Matching Items (142)
Filtering by
- Genre: Doctoral Dissertation
Description
The goal of this thesis is to test whether Alzheimer's disease (AD) is associated with distinctive humoral immune changes that can be detected in plasma and tracked across time. This is relevant because AD is the principal cause of dementia, and yet, no specific diagnostic tests are universally employed in clinical practice to predict, diagnose or monitor disease progression. In particular, I describe herein a proteomic platform developed at the Center for Innovations in Medicine (CIM) consisting of a slide with 10.000 random-sequence peptides printed on its surface, which is used as the solid phase of an immunoassay where antibodies of interest are allowed to react and subsequently detected with a labeled secondary antibody. The pattern of antibody binding to the microarray is unique for each individual animal or person. This thesis will evaluate the versatility of the microarray platform and how it can be used to detect and characterize the binding patterns of antibodies relevant to the pathophysiology of AD as well as the plasma samples of animal models of AD and elderly humans with or without dementia. My specific aims were to evaluate the emergence and stability of immunosignature in mice with cerebral amyloidosis, and characterize the immunosignature of humans with AD. Plasma samples from APPswe/PSEN1-dE9 transgenic mice were evaluated longitudinally from 2 to 15 months of age to compare the evolving immunosignature with non-transgenic control mice. Immunological variation across different time-points was assessed, with particular emphasis on time of emergence of a characteristic pattern. In addition, plasma samples from AD patients and age-matched individuals without dementia were assayed on the peptide microarray and binding patterns were compared. It is hoped that these experiments will be the basis for a larger study of the diagnostic merits of the microarray-based immunoassay in dementia clinics.
ContributorsRestrepo Jimenez, Lucas (Author) / Johnston, Stephen A. (Thesis advisor) / Chang, Yung (Committee member) / Reiman, Eric (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2011
Description
The ability to plan, execute, and control goal oriented reaching and grasping movements is among the most essential functions of the brain. Yet, these movements are inherently variable; a result of the noise pervading the neural signals underlying sensorimotor processing. The specific influences and interactions of these noise processes remain unclear. Thus several studies have been performed to elucidate the role and influence of sensorimotor noise on movement variability. The first study focuses on sensory integration and movement planning across the reaching workspace. An experiment was designed to examine the relative contributions of vision and proprioception to movement planning by measuring the rotation of the initial movement direction induced by a perturbation of the visual feedback prior to movement onset. The results suggest that contribution of vision was relatively consistent across the evaluated workspace depths; however, the influence of vision differed between the vertical and later axes indicate that additional factors beyond vision and proprioception influence movement planning of 3-dimensional movements. If the first study investigated the role of noise in sensorimotor integration, the second and third studies investigate relative influence of sensorimotor noise on reaching performance. Specifically, they evaluate how the characteristics of neural processing that underlie movement planning and execution manifest in movement variability during natural reaching. Subjects performed reaching movements with and without visual feedback throughout the movement and the patterns of endpoint variability were compared across movement directions. The results of these studies suggest a primary role of visual feedback noise in shaping patterns of variability and in determining the relative influence of planning and execution related noise sources. The final work considers a computational approach to characterizing how sensorimotor processes interact to shape movement variability. A model of multi-modal feedback control was developed to simulate the interaction of planning and execution noise on reaching variability. The model predictions suggest that anisotropic properties of feedback noise significantly affect the relative influence of planning and execution noise on patterns of reaching variability.
