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Validation Of A Virtual Auditory Space, And Its Use To Investigate How Pitch And Spatial Cues Contribute To Perceptual Segregation Of Auditory Streams, Nima Zargarnezhad

Electronic Thesis and Dissertation Repository

The human auditory system can decompose complex sound mixtures into distinct perceptual auditory objects through a process (or processes) known as Auditory Scene Analysis. Pitch and spatial cues are among the sound attributes known to influence sequential streaming (Plack 2018). In this project, the fidelity of a virtual acoustic space (the Audio Dome) in reproducing precisely located sound sources with a 9^th-order ambisonics algorithm was validated. The estimated horizontal Minimum Audible Angles aligned with previously reported values (Mills 1958) homogeneously across the space, and a robust low-frequency presentation was identified. Then, the Audio Dome was utilized to test …

Lbnp Reduces Cerebral Perfusion But Does Not Impact Executive Function, James Van Riesen

Electronic Thesis and Dissertation Repository

A growing body of literature has demonstrated that a single bout of aerobic exercise and/or hypercapnic manipulations increase cerebral blood flow (CBF) and are linked to a transient (i.e.,min) post-intervention executive function (EF) benefit. However, there are no direct studies examining whether a transient decrease in CBF elicits a post-intervention EF decrement. Accordingly, my thesis employed 10-min single bout manipulations of -30 mmHg and -50 mmHg lower-body negative pressure (LBNP) to determine whether a transient reduction in CBF impacts EF. LBNP was applied as it renders sub-atmospheric pressure to the lower limbs and redistributes blood from the upper to lower …

The Adaptor Protein P66shc Governs Central Nervous System Cell Metabolism And Resistance To Aβ Toxicity, Asad Lone

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD), a progressive and irreversible neurodegenerative disorder, and is the leading cause of dementia worldwide. It has been posited that AD is caused by the gradual deposition of toxic amyloid-b (Ab) plaques in the brain- that cause oxidative stress and eventually leads to neuronal death and synaptic loss. However, multiple therapies that either interfere with the production, or enhance the removal of Ab from the brain, have ultimately failed to slow or prevent AD. With the ever-increasing burden of AD worldwide, there exists an urgent need for novel therapeutic targets. The adult human brain is an energy demanding …

Investigating The Effects Of Infantile Hydrocephalus On Visuomotor Integration: A Study Utilizing Behavioural And Neuroimaging Analyses, Derya Adil

Electronic Thesis and Dissertation Repository

This thesis describes studies which explore the impact of infantile hydrocephalus on the posterior cortex, specifically focusing on the parietal and occipital lobes. Using resting-state functional MRI, the functional connectivity within the visuomotor integration network was investigated and connectivity was traced through the corpus callosum. We hypothesized that children with hydrocephalus would demonstrate altered functional connectivity compared to typically developing controls. Our findings revealed that patients had reduced functional connectivity in visuomotor pathways, particularly the inferior frontal occipital fasciculus, superior longitudinal fasciculus, and the frontal aslant tract, with notable impact on the left and right fusiform gyrus and precuneus. We …

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

Electronic Thesis and Dissertation Repository

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 …

Neuropsychological Outcomes After Cardiac Surgery: A Pilot Feasibility Study, Sydni G. Paleczny

Electronic Thesis and Dissertation Repository

Approximately half of patients who have cardiac surgery will experience deficits in attention, memory, and thinking speed after their operation. Given that heart surgery is one of the most common medical procedures in Canada, it is necessary to better understand the natural history of cognitive impairment after such surgery. Yet, there is no globally accepted method for measuring cognitive function in patients who undergo heart surgery. To address this, we assessed whether it was feasible to use a web-based approach to measure cognition in heart surgery patients before and after their operation. Findings showed that remote administration of cognitive testing …

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

Longitudinal Dynamics Of Cerebrospinal Fluid Aꞵ, Ptau And Strem2 Reveal Predictive Preclinical Trajectories Of Alzheimer’S Pathology, Bahaaldin Helal

Electronic Thesis and Dissertation Repository

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with limited early-stage treatment options. There is an urgent and unmet need for accurate biomarkers which can identify patients at risk for AD before cognitive symptoms emerge. Here I compared the performance of two analytical methods, univariate and multivariate classification, for identifying cognitively normal (CN) and mild cognitive impairment (MCI) patients based on their cerebrospinal fluid (CSF) biomarkers of Aβ42, pTau-181, sTREM2. Post-hoc analyses were then employed to assess patient progression in each of the SNF clusters. I found that SNF identified subgroups within the CN and MCI cohorts, based solely on …

