Neuroscience and Neurobiology Commons^™

The Role Of Adult Hippocampal Neurogenesis In Depression-Relevant Reward-Related Behaviours, Katrina Zmavc

Electronic Thesis and Dissertation Repository

The variability in the symptomatology of depressive disorders and antidepressant treatment response has led to an increased interest in the molecular, cellular, and circuit mechanisms of many aspects of affect. Evidence suggests a reduction in adult hippocampal neurogenesis (AHN) is associated with an increase in depression-like behaviour, though much of this evidence has been from studies using aversive tests (e.g., forced swim test). Here, I used touchscreen operant chambers, which allow for non-aversive and translational testing, to test the hypothesis that AHN plays a contributing role in emotion regulation. A panel of three touchscreen tests were chosen to assess different …

Executive Dysfunction Following A Sport-Related Concussion Is Independent Of Task-Based Symptom Burden, Naila Ayala Angumba

Electronic Thesis and Dissertation Repository

The present work examined whether oculomotor deficits associated with a sport-related concussion (SRC) reflect an impairment to executive-based planning mechanisms or a task-based increase in concussion symptomology (e.g., headache, vertigo). Therefore, I employed a standardized measure of SRC symptom severity (SCAT-5), antisaccade performance and pupillometry metrics in persons with a SRC during early (i.e., initial assessment: ≤12 days post-SRC) and later (i.e., follow-up assessment: 14-30 days post-SRC) stages of recovery. In the initial assessment, the SRC group yielded longer reaction times (RT) (p=0.001), increased directional errors (p=0.002) and larger task-evoked pupil dilations (TEPD) (p=0.004) than the control group. The follow-up …

Multisensory Responses In Primary Auditory Cortex Of The Cat, Catherine Boucher

Electronic Thesis and Dissertation Repository

Core auditory cortex of the cat is comprised of primary auditory cortex (A1) and the anterior auditory field (AAF). Neurons in both fields respond strongly to acoustic stimuli and are tonotopically organized. In hearing animals, a small number of cells in AAF respond to tactile stimulation. However, it is unclear if multisensory input influences responses in A1. In this study, multisensory stimuli were developed by pairing a pure tone stimulus with a flash stimulus at various stimulus onset asynchronies. A linear multielectrode array recorded multi-unit activity in A1 across cortical layers. We identified unisensory auditory, unisensory visual, bimodal, and subthreshold …

Lysosomes Mediate Rab27b-Dependent Secretion Of Beta-Amyloid, Shany Lahan

Electronic Thesis and Dissertation Repository

Extracellular deposition of beta-Amyloid (Aβ) is an early event in Alzheimer’s disease development. However, it is not known how Aβ is secreted. Lysosomes readily undergo calcium-dependent exocytosis, a process that relies on small GTPase Rab27b. In addition, lysosomal enzymes have been found within extracellular amyloid plaques. We hypothesized that lysosomes mediate Rab27b-dependent exocytosis of Aβ. Neuro-2a cells were transfected with wild-type or mutant Rab27b constructs and/or a lysosomal marker. Cells were incubated with Aβ monomers and imaged using a confocal microscope before and after stimulation of calcium-dependent exocytosis. We observed a significant decrease in lysosome and Aβ co-localization post-treatment in …

In Search Of Psychiatric Kinds: Natural Kinds And Natural Classification In Psychiatry, Nicholas Slothouber

Electronic Thesis and Dissertation Repository

In recent years both philosophers and scientists have asked whether or not our current kinds of mental disorder—e.g., schizophrenia, depression, bipolar disorder—are natural kinds; and, moreover, whether or not the search for natural kinds of mental disorder is a realistic desideratum for psychiatry. In this dissertation I clarify the sense in which a kind can be said to be “natural” or “real” and argue that, despite a few notable exceptions, kinds of mental disorder cannot be considered natural kinds. Furthermore, I contend that psychopathological phenomena do not cluster together into kinds in the way that paradigmatic natural kinds (e.g., chemical …

