ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Description
Many animals possess a blood-brain barrier, which is a layer of cells that restricts the passage of molecules into the central nervous system. The primary function of the blood-brain barrier is to preserve ionic homeostasis within the brain; however, it is also responsible for selectively importing an array of nutritional and signaling molecules to support brain function and for exporting metabolic waste. Across the species in which it has been studied, the structure and function of the blood-brain barrier dynamically regulates the interaction between the brain and peripheral physiological systems. Honeybee (Apis mellifera) workers are a firmly established neurobiological model which can be utilized to answer questions about the physiological and environmental mechanisms that regulate central nervous system health and behavior. It is likely that the honeybee blood-brain barrier plays an important role mediating the interactions between the brain and its environment, however, the blood-brain barrier is largely unconsidered in the realm of honeybee neurobiological research. In this dissertation, I provide the first in depth characterizations of the structure and function of the honeybee blood-brain barrier. First, I characterized the ultrastructural organization of the honeybee blood-brain barrier. The results of this study demonstrate its structural heterogeneity, including how this heterogeneity compares between two age groups. Next, I assessed two dimensions of blood-brain barrier permeability among three honeybee age groups and among honeybees exposed to varying amounts of infestation with the parasitic mite Varroa destructor. This study demonstrated that paracellular permeability has greater resilience than transcellular permeability, the latter of which is particularly increased by a high parasitic load. Finally, I developed a novel technique combining stable isotope labelling and Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) to demonstrate that the large, pro-social protein vitellogenin is able to cross the honeybee blood-brain barrier into the brain. Together, these studies represent the first in-depth analysis of the honeybee blood-brain barrier, establishing new directions for understanding the regulation of honeybee health, disease, and behavior.
ContributorsQuigley, Tyler (Author) / Amdam, Gro V. (Thesis advisor) / Bose, Maitrayee (Committee member) / Newbern, Jason (Committee member) / Bimonte-Nelson, Heather (Committee member) / Oland, Lynne (Committee member) / Arizona State University (Publisher)
Created2024
Description
This thesis explores the interplay of aphasia symptoms and brain connectivityusing resting-state functional Magnetic Resonance Imaging (MRI). The research presented here is a step towards understanding the neural basis of linguistic prosody in particular, and its relationship with language impairments in post-stroke aphasia. This study focuses on examining the functional connectivities of the frontal-parietal control network and the dorsal attention networks with specific regions within traditional language networks, as a growing body of research suggests that prosodic cues in speech may recruit control and attention networks to support language processing. Using resting- state fMRI, the present study examined the functional connectivity of the frontal parietal control and dorsal attention networks with traditional language regions in 28 participants who have experienced a stroke-related language impairment (i.e. aphasia) and 32 matched neurotypical adults. Overall, the study reveals significant functional connectivity differences of the frontoparietal control and dorsal attention networks between the stroke and control groups, indicating that individuals with aphasia have brain connectivity differences beyond the traditional language networks. Multiple regression analyses were then used to determine if functional connectivities of the frontoparietal control and dorsal attention networks within themselves and with traditional language regions could predict aphasia symptoms, as measured by the Western Aphasia Battery (WAB). Overall, the regression results indicate that greater functional connectivity between the frontoparietal control and dorsal attention networks with traditional language regions is associated with improved language abilities, with different connectivities predicting different types of aphasia symptoms (e.g. speech, naming / word finding, auditory comprehension, overall impairment). Altogether this study contributes to the understanding of the neural bases of language impairments post-stroke, highlighting the intricate connections between language and other cognitive networks, which may be mediated by prosody.
ContributorsMendhe, Surbhi Haridas (Author) / Rogalsky, Corianne (Thesis advisor) / Braden, B. Blair (Committee member) / Benitez, Viridiana (Committee member) / Arizona State University (Publisher)
Created2024
Description
The current program of work explores the potential efficacy of textured insoles for improving biomechanical performance and cognitive acuity during static and dynamic performance. Despite the vast conceptual framework supporting the versatile benefits of textured insoles, the current literature has primarily focused on incorporating this treatment during low-phase movements within the diseased and elderly subset populations. The current study expands this research application by administering textured insole treatments to a healthy population during a physically demanding dynamic assessment and correlating the results to subjects' sensory perception. A convenience sample of 10 subjects was evaluated for their ability to maintain bilateral standing balance in a static condition and adapt to confined lane perturbations during standard track running. These evaluations were conducted under both control and textured insole conditions. Subjects also completed a visual analog scale test, rating the insole treatments based on surface roughness to establish a statistical relationship between individual perception and biomechanical performance. Results showed that textured insole treatments given intermediate ratings of perceived surface roughness significantly enhanced performance during bilateral standing balance and standard track running perturbation adaptation.