Monitoring Intraventricular Hemorrhage In Preterm Infants, Lilian Mn Kebaya

Electronic Thesis and Dissertation Repository

Germinal Matrix-Intraventricular hemorrhage (GMH-IVH) remains a significant cause of adverse neurodevelopmental outcomes in preterm infants. Current management options for GMH-IVH rely on serial 2-dimensional cranial ultrasound (2D cUS) ventricular measurements and clinical signs. A need exists for reliable biomarkers to aid in the early detection of posthemorrhagic ventricular dilatation (PHVD) and cerebral palsy (CP). We incorporated 3-dimensional cranial US (3D cUS) and functional infrared spectroscopy (fNIRS) to monitor ventricle volumes (VV) and spontaneous functional connectivity (sFC) in preterm infants with GMH-IVH. Infants with severe GMH-IVH who underwent cerebrospinal fluid diversion showed larger VV, which correlated with decreased sFC. Our findings …

Data-Driven Neuroanatomical Subtypes In Various Stages Of Schizophrenia: Linking Cortical Thickness, Glutamate, And Language Functioning, Liangbing Liang

Electronic Thesis and Dissertation Repository

The considerable variation in the spatial distribution of cortical thickness changes has been used to parse heterogeneity in schizophrenia. We aimed to recover a ‘cortical impoverishment’ subgroup with widespread cortical thinning. We applied hierarchical cluster analysis to cortical thickness data of three datasets in different stages of psychosis and studied the cognitive, functional, neurochemical, language and symptom profiles of the observed subgroups. Our consensus-based clustering procedure consistently produced a subgroup characterized by significantly lower cortical thickness. This ‘cortical impoverishment’ subgroup was associated with a higher symptom burden in a clinically stable sample and higher glutamate levels with language impairments in …

Postexercise Executive Function Benefits And Cerebral Blood Flow: In The Lab And At Home, Benjamin Tari

Electronic Thesis and Dissertation Repository

A single bout of aerobic exercise improves executive function; however, the mechanism, or mechanisms, supporting this improvement remain unclear. One candidate mechanism is an exercise-mediated increase in cerebral blood flow (CBF) that enhances the efficiency of executive-related frontoparietal networks. To evaluate the link between exercise, CBF and executive function, three separate experiments were conducted. In the first study, separate 10-min sessions of moderate-to-heavy-intensity aerobic exercise, and a hypercapnic environment (i.e., 5% CO₂) were implemented. The hypercapnic condition was included because it increases CBF independent of the metabolic demands of exercise. The second study investigated whether exercise intensity-specific changes …

Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali

Electronic Thesis and Dissertation Repository

Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by a rapid decline in behavioural, language, and motor abilities. Advances in the understanding of FTD genetics and pathophysiology, and the subsequent development of novel disease modifying treatments have highlighted the need for tools to assess their efficacy. While structural magnetic resonance imaging (MRI) and functional imaging with ¹⁸F-flurodeoxyglucose (FDG) positron emission tomography (PET) are used for clinical diagnosis, structural changes are subtle at the early stages and PET imaging is expensive and access limited. Given the coupling of cerebral blood flow (CBF) to energy metabolism, an attractive alternative is …

Describing Functional Brain Connectivity's Role In The Relationship Of Multimodal Interventions To Improve Cognitive And Physical Function In Vulnerable (Frailty & Mild Cognitive Impairment) Older Adults., Nicholas (Nick) W. Bray

Electronic Thesis and Dissertation Repository

Aging is associated with declining cognitive and physical function. The decline accelerates in older adults diagnosed with mild cognitive impairment (MCI), a pre-dementia state, and frailty, a state of decreased physiological reserve. Previous work shows that frailty modifies the relationship between dementia pathology and clinical symptoms. Functional brain network connectivity (FBNC) refers to brain areas that are anatomically separate but temporally related in their neural signaling; it is believed to enable the completion of complex cognitive and physical functions. FBNC is considered a sensitive biomarker for monitoring the progression of dementia syndromes and investigating the efficacy of interventional strategies. Therefore, …

Protein Misfolding Toxicity And Inclusion Formation In Cellular Models Of Neurodegeneration, Sonja E. Di Gregorio

Electronic Thesis and Dissertation Repository

Protein misfolding characterizes most neurodegenerative diseases. Protein misfolding is the conversion of specific proteins from their normal, often soluble, and native three-dimensional conformation into an aberrant, often insoluble, non-functional conformation. Protein inclusions and aggregates are among the major pathological hallmarks of protein misfolding associated with many neurodegenerative diseases. Yet, the role of aggregates and inclusions is not clearly defined and heavily debated. This study utilizes powerful genetic approaches in yeast and verification in mammalian neuronal cell lines to address the misfolding and toxicity of three proteins, the Rho Guanine Nucleotide Exchange Factor (RGNEF), Matrin3, which are involved in amyotrophic lateral …

