Medical Sciences Commons^™

Deep Brain Stimulation Of The Subcallosal Cingulate Gyrus In The Treatment Of Treatment Resistant Depression, Megan Caravas, Melanie Sov

Physician Assistant Capstones, 2020-current

Objective: a systematic review to determine the efficacy of deep brain stimulation (DBS) targeting the subcallosal cingulate gyrus (SCG) for the treatment of treatment resistant depression (TRD). Methods: PubMed database was utilized in a search for clinical randomized control trials that were completed after the year 2000, using the terms deep brain stimulation, treatment resistant depression, and subcallosal cingulate gyrus. Results: Three clinical trials were chosen based on specific inclusion criteria as noted in the PRISMA flow chart (Chart 1). The results of the three articles showed various discrepancies. Two of the three studies demonstrated some statistical significance in reduction …

Association Between White Matter Hyperintensities, Cortical Thinning, And Clinical Outcomes In Mild Traumatic Brain Injury, Thomas Helmut Knoblauch

UNLV Theses, Dissertations, Professional Papers, and Capstones

Traumatic Brain Injury (TBI) is a global health challenge, with over 4.6 million confirmed cases annually in North America alone. Mild traumatic brain injuries (mTBIs) are the most common and make up approximately 81% of all TBI diagnoses worldwide [1]. Studies indicate that 10–15% of patients suffer from trauma induced symptoms (i.e. headache, loss of balance, cognitive impairments, fatigue, and mental health/affective disorders) as far as 1 year post injury [2]. Prediction and management of these post-traumatic sequalae is complicated by a lack of symptom associated neuroimaging findings. In spite of a “prominent distribution” of frontotemporal WMHs in pediatric subjects …

Applications Of Non-Invasive Neuromodulation For The Management Of Disorders Related To Covid-19, Abrahão Fontes Baptista, Adriana Baltar, Alexandre Hideki Okano, Alexandre Moreira, Ana Carolina Pinheiro Campos, Ana Mércia Fernandes, André Russowsky Brunoni, Bashar W. Badran, Clarice Tanaka, Daniel Ciampi De Andrade, Daniel Gomes Da Silva Machado, Edgard Morya, Eduardo Trujillo, Jaiti K. Swami, Joan A. Camprodon, Katia Monte-Silva, Katia Nunes Sá, Isadora Nunes, Juliana Barbosa Goulardins, Marom Bikson, Pedro Sudbrack-Oliveira, Priscila De Carvalho, Rafael Jardim Duarte-Moreira, Rosana Lima Pagano, Samuel Katsuyuki Shinjo, Yossi Zana

Publications and Research

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19.

Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders.

Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders.

Results: …

Diagnosing And Managing Post-Stroke Aphasia, Shannon M. Sheppard, Rajani Sebastian

Communication Sciences and Disorders Faculty Articles and Research

Introduction: Aphasia is a debilitating language disorder and even mild forms of aphasia can negatively affect functional outcomes, mood, quality of life, social participation, and the ability to return to work. Language deficits after post-stroke aphasia are heterogeneous.

Areas covered: The first part of this manuscript reviews the traditional syndrome-based classification approach as well as recent advances in aphasia classification that incorporate automatic speech recognition for aphasia classification. The second part of this manuscript reviews the behavioral approaches to aphasia treatment and recent advances such as noninvasive brain stimulation techniques and pharmacotherapy options to augment the effectiveness of …

Role Of Cerebral Vasculature And Effect Of Circulating Exosomes In Propagation Of Systemic Inflammatory Responses Into The Central Nervous System, Mahesh Chandra Kodali

Theses and Dissertations (ETD)

Sepsis-associated encephalopathy (SAE) is an acutely progressing brain dysfunction induced by systemic inflammation. The mechanism of initiation of neuroinflammation during SAE, which ultimately leads to delirium and cognitive dysfunction, remains elusive. The goal of this project was to study the molecular events of SAE to capture its onset and progression into the central nervous system (CNS), and further identify the cellular players involved in mediating acute inflammatory signaling. Gene expression profiling on the cerebral vessels isolated from the brains of the mice treated with peripheral lipopolysaccharide (LPS) revealed that the cerebral vasculature responds within minutes to acute systemic inflammation by …

