Neuroscience and Neurobiology Commons^™

Characterizing Persistent Developmental Dyscalculia: A Cognitive Neuroscience Approach, Stephanie D. Bugden

Electronic Thesis and Dissertation Repository

Developmental dyscalculia (DD) is a specific learning disorder of calculation abilities. In the present thesis I report a series behavioural and functional neuroimaging studies to further elucidate the core numerical deficits underlying DD. I recruited a sample of children with DD who demonstrated persistent impairments in arithmetic. In Chapter 2, to validate the selection criteria, I compared the performance of children with and without persistent DD on a test of numerical magnitude processing. The data showed that only children with persistent DD presented with deficits in numerical magnitude processing, while those with inconsistent DD perform at the level of age-matched …

Pathway-Specific Signaling And Its Impact On Fertility: A Focus On The Kisspeptin Receptor, Kiss1r, Maryse R. Ahow

Electronic Thesis and Dissertation Repository

Hypothalamic GnRH-releasing hormone (Gnrh) is the master regulator of the neuroendocrine reproductive axis and its secretion is regulated by many Gnrh neuronal-based signaling systems. Among these are Gα_q/11-coupled receptors and their ligands.In most cases examined to date, activation of these receptors lead to Gnrh neuronal membrane depolarization and Gnrh secretion. The most potent trigger of Gnrh secretion is kisspeptin (Kp), a ligand for the Kiss1r Gα_q/11-coupled receptor. Studies have shown that Kiss1r signaling is essential for attaining and maintaining fertility. We recently demonstrated that in addition to signaling via Gα_q/11, Kiss1r also couples to …

The Role Of The Rna-Binding Protein Rho Guanine Nucleotide Exchange Factor In The Cellular Stress Response, Kevin Wh Cheung

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which the pathological mechanism is heterogeneous and a cure has been elusive. Recent developments have linked specific proteins found in pathological neuronal cytoplasmic inclusions (NCIs) of ALS motor neurons to familial variants of the disease. These proteins, including TAR DNA-binding protein of 43 kDa (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS), and Rho guanine nucleotide exchange factor (RGNEF) share the common characteristic of being RNA-binding proteins that colocalize within NCIs. RGNEF is unique however in also possessing RhoA activation capacity, suggesting a role in the cell stress response. My thesis …

Advances In Image Acquisition And Filtering For Mri Neuroimaging At 7 Tesla, Andrew T. Curtis

Electronic Thesis and Dissertation Repository

Performing magnetic resonance imaging at high magnetic field strength promises many improvements over low fields that are of direct benefit in functional neuroimaging. This includes the possibility of improved signal-to-noise levels, and increased BOLD functional contrast and spatial specificity. However, human MRI at 7T and above suffers from unique engineering challenges that limit the achievable gains. In this thesis, three technological developments are introduced, all of which address separate issues associated with functional magnetic resonance neuroimaging at very high magnetic field strengths.

First, the image homogeneity problem is addressed by investigating methods of RF shimming — modifying the excitation portion …

Dissociating The Psychoactive Effects Of Distinct Cannabis Compounds In The Mesocorticolimbic Circuitry, Jordan S. Zunder

Electronic Thesis and Dissertation Repository

The discovery of the endocannabinoid system propelled understanding of the mechanisms of action of cannabinoid compounds. While marijuana is the most widely used illicit substance in the world, the neuropsychopharmacological mechanisms that underlie the diffuse effects of cannabis in the brain remain poorly understood. This is because marijuana smoke represents a complex mixture of chemical components, possessing dissociable psychoactive properties. Clinical evidence suggests a functional dissociation between the two main pharmacological components of cannabis, Δ9- tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Using a combination of cortical microinfusions during two emotional learning paradigms, and single-unit in vivo electrophysiological recording, we investigated the …

Characterization Of Human 82-Kda Choline Acetyltransferase Expression In A Newly Developed Transgenic Mouse Model, Silke M. Vanvaerenbergh