How Do Humans Process Magnitudes? An Examination Of The Neural And Cognitive Underpinnings Of Symbols, Quantities, And Size In Adults And Children, Helen Moriah Sokolowski

Electronic Thesis and Dissertation Repository

A striking way that humans differ from other species is our unique ability to represent and manipulate symbols. This ability to process numerical magnitudes symbolically (e.g., ‘three’, ‘3’) is widely thought to be supported by an ancient system that evolved to process nonsymbolic numerical magnitudes (i.e., quantities). In this thesis, I present four empirical studies to uncover whether symbolic representations are indeed supported by the system that evolved to process quantities, or if symbolic representations are sub-served by a similar but ultimately distinct system.

In experiments 1 and 2, I investigate how the adult brain processes symbols and quantities using …

How Does The Brain Represent Digits? Investigating The Neural Correlates Of Symbolic Number Representation Using Fmri-Adaptation, Celia Goffin

Electronic Thesis and Dissertation Repository

How does the brain represent numerical symbols (e.g., Arabic digits)? Activity in left parietal regions correlates with symbolic number processing. Research with functional resonance imaging adaptation (fMRI-A) indicates that the intraparietal sulcus (IPS) exhibits a rebound (increase in activation) effect when a repeatedly presented number is followed by a new number. Importantly, this rebound effect is modulated by numerical ratio as well as the difference between presented numbers (distance). This ratio-dependent rebound effect could reflect a link between symbolic numerical representation and an approximate number system (ANS). In this doctoral dissertation, fMRI-A is used to investigate mechanisms underlying symbolic number …

Cognitive, Neural, And Educational Contributions To Mathematics Performance: A Closer Look At The Roles Of Numerical And Spatial Skills, Zachary C.K. Hawes

Electronic Thesis and Dissertation Repository

The principal aims of this thesis were to (1) provide new insights into the cognitive and neural associations between spatial and mathematical abilities, and (2) translate and apply findings from the field of numerical cognition to the teaching and learning of early mathematics.

Study 1 investigated the structure and interrelations amongst cognitive constructs related to numerical, spatial, and executive function (EF) skills and mathematics achievement in 4- to 11-year old children (N=316). Results revealed evidence of highly related, yet separable, cognitive constructs. Together, numerical, spatial, and EF skills explained 84% of the variance in mathematics achievement (controlling for chronological age). …

Assessing The Role Of Drosophila Melanogaster Neuroligin 3 On Social Spacing And Climbing Behaviour, J. Wesley Robinson

Electronic Thesis and Dissertation Repository

Autism spectrum disorders can be clinically defined in part by impairments of social interactions. Social interactions can be modeled in Drosophila melanogaster with behaviours such as social spacing. Here, I examined the effects of autism-related gene neuroligin 3 on fly social spacing. I hypothesized if neuroligin 3 is mutated or gene expression is targeted for knockdown, then flies will have altered social space in males and females at different ages. Using the social space assay, I found that different mutations to neuroligin 3 change the fly’s behavior, in a mutation and sex-specific manner. Using an antibody against Nlg3, I localized …

Using Meditation To Improve Measures Of Attention In Older Adults, Sabrina Ford

Electronic Thesis and Dissertation Repository

Age-related cognitive decline greatly impacts quality of life for older adults. Previous research has indicated that meditation may act as a neuroprotective factor to prevent age-related cognitive decline. This thesis sought to replicate previous findings and investigate if a four-week meditation intervention would improve sustained attention. Participants 60 years and older (n=27, 17 female) were recruited and assigned to a focused-attention (FA) meditation or relaxation group which met for four weeks, three times a week. Resting-state EEG was used to collect individual alpha peak frequency (iAPF) and frontal alpha asymmetry (FAA). The Sustained Attention to Response Task (SART) was also …