Perampanel-Induced Cataplexy In A Young Male With Generalized Epilepsy, Kelsey Kenaan, Mohsin Zafar, Ronnie Bond, Barbara L. Gracious

HCA Healthcare Journal of Medicine

Perampanel (Fycompa) is a newer anti-epileptic drug believed to exert its effects in the central nervous system by inhibiting post-synaptic glutamate receptors. However, the precise therapeutic mechanism is unknown. The most common neuropsychiatric side effect is affective dysregulation; there are also reports of psychosis. We describe a 32 year old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, after Perampanel was added to his antiepileptic medications. Perampanel administration was temporarily withheld, and subsequently on restarting, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in …

Aci-35 And Aadvac1 Active Immunotherapy As Preventative Treatment Options For Chronic Traumatic Encephalopathy, Emily C. Boehlein

Selected Honors Theses

One of the most common, as well as one of the most dangerous injuries amongst athletes today is mild traumatic brain injury (mTBI), commonly known as concussion. Aside from physical symptoms such as nausea, dizziness, and headaches; concussions have can have longterm effects on brain physiology. A common neurological disease that can result from multiple concussions is Chronic Traumatic Encephalopathy (CTE), characterized by symptoms such as severe depression, anxiety, confusion, and aggression; amongst others.1 On the cellular level, CTE is classified by a unique pathway that leads to the hyperphosphorylation of tau protein and subsequent clumping of tau-containing neurofibrillary tangles …

A Summary Of Current Research Into Neurodegenerative Disorders Using Drosophila Melanogaster, Chase Cortese

Honors Theses

Neurodegenerative disorders such as Alzheimer’s disease are characterized by damage to neural cells causing widespread neurological deficits. Historically, these diseases were deemed as inevitable declines in cognitive and neurological function that occurred with aging. Recent research has revealed, however, that these diseases have molecular bases allowing potential clinical intervention. The groundbreaking discoveries have been made using differing model organisms, which can replicate the phenotype and physiological cause of these disorders. One major model organism that has been used is the fruit fly, Drosophila melanogaster. They have served various roles in elucidating gene pathways and neurophysiological bases seen in these diseases. …

Effects Of Neuronic Shutter Observed In The Eeg Alpha Rhythm, Kevin E. Alexander, Justin R. Estepp, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

The posterior alpha (α) rhythm, seen in human electroencephalogram (EEG), is posited to originate from cycling inhibitory/excitatory states of visual relay cells in the thalamus. These cycling states are thought to lead to oscillating visual sensitivity levels termed the “neuronic shutter effect.” If true, perceptual performance should be predictable by observed α phase (of cycling inhibitory/excitatory states) relative to the timeline of afferentiation onto the visual cortex. Here, we tested this hypothesis by presenting contrast changes at near perceptual threshold intensity through closed eyelids to 20 participants (balanced for gender) during times of spontaneous α oscillations. To more accurately and …

Acute And Chronic Dosing Of A High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody In Mice, Demi M. Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C. Zambon, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as brain drug-delivery vectors has revealed the effect of dosing regimen, valency, and affinity on brain uptake, TfR expression, and Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous dosing in mice. The effects of a high-affinity bivalent TfRMAb with a murine constant region, without a fusion partner, following extravascular dosing in mice are, however, not well characterized. Here we elucidate the plasma pharmacokinetics and safety of a high-affinity bivalent …

Conditional Loss Of Engrailed 1/2 In Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity And Decreases Overall Variability Of Eupneic Respiration, Angela P. Taylor

Theses and Dissertations (ETD)

Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but investigation into cerebellar involvement in eupneic breathing has been inconclusive. Given the view of the cerebellum (CRB) as a temporally coordinating structure, any investigation into the CRB during respiration must evaluate rhythm and variability of the respiratory sequence. In this study, we chose an elegant model of cerebellar neuropathology, Atoh1-En1/2 CKO, where mutant animals have conditional loss of the developmental patterning gene Engrailed 1/2 in rhombic lip-lineage neurons and exhibit a proportional scaling-down of neuron number in hypoplastic lobules of the CRB. We utilized whole-body unrestrained plethysmography …

Literature Review On Drosophila Research In Parkinson’S Disease, Maryann Jaquith

Honors Projects

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases. It is characterized by its main symptom of a tremor that usually starts in one limb. The four cardinal symptoms of PD are tremor, rigidity, bradykinesia, and postural instability. While the four cardinal symptoms are all motor symptoms there are non-motor symptoms for PD which include cognitive changes, sleeping disorders, lightheadedness, early satiety, and mood disorders. PD is characterized by dopaminergic (DA) neuron loss and the accumulation of Lewy bodies (LB) which are predominantly composed of α-synuclein (α-Syn) protein.

α-Syn is a protein found abundantly in the brain. It …

Predicting Amyloid Burden To Accelerate Recruitment Of Secondary Prevention Clinical Trials, O. Langford, R. Raman, R. A. Sperling, J. Cummings, C.-K. Sun, G. Jimenez-Maggiora, P. S. Aisen, M. C. Donohue, Trc-Pad Investigators

School of Medicine Faculty Publications

Background: Screening to identify individuals with elevated brain amyloid (Aβ+) for clinical trials in Preclinical Alzheimer’s Disease (PAD), such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) trial, is slow and costly. The Trial-Ready Cohort in Preclinical/Prodromal Alzheimer’s Disease (TRC-PAD) aims to accelerate and reduce costs of AD trial recruitment by maintaining a web-based registry of potential trial participants, and using predictive algorithms to assess their likelihood of suitability for PAD trials. Objectives: Here we describe how algorithms used to predict amyloid burden within TRC-PAD project were derived using screening data from the A4 trial. Design: We apply machine …

A Study Of The Relationship Between Uric Acid And Substantia Nigra Brain Connectivity In Patients With Rem Sleep Behavior Disorder And Parkinson’S Disease, Timothy M. Ellmore, Jessika Suescun, Richard J. Castriotta, Mya C. Schiess

Publications and Research

Low levels of the natural antioxidant uric acid (UA) and the presence of REM sleep behavior disorder (RBD) are both associated with an increased likelihood of developing Parkinson’s disease (PD). RBD and PD are also accompanied by basal ganglia dysfunction including decreased nigrostriatal and nigrocortical resting state functional connectivity. Despite these independent findings, the relationship between UA and substantia nigra (SN) functional connectivity remains unknown. In the present study, voxelwise analysis of covariance was used in a cross-sectional design to explore the relationship between UA and whole-brain SN functional connectivity using the eyes-open resting state fMRI method in controls without …

Nutraceutical Potential For Alzheimer's Disease Treatment, Alex Gewecke

Undergraduate Research Journal

Alzheimer’s disease (AD) is a progressive disorder involving buildup of excessive amounts of proteins such as beta amyloid in the brain that leads to memory loss, inability to perform daily functions, and an early death. By 2060, the number of cases is forecast to nearly triple current numbers. Age is the primary risk factor for AD and no new drugs have been approved since 2003. Nutraceuticals, a broad category of substances that can be utilized for both medicinal and nutritional purposes may be able to help, which is why they are being more widely researched. Overall, a number of attempts …

Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca, Natasha Hesketh

Graduate School of Biomedical Sciences Theses and Dissertations

Calcium signaling is particularly important for neuronal function. Neurons utilize a wide range of calcium-binding proteins. Dysregulation of such proteins is linked to neurodegeneration. Neurocalcin delta (NCALD), hippocalcin (HPCA), and S100B are calcium sensors that are expressed in the hippocampus, a brain region essential to memory and severely damaged in Alzheimer’s disease (AD). Despite the potential importance of these proteins, we do not fully understand the physiological significance of their relationship. Because NCALD and HPCA are known to interact with S100B, we hypothesized that the loss of S100B affects NCALD and HPCA localization, and therefore electrical properties, of hippocampal neurons. …

The Influence Of Cerebellar Transcranial Direct Current Stimulation On Motor Function In Parkinson’S Disease, Lidio Lima De Albuquerque

UNLV Theses, Dissertations, Professional Papers, and Capstones

Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disorder. PD is characterized by dopaminergic cell loss in the substantia nigra pars compacta, which leads to a reduction in dopamine in the striatum. These physiological mechanisms lead to a number of motor impairments such as bradykinesia, rigidity, tremor, and postural instability that severely limit the ability of individuals with PD to perform many essential daily living activities. Although current pharmacological, surgical, and physical exercise treatment approaches are valuable they are either only mildly effective, expensive, or associated with a variety of side effects. Therefore, …

Investigation Of The Role Of Heparin-Binding Pocket In Amyloid Fibrils Formation Of Fgf-1, I Gusti Ayu Agung Septiari

Graduate Theses and Dissertations

Human acidic fibroblast growth factor (aFGF/hFGF-1) is one of the promising molecules to be investigated to generate an in-depth understanding of the pathological mechanism of Alzheimer's disease (AD) neurodegenerative disorder characterized by the presence of amyloid fibrils. Some in vivo and human brain tissue studies proved the correlation of high-level expression of FGF-1-induced neuroinflammation and the occurrence of AD. The presence of amyloid fibrils as a hallmark of AD can be related to the generic property of the proteins to form amyloid fibrils; High level of FGF-1, in this case, may contribute to the formation of amyloid fibrils. As a …

Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

"Alzheimer’s disease (AD) is the sixth leading cause of death in the United States with approximately 5.8 million Americans currently living with AD. Due to the lack of a disease modifying treatment for AD and the aging baby boomer generation, this number is projected to grow to 13.8 million by 2050 (Gaugler et al., 2019). Amyloid-beta (Aβ) plaque accumulation, one of the major pathological hallmarks of AD, can begin > 20 years before clinical symptoms of AD. By the time AD is clinically diagnosed, neuronal loss and neuropathological lesions (Aβ plaques and tau tangles) have already occurred in many brain regions …

Two Nights Of Recovery Sleep Restores Hippocampal Connectivity But Not Episodic Memory After Total Sleep Deprivation, Ya Chai, Zhuo Fang, Fan Nils Yang, Sihua Xu, Yao Deng, Andrew Raine, Jieqiong Wang, Meichen Yu, Mathias Basner, Namni Goel, Junghoon J. Kim, David A. Wolk, John A. Detre, David F. Dinges, Hengyi Rao

Publications and Research

Sleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal …

Clinical And Basic Research Investigations Into The Long‐Term Effects Of Prenatal Opioid Exposure On Brain Development, Taylor Boggess, W. Chris Risher

Biomedical Sciences

Coincident with the opioid epidemic in the United States has been a dramatic increase in the number of children born with neonatal abstinence syndrome (NAS), a form of withdrawal resulting from opioid exposure during pregnancy. Many research efforts on NAS have focused on short‐term care, including acute symptom treatment and weaning of the infants off their drug dependency prior to authorizing their release. However, investigations into the long‐term effects of prenatal opioid exposure (POE) on brain development, from the cellular to the behavioral level, have not been as frequent. Given the importance of the perinatal period for human brain development, …

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …

Regulating Neuronal Growth With Structurally Defined Glycans, Gabriella D. Hartman