ContributorsBoll, Christopher Marly (Author) / Coza, Aurel (Thesis advisor) / Santello, Marco (Committee member) / Lockhart, Thurmon (Committee member) / Arizona State University (Publisher)
Created2024
Description
The rate at which an operant is produced has often functioned as a fundamental measure of the efficacy of a reinforcer. Previous research has shown that operant behavior is typically organized into bouts implying that rate of responding is a composite of bout-initiation rate, within-bout response rate, and mean bout length. However, it is still unclear whether this organization of behavioral responses into bouts is a product of the motivational processes or a property that arises from the location of an organism in space. To test this proximity hypothesis, two-response sequences were intermittently reinforced: either pressing one lever twice (manipulandum proximal to response termination) or pressing each of two levers, located on either side of an operant chamber, once (manipulandum distal to response termination). In Experiment 1, rats were first trained to lever press for food on a VI schedule before being exposed to the alternation paradigm. Experiment 1 consisted of three phases. In Phase 1, food-deprived rats learned the alternation paradigm under a tandem variable time (VT) 150-s fixed-ratio (FR) 1 schedule of reinforcement. Phase 2 and 3 increased the FR requirement from 1 to 3 or 5 and removed food deprivation, respectively, to examine their effect on response-rate components. In Experiment 2, rats switched between trials consisting of pressing a single lever repeatedly or alternating between two levers for reward. Following stable behavior, lever pressing was extinguished in both trial types to the effect of extinction on response-rate components. Overall, behavioral bouts persisted under the alternation paradigm suggesting that they reflect motivational states and not just location. Additionally, bout-initiation rate decreased with increased response effort and decreased deprivation. Taken together, these results provide support for the use of response-bout analysis to evaluate the value of a reinforcer and its sensitivity to pharmacological manipulations.
ContributorsGildea, Matthew (Author) / Sanabria, Federico (Thesis advisor) / Gewirtz, Jonathan (Committee member) / Verpeut, Jessica (Committee member) / Arizona State University (Publisher)
Created2024
Description
The ability to detect and correct errors during and after speech production is essential for maintaining accuracy and avoiding disruption in communication. Thus, it is
crucial to understand the basic mechanisms underlying how the speech-motor system
evaluates different errors and correspondingly corrects them. This study aims to explore
the impact of three different features of errors, introduced by formant perturbations, on
corrective and adaptive responses: (1) magnitude of errors, (2) direction of errors, and (3)
extent of exposure to errors. Participants were asked to produce the vowel /ε/ in the
context of consonant-vowel-consonant words. Participant-specific formant perturbations
were applied for three magnitudes of 0.5, 1, 1.5 along the /ε-æ/ line in two directions of
simultaneous F1-F2 shift (i.e., shift in the ε-æ direction) and shift to outside the vowel
space. Perturbations were applied randomly in a compensation paradigm, so each
perturbed trial was preceded and succeeded by several unperturbed trials. It was observed
that (1) corrective and adaptive responses were larger for larger magnitude errors, (2)
corrective and adaptive responses were larger for errors in the /ε-æ/ direction, (3)
corrective and adaptive responses were generally in the /ε-ɪ/ direction regardless of
perturbation direction and magnitude, (4) corrective responses were larger for
perturbations in the earlier trials of the experiment.
ContributorsSreedhar, Anuradha Jyothi (Author) / Daliri, Ayoub (Thesis advisor) / Rogalsky, Corianne (Committee member) / Zhou, Yi (Committee member) / Arizona State University (Publisher)
Created2024
Description
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor function. Pathological mechanisms and clinical measures vary extensively from patient to patient, creating a spectrum of disease phenotypes with a poorly understood influence on individual outcomes like disease duration. The inability to ascertain patient phenotype has hindered clinical trial design and the development of more personalized and effective therapeutics. Wholistic analytical methods (‘-omics’) have provided unprecedented molecular resolution into cellular and system level disease processes and offer a foundation to better understand ALS disease variability. Building off initiatives by the New York Genome Center ALS Consortium and Target ALS groups, the goal of this work was to stratify a large patient cohort utilizing a range of bioinformatic strategies and bulk tissue gene expression (transcriptomes) from the brain and spinal cord. Central Hypothesis: Variability in the onset and progression of ALS is partially captured by molecular subgroups (subtypes) with distinct gene expression profiles and implicated pathologies. Work presented in this dissertation addresses the following: (Chapter 2): The use of unsupervised clustering and gene enrichment methods for the identification and characterization of patient subtypes in the postmortem cortex and spinal cord. Results obtained from this Chapter establish three ALS subtypes, identify uniquely dysregulated pathways, and examine intra-patient concordance between regions of the central nervous system. (Chapter 3): Patient subtypes from Chapter 2 are considered in the context of clinical outcomes, leveraging multiple survival models and gene co-expression analyses. Results from this Chapter establish a weak association between ALS subtype and clinical outcomes including disease duration and age at symptom onset. (Chapter 4): Utilizing differential expression analysis, ‘marker’ genes are defined and leveraged with supervised classification (“machine learning”) methods to develop a suite of classifiers design to stratify patients by subtype. Results from this Chapter provide postmortem marker genes for two of the three ALS subtypes and offer a foundation for clinical stratification. Significance: Knowledge gained from this research provides a foundation to stratify patients in the clinic and prior to enrollment in clinical trials, offering a path toward improved therapies.
