Neuroscience and Neurobiology Commons^™

Quantifying Resting-State Functional Connectivity In Critically Brain-Injured Patients: A Graph-Theoretical Approach With Fnirs, Ira Gupta

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Assessment of consciousness in behaviourally unresponsive patients with critical brain injuries continues to be a challenge. There remains a need for robust tools that can accurately characterize preserved cortical function and predict patient outcomes. In the present study, functional near-infrared spectroscopy is employed in conjunction with graph theory and machine learning to quantify resting-state functional connectivity in 16 acutely brain-injured patients and 23 healthy controls. Results revealed significant channel-level differences between the groups for three graph metrics, including degree, clustering coefficient, and local efficiency. Further investigation using machine learning algorithms revealed that these metrics can be used to distinguish between …

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

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

Transferring Organelles Into Native Neurons: A Disease-Modifying Therapy For Neurodegenerative Disorders, Lohiny Balendran

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Currently, there are no disease-modifying therapies to counter the progression of neurodegenerative diseases that are associated with mitochondrial dysfunction in the early stages. In this study, we have used a novel strategy of cell fusion to transfer mitochondria from one cell to another using fusogens (syncytin 1 and syncytin 2). Syncytins are placental proteins encoded by endogenous retroviral envelope genes that promote cellular fusion. In this study, we have proposed that donor cells engineered to stably express syncytin when cocultured with recipient cells will allow fusion and facilitate the transfer of mitochondria into recipient cells. Syncytin-mediated systems revealed about 16.6-18.5% …

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

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While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …

Myeloarchitectonic Maps Of Cat Auditory Cortex, Austin Robertson

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The cerebral cortex contains myriad cortical areas that differ in structure, function, and connectivity. Current methods of delineating cortical structures and their subregions are insufficient for in vivo applications, either being highly invasive or requiring a detailed knowledge of a region’s tuning properties. To address this, we seek to establish a structural biomarker capable of delineating the cortex that possesses a non-invasive correlate. We explore myelin as a potential candidate by evaluating its efficacy in parcellating the feline auditory cortex through the generation of depthwise myelin density profiles for each of the 13 auditory cortical subregions. Our analyses revealed significant …

Dopaminergic Modulation Of A Fast Visuomotor Pathway In Parkinson's Disease, Madeline C. Gilchrist

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Parkinson’s disease (PD) is associated with reduced dopaminergic (DA) input to the dorsal striatum (DS). This study investigated the role of DA in modulating automatic, stimulus-driven reactions by assessing contextual control of stimulus-locked responses (SLRs) in 10 PD patients off and on DA medication. The SLR is the rapid recruitment of limb muscles that drives the arm towards suddenly appearing stimuli. Participants reached away from (anti-reach) or towards (pro-reach) a target on a screen, depending on instruction appearing 500 or 1000ms before target appearance. Modulation of SLRs was assessed by comparing SLR magnitude on anti- and pro-reach trials using surface …

Inter-Subject Correlation Using Movie-Driven Fmri In Drug-Resistant Epilepsy, Hana H. Abbas

Electronic Thesis and Dissertation Repository

Treating drug-resistant epilepsy with surgery requires the localization of the epileptic focus. We explored the potential for movie-driven functional magnetic resonance imaging (fMRI) to act as a sensitive, non-invasive, and cost-effective tool to identify functionally disturbed networks. We assessed neural synchronization (inter-subject correlation; ISC) between presurgical epilepsy patients (n = 18) and healthy controls (n = 24) as they watched a suspenseful movie clip in the scanner. To optimize denoising, we compared ISC values with and without an automated Independent Components Analysis-based denoising step (ICA-AROMA). We found that denoising with ICA-AROMA elicited augmented correlation values, supporting its use …

Potential Sex-Related Differences In Neurophysiology Post-Concussion, Alexandra N. Pauhl

Electronic Thesis and Dissertation Repository

The purpose of this study was to examine potential sex-related differences in neurophysiology in concussed and healthy individuals. There was a total of 21(9 F) participants in each group. The concussion (CONC) group reported to the lab within 72 hours, 1- and 2-weeks post-injury. The control (CONT) group followed a similar measurement schedule once recruited. Motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration was measured in the first dorsal interosseous muscle using transcranial magnetic stimulation. There were no significant differences in MEP amplitude or CSP duration between the CONC and CONT group. As well, there was no …

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

Electronic Thesis and Dissertation Repository

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

Computational Unfolding Of The Human Hippocampus, Jordan M. K. Dekraker

Electronic Thesis and Dissertation Repository

The hippocampal subfields are defined by their unique cytoarchitectures, which many recent studies have tried to map to human in-vivo MRI because of their promise to further our understanding of hippocampal function, or its dysfunction in disease. However, recent anatomical literature has highlighted broad inter-individual variability in hippocampal morphology and subfield locations, much of which can be attributed to different folding configurations within hippocampal (or archicortical) tissue. Inspired in part by analogous surface-based neocortical analysis methods, the current thesis aimed to develop a standardized coordinate framework, or surface-based method, that respects the topology of all hippocampal folding configurations. I developed …

Assessment Of Intrinsic Hand Neuromuscular Physiology, Philemon Tsang

Electronic Thesis and Dissertation Repository

Alterations to the peripheral nervous system and neuromuscular physiology may impact hand function in a typical or clinical population, such as individuals with ulnar neuropathy. The mechanisms that influence these positive and negative changes are still not well understood. The three studies within my thesis aim to validate the reliability of decomposition-based quantitative electromyography (DQEMG) measurements and explore the changes in intrinsic hand neuromuscular physiology in a typical aging population and individuals recovering from a surgical intervention for severe ulnar neuropathy.

