Medicine and Health Sciences Commons^™

Investigating The Relationship Between Subcortical And Cortical Auditory Processing, Sonia Varma

Electronic Thesis and Dissertation Repository

The auditory system is highly integrative, with feedforward and feedback connections from periphery to cortex (and stages in between). In order to understand how the different levels of the human auditory system interact, it is necessary to simultaneously measure responses from multiple auditory levels. A novel stimulus was paired with electroencephalography (EEG) in 29 young, normal-hearing participants (17-34 years) to examine interactions among stages of the auditory pathway. Temporal regularity was manipulated by continuously accelerating and decelerating the rate of a click-train stimulus (i.e., ~3.5 Hz frequency modulation of the click rate). Adaptation of the brainstem (cochlear nucleus and inferior …

Neurodevelopmental Outcomes Of Infantile Hydrocephalus: An Fmri Case Study, Ikhlas Ahmed Hashi

Electronic Thesis and Dissertation Repository

Ventricle dilatation caused by infantile hydrocephalus may result in extensive damage of the posterior cortex (parietal and occipital lobes). We hypothesize that pathological changes in the development of the posterior cortex can be linked to non-verbal learning disabilities in children with previous infantile hydrocephalus. This case study will investigate the neurodevelopmental outcomes of 3 treated hydrocephalus patients, when compared to a group of healthy control children (n = 12). Within the hydrocephalus group, patients displayed differences in non-verbal test performance as well as parietal brain activation during an fMRI number comparison task. We associated these differences with clinical variables such …

Resedent Study- Reducing Sedentary Behaviour May Slow Cognitive Decline In Older Adults With Mild Cognitive Impairment: A Pilot Study, Kirsten B. Dillon

Electronic Thesis and Dissertation Repository

Physical activity (PA) has been shown to slow down dementia. Unfortunately, older adults spend most of their day in sedentary behaviours (SB). Breaking up prolonged bouts of sitting with intermittent bouts of light intensity PA may reduce glycemic variability in the brain; potentially mitigating cognitive decline. This study investigated how interrupting SB with 10 min bouts of light intensity PA 3x a day would affect mild to moderate cognitive impairment progression (primary outcome) in older adults residing in an assisted living facility. Participants (n=25) were assigned in clusters into a two arm 10-week single site pilot randomized controlled trial. Secondary …

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 …

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 …

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 …

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 …

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 …

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 …

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that …

A Diffusion Tensor Imaging Study Of Motor Fibre Path Integrity And Overt Responsiveness In Disorders Of Consciousness, Clara A. Stafford

Electronic Thesis and Dissertation Repository

This study investigated the relationship between motor thalamo-cortico-cerebellar fibre path integrity and overt responsiveness in patients with disorders of consciousness (DOC). Additionally, we investigated the potential of imaging these motor tracts at ultra-high fields. Study I and II aimed to map the white matter connections of motor execution fibres in DOC patients. Our results showed significant reductions in motor fibre path integrity across DOC diagnostic categories. Study III and IV aimed to develop a 7T MRI Diffusion Tensor Imaging (DTI) sequence. We optimized this sequence to image motor fibre paths in DOC patients. We concluded that, in healthy controls, probabilistic …

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 …

Communicating Through A Brain-Computer Interface: Towards The Assessment Of Quality Of Life In Minimally Conscious And Covertly Aware Vegetative State Patients, Jasmine Tung

Electronic Thesis and Dissertation Repository

Neuroimaging has been utilized to establish communication, using a brain-computer interface, with select patients with severe brain injuries and profound communication impairments. Due to the severe injuries sustained by these patients, traditional techniques used to develop quality of life instruments cannot be used. The Aware Study used a novel approach to establish the key dimensions for assessing the quality of life of patients who can only communicate using this sophisticated technology. Consensus methodology was employed, with the assistance of a multidisciplinary panel of experts, to collectively decide which dimensions are essential for the inclusion in a quality of life instrument …

The Neuroprotective Effects Of Endurance Training On The Aging Brain, Katelyn Norton

Electronic Thesis and Dissertation Repository

Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known and may relate to alterations in brain structure (e.g. cortical atrophy) and/or altered neural function, particularly in regions related to the cortical autonomic network, namely, the medial prefrontal cortex (MPFC), insula cortex (IC), and hippocampus (HC). Exercise exerts beneficial effects on brain structure and, in the case of cognition, neurologic function; however, how exercise affects regions of the brain related to autonomic function are not known. This thesis tested …

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 …

Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad

Electronic Thesis and Dissertation Repository

PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT_2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the CRFR1 PDZ-binding motif. …

Unravelling The Subfields Of The Hippocampal Head Using 7-Tesla Structural Mri, Jordan M. K. Dekraker

Electronic Thesis and Dissertation Repository

Probing the functions of human hippocampal subfields is a promising area of research in cognitive neuroscience. However, defining subfield borders in Magnetic Resonance Imaging (MRI) is challenging. Here, we present a user-guided, semi-automated protocol for segmenting hippocampal subfields on T2-weighted images obtained with 7-Tesla MRI. The protocol takes advantage of extant knowledge about regularities in hippocampal morphology and ontogeny that have not been systematically considered in prior related work. An image feature known as the hippocampal ‘dark band’ facilitates tracking of subfield continuities, allowing for unfolding and segmentation of convoluted hippocampal tissue. Initial results suggest that this protocol offers sufficient …