ContributorsApker, Gregory Allen (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Santos, Veronica (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2012
Description
Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control from the brain. In the case of incomplete paraplegia, locomotion is impaired and often results in increased incidence of foot drag and decreased postural stability after injury. The overall goal of this work is to understand how changes in kinematics of movement and neural control of muscles effect locomotor coordination following SCI. Toward this end, we examined musculoskeletal parameters and kinematics of gait in rats with and without incomplete SCI (iSCI) and used an empirically developed computational model to test related hypotheses. The first study tested the hypothesis that iSCI causes a decrease in locomotor and joint angle movement complexity. A rat model was used to measure musculoskeletal properties and gait kinematics following mild iSCI. The data indicated joint-specific changes in kinematics in the absence of measurable muscle atrophy, particularly at the ankle as a result of the injury. Kinematic changes manifested as a decrease in complexity of ankle motion as indicated by measures of permutation entropy. In the second study, a new 2-dimensional computational model of the rat ankle combining forward and inverse dynamics was developed using the previously collected data. This model was used to test the hypothesis that altered coordination of flexor and extensor muscles (specifically alteration in burst shape and timing) acting at the ankle joint could be responsible for increases in incidence of foot drag following injury. Simulation results suggest a time course for changes in neural control following injury that begins with foot drag and decreased delay between antagonistic muscle activations. Following this, beneficial adaptations in muscle activation profile and ankle kinematics counteract the decreased delay to allow foot swing. In both studies, small changes in neural control caused large changes in behavior, particularly at the ankle. Future work will further examine the role of neural control of hindlimb in rat locomotion following iSCI.
ContributorsHillen, Brian (Author) / Jung, Ranu (Thesis advisor) / Abbas, James (Committee member) / Muthuswamy, Jit (Committee member) / Jindrich, Devin (Committee member) / Yamaguchi, Gary (Committee member) / Arizona State University (Publisher)
Created2012
Description
This dissertation constructs a new computational processing framework to robustly and precisely quantify retinotopic maps based on their angle distortion properties. More generally, this framework solves the problem of how to robustly and precisely quantify (angle) distortions of noisy or incomplete (boundary enclosed) 2-dimensional surface to surface mappings. This framework builds upon the Beltrami Coefficient (BC) description of quasiconformal mappings that directly quantifies local mapping (circles to ellipses) distortions between diffeomorphisms of boundary enclosed plane domains homeomorphic to the unit disk. A new map called the Beltrami Coefficient Map (BCM) was constructed to describe distortions in retinotopic maps. The BCM can be used to fully reconstruct the original target surface (retinal visual field) of retinotopic maps. This dissertation also compared retinotopic maps in the visual processing cascade, which is a series of connected retinotopic maps responsible for visual data processing of physical images captured by the eyes. By comparing the BCM results from a large Human Connectome project (HCP) retinotopic dataset (N=181), a new computational quasiconformal mapping description of the transformed retinal image as it passes through the cascade is proposed, which is not present in any current literature. The description applied on HCP data provided direct visible and quantifiable geometric properties of the cascade in a way that has not been observed before. Because retinotopic maps are generated from in vivo noisy functional magnetic resonance imaging (fMRI), quantifying them comes with a certain degree of uncertainty. To quantify the uncertainties in the quantification results, it is necessary to generate statistical models of retinotopic maps from their BCMs and raw fMRI signals. Considering that estimating retinotopic maps from real noisy fMRI time series data using the population receptive field (pRF) model is a time consuming process, a convolutional neural network (CNN) was constructed and trained to predict pRF model parameters from real noisy fMRI data
ContributorsTa, Duyan Nguyen (Author) / Wang, Yalin (Thesis advisor) / Lu, Zhong-Lin (Committee member) / Hansford, Dianne (Committee member) / Liu, Huan (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2022
Description
Cocaine use disorders (CUDs) and human immunodeficiency virus (HIV) are a common comorbidity, although it is largely unknown whether HIV interacts with cocaine abstinence to uniquely alter neuroimmune function and whether HIV may modulate the efficacy of medications intended to treat CUDs. My dissertation research demonstrates using preclinical rodent models of drug self-administration and craving that systemic exposure to the HIV protein gp120 produces a unique profile of neuroimmune changes within the nucleus accumbens core (NAc core) that is distinct from early cocaine abstinence alone. After a protracted period of abstinence, gp120 exposure abolished the effect of the dopamine D3 receptor (D3R) partial agonist MC-25-41, which successfully attenuated cue-induced cocaine seeking in non-exposed rats. Further probing the role of downstream, intracellular neuroimmune function on cue-induced cocaine seeking, I examined the role of the nuclear factor kappa B (NF-κB) signaling pathway within the NAc core on cue-induced cocaine seeking after a period of protracted abstinence across sex and reinforcer type. I demonstrated that knockdown of the p65 subunit of NF-κB results in a decrease in cue-induced cocaine seeking in males, but not in females. This effect was specific to cocaine, as p65 knockdown did not affect cue-induced sucrose seeking in either males or females. Moreover, I examined expression levels of the extracellular matrix enzyme MMP-9 within the NAc core, as it is regulated by NF-κB and is an important mediator of cue-induced cocaine seeking and associated synaptic plasticity. I demonstrated that males express higher levels of MMP-9 within the NAc compared to females, and that p65 knockdown decreases NAc core MMP-9 in males but not females among cocaine cue-exposed animals. Altogether, these results suggest that immunotherapeutic medications may be useful tools in the treatment of CUDs, particularly among males that are disproportionately impacted by HIV.