The purpose of the first study was to determine the test-retest reliability of near-fibre (NF) jiggle, a measure of …

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

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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 …

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 – …

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 …

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 …

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 …

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

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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 …

Role Of Anterior Cingulate Cortex In Saccade Control, Sahand Babapoor-Farrokhran

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Cognitive control is referred to the guidance of behavior based on internal goals rather than external stimuli. It has been postulated that prefrontal cortex is mainly involved in higher order cognitive functions. Specifically, anterior cingulate cortex (ACC), which is part of the prefrontal cortex, is suggested to be involved in performance monitoring and conflict monitoring that are considered to be cognitive control functions.

Saccades are the fast eye movements that align the fovea on the objects of interest in the environment. In this thesis, I have explored the role of ACC in control of saccadic eye movements. First, I performed …

The Neuroprotective Effects Of Endurance Training On The Aging Brain, Katelyn Norton

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Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known and may relate to alterations in brain structure (e.g. cortical atrophy) and/or altered neural function, particularly in regions related to the cortical autonomic network, namely, the medial prefrontal cortex (MPFC), insula cortex (IC), and hippocampus (HC). Exercise exerts beneficial effects on brain structure and, in the case of cognition, neurologic function; however, how exercise affects regions of the brain related to autonomic function are not known. This thesis tested …

Unravelling The Subfields Of The Hippocampal Head Using 7-Tesla Structural Mri, Jordan M. K. Dekraker

Electronic Thesis and Dissertation Repository

Probing the functions of human hippocampal subfields is a promising area of research in cognitive neuroscience. However, defining subfield borders in Magnetic Resonance Imaging (MRI) is challenging. Here, we present a user-guided, semi-automated protocol for segmenting hippocampal subfields on T2-weighted images obtained with 7-Tesla MRI. The protocol takes advantage of extant knowledge about regularities in hippocampal morphology and ontogeny that have not been systematically considered in prior related work. An image feature known as the hippocampal ‘dark band’ facilitates tracking of subfield continuities, allowing for unfolding and segmentation of convoluted hippocampal tissue. Initial results suggest that this protocol offers sufficient …

Deep Brain Stimulation And Its Effects On Parkinson Disease Spatiotemporal Gait Parameters., Greydon Gilmore

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Subthalamic (STN) deep brain stimulation (DBS) alleviates common appendicular PD symptoms, such as: tremor, rigidity and bradykinesia. However, the effect STN-DBS has on modulating axial gait features has not been properly quantified objectively. The purpose of the present thesis was to investigate the role STN-DBS plays in modulating specific gait features such as pace, asymmetry, variability, rhythm and postural control. It is hypothesized that axial gait function is regulated predominantly by non-dopaminergic control systems. In the acute immediate post-operative phase a surgical effect, named the microlesion effect (MLE), is thought to produce a transient improvement of appendicular and axial symptoms. …

Quantifying The Effects Of Systematic Stn-Dbs Programming On Rest And Postural Tremor In Idiopathic Parkinson Disease Patients, Kristina Ognjanovic

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is a complex neurodegenerative disorder that encompasses both motor and non-motor symptoms. These symptoms and their severity are typically assessed by scale based measures in a clinical setting. Scale- based assessments of PD patients undergoing bilateral subthalamic nucleus deep brain stimulation surgery (STN-DBS) such as the Unified Parkinson Disease Rating Scale (UPDRS) are commonly used in a clinical setting to assess symptom severity and progression. However, the subjective nature of these and other clinical scales call into question both the sensitivity and accuracy of patient assessment over time. An objective quantification of rest and postural tremor of …

Modulation Of Synaptic Plasticity By Hippocampal Theta Rhythm, Clayton Law

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The hippocampal theta rhythm facilitates memory formation. This study investigated the temporal relation of long-term potentiation (LTP) with the hippocampal theta rhythm. Theta rhythm consists of a wave of somatodendritic depolarization, but the depolarization of apical and basal dendrites of hippocampal CA1 pyramidal cells peak at a similar theta phase. Thus, we hypothesize that the population spike excitability evoked by excitation of the apical and basal dendrites peak at a similar phase of the theta rhythm. We also expect that LTP at the basal and apical dendritic synapses to be maximal at a similar theta phase.

Rats (~300 g) were …

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 …

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

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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 …

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 …

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

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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 …

Investigating The Pathological Response To Beta Amyloid Toxicity In Rats: The Role Of Age And The Antioxidant Catalase-Skl, Hayley J. Nell

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Accumulation of beta-amyloid (Aβ) in the brain is a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer’s disease (AD). In part, Aβ exerts its toxic effects by increasing reactive oxygen species (ROS) and neuroinflammation in the brain. Aging, a major risk factor for AD is also associated with increased production of ROS. This study investigated the age-related pathological response to Aβ toxicity and examined whether catalase-SKL(CAT-SKL), a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase, is able to reduce Aβ toxicity. Bilateral intracerebroventricular (icv) injections of the Aβ_25-35 peptide was used to model Aβ …