ContributorsEshima, Jarrett (Author) / Smith, Barbara S (Thesis advisor) / Plaisier, Christopher L (Committee member) / Tian, Xiaojun (Committee member) / Fricks, John (Committee member) / Bowser, Robert (Committee member) / Arizona State University (Publisher)
Created2024
Description
Development of the central nervous system is an incredible process that relies on multiple extracellular signaling cues and complex intracellular interactions. Approximately 1500 genes are associated with neurodevelopmental disorders, many of which are linked to a specific biochemical signaling cascade known as Extracellular-Signal Regulated Kinase (ERK1/2). Clearly defined mutations in regulators of the ERK1/2 pathway cause syndromes known as the RASopathies. Symptoms include intellectual disability, developmental delay, cranio-facial and cardiac deficits. Treatments for RASopathies are limited due to an in complete understanding of ERK1/2’s role in brain development. Individuals with Neurofibromatosis Type and Noonan Syndrome, the two most common RASopathies, exhibit aberrant functional and white matter organization in non-invasive imaging studies, however, the contributions of neuronal versus oligodendrocyte deficits to this phenotype are not fully understood. To define the cellular functions of ERK1/2 in motor circuit formation, this body of work focuses on two long-range projection neuron subtypes defined by their neurotransmitter. With genetic mouse models, pathological ERK1/2 in glutamatergic neurons reduces axonal outgrowth, resulting in deficits in activity dependent gene expression and the ability to learn a motor skill task. Restricting pathological ERK1/2 within cortical layer V recapitulates these wiring deficits but not the behavioral learning phenotype. Moreover, it is uncovered that pathological ERK1/2 results in compartmentalized expression pattern of phosphorylated ERK1/2. It is not clear whether ERK1/2 functions are similar in cholinergic neuron populations that mediate attention, memory, and motor control. Basal forebrain cholinergic neuron development relies heavily on NGF-TrKA neurotrophic signaling known to activate ERK1/2. Yet the function of ERK1/2 during cholinergic neuronal specification and differentiation is poorly understood. By selectively deleting ERK1/2 in cholinergic neurons, ERK1/2 is required for activity-dependent maturation of neuromuscular junctions in juvenile mice, but not the establishment of lower motor neuron number. Moreover, ERK1/2 is not required for specification of choline acetyltransferase expressing basal forebrain cholinergic neurons by 14 days of age. However, ERK1/2 may be necessary for BFCN maturation by adulthood. Collectively, these data indicate that glutamatergic neuron-autonomous decreases in long-range axonal outgrowth and modest effects on later stages of cholinergic neuron maintenance may be important aspects of neuropathogenesis in RASopathies.
ContributorsRees, Katherina Pavy (Author) / Newbern, Jason (Thesis advisor) / Olive, Foster (Committee member) / Qiu, Shenfeng (Committee member) / Sattler, Rita (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2024
Description
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the deterioration of both upper and lower motor neurons in the brain, brain stem, and spinal cord. Multiple missense mutations have been connected to ALS, including mutations in the Matr3 gene. Matrin-3 is an RNA and DNA-binding protein encoded by the Matr3 gene. Normally found in the nuclear matrix, Matrin-3 plays several roles vital to RNA metabolism, including splicing, mRNA transport, mRNA stability, and transcription. The most common Matr3 mutation identified in familial ALS (fALS) patients is the S85C mutation, but the mechanisms through which it contributes to ALS pathology remain unknown. This makes mouse models particularly useful in elucidating pathological mechanisms, having the potential to serve as preclinical models for therapeutic drugs. For this thesis project, an ALS mouse model for the Matr3 S85C mutation was created, specifically generating a CRISPR/Cas9 mediated knock-in mouse model containing the Matr3 S85C mutation expressed under the control of the endogenous promoter. The Matr3S85C/S85C mice displayed significant phenotypic differences, such as reduced size, impaired motor coordination, and shortening of lifespan. Moreover, the Matr3S85C/S85C mice exhibited ALS-like pathology in both the muscle and central nervous system (CNS). Muscle pathology included decreased muscle fiber size and Matrin-3 loss. CNS pathology included selective neurodegeneration, Matrin-3 loss, neuroinflammation, and reduction of N6-methyladenosine (m6A) RNA modifications. Bulk RNA sequencing (RNA-seq) revealed significant differential gene expression in the Matr3S85C/S85C mice compared to Matr3+/+ mice, with synaptic pathways being particularly affected. Overall, the Matr3 S85C mutation induced both phenotypic effects and ALS-like pathology in vivo.
ContributorsHouchins, Nicole (Author) / Medina, David (Thesis advisor) / Velazquez, Ramon (Thesis advisor) / Tseng, Jui-Heng (Committee member) / Arizona State University (Publisher)
Created2024