Nervous System Diseases Commons^™

Exploring The Experience Of Sexuality And Gender During The Healthcare Transition Of The Youth With Cerebral Palsy, Umma Salma

Electronic Thesis and Dissertation Repository

Background: Transition from the pediatric to adult health care system is an important phase of healthcare for youth with cerebral palsy (CP). Sexuality and gender are two very important components of health that are mostly ignored in the healthcare transition process. It is possible that health care providers only see a client’s disability, and therefore, key aspects of sexuality and gender diversity may be ignored, or deemed irrelevant as a result of their disability status. Therefore, the purpose of our study is to explore how gender and sexuality may influence the experience of health care transition for youth with cerebral …

Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas

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Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after …

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

Electronic Thesis and Dissertation Repository

While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …

Effect Of Levodopa On Eeg Connectivity In Parkinson's Patients, Sepehr Torab Parhiz

Electronic Thesis and Dissertation Repository

Levodopa is a dopamine replacement medication administered to patients with Parkinson’s disease (PD) to alleviate their motor symptoms. However, its long-term use can cause adverse side effects, including involuntary motor movements. We studied 16 PD patients before and after taking Levodopa based on resting-state electroencephalography (EEG) recordings to determine how Levodopa affects the functional connectivity of their brain networks. We used several metrics from graph theory, in particular the minimum spanning tree (MST) metric, and analyzed how they change after subjects take Levodopa. We observed significant changes in the lower alpha band toward a more path-like and less globally efficient …

Spinal Excitability Changes Following Sensory Electrical Stimulation Of The Forearm, Devin K. Box

Electronic Thesis and Dissertation Repository

Sensory electrical stimulation can be used to suppress tremor in Parkinson’s disease. This study investigated the central mechanism underlying this suppression in healthy participants. Reciprocal inhibition (RI) of the wrist flexors before and after a session of sensory electrical stimulation (SES) applied to the antagonistic extensor muscles was assessed using electromyography. It was hypothesized that a 15-minute session of SES, rated by participants as a 3 on a 0-10 pain scale, would produce an increase in RI. Seven of the 18 participants experienced an increase in RI at 0-5 minutes post stimulation, which returned to baseline at 10-15 minutes. The …

Exploring The Burden Experiences Of Care Partners For People With Parkinson's Disease Living In Southwestern Ontario, Lisa A. Moszczynski

Electronic Thesis and Dissertation Repository

This thesis quantitatively explored the burden experiences of care partners of people with Parkinson’s Disease in Southwestern Ontario. Thirty-five complete responses (27 females, 8 males) and three partial responses to an online survey were obtained. The survey included a demographic section (41 items), two measures of burden and a quality of life measure. Care partner data were stratified based on Zarit Burden Inventory scores for analysis. Of the Little to No Burden (n=4), Mild Burden (n=15), Moderate Burden (n=8), and Severe Burden (n=4) groups, weekly hours spent on care duties and years in the care partner role were similar. The …

Cardiovascular Effects Of Exercise And Use Of Abdominal Binder In Patients Of Parkinson’S Disease With Orthostatic Hypotension, Faizan Ahmed

Electronic Thesis and Dissertation Repository

Orthostatic hypotension (OH) is a common manifestation of autonomic dysfunction in Parkinson’s Disease. It can adversely affect a patient’s functional capacity, exercise tolerance and quality of life, while increasing the risk of falls, cerebrovascular disease and overall mortality. Use of an abdominal binder (AB) can help counter OH; however, this has not been sufficiently studied in patients with Parkinson’s Disease (PwPD). Moreover, the hemodynamic effects of upper and lower extremity exercise are unclear in PwPD with OH. Although OH can impair the cerebral circulation, the consequences on the cerebral hemodynamics of wearing an AB or performing exercise are unknown in …

An Approach For The In-Vivo Characterization Of Brain And Heart Inflammation In Duchenne Muscular Dystrophy, Joanne Tang

Electronic Thesis and Dissertation Repository

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss—notably within muscles and CNS neurons. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies improved life expectancy, but this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, there is an increasing need to both better understand and track disease pathophysiology in the dystrophic heart and brain prior to onset of severe degenerative symptoms. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration, however chronic neuroinflammation’s role is largely unknown in …

Assessment Of Intrinsic Hand Neuromuscular Physiology, Philemon Tsang

Electronic Thesis and Dissertation Repository

Alterations to the peripheral nervous system and neuromuscular physiology may impact hand function in a typical or clinical population, such as individuals with ulnar neuropathy. The mechanisms that influence these positive and negative changes are still not well understood. The three studies within my thesis aim to validate the reliability of decomposition-based quantitative electromyography (DQEMG) measurements and explore the changes in intrinsic hand neuromuscular physiology in a typical aging population and individuals recovering from a surgical intervention for severe ulnar neuropathy.