Electronic Thesis and Dissertation Repository

Expression of human 82-kDa choline acetyltransferase (ChAT) protein in nuclei of cultured neurons from Alzheimer’s disease model APP/PS1 transgenic mice results in a reduction in Aβ release, suggesting a protective role. This thesis characterizes the expression of human 82-kDa ChAT in 82-hChAT;NkCre transgenic mice by PCR-based examination of genomic DNA and localization of the protein in mice brains. First, I demonstrate in a cultured cell model that Cre recombinase-mediated excision of a floxed LacZ gene is necessary for human 82-kDa ChAT protein expression from pcCALL2:82-ChAT, the plasmid used to create founder transgenic mice. Second, I confirmed that human 82-kDa ChAT …

Mindfulness Meditation Versus Eeg-Alpha Neurofeedback: The Role Of Eeg-Alpha Enhancement In Attentional Control, Theodore Chow

Electronic Thesis and Dissertation Repository

This thesis directly compared two active interventions known to enhance the EEG-Alpha rhythm, mindfulness meditation (MM) with EEG-Alpha enhancement neurofeedback (NFB), relative to a non-active Sham-NFB control. Seventy-three university students were randomized to one of the three 15-minute single-session interventions. Participants were subsequently compared on their ability to enhance EEG-Alpha amplitude as well as regarding Stroop behavioural performance, EEG event-related potentials, and EEG-Alpha event-related desynchronization (ERD) as markers of attentional control. Participants randomized to MM, NFB, and Sham did not differ in their ability to modulate the EEG-Alpha rhythm post-intervention. However, enhancements in EEG-Alpha amplitude were seen within the MM …

Synaptic Architecture Of The Acoustic Startle Response Pathway, Mahabba Smoka

Electronic Thesis and Dissertation Repository

The acoustic startle response (ASR) is mediated by a simple pathway which includes the giant neurons of the caudal pontine reticular nucleus (PnC). Habituation is theorized to occur via hyperpolarizing big potassium (BK) channels localized at glutamatergic terminals of auditory afferents in the PnC. Prepulse inhibition is suggested to be mediated by cholinergic innervation of PnC giant neurons, with possible glutamate and/or GABA co-release. Animals were injected with Fluorogold at C3/C4 to label a subpopulation of PnC giant neurons, and following a startle experiment, brainstems were processed for pCREB expression. Using their respective markers, BK channels, glutamatergic, GABAergic, and cholinergic …

Investigating The Multiple Hit Hypothesis Of Parkinson Disease Using Transgenic Lrrk2-R1441g Rats, Komal T. Shaikh

Electronic Thesis and Dissertation Repository

The ‘multiple hit’ hypothesis of Parkinson disease (PD) suggests that the combination of several risk factors leads to the development of PD. Here, we explore the interaction between two potential causes of PD; a genetic mutation in the leucine-rich repeat kinase 2 (LRRK2) gene and exposure to the neurotoxin, Paraquat. This project characterizes transgenic BAC rats expressing human LRRK2 bearing the familial PD mutation, R1441G. These rats were tested for PD-related deficits at 3, 6, 9 & 12 months. These rats were then exposed to intraperitoneal injections of Paraquat. We hypothesized that LRRK2^R1441G rats will show increased vulnerability …

Investigating The Primate Prefrontal Cortex Correlates Of Cognitive Deficits In The Ketamine Model Of Schizophrenia, Kevin J. Skoblenick

Electronic Thesis and Dissertation Repository

The World Health Organization has classified schizophrenia as one of the five leading causes of disability worldwide. Afflicting almost 1% of the world’s population, the disease’s greatest impact stems from its reduction in patients’ cognitive faculties. In order to better study these impairments, a pharmacological model has been developed using the NMDA antagonist, ketamine. This disease model successfully recreates the cognitive dysfunction of schizophrenia, allowing researchers to search for associated electrophysiological changes.