Evaluating Anesthetic Protocols For Non-Human Primate Functional Neuroimaging, Megha Verma

Electronic Thesis and Dissertation Repository

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to measure a proxy of neural activity in vivo with high spatial specificity. One subject can be followed for a long period of time to assess changes in functional brain organization. However, fMRI is extremely sensitive to motion. The challenges of training non-human primates to reduce motion in an MRI scanner motivate the study of anesthesia which is commonly used to substitute for this training. In this thesis, I compare three different commonly used anesthetic protocols: isoflurane, propofol-fentanyl in combination, and fentanyl alone, to test which of …

The Impact Of Levodopa Administration On Learning From Short-Term And Long-Term Action Consequences: A Paradigm Validation., Masood Rezaei

Electronic Thesis and Dissertation Repository

Behavioral and neuroimaging studies have identified two valuation systems in the human brain for controlling behavior known as model-free (MF) and model-based (MB). MF is based on immediate evaluation and MB is based on long-term evaluation of the outcome of our decisions. Previous studies suggest that dopamine baseline activity may play an important role in the balance between the two systems and determine how they compete or interact in controlling our actions. The overarching aims of this study is to investigate the impact of levodopa administration on learning from immediate and long-term action consequences, and to dissociate the role of …

Examining Brain Connectivity And Reading Ability In Children, Alexandra M. Cross

Electronic Thesis and Dissertation Repository

In this thesis, I investigated the relationship between functional and structural connectivity and reading ability in children. Prior research has tended to use single word reading measures or composite measures, however this is problematic as reading is a complex skill relying on multiple subskills, such as decoding efficiency, sight word reading efficiency, reading comprehension, and rapid automatized naming. As a result, the multi-faceted relationship between brain connectivity and reading ability is not well understood. I aimed to address this issue by considering multiple reading subskills while examining the neural substrates of reading. In Chapter 2, I examined how individual differences …

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 …

High Frequency Oscillations Are Phase-Amplitude Coupled In Stress Induced Seizures Following Traumatic Brain Injury, Paul Jung

Electronic Thesis and Dissertation Repository

Traumatic Brain Injury (TBI) often leads to the development of epilepsy, especially with the occurrence of stressful events. Stressors increase the levels of corticotropin-releasing factor (CRF) in the amygdala, which can be damaged by the secondary effects of TBI. It is hypothesized that the activity of CRF receptor type 1 (CRFR₁) in the amygdala is altered post-TBI and supports the generation of epileptiform waves, namely high-frequency oscillations (HFOs). Sprague-Dawley rats were given a moderate TBI and in vivo recordings of the amygdala were taken during the administration of an acute tail pinch stressor. The stressor increased broadband activity …

Comorbid Metabolic Syndrome And Prodromal Alzheimer's Disease In A Rat Model, Nadezda Ivanova

Electronic Thesis and Dissertation Repository

Metabolic syndrome (MetS), the development of which is associated with high-caloric Western diet intake, represents a risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and appears to contribute to AD progression when MetS and AD are comorbid. The interaction between AD and MetS might be through white matter inflammation, since white matter abnormalities and inflammation are important early events in the etiopathogenesis of both diseases. In these investigations, the effect of a high-caloric diet (HCD), to induce metabolic disturbances, on white matter neuroinflammation and cognitive function was investigated in a transgenic (TG) rat model of prodromal AD …

The Role Of Atf4 In Amyloid-Beta-Induced Neuronal Death., Gillian Petroff

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is partially characterized by excessive accumulation of amyloid-b (Ab) in the brain. Ab oligomers have greater toxicity than Ab fibrils and induce neuronal stress. The Integrated Stress Response (ISR) is activated in response to cellular stress and increases expression of activating transcription factor 4 (ATF4) and its target genes. Prolonged activation has been shown to induce aberrant cell death, and increased markers of the ISR have been found in the brains of AD patients. However, the exact mechanism of amyloid-b-induced death is largely unknown. We aimed to determine if Ab-induced neuronal death occurs through ATF4-mediated upregulation of …

Effects Of A Unilateral Injection Of Botulinum Neurotoxin Subtype-A In The Subthalamic Nucleus Of A Parkinsonian Rat Model, Olga Khazov

