Life Sciences Commons^™

Characterizing Mekk1: Candidate Behavioural Isolation Gene, Caryn Dooner

Electronic Thesis and Dissertation Repository

Behavioural isolation can occur due to divergence in aspects of courtship and mating, and can contribute to reproductive isolation. The purpose of this study is to determine how a gene, Mekk1, contributes to female rejection behaviour between D. melanogaster and D. simulans. Unique polymorphisms were identified within D. simulans Mekk1 that could contribute to behaviour, most of which are non-coding. Both transcripts of Mekk1 appear to be expressed at similar levels in D. simulans and D. melanogaster. These data also indicate that Mekk1 may be expressed in a specific region of the brain called the mushroom body, …

Oculomotor Executive Dysfunction During The Early And Later Stages Of Sport-Related Concussion Recovery, Brandon Webb

Electronic Thesis and Dissertation Repository

Executive dysfunction represents a persistent concussion deficit; however, it is largely unclear whether the deficit persists in an athlete after they have been deemed safe to return to play. In the present work, athletes with a sport-related concussion, and their age- and sex-matched controls, completed prosaccades and executive-related antisaccades: (1) 2-6 days post-concussion (i.e., initial assessment), and (2) 14-20 days after initial assessment and only when an athlete was medically cleared for safe return to play (i.e., follow-up assessment). Initial assessment antisaccades for the concussed group produced longer reaction times (RT) and more directional errors than the control group. The …

Investigating Cognitive Control And Task Switching Using The Macaque Oculomotor System, Jason L. Chan

Electronic Thesis and Dissertation Repository

Cognitive control is crucial to voluntary behaviour. It is required to select appropriate goals and guide behaviour to achieve the desired outcomes. Cognitive control is particularly important for the ability to adapt behaviour to changes in the external environment and internal goals, and to quickly switch between different tasks. Successful task switching involves a network of brain areas to select, maintain, implement, and execute the appropriate task. Uncovering the neural mechanisms of this goal-directed behaviour using lesions, functional neuroimaging, and neurophysiology studies is central to cognitive neuroscience.

The oculomotor system provides a valuable framework for understanding the neural mechanisms of …

The Neural Mechanisms Underlying The Perception And Production Of Learned Vocalizations In Songbirds, Shannon Katie Mischler

Electronic Thesis and Dissertation Repository

Songbirds produce a wide array of vocalizations, including song, and learned and innate calls. Songs and calls can be functionally defined. Songs are typically used to attract potential mates and defend one’s territory, whereas calls are used for everything else, such as advertising the presence of a predator, or location of a food source, and maintaining contact with members of one’s flock. The purpose of this thesis was to better understand the neural mechanisms underlying call production and perception in two songbird species; the black-capped chickadee (Poecile atricapillus) and the zebra finch (Taeniopygia guttata). My objectives …

Role Of The Swi/Snf Chromatin Remodelling Complex In The Axon Development Of The Drosophila Mushroom Body, Melissa C. Chubak

Electronic Thesis and Dissertation Repository

The SWI/SNF complex is an evolutionarily conserved ATP-dependent chromatin remodelling complex that has been implicated in the aetiology of intellectual disability (ID). Among the dominant ID genes, the SWI/SNF complex is the most highly enriched protein complex. However, its role in the nervous system is not yet understood. I systematically investigated the role of this complex in the development of the Drosophila mushroom body (MB), a complex brain structure required for learning and memory. Gross MB morphology was assessed using confocal microscopy to identify morphological defects following RNAi-mediated knockdown of the 15 individual SWI/SNF genes in the MB. Knockdown of …

Identifying Electrophysiological Components Of Covert Awareness In Patients With Disorders Of Consciousness, Geoffrey Laforge

Electronic Thesis and Dissertation Repository

Naturalistic stimuli evoke synchronous patterns of neural activity between individuals in sensory and higher cognitive, “executive” networks of the brain. fMRI paradigms developed to measure this inter-subject synchronization have been extended to test for executive processing in behaviourally non-responsive patients as a neural marker of awareness. This thesis adapted one such paradigm for use in EEG, a low-cost, portable neuroimaging technique that can be administered at a patient’s bedside. Healthy participants listened to a suspenseful auditory narrative during EEG recording. Significant inter-subject synchronization was found throughout the audio but was significantly reduced during a scrambled control condition. This paradigm was …