In this project I examined the behavioural and neurophysiological effects of ketamine on non-human primates performing the anti-saccade task. Success in this task requires a degree of cognitive …

Statistical Summaries In Action: Evidence From The Antisaccade Task, Caitlin Gillen

Electronic Thesis and Dissertation Repository

Antisaccades require the top-down process of decoupling a stimulus and a response and executing a saccade mirror-symmetrical to a target. Notably, research has yet to characterize the endpoint properties of antisaccades. Experiment One had participants antisaccade in two trial blocks that contained the same number of target eccentricities but differed in respect to their magnitudes. Experiment Two manipulated the frequency that individual target eccentricities were presented within a block of trials. Notably, Experiments One and Two were designed to determine whether the top-down control of antisaccades renders the processing of target features via a strategy of perceptual averaging. Results showed …

Understanding The Role Of Cholinergic Tone In The Pedunculopontine Tegmental Nucleus, Kaie Rosborough

Electronic Thesis and Dissertation Repository

Genetically modified mice targeting the vesicular acetylcholine transporter (VAChT) gene have been used as a tool to better understand the role of ACh signaling in specific regions of the brain (Prado et al., 2006; Guzman et al., 2011; de Castro et al., 2009). VAChT stores acetylcholine (ACh) in synaptic vesicles, and changes in this transporter expression directly interferes with ACh release. Here, we use a mouse line with VAChT deletion in the pedunculopontine tegmental nucleus (PPT) to evaluate the consequences of decreased cholinergic signaling from the PPT in vivo. Based on the efferent connectivity from the PPT, our hypothesis is …

Revisiting Working Memory: Are Domain, Process And Global Models Mutually Exclusive, Nested Or Orthogonal?, Jeffrey P. Wong

Electronic Thesis and Dissertation Repository

Working memory (WM) is a cognitive function whereby task-relevant information is actively maintained and manipulated in mind for goal-directed behaviour. Three competing models, here dubbed the global, domain and process models, have attempted to explain its neural underpinnings. Despite extensive research however, no consensus has been reached. Here, we use two new WM paradigms to demonstrate that all three models are partially correct. In the first experiment, our results show that selected frontoparietal regions (MD), from the global model, are largely stimulus-independent. However, more posterior and caudal frontoparietal regions show stimulus-dependent activations as described by the domain model. In the …

Sox9 Conditional Knockdown Reduces Chondroitin Sulphate Proteoglycan Expression, Increases Neuroplasticity, And Improves Motor Function In A Mouse Model Of Spinal Cord Injury, William M. Mckillop

Electronic Thesis and Dissertation Repository

This thesis investigates the effect of Sox9 knockdown on anti-regenerative scar gene expression, neuroplasticity, and hind limb functional recovery following mouse spinal cord injury. We hypothesized that Sox9 knockdown would reduce expression of anti-regenerative chondroitin sulfate proteoglycans both at the lesion site and at sites distant to the injury, thus providing an avenue for increased neuroplasticity and locomotor recovery after spinal cord injury. The first chapter provides a general introduction to the biological problem of spinal cord injury. The development of the glial scar and expression of the anti-regenerative chondroitin sulfate proteoglycan extracellular matrix is introduced, and Sox9 is identified …

Spatial And State-Dependent Effects Of Transcranial Magnetic Stimulation Of Prefrontal Cortex In Non-Human Primates, Chao Gu

Electronic Thesis and Dissertation Repository

The indirect effects of transcranial magnetic stimulation (TMS) within a distributed neural network are still largely unknown. Here we propose to use the non-human primate (NHP) oculomotor system as an animal model for investigating the effects of TMS. Across three animals, single pulses of TMS to the prefrontal cortex (PFC), including the frontal eye fields (FEF), reliably evoked a contralateral head turning synergy, similar to what is seen following intracortical microstimulation. Furthermore, double pulses of TMS paired with the memory-guided saccade paradigm only evoked neck muscle activity preceding contralateral saccades, showing similar state-dependency as previously observed in human TMS studies. …