Pupil Size Tracks Semantic Ambiguity As Well As Noise, Mason Kadem

Electronic Thesis and Dissertation Repository

Effortful listening is experienced by listeners when speech is hard to understand because it is degraded or masked by environmental noise. Pupillometry (i.e., measure of pupil size) can detect effortful listening: pupil size increases when speech is degraded compared to when it is clear. However, the pupil responds to a range of cognitive demands, including linguistic challenges such as syntactic complexity. Here I investigate whether it responds to the need to disambiguate words with more than one meaning, such as ‘bark’ or ‘bank’. Semantic ambiguity is common in English, and previous work indicates that it imposes a processing load. We …

Pattern Separation In The Ventral Visual Stream, Kayla Ferko

Electronic Thesis and Dissertation Repository

Pattern separation is a neural computation thought to underlie our ability to form distinct memories of similar events. It involves transforming overlapping inputs into less overlapping outputs. In the ventral visual stream (VVS) there is considerable evidence for hierarchical transformation from feature-based visual representations to conjunctive whole-object representations, with the latter allowing for distinct coding even when objects have significant feature overlap. In the current study, we asked whether this transformation can be understood as pattern separation, and whether pattern separation can be observed even outside the context of classic recognition-memory tasks. To investigate pattern separation in the VVS, we …

Improving Stimulus Realism: The Effect Of Visual Dimension On Affective Responding, Shannon Compton

Electronic Thesis and Dissertation Repository

For decades researchers have used 2D stimuli under the assumption that they accurately represent real objects. This assumption has been challenged by recent vision and neuroeconomics research which has found that 2D images can evoke different neural and behavioural responses than real objects. The current study continues this line of research in the field of affective cognitive neuroscience; a field where small effect sizes are common and rapid habituation to affective stimuli used in the lab often occurs. The present study uses realistic 2D and 3D emotional images to determine the impact of visual dimension on affective responding. Subjective ratings …

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 …

Differential Thickening And Thinning Of Auditory Cortex In Deaf Cats Revealed With Ultra-High-Field Mri, Stephen G. Gordon

Electronic Thesis and Dissertation Repository

In the absence of hearing, the brain must adapt and repurpose the former auditory cortex. In this study we scanned normal hearing (n=29) and deaf (n=26) cats to identify cortical areas of differing thickness using the auditory regions from a 3D cortical atlas. Compared to hearing controls, differential thickening and thinning was observed in specific regions of the deaf auditory cortex. More dorsal auditory regions tended to be bilaterally thicker in the deaf group, while more ventral regions in the left hemisphere were thinner. The location and nature of these changes creates a gradient along the dorsoventral axis wherein dorsal …

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 …

Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, So Young Eo

Electronic Thesis and Dissertation Repository

Concussion is the most common form of mild traumatic brain injury (mTBI). TBI resolution is modulated by neuroinflammation, which is augmented by the infiltration of innate immune cells from the circulation. Peripheral, myeloid immune cells not only invade neural tissues but other organs as well causing local inflammation and tissue damage, known as systemic inflammatory response syndrome. Here, I assessed the temporal and anatomical nature of the neural and systemic cellular inflammatory response to repetitive, mTBI in a 3-hit mouse model of concussion. The results showed significant microglial activity, accumulation of peripheral myeloid cells and prominent axonal damage post-injury. The …

Resting State Network Dynamics Across Wakefulness And Sleep, Evan Houldin

Electronic Thesis and Dissertation Repository

The function of sleep is a longstanding mystery of the brain. By contrast, the function of resting state networks (RSNs) is one of its most recent mysteries. The relationship between RSNs and neuronal activity has been unclear since RSNs were discovered during the advent of functional magnetic resonance imaging (fMRI). Somewhat paradoxically, investigating these enigmatic phenomena in parallel can help to illuminate the function of both. The three studies described as part of this thesis all involve an evaluation of RSN dynamics across wakefulness and sleep. They are all based on the same dataset, derived from an experimental paradigm in …

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 …

Investigating How Neural Entrainment Relates To Beat Perception By Disentangling The Stimulus-Driven Response, Aaron Wc Gibbings