Phosphorylation Of Tau Protein At Thr175 Is A Toxic Event Associated With Neurodegeneration, Alexander Moszczynski

Electronic Thesis and Dissertation Repository

Aberrant phosphorylation and pathological deposition of the microtubule associated protein tau (tau protein) is associated with toxicity and cellular death in a number of neurodegenerative diseases (tauopathies). Specific phosphorylation sites are of interest in the processes leading to tau protein toxicity. One site of interest on tau protein is Thr¹⁷⁵ (pThr¹⁷⁵), which has been identified in diseased brain tissue from individuals with amyotrophic lateral sclerosis with cognitive impairment (ALSci) and Alzheimer’s disease. In vitro, pseudophosphorylation at this residue has been shown to induce the formation of pathological tau fibrils and, apoptotic cell death.

In my thesis, …

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 …

Early Life Immune And Physical Stress Directly Influences Anxiety-Like Behaviour In Adolescent Rats: Examining Sex Differences, Jordan M. Ward

Electronic Thesis and Dissertation Repository

This thesis examined the effects of neonatal acute immune activation with the endotoxin, lipopolysaccharide (LPS) on postnatal days 3 and 5 on adolescent anxiety-like behaviour in rats before and after a stress period. Previous research has shown that adults rats exposed to LPS during the neonatal stage show anxiety-like behaviour following a period of stress. This thesis investigated this effect in adolescence. The present results showed significantly higher anxiety-like behaviour in saline controls, and a potential neuroprotective effect of low dose LPS (15 µg/kg) contrary to what was reported in adult rats. As well, a phase of stressful, aversive conditioning …

Dopamine-Dependent Task Performance Over The Menstrual Cycle, Alexandra A. De La Rua

Electronic Thesis and Dissertation Repository

Estradiol (E2) has been found to influence dopamine (DA) activity in the nonhuman animal brain. While there has been very little research performed looking at E2’s effects on DA-related cognitive function in humans, recent research found that women tested during high E2 phases of the menstrual cycle had significantly better performance on a DA-dependent spatial working memory task, than women tested during the lowest E2 phase. The current study utilized the natural hormone fluctuations that occur over the menstrual cycle to determine if E2 is associated with DA-dependent task performance. Using a repeated measures design, 47 women completed a battery …

Mechanisms Underlying Executive Function Deficits, Sagar Jayawantrao Desai

Electronic Thesis and Dissertation Repository

In our daily life, we come across situations where we meet unanticipated challenges, we must take certain decisions, pay attention, be flexible and inhibit impulsive actions to achieve goal directed behaviour. During these processes, we unknowingly use sets of interdependent cognitive processes collectively called ‘executive function’. Executive function is mainly regulated by the frontal lobe. Impaired executive function is associated with disorders such as schizophrenia, Alzheimer’s disease, autism and attention deficit hyperactivity disorder (ADHD).

In this thesis, we investigated neurotransmitters and interactions among them regulating executive function. Further, we investigated mechanisms underlying those interactions mediating executive function in rats using …

Movie-Driven Fmri Reveals Network Asynchrony And Connectivity Alterations In Temporal Lobe Epilepsy, Alenka Bullen

Electronic Thesis and Dissertation Repository

Mesial temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is often resistant to medication. Recent studies have noted brain-wide disruptions to several neural networks in so-called “focal” epilepsy, notably TLE, leading to it being recognized as a network disease. We aimed to assess the integrity of functional networks while they were simultaneously activated in an ecologically valid manner, using an actively engaging, richly stimulating audio-visual film clip. This stimulus elicits widespread, dynamic patterns of time-locked brain activity, measurable using functional magnetic resonance imaging. Thirteen persons with drug-resistant TLE (persons with epilepsy; PWE) and 10 demographically …

Investigating The Protective Effects Of Telomerase Reverse Transcriptase On Neuronal Metabolism And Resistance To Amyloid-Beta, Olivia Singh