ContributorsNamba, Mark Douglas (Author) / Neisewander, Janet L (Thesis advisor) / Olive, M Foster (Thesis advisor) / Sanabria, Federico (Committee member) / Ferguson, Deveroux (Committee member) / Arizona State University (Publisher)
Created2022
Description
Electrical stimulation of the human peripheral nervous system can be a powerful tool to treat various medical conditions and provide insight into nervous system processes. A critical challenge for many applications is to selectively activate neurons that have the desired effect while avoiding the activation of neurons that produce side effects. To stimulate peripheral fibers, the longitudinal intrafascicular electrode (LIFE) targets small groups of fibers inside the fascicle using low-amplitude pulses and is well-suited for chronic use. This work aims to understand better the ability to use intrafascicular stimulation with LIFEs to activate small groups of neurons within a fascicle selectively.A hybrid workflow was developed to simulate: 1) the production/propagation of the electric field induced by the stimulation pulse and 2) the effect of the electric field on fiber activation (recruitment). To create efficient and robust strategies for the selective recruitment of axons, recognizing the effect of each parameter on their recruitment and activation pattern is essential. Thus, using this hybrid workflow, the effects of various factors such as fascicular anatomy, electrode parameters, and stimulation pulse parameters on recruitment have been characterized, and the sensitivity of the recruitment patterns to these parameters has been explored.
Results demonstrated the potential advantages of specific stimulation strategies and the sensitivity of recruitment patterns to electrode placement and tissue properties. For example, it is demonstrated: the significant effect of endoneurium conductivities on threshold levels; that a configuration with a LIFE as a local ground can be used to deselect its surrounding axons; the advantages of changing the delay between pulses in dual monopolar stimulation in targeting different axons clusters and increasing the activation frequency of some axons; how monopolar and bipolar configurations can be used to enhance spatial selectivity; the effect of longitudinal displacement of axons, electrode length and electrode movement on the recruitment and the activation pattern. In summary, this work forms the foundation for developing stimulation strategies to enhance the selectivity that can be achieved with intrafascicular stimulation.