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

Electronic Thesis and Dissertation Repository

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

A series of experiments were conducted in a …

Associations Between Hypothalamic-Pituitary-Adrenal Axis System Gene Variants And Cortisol Reactivity In Preschoolers: Main Effects And Gene-Environment Interactions, Haroon I. Sheikh

Electronic Thesis and Dissertation Repository

Exposure to stressful events during early development has consistently been shown to produce long lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis, which may increase vulnerability to mood and anxiety disorders. Recently reported genetic association studies indicate that these disorders may be influenced, in part, by gene-environment interactions (GxE) involving polymorphisms within the corticotrophin-releasing hormone and monoaminergic system genes. However, little is known about how genetic variants and life stress work to shape children’s neuroendocrine reactivity and emerging symptoms. Therefore, the aim of this thesis is to examine main effects of candidate genes and GxE on the neuroendocrine stress response and …

Optimizing The Analysis Of Electroencephalographic Data By Dynamic Graphs, Mehrsasadat Golestaneh

Electronic Thesis and Dissertation Repository

The brain’s underlying functional connectivity has been recently studied using tools offered by graph theory and network theory. Although the primary research focus in this area has so far been mostly on static graphs, the complex and dynamic nature of the brain’s underlying mechanism has initiated the usage of dynamic graphs, providing groundwork for time sensi- tive and finer investigations. Studying the topological reconfiguration of these dynamic graphs is done by exploiting a pool of graph metrics, which describe the network’s characteristics at different scales. However, considering the vast amount of data generated by neuroimaging tools, heavy computation load and …

When Faces "Feel" Familiar: The Role Of Affective Signals In Face Recognition, Lauren E. Dunphy

Electronic Thesis and Dissertation Repository

Previous research has suggested that there may be an increase in positive affect and autonomic arousal in response to seeing a familiar face. These studies rarely distinguish between faces for which there is only a “feeling” of familiarity, and faces for which this feeling is accompanied by the retrieval of semantic knowledge about the individual. In the current study we aimed to make that distinction. Participants made recognition judgments on famous and non-famous faces while galvanic skin responses (GSR), zygomatic muscle activity, and heart rate (HR) were recorded. We found increases in GSR (autonomic arousal), and zygomatic muscle activity (positive …

Where Do I Know That? A Distributed Multimodal Model Of Semantic Knowledge, Kevin M. Stubbs

Undergraduate Honors Theses

As computers have grown more and more powerful, computational modeling has become an increasingly valuable tool for evaluating real world findings. Likewise, brain imaging has become increasingly powerful as is evidenced by recent fMRI findings which support the exciting possibility that semantic memory is segregated by modality in the brain (Goldberg et al., 2006b). The present study utilizes connectionist modeling to put the distributed multi-modal framework of semantic memory to the test, and represents the next step forward in the line of sensory-functional models. This model, based around the McRae et al. (2005) feature production norms, includes individual implementations of …

Differential Effects Of Early-Life Seizures On Neuronal Inhibition In The Hippocampus Of Seizure-Prone And Seizure-Resistant Rats, Amir Abbas Mohseni Zonoozi

Electronic Thesis and Dissertation Repository

The aim of this study is to investigate the long-term physiological consequences of early-life seizures in rats of different genetic backgrounds. Rats bred to be prone (Fast) or resistant (Slow) to amygdala kindling were induced with status epilepticus (SE) on postnatal day (PND) 10 by injecting 3 mg/kg i.p. kainic acid; SE consisted of seizures for 2 h, including stage 5 seizures (lying down with four limb tonic-clonic convulsions). Littermates injected with the same volume of saline i.p. served as controls. On PND 40-55, population spikes (PSs) were recorded at the CA1 pyramidal cell layer in hippocampal slices in vitro …