The purpose of the first study was to determine the test-retest reliability of near-fibre (NF) jiggle, a measure of …

Optimizing Fecal Microbiota Transplantations For Therapeutic Use Beyond Clostridioides Difficile Infection, Laura J. Craven

Electronic Thesis and Dissertation Repository

Fecal microbiota transplantation (FMT) is an emerging and effective therapy for the treatment of recurrent Clostridioides difficile infection. Members of the gut microbiome have been implicated in other diseases and FMT has been considered as a potential therapy. Two such conditions include non-alcoholic fatty liver disease (NAFLD) and multiple sclerosis (MS), both of which involve increased small intestinal permeability believed to contribute to the development and disease progression. One of the aims of this project was to determine if FMT could be safely used in patients with NAFLD and MS to improve health outcomes. Before starting the clinical studies, optimal …

Investigation Of Visual Perceptions In Parkinson's Disease And The Development Of Disease Monitoring Software, Matthew Bernardinis

Electronic Thesis and Dissertation Repository

Non-motor Parkinson’s Disease (PD) symptoms are substantial factors of PD arising throughout disease stages, yet their diagnosis and monitoring remain a challenge. Sensory abnormalities in PD occur across sensory systems and disease stages, contributing to disease-related impairments. However, the extent of symptoms is unknown, with inadequate monitoring and treatment options furthering disease management difficulties. The current work studies movement-independent visual perceptions of time, displacement and velocity in PD patients across disease stages using levodopa, deep brain stimulation (DBS), or no PD therapy. Perceptual tasks were conducted using a computer-generated graphical device designed with a focus on simplicity and flexibility. Perception …

Differentiating The Substantia Nigra And Ventral Tegmental Area In Early-Stage Parkinson's Disease Using Iron Imaging, Erind Alushaj

Electronic Thesis and Dissertation Repository

Excessive midbrain iron accumulation in Parkinson’s Disease (PD) contributes to degeneration of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Despite this understanding, there are no validated PD biomarkers. Magnetic resonance imaging (MRI) can localize and quantify brain iron for diagnosis of PD. Seventeen early-stage PD patients and twenty-one controls were scanned at 3T and 7T MRI. Using quantitative susceptibility mapping (QSM) and R2* relaxometry, we analyzed the average iron content in the SNc, substantia nigra pars reticulata (SNr), and VTA. QSM detected significantly higher SNc iron content in PD patients compared to controls at both …

Improving The Assessment And Understanding Of Neurogenic Orthostatic Hypotension, Jacquie Baker

Electronic Thesis and Dissertation Repository

Neurogenic Orthostatic Hypotension (NOH) is a cardinal feature of autonomic failure. Patients with NOH experience a persistent and consistent drop in blood pressure when standing due to failure of the autonomic nervous system to reflexively increase sympathetic outflow. NOH affects individuals worldwide, presenting as both a primary feature (i.e. Multiple Systems Atrophy, Pure Autonomic Failure) and secondary to several common disorders including diabetes and Parkinson’s Disease. However, there are still several gaps in our overall understanding and assessment of patients with NOH. Therefore, the six studies presented in this thesis aimed to address some of these gaps in our current …

Ultra-High Field Magnetic Resonance Imaging For Stereotactic Neurosurgery, Jonathan Lau

Electronic Thesis and Dissertation Repository

Stereotactic neurosurgery is a subspecialty within neurosurgery concerned with accurate targeting of brain structures. Deep brain stimulation (DBS) is a specific type of stereotaxy in which electrodes are implanted in deep brain structures. It has proven therapeutic efficacy in Parkinson’s disease and Essential Tremor, but with an expanding number of indications under evaluation including Alzheimer’s disease, depression, epilepsy, and obesity, many more Canadians with chronic health conditions may benefit. Accurate surgical targeting is crucial with millimeter deviations resulting in unwanted side effects including muscle contractions, or worse, vessel injury. Lack of adequate visualization of surgical targets with conventional lower field …