Electronic Thesis and Dissertation Repository

Beat perception – the ability to perceive a steady pulse in music – is nearly ubiquitous in humans, but the neural mechanisms underlying this ability are unknown. A growing number of electroencephalography (EEG) studies suggest that beat perception is related to neural entrainment, a phenomenon in which cyclic changes in the excitability of populations of neurons synchronize with a rhythmic stimulus. However, the relationship between acoustically-driven and entrainment-driven neural activity is unclear. This thesis presents EEG research that extends our understanding neural entrainment is related to beat perception by characterizing, equating, and finally removing the stimulus-driven response in the neural …

The Dissociable Impact Of Auditory Vs. Visual Emotional Cues On Visual Processing, Emma K. Stewart Bsc, Derek Gv Mitchell Phd

Western Research Forum

Background: Emotional information has privileged access to processing resources, which can cause it to have a distracting or facilitating effect on task performance for reasons that are poorly understood. The sensory modality through which it is presented may be one determining factor. Some findings suggest that auditory stimuli facilitate visual task performance while visual stimuli interfere with it, but there are conflicting findings.

Hypothesis: We hypothesize that emotional content of a different sensory modality from the task improves task-related performance via a general alerting and arousing effect for all stimuli, while emotional content of the same modality disrupts performance when …

Optimization Of The Touchscreen-Based Visuomotor Conditional Learning Task In Mice, Oren Princz-Lebel, David I. Wasserman, Miguel Skirzewski, Penny A. Macdonald, Lisa M. Saksida, Tim J. Bussey

Western Research Forum

The translational gap between animal models and clinical trials is a longstanding, yet largely unresolved, limitation in the study of cognition. This discrepancy is largely due to the differences in how cognition is assessed in animal models compared to those in clinical populations. In the stimulus-response (S-R) learning literature, for example, the techniques used to assess the acquisition of habitual behaviour differ greatly across species, leading to poor cross-species translation and often conflicting results. As a result, we set out to optimize a S-R learning task in mice using the touchscreen-based operant technologies. Similar to human studies, this touchscreen technique …

Relationship Among Neurogenic Orthostatic Hypotension, Cerebral Hemodynamics, And Cognitive Functioning, Lindsay Robinson

Electronic Thesis and Dissertation Repository

Neurogenic orthostatic hypotension (NOH) is characterized by a drop in systolic blood pressure ≥20mmHg or diastolic blood pressure ≥10mmHg within three minutes of upright posture. A large drop in blood pressure can trigger cerebral hypoperfusion, which has been linked to deficits in cognitive function. The current thesis aimed to measure cerebral hemodynamics and cognitive function in 20 NOH patients and 20 controls in the supine and head-up tilt (HUT) positions. Information processing speed (IPS) was assessed using the Symbol-Digit Modalities Test and attention was measured using the Stroop Test. NOH patients had significantly slower IPS in both the supine(p

The Origins And Development Of Visual Categorization, Laura Cabral

Electronic Thesis and Dissertation Repository

Forming categories is a core part of human cognition, allowing us to make quickly make inferences about our environment. This thesis investigated some of the major theoretical interpretations surrounding the neural basis of visual category development. In adults, there are category-selective regions (e.g. in ventral temporal cortex) and networks (which include regions outside traditional visual regions—e.g. the amygdala) that support visual categorization. While there has been extensive behavioural work investigating visual categorization in infants, the neural sequence of development remains poorly understood. Based on behavioral experiments, one view holds that infants are initially using subcortical structures to recognize faces. Indeed, …

Optimization Of Simultaneous Facial Emg And Fmri, Maggie Prenger

Western Research Forum

The scientific study of emotion began in the 19^th century with Duchenne’s study of the “universal and immutable” language of facial expressions. In The Mechanism of Human Physiognomy, he manipulates human facial expressions by electrically stimulating facial muscles. Facial electromyography (EMG) is a modern technique that is reminiscent of Duchenne’s work; it allows researchers to measure facial muscle activity through surface recording electrodes, providing a real-time measure of natural emotional reactions.