Honors Theses

Chondroitin sulfate proteoglycans (CSPGs) and keratan sulfate proteoglycans (KSPGs) play an important role in neural development. Aggrecan, a CSPG, operates in the neural extracellular matrix where it negatively regulates neurite outgrowth to prevent aberrant process formation. Unfortunately, this aggrecan or CSPG-rich/KSPG-rich barrier can also prevent neuronal regeneration, which contributes to the inability to repair brain and spinal cord injuries. Removal of CSPGs and KSPGs has been shown to increase neurite outgrowth. We extend these findings by testing the ability of structurally-defined glycans to outcompete aggrecan and allow neurite outgrowth. Our overall goal is to determine if there is a particular …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

Depressed Neuromuscular Transmission Causes Weakness In Mice Lacking Bk Potassium Channels, Xueyong Wang, Steven R.A. Burke, Robert J. Talmadge, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Mice lacking functional large-conductance voltage- and Ca2+-activated K+ channels (BK channels) are viable but have motor deficits including ataxia and weakness. The cause of weakness is unknown. In this study, we discovered, in vivo, that skeletal muscle in mice lacking BK channels (BK−/−) was weak in response to nerve stimulation but not to direct muscle stimulation, suggesting a failure of neuromuscular transmission. Voltage-clamp studies of the BK−/− neuromuscular junction (NMJ) revealed a reduction in evoked endplate current amplitude and the frequency of spontaneous vesicle release compared with WT littermates. Responses to 50-Hz stimulation indicated a reduced probability of vesicle release …

Synaptic Protein Expression In Human Postmortem Brain Tissue Of Autism Spectrum Disorder, Alexandra Duggan

Undergraduate Honors Theses

It is estimated that one in 59 children in the US are affected by autism spectrum disorder (ASD). ASD is distinguished by social and communication deficits that can be displayed throughout a wide range of severity. This resulting spectrum of behaviors observed in ASD suggests that a complex etiology is involved. Previous studies have shown a genetic susceptibility to autism including paternal age, twin and sibling concordance. Genetic sequencing of those affected as well as first order relatives have identified alterations in genes associated with neuronal synaptic communication. However, very little information is available regarding the pathophysiology of synapses in …

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …

Adverse Aftereffects Of Methotrexate As Chemotherapy On Cognitive Deficits In Rat Models, Jubin Kang

Senior Honors Theses

Patients with acute lymphoblastic leukemia have a high five-year survival rate thanks to methotrexate (MTX). However, cognitive side effects are reported, characterized as chemo brain. The study investigated if impulsiveness is part of the aberrant cognitive functions after being exposed to MTX in the early stage of physical development. Adolescent rats were injected with either phosphate-buffered saline (PBS) or MTX. The novel object recognition (NOR) task was conducted a month after the injections to measure the memory deficits. The discounting task was performed after the rats completed training on a fixed-ratio one schedule for both levers. The NOR test showed …

Anxiety In Alzheimer's Disease, Zachary Cooper

Senior Honors Theses

Researchers familiar with Alzheimer’s disease have often noted the presence of comorbid anxiety symptomatology. Likewise, the occurrence of anxiety before the development of Alzheimer’s disease has been prevalent enough to warrant attention. This review seeks to elaborate on the pathophysiology behind these two conditions, and to accentuate overlapping aspects that promote a causal relationship between these two pathologies on the macroscopic and cellular levels. Subsequent evidence will show that these pathologies are not independent of each other, and that cellular mechanisms of pathology hint at their interrelatedness. Areas requiring further research that would clarify the relationship between Clinical Anxiety and …

Covid 19 What You Need To Know, Dawn P. Wooley, Giancarlo Mariani, Craig Woolley, Laura M. Luehrmann

Neuroscience, Cell Biology & Physiology Faculty Publications

This is the first presentation in the new Shelter-in-Place lecture series. This first lecture is two-fold. First, it covers the basics of the COVID-19 virus including: how it spreads, possible origin, and other pertinent information. This portion of the presentation was followed by an overview of the international recruitment efforts in response to the virus, including: student perspectives, recruitment methods, and other important information.