Electronic Thesis and Dissertation Repository

Dopaminergic degeneration in Parkinson’s disease (PD) leads to altered functional activity within the basal ganglia (BG) circuitry, including hyperactivity of the subthalamic nucleus (STN). Treatments restoring the BG functional circuitry often result in improvements in parkinsonian symptoms in patients and animal models. A recent study from our laboratory identified that infusing botulinum toxin (BoNT-A) into the internal globus pallidus provided a transient restoration of motor asymmetry and goal-directed locomotion in a rat model of PD. We hypothesized that infusions of BoNT-A into the STN in a parkinsonian rat model will improve motor asymmetry and locomotor abnormalities. Infusions of BoNT-A into …

Connectomic Analysis Of Substantia Nigra Pars Compacta And Ventral Tegmental Area Projections To The Striatum And Cortex, Nicholas Handfield-Jones

Electronic Thesis and Dissertation Repository

We investigated the connectivity of dopamine (DA) neurons emerging from the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) and targeting the dorsal striatum (DS), ventral striatum (VS), and prefrontal cortex (PFC). We used diffusion magnetic resonance imaging (dMRI) probabilistic tractography on human connectome project MRI data. We found that unlike conventional descriptions of DA pathways (i.e., nigrostriatal, mesolimbic, mesocortical), connectivity from both SNc and VTA each targeted DS, VS, and PFC. We also found that from the DS, VS, and PFC, a greater proportion of connections targeted the SNc as compared to the VTA. These findings suggest …

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 …

The Role Of The Tau N-Terminal Phosphatase-Activating Domain And Phosphorylation At Thr175 In The Formation Of Tau Cytoplasmic Inclusions, Matthew A. Hintermayer

Electronic Thesis and Dissertation Repository

Cytoplasmic inclusions and fibrils of the microtubule-associated protein tau (tau protein) are a key neuropathological hallmark in tauopathies, including Alzheimer’s disease, chronic traumatic encephalopathy, and amyotrophic lateral sclerosis with cognitive impairment. Previous research has demonstrated that the phosphorylation of tau protein at Thr¹⁷⁵ is sufficient for the initiation of fibril formation both in vitro and in vivo. Here we use mutated tau protein constructs to demonstrate that phosphorylation at Thr¹⁷⁵ results in the aberrant exposure of an N-terminal phosphatase-activating domain (PAD). The tau PAD interacts with protein phosphatase 1 (PP1) leading to the activation of glycogen synthase …

Neural Correlates Of Enhanced Attentional Filtering Of Distractors Across Vs. Within Visual Hemifields In The Lateral Prefrontal Cortex, Maryam Nouri Kadijani

Electronic Thesis and Dissertation Repository

Attention allows us to focus on only important sensory stimuli in a world full of distractors. However, the ability to allocate attention to important targets becomes more difficult when the distractors are located within the same as compared to when they are in the opposite visual hemifield. The neural mechanisms underlying this effect remains unclear. We recorded neuronal responses in lateral prefrontal cortex (LPFC), an area involved in the generation of signals related to attention, of two macaque monkeys while they performed a covert spatial attention task in two different conditions. Two stimuli were either separate in the left and …

Investigating The Role Of Endogenous Atf4 Upregulation On Neuronal Glutathione Level, Fatemeh Mirshafiei

Electronic Thesis and Dissertation Repository

ATF4 is a transcription factor that is activated in response to integrated stress response (ISR). In neurons specifically, ATF4 has been suggested to act as a pro-apoptotic transcription factor. The expression of ATF4, as well as its downstream gene targets have been implicated in both in vivo and in vitro models of Alzheimer’s and Parkinson’s Disease. However, the mechanism by which ATF4 promotes cell death remains unclear. It was previously shown that overexpression of ATF4 in primary cortical neurons caused a reduction in glutathione levels, resulting in oxidative stress-induced cell death. The aim of this project was to investigate whether …

Medial Geniculate Projections To Auditory And Visual Cortex In Hearing And Deaf Cats, Benjamin Trachtenberg

Electronic Thesis and Dissertation Repository

Following early-onset deafness, studies have demonstrated crossmodal plasticity, throughout “deaf” auditory cortex. Crossmodally reorganized auditory cortex shows increased dendritic spine density, which suggests increased numbers of axon terminals. I examined projections from the medial geniculate body (MGB) of hearing and early-deaf cats in order to reveal the distribution of synaptic boutons in the cortex, originating from MGB neurons. Anterograde fluorescent dextran tracers were deposited bilaterally in the MGB in order to label cortical axon terminals. Deafness resulted in axon terminal increases in visual cortex, and conservation of auditory axon terminal distribution. Visual areas PLLS and area 18 received increased projections …

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 …