Neuroscience and Neurobiology Commons^™

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

Electronic Thesis and Dissertation Repository

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 …

Postexercise Executive Function Benefits And Cerebral Blood Flow: In The Lab And At Home, Benjamin Tari

Electronic Thesis and Dissertation Repository

A single bout of aerobic exercise improves executive function; however, the mechanism, or mechanisms, supporting this improvement remain unclear. One candidate mechanism is an exercise-mediated increase in cerebral blood flow (CBF) that enhances the efficiency of executive-related frontoparietal networks. To evaluate the link between exercise, CBF and executive function, three separate experiments were conducted. In the first study, separate 10-min sessions of moderate-to-heavy-intensity aerobic exercise, and a hypercapnic environment (i.e., 5% CO₂) were implemented. The hypercapnic condition was included because it increases CBF independent of the metabolic demands of exercise. The second study investigated whether exercise intensity-specific changes …

Regulation Of Hedgehog And Wnt Signaling In Neural Differentiation Of P19 Embryonal Carcinoma Cells, Danielle Margaret Spice

Electronic Thesis and Dissertation Repository

The Hedgehog (Hh) and Wnt protein signaling pathways are essential in the differentiation of neurons and astrocytes. As there are many known and new players involved in regulating these pathways, the role of the regulators Suppressor of Fused (SUFU) and Never in Mitosis Kinase 2 (Nek2) have either not been previously reported or have not been thoroughly explored. To address this shortfall CRISPR gene editing was used to target SUFU and Nek2 in the mouse P19 embryonal carcinoma cell model of neural differentiation. Hh and Wnt signaling were explored in normal P19 neural differentiation, which occurs in the presence of …

The Clinical Value Of Oculomotor Assessments Across The Continuum Of Concussion, Dillon Richards

Electronic Thesis and Dissertation Repository

Concussions are complex conditions that are difficult to manage medically. Variations in symptom presentation, intricate neurophysiological processes, and the availability of a variety of possible assessment tools may contribute to this complexity. Clinicians must use a broad approach, employing both subjective symptom assessment and objective assessments to confirm a diagnosis and/or monitor progression and recovery. Oculomotor function after concussion may be an important indicator of injury, given the interconnectedness of oculomotor function, vestibulo-ocular and visual systems, and even cognition. Oculomotor function may be assessed objectively or indirectly using patient-reported symptom checklists as part of subjective assessments. One way of objectively …

The Effect Of Active Learning On Viewpoint Dependence For Novel Objects, Cassandra Wallace Bacher

Electronic Thesis and Dissertation Repository

Active learning of novel objects can facilitate subsequent object recognition and discrimination, but the reasons for its beneficial effects remain unclear. One potential explanation is that active learning enables the formation of a more detailed, realistic, or useful neural object representation than does passive learning. The current study addressed the question of whether active vs. passive learning of objects affects viewpoint discrimination. Participants learned novel wire-like objects either actively or passively and then completed a psychophysical task which they discriminated object orientation. This study did not find a significant difference in viewpoint discrimination between actively and passively learned object representations, …

Using Machine Learning To Identify Neural Mechanisms Underlying The Development Of Cognition In Children And Adolescents With Adhd, Brian Pho

Electronic Thesis and Dissertation Repository

Childhood and adolescence are marked by improvements to cognition and by the emergence of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). What neural mechanisms are associated with cognitive development in ADHD? In this study, I applied machine learning models to functional connectivity profiles to identify patterns of network connectivity that predict various cognitive abilities in a group of participants ages 6 to 16 with ADHD. The models successfully predicted IQ, visual spatial, verbal comprehension, and fluid reasoning in children ages 6 to 11, but not adolescents. Furthermore, the models identified connections with the default mode, memory retrieval, and …

The Express Sensorimotor Response Selects Visual Features Based On Instruction, David Youhanna Mekhaiel

Electronic Thesis and Dissertation Repository

In time-sensitive situations, orienting reflexes allow us to move rapidly in response to stimuli. The express sensorimotor response (ESR) is an orienting reflex presenting as a brief burst of muscle recruitment. Previous studies have identified commonalities between ESRs and express saccades, another orienting reflex.