Electronic Thesis and Dissertation Repository

Maintenance of telomere length during cell division is dependent on the catalytic subunit telomerase reverse transcriptase (TERT), which adds TTAGGG repeats to the ends of chromosomes to prevent telomere shortening during DNA replication. However, non-telomeric roles of TERT have emerged under oxidative stress whereby TERT translocates from the nucleus to the mitochondria and protects against mitochondrial dysfunction through a poorly defined mechanism. A major pathological feature of Alzheimer’s Disease (AD) is the progressive accumulation of amyloid-beta (Aβ) peptide within the cortex and hippocampus. Aβ can directly interfere with mitochondrial respiration and promote mitochondrial dysfunction, ROS production, and neuronal cell death. …

Mechanisms Involved In The Assessment Of Cumulative Long-Term Familiarity Of Object Concepts: An Erp Study, Haopei Yang

Electronic Thesis and Dissertation Repository

We investigated the sensitivity of ERP components implicated in recognition memory to degree of experimentally controlled and lifetime cumulative exposures during explicit memory judgements. A parietally distributed ERP component spanning both the FN400/N400 and the LPC time windows tracked both types of judgements. This effect appears to be an LPC effect with an early onset, and differs from previously reported effects of repetition linked to implicit memory. Based on recent evidence, we interpreted it as response-related evidence accumulation processes that are in line with both single-process models and continuous dual-process models. We also observed more positive ERPs in the left …

Prefrontal Cortex Dopamine Transmission Regulates Emotional Memory Processing And Morphine Reward Salience: Implications For Post-Traumatic Stress Disorder And Addiction Comorbidity, Jing Jing Li

Electronic Thesis and Dissertation Repository

Post-Traumatic Stress Disorder (PTSD) and addiction are strongly comorbid. However, the underlying neural mechanisms by which traumatic memory recall may increase addiction liability are poorly understood. The inability to suppress memory recall related to either stressful or rewarding, drug-related experiences may be an underlying neuropsychological feature capable of triggering both PTSD or addiction-related behaviours. Our previous research has shown that transmission through dopamine (DA) D₄ and D₁ receptor subtypes (D₄R, D₁R) within the prefrontal cortex (PFC) strongly modulates emotional memory acquisition and recall (Lauzon et al., 2009). Using olfactory fear conditioning and morphine conditioned …

Conditional Sox9 Ablation 30 Days After Spinal Cord Injury: Testing The Therapeutic Value Of A Successful Acute Strategy To Increase Neuroplasticity In A Model Of Chronic Spinal Cord Injury, Natalie M. Ossowski

Electronic Thesis and Dissertation Repository

Many individuals who have suffered from spinal cord injury (SCI) have longstanding damage. The molecular environment of the spinal cord is not permissive to axonal growth and neuroplasticity after injury is limited. Perineuronal nets containing chondroitin sulfate proteoglycans (CSPGs) are major inhibitors of axonal sprouting. Our laboratory has identified that the transcription factor SOX9 regulates a battery of genes involved in CSPG biosynthesis. Using Sox9 conditional knockout mice, we have shown that ablating Sox9 before injury decreases CSPG levels in the cord, increases reparative sprouting, and leads to improved locomotor recovery. However, it is unknown whether Sox9 ablation following SCI …

Decoding Mental States After Severe Brain Injury, Raechelle M. Gibson

Electronic Thesis and Dissertation Repository

Some patients with disorders of consciousness retain sensory and cognitive abilities that are not apparent from their outward behaviour. It is crucial to identify and characterise these covert abilities for diagnosis, prognosis, and medical ethics. This thesis uses neuroimaging techniques to investigate cognitive preservation and awareness in patients who are behaviourally non-responsive due to acquired brain injuries. In the first chapter, a large sample of healthy volunteers, including experienced athletes and musicians, imagined actions of varying complexity and familiarity. Motor imagery involving certain complex, familiar actions correlated with a more robust sensorimotor rhythm. In the second chapter, several patients with …

Navigating The "Little Brain": Comprehensive Mapping Of Functional Organisation, Maedbh King

Electronic Thesis and Dissertation Repository

Two decades of neuroimaging research suggests that the cerebellum is functionally involved in a range of cognitive and motor processes. However, missing from the literature is a comprehensive map detailing a clear functional organisation of the cerebellum. Previous studies have used a restricted task-mapping approach to localise task-specific functional activation to cerebellar lobules. However, this approach, which is often limited to one or two functional domains within individual subjects, fails to characterise the full breadth of functional specialisation within the cerebellum. To overcome this restricted task-mapping problem, we tested 17 subjects on a condition-rich task battery (61 task conditions) across …