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 …

Limbic System Involvement In Absence Seizures, Rukham Ajaz

Electronic Thesis and Dissertation Repository

Absence epilepsy is characterized by brief spells of absent stare and spike wave discharges (SWDs), generally believed to be generated by a thalamocortical network. Our lab showed that hippocampal neuronal firings were synchronous with SWDs in a gamma butyrolactone (GBL) model of absence epilepsy in rats (Arcaro et al., 2016). We hypothesize that, in a GBL model of absence seizures, 30-400 Hz oscillations in the spontaneous local field potentials (LFPs) in the hippocampus and other parts of limbic system (amygdala and nucleus accumbens) are phase modulated by SWDs, and this modulation is mediated through nucleus reuniens of midline thalamus (RE). …

The Brain-Heart Connection: Establishment Of A Novel Rodent Model Of Focal Insular Ischemic Stroke To Examine The Pathophysiology Of Stroke-Induced Heart Injury, Victoria Thorburn

Electronic Thesis and Dissertation Repository

The neurological influence of ischemic stroke in the generation of stroke-induced heart injury (SIHI) has been acknowledged for several years. However, pathophysiological mechanisms remain uncertain. Clinically, it is hypothesized that stroke involving the insular cortex (IC) initiates SIHI, since the IC controls autonomic regulation of cardiovascular function. Yet, given the high prevalence of shared risk factors between ischemic stroke and cardiovascular disorders, mechanistic conclusions from clinical studies are largely speculative. We therefore sought to establish a novel rodent model of focal insular ischemic stroke, used to evaluate chronic outcomes of SIHI. Focal ischemic stroke was induced into the right or …

Evaluating White Matter Changes And Executive Function In Rat Models Of Mediodorsal Thalamic Stroke And Neuroinflammation, Jessica Garabon

Electronic Thesis and Dissertation Repository

Recent literature has supported a relationship between vascular disease and its role in the progression of cognitive impairment. Previous studies have demonstrated that white matter inflammation (WMI) in the brain is a common pathological outcome following stroke. Moreover, WMI has been shown to be the strongest predictor of cognitive decline following stroke. Finally, previous work in our lab has demonstrated, using a rodent model of striatal stroke, that WMI is correlated with post-stroke cognitive impairment. The current study aimed to further investigate the role of WMI in post-stroke cognitive impairment by utilizing a mediodorsal thalamic (MD) stroke model in the …

Role Of The Dorsal Striatum In Learning And Decision Making, Nole M. Hiebert

Electronic Thesis and Dissertation Repository

The striatum, the input region of the basal ganglia, has been shown to mediate many cognitive functions. The striatum itself can be functionally segregated into dorsal (DS) and ventral striatum (VS). For more than 60 years, DS has been reported to mediate stimulus-response learning, though evidence has been accruing pointing to a role in decision making. These literatures have been growing independently and an aim of this thesis was to bridge these two bodies of knowledge. We directly investigated the role of DS in stimulus-response learning versus decision making using functional magnetic resonance imaging (fMRI) in patients with Parkinson’s disease …

Brain Networks In People After A First Unprovoked Seizure, Kristin M. Ikeda

Electronic Thesis and Dissertation Repository

Background: A single unprovoked seizure occurs in up to 10% of the population. Some develop epilepsy, but the majority do not. Brain network changes are observed in people with epilepsy, but it is unknown if they are present after this first seizure. This study examines network connectivity after the first seizure to determine if any changes exist.

Methods: Twelve patients after a single unprovoked seizure and twelve age- and sex-matched healthy controls were recruited. All underwent 7T resting-state fMRI scanning. Whole brain and limbic, default mode and salience network connectivity were analyzed with graph theory.

Results: Baseline characteristics were similar …

Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic glycolysis …

Hsp90 And Its Co-Chaperones Modify Tdp-43 Localization, Aggregation, And Toxicity, Lilian T. Lin

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with protein misfolding and protein aggregation. In particular, the TAR DNA-binding protein (TDP-43) is often found in the pathological inclusions in neurons of ALS patient brains and spinal cords. This phenomenon is known as TDP-43 proteinopathy, the mislocalization of TDP-43 from the cell nucleus and the formation of aggregates in the cytoplasm. Numerous mutations in the gene encoding TDP-43 have also been linked to familial cases of ALS (fALS) and cause TDP-43 proteinopathy. This study attempts to decipher how the molecular chaperone Hsp90 and its co-chaperones, Aha1, Sti1, and Cdc37, modulate …

Behavioural Inflexibility And White Matter Inflammation In An Aged Happ Rat With Subcortical Stroke, Aaron M. Regis

