Life Sciences Commons^™

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 …

Learning Expands The Preplanning Horizon In Finger Sequence Tasks, Neda Kordjazi

Electronic Thesis and Dissertation Repository

Many everyday skills involve the production of complex sequences of movements. However, the dynamics of the interplay between action selection and execution processes in sequential movements is poorly understood.Here, we set out to investigate the extent to which information regarding upcoming actions is utilized by the motor system to preplan into the future and furthermore, how this ability is influenced by learning. We designed a finger sequence taskwhere participants were shown only a fixed number of upcoming cues regarding future presses in every trial (viewing window, W). W varied between 1 (next digit revealed with pressing the current digit – …

Characterizing The Sensorimotor Properties Of A Rapid Visuomotor Reach Movement On Human Upper Limb Muscles, Chao Gu

Electronic Thesis and Dissertation Repository

Humans and other primates rely heavily on vision as a primary sensory input to drive our upcoming volitional motor actions. Our motor system makes so many of these visual-to-motor transformations that they become ubiquitous in our daily lives. However, a central question in systems neuroscience is how does the brain perform these transformations?

Reaching movements have been an ideal model for studying volitional motor control in primates. Broadly, these visually-guided reach movements contain three inherent sensorimotor components: an action selection component, a motor execution component, and a motor learning component. A core assumption is that as reach movements become more …

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 …

Assessing Cognition In A Mouse Model Of Alzheimer’S Disease, Justin B. Mels

Electronic Thesis and Dissertation Repository

A major challenge in behavioural testing of Alzheimer’s disease (AD) mouse models is a low degree of standardization and translatability of tasks to humans. Bussey-Saksida touchscreen systems employ numerous tasks allowing for assessment of advanced cognitive function in mice using paradigms similar to those used in humans. This system can be used to assess cognitive deficits in dementia.

Our study focused on testing visual discrimination, cognitive flexibility and attention of the APP/PS1 familial AD mouse model longitudinally to assess behavioural changes related to cognitive decline. Surprisingly, APP/PS1 mice did not demonstrate impairments in the 5-Choice Serial Reaction Time Task, which …

Characterizing The Cortical Contributions To Working Memory-Guided Obstacle Locomotion, Carmen Wong

Electronic Thesis and Dissertation Repository

While walking in complex environments, the ability to acquire information about objects in our surroundings is essential for successful obstacle negotiation. Furthermore, the ease with which most animals can traverse cluttered terrain while grazing, exploring, or hunting is facilitated by the capacity to store obstacle information in working memory (WM). However, the underlying neural substrates supporting such complex behaviours are poorly understood. Therefore, the goal of this thesis is to examine the neural underpinnings of WM-guided obstacle negotiation in the walking cat.

Obstacle locomotion was studied in two main paradigms, characterized by whether obstacle presence was detected via vision or …

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 …

The Effect Of Seizures (Afterdischarges) On Hippocampal Long-Term Potentiation, Vishaka Rajan

Electronic Thesis and Dissertation Repository

This study investigated whether an electrographic seizure, or an afterdischarge (AD), inhibits long-term potentiation (LTP) in the hippocampus. Neuromodulation by acetylcholine (ACh) and genetic modification by loss of the ATRX gene on LTP was also examined through the use of VAchT knockout mice and ATRX knockout mice, respectively. Evoked potentials were recorded in the hippocampal CA1 region in freely behaving mice and urethane-anesthetized mice. Basal dendritic LTP was suppressed when elicited 1 h after an AD in all behaving mice, regardless of mouse genotype; LTP was unaffected when induced 1 day or 1 week following an AD. At 1 h …

Comparative Study Of Beat And Temporal Pattern Perception In A Songbird, Brendon Samuels