Comparing The Influence Of Music Enjoyment And Beat Perception Ability On Spatiotemporal Gait Parameters Among Healthy Young And Older Adults, Brittany S. Roberts

Electronic Thesis and Dissertation Repository

Rhythmic Auditory Stimulation (RAS) involves synchronizing footsteps to music or a metronome thereby eliciting gait improvements in speed and stability among patients with Parkinson’s Disease. However, gait responses are inconsistent (Dalla Bella et al., 2017). Music enjoyment may influence gait responses, but exactly how it may do this has never been assessed. Moreover, individual differences in beat perception ability are likely to influence gait responses to music, particularly if instructed to synchronize to the beat. Here, we investigated whether music enjoyment influences gait, comparing responses based on beat perception ability (good vs poor) and instruction type (“walk freely” vs “synchronize …

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 …

An Investigation Of Propranolol As An Agent For The Experimental Manipulation Of Interoception., Jane Evguenia Kouptsova

Electronic Thesis and Dissertation Repository

Interoception has recently come under research focus as a potential influence on emotional and epistemic feelings. However, existing means to manipulate it experimentally have conceptual or logistical drawbacks. We investigated whether 20 mg of propranolol is a viable agent for experimentally manipulating interoception. Thirteen participants completed a double-blind, placebo-controlled crossover study, performing two heartbeat perception tasks, control tasks and measures of anxiety and alertness. All measures were obtained at the beginning and end of both sessions. Propranolol significantly decreased heart rate and systolic blood pressure. Heartbeat detection performance numerically decreased under propranolol, although this effect failed to reach statistical significance. …

The Role Of Individual Differences In Bilingual Language Processing, Emily S. Nichols

Electronic Thesis and Dissertation Repository

In this thesis, I investigated the neural correlates of bilingualism, and how individual differences in both brain and behaviour affect second language processing. To date, theories of bilingualism have tended to treat bilinguals as a uniform group, while in practice they vary greatly in both experience and ability. By examining how individual differences in proficiency and age of acquisition contribute to second language learning and processing, I sought to address this issue. In chapter two, I used event-related potentials to investigate how age of acquisition and proficiency modulate processing of a novel versus a grammatical rule that is similar across …

Characterizing Tool-Selective Areas With Human Neuroimaging, Scott N. Macdonald

Electronic Thesis and Dissertation Repository

Humans, unlike any other species, use tools to achieve complex goals. New Caledonian Crows, among the best of avian tool-makers, use twigs to retrieve food in crevices, and veined octopuses use coconut shells as shelters. Humans, however, go above and beyond these simple behaviours. Even when compared to orders that are evolutionarily closest to humans such as non-human primates, tool use is indisputably more advanced in humans. Conventionally, neuroimaging researchers who have studied complex tool use in humans do so by presenting pictures of tools and measuring the brain activity evoked by actions potentiated by the tools. This method has …

Investigating The Role Of Cortical Inhibition In Tinnitus, Krystal Beh

Electronic Thesis and Dissertation Repository

Subjective tinnitus is characterized as the perception of a phantom sound with no external acoustic source, and is often described as a “ringing in the ears” sensation. While evidence supports a central origin for tinnitus, the underlying neural mechanisms for this condition remain elusive. The studies presented in this thesis offer significant contributions to understanding the neural basis of tinnitus by (1) validating a behavioural paradigm that can successfully screen rats for transient noise-induced tinnitus without any indications of false-positives, and (2) demonstrating that a local loss of inhibition is sufficient to induce gain enhancement in the primary auditory cortex, …

A Single-Bout Of Aerobic Exercise Improved Executive Control: Evidence From The Antisaccade Task, Ashna Samani