Electronic Thesis and Dissertation Repository

The interactions between Alzheimer’s disease (AD) and ischemic stroke pathology are of key interest in the development of post-stroke cognitive decline. While clinical and experimental studies have suggested an interaction, the mechanisms whereby these conditions interact to worsen cognition haven’t been fully revealed. This study aimed to combine rodent models of AD and stroke in an aged rat and assess the behavioural and histological outcomes. An injection of endothelin-1 (ET-1), a potent vasoconstrictor into the basal ganglia of a rat with human amyloid precursor protein (hAPP) overexpression (F344Tg) was followed up 3 months later to assess behavioural flexibility, memory and …

Is Online Motor Control Really Impaired In Parkinson's Disease?, Kate E. Merritt

Electronic Thesis and Dissertation Repository

Patients with Parkinson’s disease (PD) are thought to be selectively impaired in consciously-mediated online automatic motor control, whereas the ability to perform subconscious online adjustments remains intact. This present study evaluates the hypothesis that the previously alleged deficits in online motor control in PD are not due to the consciousness of the correction, but rather are attributable to aspects of the prior experimental designs disproportionately penalizing patients for PD-related bradykinesia. Here, we implemented a modified traditional double-step paradigm to investigate consciously-mediated online motor control in PD, in a manner that would be unconfounded by disease-related bradykinesia. Further, we investigated the …

Characterization And Personalization Of Botulinum Toxin Type A Therapy For Upper Limb Tremor In Parkinson Disease And Essential Tremor Patients Using Multi-Sensor Kinematic Technology, Olivia Samotus

Electronic Thesis and Dissertation Repository

Tremor commonly affects the upper extremities in essential tremor (ET) and Parkinson disease (PD) patients where many experience functional disability and ultimately seek therapy. As ET and PD tremor features overlap and clinical assessment is challenging due to its highly complex nature, misdiagnosis is common resulting in unsuitable therapies and prognosis. Current treatment options for ET and PD tremor include pharmacotherapy, focal therapy with botulinum toxin type A (BoNT-A) injections, and surgical interventions which provide modest relief of tremor. However, such therapies are commonly associated with significant adverse events and lack long-term efficacy and tolerability. Hence lack of standardized, objective …

The Rho Gtpases Rac1, Cdc42, And Rhoa Regulate App Transport To Lysosomes And Aβ Production, Justin K. Chiu .

Electronic Thesis and Dissertation Repository

Alzheimer’s Disease (AD) is characterized by Beta-Amyloid (Aβ) plaques within the brain. Aβ peptides are produced by the cleavage of Amyloid Precursor Protein (APP). Our lab has previously discovered a novel pathway for APP internalization mediated by ADP-ribosylation factor 6 (Arf6). This pathway resembles macropinocytosis, transporting cell surface APP directly to lysosomes, a possible site for Aβ production. We set out to characterize the effectors downstream of Arf6. In SN56 and N2A cells we co-transfected HA-tagged APP (to label cell-surface APP) with compartment markers, to visualize APP trafficking. We used dominant negative and constitutively active mutants, pharmacological inhibitors, and siRNA …

Towards The Development Of A Wearable Tremor Suppression Glove, Yue Zhou

Electronic Thesis and Dissertation Repository

Patients diagnosed with Parkinson’s disease (PD) often associate with tremor. Among other symptoms of PD, tremor is the most aggressive symptom and it is difficult to control with traditional treatments. This thesis presents the assessment of Parkinsonian hand tremor in both the time domain and the frequency domain, the performance of a tremor estimator using different tremor models, and the development of a novel mechatronic transmission system for a wearable tremor suppression device. This transmission system functions as a mechatronic splitter that allows a single power source to support multiple independent applications. Unique features of this transmission system include low …

Intracellular Trafficking Governs The Processing Of The Amyloid Precursor Protein And The Secretion Of Beta-Amyloid, Joshua Hoi Ki Tam

Electronic Thesis and Dissertation Repository

One of the hallmarks of Alzheimer’s disease (AD) is the pathological accumulation of β-amyloid (Aβ) in the brains of AD patients. Oligomeric and fibrillar aggregates of Aβ have been shown to be neurotoxic to neurons and hippocampal slices. Therefore, limiting Aβ production is an important area of research in order to delay or stop AD progression. Aβ is produced by amyloidogenic cleavage of amyloid precursor protein (APP). Amyloidogenic cleavage requires ectodomain removal by β-secretase and intramembrane γ-cleavage by γ-secretase to release Aβ products ranging from 38-43 residues. Work from our lab has shown that APP and γ-secretase are resident proteins …