Electronic Thesis and Dissertation Repository

When humans listen to musical rhythms they sense a beat, the regular pulse that one might tap their foot to. Much about the functions, evolution and neural substrates of beat perception remains unclear. Research has considered whether other species perceive beat, yet more empirical data is needed. Songbirds produce learned rhythmic vocalizations, but can they perceive a beat? To answer this question, I developed a behavioural task that tested whether humans could discriminate rhythms that contained or lacked a beat. I applied an equivalent procedure to test European starlings. I found that humans learned the task with minimal instructions, but …

Characterizing The Cognitive And Emotional Effects Of Delta-9-Tetrahydrocannabinol In Distinct Hippocampal Sub-Regions, Dinat Khan

Electronic Thesis and Dissertation Repository

The objective of this study is to determine the potential differential effects of THC in the DH or VH sub-regions, as well as the upstream effects on PFC neuronal activity and oscillations. Rodents used for electrophysiology were infused with THC or vehicle in the DH or VH regions, combined with PFC recordings. Additionally, a battery of behavioural paradigms was performed. Deficits in short-term memory when THC was infused into both regions was observed, however working memory was impaired with VH infusions only. This could be due to THC-induced dysregulation in the PFC, as beta oscillations were significantly decreased selectively in …

Synaptic Correlates For Stress Sensitization, Julia Kj Sunstrum

Electronic Thesis and Dissertation Repository

The stress response is essential for survival, but it can be detrimental when persistently activated during chronic stress. Therefore, the magnitude of the stress response must be finely-tuned in order to be adaptive. Indeed, an animal’s stress response system normally undergoes habituation that decreases responses to a repeated, familiar stressor. Importantly, the same animal still responds normally, or even becomes sensitized, to an unfamiliar (novel) stressor. This indicates that chronic stress simultaneously induces two opposing types of plasticity, one that underlies habituated responses and another that drives sensitized responses. The activation of the hypothalamic-pituitary-adrenal (HPA) axis — a hallmark of …

Evaluating Devices For The Measurement Of Auditory-Evoked Fetal Movement, Patrick Gatutsi

Electronic Thesis and Dissertation Repository

Determining normal and abnormal fetal function in utero in order to better predict which fetuses are at risk for adverse outcome is critical. However, the medical imaging tools that could assist with diagnosis are very expensive and rarely available in the developing world. In this study, we developed a prototype audio-motio-tachograph (AMTG), which measures fetal movements through the recording of abdominal wall deformations and tested it in Rwanda. First, we showed that AMTG detected fetal signals and that fetuses respond to complex acoustic stimuli. In order to improve the sensitivity of the device, we then measured whole abdominal wall deformations …

Regulation Of Lps-Induced Neuroinflammation By Targeting Microglia In Vivo Using Chemogenetics, William Chett Binning

Electronic Thesis and Dissertation Repository

Peripheral inflammation can profoundly alter motivational processes and generate behavioral symptoms of sickness. Microglia, the innate immune cells of the brain, orchestrate neuroinflammation and have long been thought to be important for sickness behavior. However, their precise roles remain obscure due to their complex bidirectional interactions with neurons in vivo, which regulate how microglia respond to inflammatory signals and interact with neurons. Neuron-microglia interactions can be at least partially mediated by various types of G-protein coupled receptors (GPCRs) expressed by microglia. Here, we generated a microglia specific hM3Gq-DREADD (designer receptors exclusively activated by designer drugs) mouse line in which hM3Gq …

Behavioural And Anatomical Effects Of Unilateral Injection Of Botulinum Neurotoxin A In The Entopeduncular Nucleus Of A Parkinsonian Rat Model, Adrianna Tsang

Electronic Thesis and Dissertation Repository

Loss of dopamine in Parkinson’s disease is associated with glutamatergic hyperactivity of the subthalamic nucleus. Pharmacological and electrical therapies aimed to suppress this overactivity favourably alleviate parkinsonian motor symptoms. No study has explored the potential of botulinum neurotoxin A in the central nervous system beyond cholinergic blockage despite evidence of its ability to inhibit glutamate release. Thus, the present study investigates the effect of selective suppression of hyperactive glutamatergic input from the subthalamic nucleus to the entopeduncular nucleus by botulinum neurotoxin A in a parkinsonian model. Unilateral 6-hydroxydopamine lesioned rodents received microinfusions of botulinum neurotoxin A or vehicle into the …

