stroke is also the 2^nd leading cause of death in American women {2}. Women are 33% more likely to require nursing home care then men, have a higher lifetime risk of stroke and are 13% less likely to receive thrombolytic (clot busting) treatment than men {2}. Interleukin 6 (IL-6) is a pro-inflammatory cytokine involved in the regulation of the immune system in multiple disease states such as rheumatoid …

Characterization Of Theranostic Peptides For Glioblastoma Multiforme, Aaron Mellesmoen

All NMU Master's Theses

Glioblastoma multiforme (GBM) is a type of primary CNS tumor in which viable treatment options do not exist. Standard of care including tumor resection, chemotherapy, and radiation does little to extend the 5-year survival expectancy past 5.1%. Herein, two small-peptide molecules with inherent antitumor activity, blood-brain barrier permeability, and capability for tumor-specific drug deliverance and intraoperative visualization (termed theranostic) were of focus. Confocal microscopy was employed to characterize in vitro specificity of chlorotoxin, a 4 kDa scorpion venom peptide, and rBSG, the recombinant 25 kDa non-glycosylated extracellular domain of extracellular matrix metalloproteinase inducer (EMMPRIN; Basigin) isoform …

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

Ube4b Levels Determine The Efficacy Of Egfr And Stat5 Inhibitors In Treatment Resistant Neuroblastoma, David James Savage

Dissertations & Theses (Open Access)

Neuroblastoma is the most common malignancy in infants. Overexpression of the epidermal growth factor receptor (EGFR) in neuroblastoma tumors can result in enhanced EGFR signaling, uncontrolled proliferation, and may provide a mechanism for chemotherapy resistance. UBE4B, an E3/E4 ubiquitin ligase, ubiquitinates the EGFR and promotes its lysosomal degradation ultimately attenuating EGFR signaling. Interestingly, the UBE4B gene lies in a chromosomal region (1p36) whose loss is correlated with poor patient outcomes due to inefficient EGFR degradation and enhanced cell proliferation. We examined whether depletion of UBE4B in a chemoresistant neuroblastoma cell line would affect tumor responses to drugs that specifically target …

The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy, Matthew D. Howe

Dissertations & Theses (Open Access)

In healthy brain tissue, toxic amyloid-β (Aβ) proteins are transported by the pulsatile flow of cerebrospinal fluid (CSF) along perivascular drainage pathways. Ischemic stroke may disrupt this process, leading to a perivascular build-up of Aβ, termed cerebral amyloid angiopathy (CAA). I hypothesize that an abnormal pattern of extracellular matrix deposition within the vascular basement membrane, termed fibrosis, impairs Aβ drainage from the aged brain after stroke. I further hypothesize that inhibition of astrocytic transforming growth factor-β (TGF-β) signaling can reverse these phenotypes. Finally, I also hypothesize that serum biomarkers of perivascular fibrosis can be used to diagnose CAA following intracerebral …

Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa

Master of Science in Integrative Biology Theses

Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like …

Investigating The Cortical, Metabolic And Behavioral Effects Of Transcranial Direct Current Stimulation In Preparation For Combined Rehabilitation, Kayla N. Ryan

Electronic Thesis and Dissertation Repository

The goal of this thesis was to determine the cortical reorganization that occurs in patients with cervical spondylotic myelopathy (CSM) after surgical decompression and to implement this knowledge into a new rehabilitation strategy. Transcranial direct current stimulation (tDCS) is a non-invasive technique to modulate human behavior. Due to the novel electrode montage used, it was first pertinent that we determine how tDCS would modulate cortical, metabolic and motor behavior in healthy individuals.

We observed the longitudinal functional adaptations that occur in patients with CSM using functional MRI. Enhanced excitation of supplementary motor area (SMA) was observed following surgical decompression and …

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …

The Ugly Sequestosome1:The Role Of P62/Sqstm1 In Autophagy And Multisystem Proteinopathy, Eugene Lee

Arts & Sciences Electronic Theses and Dissertations

Multisystem proteinopathy (MSP) defines a spectrum of degenerative diseases unified by TDP-43 pathology that affect muscle, brain and bone. Mutations in several proteins (VCP, p62/SQSTM1, HNRNPA2B1, HNRNPA1) can all cause MSP via impairments in autophagic protein degradation (VCP and SQSTM1) or RNA granule dynamics (HNRNPA2B1 and HNRNPA1). Phenotypically, MSP mutations lead to variable penetrance of several phenotypes: Paget’s disease of the bone (PDB), rimmed vacuolar inclusion body myopathy (RV-IBM), amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). However, how a same mutation of a protein can develop different diseases remains unclear. Understanding of p62/SQSTM1 (SQSTM1) function is critical to answer …

Identification Of The Smallest Perceivable Interaural Time Differences, Sinthiya Thavam

Electronic Thesis and Dissertation Repository

Several studies have reported human threshold interaural time differences (ITDs) near 10 μs; however, none of these studies aimed to find the stimulus and experimental method that yields the lowest threshold. The goal of the current study is to systematically determine the stimulus and the experimental paradigm that yields the smallest threshold ITD and to provide an accurate reference value. We systematically varied seven parameters: stimulus waveform, stimulus level, stimulus duration, adaptive versus constant stimulus procedure, number of reference intervals, inter-stimulus pause duration, and inclusion versus exclusion of onset and offset ITD. The condition yielding the lowest threshold ITD was …

Neurocognitive Markers Of Cognitive Control In Schizophrenia And Functional Outcomes, Sephira Ryman

Psychology ETDs

Impaired cognitive function results in decreased objective quality of life and community functioning in schizophrenia, resulting in the largest indirect costs from the disease. Disrupted proactive cognitive control, a form of early selection and active goal maintenance, is hypothesized to underlie the broad cognitive deficits observed in patients with schizophrenia. The current study utilized novel electrophysiological (EEG) analytic approach to examine proactive and reactive cognitive control deficits in schizophrenia patients. Behavioral results highlight that patients exhibited a general reduction in reaction time across two multisensory cognitive control tasks, with selective deficits on proactive conditions relative to reactive conditions. The relative …

Precision Gene Therapy For Charcot-Marie-Tooth Disease: From Identifying Genetic Modifiers To Developing Allele-Specific Therapies, Kathryn H. Morelli Ph.D.

Electronic Theses and Dissertations

Charcot-Marie-Tooth Disease (CMT) is a clinically and genetically heterogeneous collection of inherited peripheral neuropathies generally characterized by progressive muscle atrophy, weakness, and loss of sensation in the distal extremities. This inherited disorder, for which there is currently no curative treatment, is the most common inherited disease of the peripheral nervous system, affecting 1:2,500 individuals worldwide.

Clinically, CMT is broadly divided into demyelinating (type 1) and axonal (type 2) forms. Although the clinical presentation can vary greatly in severity and progression within individual patients. Genetically, over 1,000 mutations in over 80 loci in the human genome have been linked to specific …