In this study, we investigate if ESRs share in a characteristic of express saccades: preference for faces. In separate blocks, participants were instructed to reach toward one of two simultaneously appearing targets: a face and another image. Muscle activity in the pectoralis major muscle of the reaching arm was recorded using skin surface EMGs.

We …

Human Neuroimaging Reveals That Agency In A Video Game Boosts Functional Connectivity Within And Between Networks, Emily J. Davidson

Electronic Thesis and Dissertation Repository

In naturalistic settings, brains continuously interface with a dynamic and interactive external environment. The inclusion of such an environment in an fMRI study is difficult, given the practical constraints imposed by the machine itself. This study sought to test whether the ecological validity of fMRI could be enhanced by testing a new paradigm that incorporated a dynamic and interactive virtual environment (DIVE). To determine the viability of this paradigm, functional connectivity was assessed during a DIVE condition and compared to functional connectivity patterns acquired in conditions with equally dynamic stimuli but that lacked interactivity with the environment. This study found …

The Effect Of Propionic Acid On The Habituation To Social And Non-Social Odour Cues In Adult Male Rats, Cashmeira-Dove P. Tyson

Electronic Thesis and Dissertation Repository

The enteric bacterial metabolite, propionic acid (PPA), elicits physiological and behavioural changes in rodents reminiscent of autism spectrum disorder (ASD). This includes abnormal sensory processing and social behaviour. ASD may contribute to social deficits through impaired habituation; therefore, the present study examined the effects of intraperitoneal PPA on the habituation to social and non-social odours. Adult male rats were injected daily with PPA or the vehicle control, and for 3 days, habituated to a conspecific odour or vanilla extract for 10 minutes. On day 4, rats were exposed to a novel conspecific odour or almond extract for 10 minutes to …

Examining The Relationships Between Socio-Cognitive Factors And Neural Synchrony During Movie Watching Across Development, Kathleen M. Lyons

Electronic Thesis and Dissertation Repository

While different cognitive abilities mature, the conscious experiences of children likely become richer and more elaborate. A challenge in investigating relationships between cognitive development and real-world experiences is having measures that assess naturalistic processing. Movie watching offers a solution, since following the plot of a film requires cognitive processes that are similar to real-world experiences. When different adults watch the same film, their brain activity begins to align (known as neural synchrony). The strength of this alignment has been shown to reflect the degree to which different individuals are having a similar experience of the movie. While this phenomenon has …

Role Of The Default-Mode Network During Narrative Integration In Major Depressive Disorder, Darren Ri-Sheng Liang

Electronic Thesis and Dissertation Repository

How brain activity is synchronized across individuals during narrative comprehension has previously been characterized by functional magnetic resonance imaging (fMRI) in healthy and patient populations. To our knowledge, there has been limited investigation as to how it is affected by major depressive disorder (MDD). We addressed this issue with fMRI through examination of inter-subject synchronization in the default mode network (DMN), brain structures which have previously been implicated in MDD pathology. Twenty-two patients with MDD and 20 matched control participants listened to Intact versus Scrambled versions of an auditory narrative; these experimental conditions differed in the degree of temporal integration …

Exploring The Inter-Relationship Between Cognitive And Motor Function In People With Lower Limb Amputations, Humberto Adolfo Omaña Moreno

Electronic Thesis and Dissertation Repository

The main objective of the present dissertation was to expand our understanding of the inter-relationship between cognition and mobility in people with lower limb amputations (PLLA). Study 1 systematically reviewed the literature to assess the effects of dual-task testing on the balance and gait of PLLA. A total of twenty-two studies were included. Overall, PLLA demonstrated a disproportionately greater dual-task effect than controls, characterized by increased sway velocity and reduced pace and rhythm, and increased asymmetry when balance or walking was paired with a secondary task. Additionally, the dual-task effect was not influenced by differences in etiology, level of amputation, …