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 …

Girls’ Internalizing Symptoms And White Matter Tracts In Cortico-Limbic Circuitry, Ola Mohamed Ali

Electronic Thesis and Dissertation Repository

Dysfunction in cortico-limbic circuitry is implicated in internalizing disorders, but less is known about whether structural abnormalities precede disorder, thus potentially marking risk. I therefore examined associations between white matter tract integrity in cortico-limbic circuitry at age 7, obtained using Diffusion Tensor Imaging, and concurrent and longitudinal patterns of internalizing symptoms, over a 5-year period, in 42 typically developing girls. Using Automated Fiber Quantification, diffusion properties were examined at multiple points along tract length (cf., an average diffusion measure of the entire tract). Concurrent internalizing symptoms were associated with reduced fractional anisotropy in segments of the cingulum bundle and uncinate …

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 …

Finding Nonlinear Relationships In Functional Magnetic Resonance Imaging Data With Genetic Programming, James Hughes

Electronic Thesis and Dissertation Repository

The human brain is a complex, nonlinear dynamic chaotic system that is poorly understood. When faced with these difficult to understand systems, it is common to observe the system and develop models such that the underlying system might be deciphered. When observing neurological activity within the brain with functional magnetic resonance imaging (fMRI), it is common to develop linear models of functional connectivity; however, these models are incapable of describing the nonlinearities we know to exist within the system.

A genetic programming (GP) system was developed to perform symbolic regression on recorded fMRI data. Symbolic regression makes fewer assumptions than …

Role Of Stip1 In Tdp-43 Mediated Toxicity And Proteinopathy In Neurodegenerative Disorders, Abdul Razzaq

Electronic Thesis and Dissertation Repository

A common hallmark of neurodegenerative disorders is the abnormal aggregation of misfolded proteins. Aggregates of phosphorylated TAR-DNA-binding protein-43 (TDP-43) are found in multiple neurodegenerative disorders. The molecular chaperones Hsp70 and Hsp90 have been shown to be key modulators of TDP-43 phosphorylation and expression, however the mechanisms behind how this interaction occur are unclear. Stress-Inducible PhosphoProtein 1 (STIP1) is a critical co-chaperone linking Hsp90 to Hsp70 to modulate chaperone client stability. In this study, we evaluated the potential role of STIP1 in TDP-43 stability and cellular toxicity. We demonstrated that STIP1 interacts with TDP-43 and the deletion of STIP1 leads to …

Dopaminergic Medication Decreases Motor Impulsivity On The Go/No-Go Task In Parkinson's Disease, Xue Qing Yang

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is characterized by resting tremor, rigidity, and bradykinesia. Dopaminergic medications treat motor symptoms, but have complex effects on cognition, including impulse control. Impulsivity is multifaceted in nature. Motor impulsivity involves inability to withhold prepotent, automatic responses whereas cognitive impulsivity refers to increased risk-taking and reward-seeking. We anticipated that dopaminergic therapy would decrease motor impulsivity. We employed the Go/No-go paradigm to assess motor impulsivity. PD patients were tested on and off their dopaminergic medication. PD patients on medication had a significantly higher proportion of Go Timeouts (i.e., Go responses not completed by the 750 millisecond deadline) compared to …

Examining Motor Unit Stability Of First Dorsal Interosseous (Fdi) And Biceps Brachii (Bb) Muscles In Healthy And Older Adults Using Decomposition-Based Quantitative Electromyography (Dqemg), Igor Angelovski

Electronic Thesis and Dissertation Repository

Aging of the human neuromuscular system is associated with gradual decline in motor unit (MU) number leading to denervation of muscle fibers and subsequent compensatory reinnervation from surviving MUs. Lower limb muscles exhibit age-related increased MU instability (measured electrophysiologically), however not much is known regarding MU stability of aging upper limb muscles. The purpose of this study was to examine agerelated MU loss in upper limb muscles (first dorsal interosseous [FDI] and biceps brachii [BB]) and the impact on MU stability in younger and older healthy subjects using electrophysiological near fiber analysis from decomposition-based quantitative electromyography (DQEMG). FDI and BB …