Although facial EMG is a reliable measure of emotional behavior, it fails to provide any information about brain activity responsible for emotional processes. Functional magnetic resonance imaging (fMRI) …

Spontaneous Mimicry Of Emotional Facial Expressions As A Function Of Trait Sadism, Cathleen Fleury, Mary Ritchie, Derek Mitchell

Western Research Forum

Using electromyography (EMG), it has been shown that facial muscles imperceptibly mirror the facial expressions of others, a phenomenon referred to as spontaneous facial mimicry. Facial mimicry may be involved in empathy processing, and is impaired in several empathy deficit disorders. It was previously believed to follow the direct-matching principle, a theory postulating that spontaneous facial mimicry involves the observer mirroring their partner’s expression exactly. However, several recent studies have demonstrated that context and individual differences may be influencing factors of spontaneous facial mimicry. In the present study, we propose to investigate the relationship between facial mimicry and empathy through …

Psychological Stress Modulates Synaptic Mechanisms For Prostaglandin E2-Mediated Hpa Axis Activation, Meagan Wiederman

Electronic Thesis and Dissertation Repository

Immune-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis elevates glucocorticoids, anti-inflammatory hormones, promoting the effective resolution of inflammation. Psychological stress can modulate this anti-inflammatory mechanism, but the mechanisms underlying this modulation remain largely unknown. The immune-induced HPA axis activation is, in large part, mediated by prostaglandin E₂ (PGE₂), an inflammatory mediator. In the brain, PGE₂ attenuates GABAergic synaptic transmission onto corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) that act as the apex of the HPA axis. The removal of GABA-mediated inhibition (i.e. disinhibition) excites CRH neurons and, consequently, activates the HPA axis. …

Investigating The Role Of Atrx In Glutamatergic Hippocampal Neurons, Renee Tamming

Electronic Thesis and Dissertation Repository

Mutations in ATRX, a Snf2-type chromatin remodeler, frequently lead to intellectual disability. However, the function of ATRX within the brain in cognition and synaptic transmission are incompletely understood. The aim of this study was to investigate the role of ATRX in the adult mouse brain. While complete loss of ATRX in the embryonic mouse brain results in perinatal lethality, mosaic expression of ATRX stunted growth and perturbed circulating IGF-1 levels. Mosaic expression of ATRX also impaired adult cognition, specifically recognition memory and spatial learning and memory. However, there were confounding factors that led me to a new model in …

Role Of Cholinergic Receptors In Prefrontal Activity Of Nonhuman Primates During An Oculomotor Rule-Based Working Memory Task, Alex J. Major

Electronic Thesis and Dissertation Repository

The ability to flexibly react to our dynamic environment is a cardinal component of cognition and our human identity. Millions across the globe are affected by disorders of cognition, affecting their ability to live independently. Prefrontal cortex is required for optimal cognitive functioning, but its circuitry is often disrupted in conditions of impaired cognition. In addition, the cholinergic system is vital to optimal executive function, but this is disrupted in a number of conditions, including Alzheimer’s disease and schizophrenia. The actions of cholinergic receptors were explored in this project with local application of cholinergic compounds onto prefrontal neurons as rhesus …

Effect Of Atrx Inactivation On Hippocampal Synaptic Plasticity In Mice, Radu Gugustea

Electronic Thesis and Dissertation Repository

The ATRX gene encodes an ATP-dependent chromatin remodeling factor and gene mutations cause developmental defects and intellectual disability. Conditional ablation of Atrx in mouse postnatal forebrain excitatory neurons (ATRX-KO) leads to spatial learning and memory impairments. Thus, we hypothesized that hippocampal synaptic transmission and plasticity are disrupted in ATRX-KO mice. Long-term potentiation (LTP), a cellular correlate of memory, and input-output relation of paired-pulse responses were studied in urethane-anesthetized mice in vivo. Theta-burst stimulation (TBS) of stratum oriens induced robust basal dendritic LTP in CA1 of both ATRX-KO and control mice, while paired-pulse facilitation (PPF) during baseline was lower in ATRX-KO …