Electronic Thesis and Dissertation Repository

A single-bout of moderate-to-vigorous intensity exercise increases activity within frontoparietal networks, producing a temporary ‘boost’ to executive-related cognitive control – an effect that is thought to be selective to exercise durations greater than 20 minutes. It is possible that previous tasks evaluating executive control did not provide the requisite resolution to detect executive changes associated with shorter exercise durations. To that end, I had participants perform a 10-minute bout of moderate-to-vigorous intensity aerobic exercise, examining pre- and post-exercise executive control via the antisaccade task. Extensive literature has shown that antisaccades are mediated via frontoparietal networks, modulated following exercise training. Results …

Pore-Lining Residues And Intracellular Magnesium Concentration Influence Connexin50 Gap Junction Unitary Channel Conductance, Mary Grace M. Tejada

Electronic Thesis and Dissertation Repository

Gap junction (GJ) channels mediate direct intercellular communication. Each GJ channel consists of two hemichannels and each hemichannel is a hexamer of connexins. GJs formed by different connexins display different unitary channel conductance (γ_j) and intracellular magnesium modulation. The underlying mechanisms are not fully clear. The present study investigates the effect of mutating putative pore-lining residues (G8, G46, and V53 individually or together) into glutamate in Cx50 on homotypic GJ channel properties. Expression of the triple and individual mutants in GJ-deficient N2A cells resulted in the formation of functional GJ channels similar to that of Cx50 GJs. However, …

Altered Cortical Oscillations: Investigations Into A Putative Neural Correlate Of Tinnitus, Gregory G P Sigel

Electronic Thesis and Dissertation Repository

Abnormal cortical oscillations have been implicated in tinnitus generation. To gain further insight into this relationship, we performed two Experimental Series, both employing behavioural, pharmacological, and in vivo electrophysiological techniques in an animal model. To that end, we revealed three novel findings: (1) While exposure to 250 mg/kg sodium salicylate or transient loud noise induced behavioural evidence of tinnitus, these insults caused dissimilar effects on spontaneous cortical oscillations; (2) Despite these dissimilar effects, sodium salicylate and loud noise exposure caused similar deficits in the evoked oscillatory activity elicited by the auditory steady state response; and (3) Manipulation of medial geniculate …

A Naturalistic Paradigm To Probe Conscious Information Processing During Sleep, Max M. Silverbrook

Electronic Thesis and Dissertation Repository

Sleep was long considered a passive mental state. The extent to which external information is integrated in, and consciously processed during sleep remains unknown. Here, simultaneous electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data were collected from sleeping participants. First, the stimulus elicited significantly correlated fMRI activity in the auditory and fronto-parietal networks of awake participants. Behavioural testing found individuals to perceive the story’s suspense similarly. Then neural activity related to high-level processing of the story was investigated in 5 individuals who slept through it. Fronto-parietal activity in 1 individual in rapid eye movement (REM) sleep followed that of …

Cognitive And Non-Cognitive Dysfunction In A Mouse Model Of Alzheimer's Disease, Wai-Jane V. Lee

Electronic Thesis and Dissertation Repository

Sensitive and translational tasks that efficiently and accurately assess cognitive function during pre-clinical trials would be useful in developing novel treatments for Alzheimer's disease (AD) patients. The Bussey-Saksida touchscreens employ various tasks similar to those used in humans to effectively evaluate high-level cognitive and executive functions in mice. This face validity provides the best chance of successful cognitive translation across species.

In our study, donepezil had minor effects on the performance of 5xFAD mice in the 5-CSRTT, a touchscreen task evaluating attention. Additionally, 5xFAD mice do not demonstrate impairments in the PVD task, which assesses visual discrimination/ cognitive flexibility. However, …

Dynamic Functional Connectivity Reveals Temporal Differences In Wake And Stage-2 Sleep, Mazen El-Baba

Electronic Thesis and Dissertation Repository

The transition from wakefulness to sleep is marked by changes in neurophysiology, suggesting that changes in consciousness might be accompanied by changes in functional network organization. Brain activity of 21 healthy participants was measured via simultaneous EEG-fMRI as participants transitioned from wakefulness into sleep. All fMRI volumes were ICA-decomposed, yielding 42 neurophysiological sources. Independent component time courses were used to estimate mean functional connectivity (FC) and dynamic FC using a sliding window technique. Windowed matrices were submitted to k-means clustering (k = 7, L2-norm). Mean FC in Wake and Stage-2 Sleep (S2S) were similar. Dynamic analysis revealed differences in temporal …