The Effects Of Transcranial Direct Current Stimulation On Beat Perception And Motor Performance, Marina Emerick

Electronic Thesis and Dissertation Repository

Humans have an intrinsic tendency to move to music. However, our understanding of the neural mechanisms underlying the music-movement connection remains limited, and most studies have used correlational methods. Here, we used transcranial direct current stimulation (tDCS) to causally investigate the role of four motor brain regions involved in movement timing and beat perception: the supplementary motor area (SMA), left and right premotor cortices (PMC), and cerebellum. Subjects were randomly assigned to a brain region to be stimulated and received anodal, cathodal, or sham stimulation on three different days while they reproduced rhythmic sequences. The sequences had either a strong …

Prefrontal Coding Of Naturalistic Working Memory: Mechanisms During Normal Maintenance And Modelled Disease, Megan P. Roussy

Electronic Thesis and Dissertation Repository

Neural activity in the primate lateral prefrontal cortex (LPFC) has been causally linked to working memory (WM) ⁠— the brief maintenance and mental manipulation of information. Primates use WM to perform tasks in complex contexts; however, neural mechanisms of WM and the pathophysiology related to WM deficits have traditionally been studied using simple tasks that deviate from naturalistic conditions. This raises the question, how is WM processed in naturalistic conditions? To explore this, I trained two macaque monkeys on a spatial WM task set in a naturalistic virtual environment. During the task, a target was presented in 1 of 9 …

Myeloarchitectonic Maps Of Cat Auditory Cortex, Austin Robertson

Electronic Thesis and Dissertation Repository

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 …

Durability Of Motor Learning By Observation, Natalia Mangos

Electronic Thesis and Dissertation Repository

Recent evidence suggests that neural representations of novel movement dynamics can be acquired by observing someone else experiencing them first-hand. Visual information about another person’s movement kinematics can be transformed into an adaptation of feedforward limb control for the observer; however, little is known about the durability of this adaptation. Despite the longevity of changes in the motor system being a defining characteristic of motor learning, studies to date have only examined observation-related effects shortly after observation has occurred, leaving unknown whether such effects are transient phenomena or products of learned, durable changes in neural systems. We measured human participants’ …

Coordinate Frame For Proprioception Acuity Changes Accompanying Motor Learning, Heba Hussian

Electronic Thesis and Dissertation Repository

Proprioception is important for skilled motor control. Improvements in proprioception occur in conjunction with motor learning. However, it has not been established whether these improvements occur within intrinsic or extrinsic coordinate frames. In Experiment 1 we gave participants a perceptual test of sensed limb position and a motor learning task in the same location of the workspace or in two different locations of the workspace. Participants performed better on the proprioception test when the motor learning task was completed in the same location as the proprioception test. In Experiment 2 we tested whether this perceptual improvement occurred in an intrinsic …

Examining The Association Between Brain Mri Measures At 7 Tesla And Cognition Following Covid-19 Infection, Helma Heidari

Electronic Thesis and Dissertation Repository

The long-term neuropsychological, cognitive, and neurobiological effects of the severe acute respiratory syndrome (SARS-CoV-2) in survivors with milder symptoms are still poorly understood. In this thesis we evaluated cognitive and psychological changes approximately five weeks after a wide range of symptoms in COVID-19 illness and determined whether advanced diffusion magnetic resonance imaging measures within subcortical brain structures of the limbic system were related to neurological, respiratory, psychiatric, and gastric symptoms experienced during the acute phase of illness. Cognitive and neuropsychological evaluations were performed in 45 participants who experienced neurological symptoms during the acute phase of COVID-19 illness. Participants also underwent …

Neural Circuitry Of The Midbrain Pedunculopontine Tegmental Nucleus Regarding Its Role In Sensorimotor Gating, Niveen Fulcher