Assessing Cognitive Function In Chronic Sport-Related Head Impacts And Aging, Danielle Brewer-Deluce

Electronic Thesis and Dissertation Repository

Healthy normal aging and cumulative head trauma (concussion and subconcussion), can influence cognition independently and concomitantly leading to substantial late-life cognitive impairments (e.g., as seen in increased rates of dementia). With this as motivation, this dissertation explores three aspects of aging, head injury and cognition using the Cambridge Brain Sciences (CBS) cognitive battery (www.cambridgebrainsciences.com).

Study 1 (Chapter 2): Concussion-specific testing combines assessments from multiple domains to evaluate a variety of functions. While clinically relevant, their succinct nature limits the amount of cognitive information available. Eighteen male football athletes were examined at baseline using the Sport Concussion Assessment Tool (SCAT) 3, …

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 …

A Role For The Somatosensory System In Motor Learning By Observing, Heather R. Mcgregor

Electronic Thesis and Dissertation Repository

An influential idea in neuroscience is that action observation activates an observer’s sensory-motor system. This idea has recently been extended to motor learning; observing another individual undergoing motor learning can promote sensory-motor plasticity as well as behavioural changes in both the motor and somatosensory domains. While previous research has suggested a role for the motor system in motor learning by observing, this thesis presents a series of experiments testing the hypothesis that the somatosensory system is also involved in motor learning by observing.

The experiments included in this thesis used force field (FF) adaptation as a model of motor learning, …

Object Processing In The Medial Temporal Lobe: Influence Of Object Domain, Anna Blumenthal

Electronic Thesis and Dissertation Repository

We live in a rich visual world, surrounded by many different kinds of objects. While we may not often reflect on it, our ability to recognize what an object is, detect whether an object is familiar or novel, and bring to mind our general knowledge about an object, are all essential components of adaptive behavior. In this dissertation, I investigate the neural basis of object representations, focusing on medial temporal lobe (MTL) structures, namely, perirhinal cortex, parahippocampal cortex, and hippocampus. I use what type of thing an object is, or more specifically, the broader category (e.g., “face” or “house”) or …

Psychotropic Effects Of Cannabis Components On The Mesolimbic Dopaminergic System, Christopher Norris

Electronic Thesis and Dissertation Repository

The two most abundant phytochemical compounds in cannabis are cannabidiol (CBD) and ∆⁹-tetrahydrocannabinol (THC). THC is the primary psychoactive component of cannabis and is a partial CB₁ receptor (CB₁R) agonist. THC is believed to be responsible for the motivational and dependence-producing effects of cannabis and causes psychotomimetic and affective processing disturbances. Conversely, CBD, is non-psychoactive, acts as a 5-HT_1A receptor agonist, antagonizes CB₁Rs, and possesses both anti-psychotic and anxiolytic properties. The neural substrate believed to be responsible for many of the effects of cannabis is the dopaminergic, mesolimbic reward pathway which is …

Chromatin Organizer Ctcf In Brain Development And Behaviour, Adrienne Elbert

Electronic Thesis and Dissertation Repository

Chromatin architecture is an important regulator of gene expression, which dictates development. Mutations in one copy of the CTCF chromatin organizer gene cause intellectual disability and autism. Polymorphisms in CTCF have also been associated with increased risk for schizophrenia, a condition that overlaps in biological etiology with autism and intellectual disability. In this thesis, we sought to understand the role of CTCF in neurodevelopment using brain-specific conditional knockout and heterozygote mouse models. Using the Ctcf-null animals, we identify a cell-autonomous role for CTCF in regulating cortical interneuron development in the medial ganglionic eminence (MGE) through the transcriptional control of …