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Deep Brain Stimulation And Its Effects On Parkinson Disease Spatiotemporal Gait Parameters., Greydon Gilmore

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) alleviates common appendicular PD symptoms, such as: tremor, rigidity and bradykinesia. However, the effect STN-DBS has on modulating axial gait features has not been properly quantified objectively. The purpose of the present thesis was to investigate the role STN-DBS plays in modulating specific gait features such as pace, asymmetry, variability, rhythm and postural control. It is hypothesized that axial gait function is regulated predominantly by non-dopaminergic control systems. In the acute immediate post-operative phase a surgical effect, named the microlesion effect (MLE), is thought to produce a transient improvement of appendicular and axial symptoms. …

Quantifying The Effects Of Systematic Stn-Dbs Programming On Rest And Postural Tremor In Idiopathic Parkinson Disease Patients, Kristina Ognjanovic

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is a complex neurodegenerative disorder that encompasses both motor and non-motor symptoms. These symptoms and their severity are typically assessed by scale based measures in a clinical setting. Scale- based assessments of PD patients undergoing bilateral subthalamic nucleus deep brain stimulation surgery (STN-DBS) such as the Unified Parkinson Disease Rating Scale (UPDRS) are commonly used in a clinical setting to assess symptom severity and progression. However, the subjective nature of these and other clinical scales call into question both the sensitivity and accuracy of patient assessment over time. An objective quantification of rest and postural tremor of …

Contribution Of The Dorsolateral Prefrontal Cortex To Attentional And Mnemonic Processes In Visual Search, Brandon Belbeck

Electronic Thesis and Dissertation Repository

A key characteristic of selective visual attention is that it may be deployed on the basis of our knowledge or goals of the task at hand. Here, we used cryogenic deactivation to investigate the contribution of the dorsolateral PFC to cognitive flexibility and working memory, as well as their relation to the deployment of attention. Macaque monkeys performed visual search tasks requiring them to foveate a target in an array of stimuli. These included a feature search, a constant-target conjunction search, a variable-target search and variable-target with delay search task, with each being more cognitively demanding than the last. Bilateral …

Resting-State Functional Network Disruptions In A Rodent Model Of Mesial Temporal Lobe Epilepsy (Tle), Ravnoor Singh Gill

Electronic Thesis and Dissertation Repository

Mesial temporal lobe epilepsy (TLE) is the most common form of drug-refractory epilepsy. The clinical application of non-invasively mapped networks using resting-state functional magnetic resonance imaging (rsfMRI) in humans has been rather limited due to heterogeneous (varying etiology, drugs, onset, latent period, etc.) patient groups. We employed a pharmacological (kainic acid) rodent model of TLE to measure the extent of functional network disruptions using rsfMRI, and study selected behaviors and olfactory to hippocampus transmission. Graph theoretical network modelling and analysis revealed significant increase in functional connectivity connectivity to the temporal lobe (hippocampus) in epileptic-rats compared to controls in the limbic …

A Non-Contrast Magnetic Resonance Imaging Technique To Assess Blood-Brain Barrier Permeability, Harini Pandithasekera

Electronic Thesis and Dissertation Repository

The Blood-brain barrier (BBB) regulates the entry of compounds between the blood and the brain, thus plays an important role in brain homeostasis. Studies indicate in disease states such as Alzheimer’s the BBB integrity is compromised. The motive of this project is to investigate the sensitivity of the diffusion-weighted arterial spin labeling (DW-ASL) technique to detect water exchange. Testing the sensitivity requires a reliable method of opening the barrier at specific locations of the brain. Here, a unique technology named focused ultrasound (FUS) has been used to mimic a compromised BBB environment.

A series of experiments were conducted in a …

Investigation Of Auditory Encoding And The Use Of Auditory Feedback During Speech Production, Laura E. Beamish

Electronic Thesis and Dissertation Repository

Responses to altered auditory feedback during speech production are highly variable. The extent to which auditory encoding influences this varied use is not well understood. Thirty-nine normal hearing adults completed a first formant (F1) manipulation paradigm where F1 of the vowel /ε/ was shifted upwards in frequency towards an /æ/–like vowel in real-time. Frequency following responses (FFRs) and envelope following responses (EFRs) were used to measure neuronal activity to the same vowels produced by the participant and a prototypical talker. Cochlear tuning, measured by SFOAEs and a psychophysical method, was also recorded. Results showed that average F1 production changed to …

Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …

Magnetic Resonance Imaging Of Brain Tissue Abnormalities: Transverse Relaxation Time In Autism And Tourette Syndrome And Development Of A Novel Whole-Brain Myelin Mapping Technique, Yann Gagnon

Electronic Thesis and Dissertation Repository

The transverse relaxation time (T2) is a fundamental parameter of magnetic resonance imaging sensitive to tissue microstructure and water content, thus offering a non-invasive approach to evaluate abnormalities of brain tissue in-vivo. Prevailing hypotheses of two childhood psychiatric disorders were tested using quantitative T2 imaging and automated region of interest (ROI) analyses. In autism, the under-connectivity theory, which proposes aberrant connectivity within white matter (WM) was assessed, finding T2 to be eleveted in the frontal and parietal lobes, while dividing whole brain data into neurodevelopmentally relevant WM ROIs found increased T2 in bridging and radiate WM. In Tourette syndrome, tissue …