Electronic Thesis and Dissertation Repository

The brain is a complicated structure that receives copious amounts of information at any given time. The pedunculopontine tegmental nucleus (PPTg) is involved in many innate functions like arousal, rapid eye-movement (REM) sleep, reward association and sensorimotor gating. Although commonly referred to as a cholinergic structure, it also contains glutamatergic and GABAergic neurons. Based on chronic PPTg lesions that disrupted PPI, cholinergic PPTg neurons were long assumed to mediate prepulse inhibition (PPI) of startle, a measure of sensorimotor gating. Deficits of PPI are observed in a variety of neurological disorders, including Autism Spectrum Disorder (ASD), Obsessive-Compulsive Disorder (OCD), and is …

The Influence Of Intersegmental Dynamics On Limb Position Sense, Peyman R. Heidari

Electronic Thesis and Dissertation Repository

During multijoint limb movement, the motion of limb segments can be driven actively, by muscle torque, and/or passively, by interaction torque–rotational force that arises passively at one joint due to motion of an adjacent limb segment about another joint. Proprioception plays a critical role in compensating for interaction torques, and deafferented patients have marked deficits in this aspect of motor control. This observation is seemingly at odds with the widely-held belief that proprioceptive sense is poor during motion that is not driven by active muscle contraction, and suggests that proprioceptive acuity might be preserved during motion that is driven by …

Neural Correlates Of Familiarity Across Time Scales And Their Involvement In Explicit Memory Decisions, Haopei Yang

Electronic Thesis and Dissertation Repository

Familiarity is a type of memory signal that can support recognition of prior occurrences without retrieval of associated contextual information. It is typically probed with respect to recent laboratory exposure in recognition-memory studies involving human participants. This line of work has revealed several neural correlates including event-related potentials (ERPs) and blood-oxygenation-level-dependent (BOLD) activity in several regions. However, few studies have examined familiarity accumulated outside of laboratory settings through lifetime experience. Hence, it is currently unclear whether similar neural correlates are involved. The fluency-attribution framework decomposes familiarity judgement into automatic and decision-related processes. Since recent and lifetime familiarity are phenomenologically and …

An Implementation Of Integrated Information Theory In Resting-State Fmri, Idan E. Nemirovsky

Electronic Thesis and Dissertation Repository

Integrated Information Theory (IIT) is a framework developed to explain consciousness, arguing that conscious systems consist of interacting elements that are integrated through their causal properties. In this study, we present the first application of IIT to functional magnetic resonance imaging (fMRI) data and investigate whether its principal metric, Phi, can meaningfully quantify resting-state cortical activity patterns. Data was acquired from 17 healthy subjects who underwent sedation with propofol, a short acting anesthetic. Using PyPhi, a software package developed for IIT, we thoroughly analyze how Phi varies across different networks and throughout sedation. Our findings indicate that variations in Phi …

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant

Electronic Thesis and Dissertation Repository

Transfer RNAs (tRNAs) physically link the genetic code to an amino acid sequence, by recruiting amino acids to three-nucleotide codons in messenger RNAs. To ensure that the genetic code is translated as intended, tRNAs must be accurately aminoacylated and faithfully recognize codons in the ribosome during protein synthesis. Given the critical function of tRNAs, it has often been assumed that mutations in human tRNA genes would be either lethal to cells or not significantly impair tRNA function. My goal was to rigorously test this assumption in mammalian cell models, prompted by the recent discovery of unprecedented variation in human tRNA …

Mapping The Functional Organization Of Human Frontoparietal Cortex With Fmri, Geetika Gupta

Electronic Thesis and Dissertation Repository

Higher-order cognitive functions, such as working memory, attention, and decision making, depend strongly on the functional integrity of frontal and parietal cortices. However, the internal workings of the frontoparietal network (FPN) are not well understood. A major contributor to this knowledge gap is our limited understanding of the intrinsic functional organization of the FPN. In order to address this gap, we examine task-dependent reconfigurations of functional connectivity (FC) within the FPN. We analyzed fMRI task-state data from 924 individuals from the Human Connectome Project Young Adult study. Our results show that FC within the FPN is highly stable across time …