ContributorsRouhani, Morteza (Author) / Abbas, James J (Thesis advisor) / Crook, Sharon M (Thesis advisor) / Baer, Steven M (Committee member) / Sadleir, Rosalind (Committee member) / Gardner, Carl (Committee member) / Arizona State University (Publisher)
Created2022
Description
For patients with focal drug-resistant epilepsy, surgical remediation can be a hopeful last resort treatment option, but only if enough clinical signs can point to an epileptogenic tissue region. Subdural grids offer ample cortical surface area coverage to evaluate multiple regions of interest, yet they lack the spatial resolution typical of penetrating electrodes. Additionally, subthreshold stimulation through subdural grids is a stable source for detecting eloquent cortex surrounding potential epileptic tissue. Researchers have each tried introducing microelectrodes to increase the spatial resolution but ran into connectivity challenges as the desired surface area increased. Meanwhile, clinical hybrid options have shown promise by combining multiple electrode sizes, maintaining surface area coverage with an increased spatial resolution where necessary. However, a benchtop method to quantify spatial resolution or test signal summation, without the complexity of an in vivo study, has not been found in the literature; a subdural grid in gel solution has functioned previously but without a published method. Thus, a novel hybrid electrode array with a telescopic configuration including three electrode geometries, called the M$^3$ array, is proposed to maintain cortical surface area coverage and provide spatial clarity in regions of interest using precision microfabrication techniques. Electrophysiological recording with this array should enhance the clinical signal portfolio without changing how clinicians interface with the broad surface data from macros. Additionally, this would provide a source for simultaneous recording and stimulation from the same location due to the telescopic nature of the design. A novel benchtop test method should remove complexity from in vivo tests while allowing direct comparison of recording capabilities of different cortical surface electrodes. Implementing the proposed M$^3$ electrode array in intracranial monitoring improves the current technology without much compromise, enhancing patient outcomes, reducing risks, and encouraging swift clinical translation.
ContributorsGarich, Jonathan Von (Author) / Blain Christen, Jennifer M (Thesis advisor) / Abbas, James J (Committee member) / Helms Tillery, Stephen I (Committee member) / Muthuswamy, Jitendran (Committee member) / Raupp, Gregory B (Committee member) / Arizona State University (Publisher)
Created2022
Description
Stroke is the leading cause of long-term disability in the U.S., with up to 60% of strokescausing speech loss. Individuals with severe stroke, who require the most frequent, intense speech therapy, often cannot adhere to treatments due to high cost and low success rates. Therefore, the ability to make functionally significant changes in individuals with severe post- stroke aphasia remains a key challenge for the rehabilitation community. This dissertation aimed to evaluate the efficacy of Startle Adjuvant Rehabilitation Therapy (START), a tele-enabled, low- cost treatment, to improve quality of life and speech in individuals with severe-to-moderate stroke. START is the exposure to startling acoustic stimuli during practice of motor tasks in individuals with stroke. START increases the speed and intensity of practice in severely impaired post-stroke reaching, with START eliciting muscle activity 2-3 times higher than maximum voluntary contraction. Voluntary reaching distance, onset, and final accuracy increased after a session of START, suggesting a rehabilitative effect. However, START has not been evaluated during impaired speech. The objective of this study is to determine if impaired speech can be elicited by startling acoustic stimuli, and if three days of START training can enhance clinical measures of moderate to severe post-stroke aphasia and apraxia of speech. This dissertation evaluates START in 42 individuals with post-stroke speech impairment via telehealth in a Phase 0 clinical trial. Results suggest that impaired speech can be elicited by startling acoustic stimuli and that START benefits individuals with severe-to-moderate post-stroke impairments in both linguistic and motor speech domains. This fills an important gap in aphasia care, as many speech therapies remain ineffective and financially inaccessible for patients with severe deficits. START is effective, remotely delivered, and may likely serve as an affordable adjuvant to traditional therapy for those that have poor access to quality care.
ContributorsSwann, Zoe Elisabeth (Author) / Honeycutt, Claire F (Thesis advisor) / Daliri, Ayoub (Committee member) / Rogalsky, Corianne (Committee member) / Liss, Julie (Committee member) / Schaefer, Sydney (Committee member) / Arizona State University (Publisher)
Created2022
Description
This dissertation research project developed as an urgent response to physical inactivity, which has resulted in increased rates of obesity, diabetes, and metabolic disease worldwide. Incorporating enough daily physical activity (PA) is challenging for most people. This research aims to modulate the brain's reward systems to increase motivation for PA and, thus, slow the rapid increase in sedentary lifestyles. Transcranial direct current stimulation (tDCS) involves brain neuromodulation by facilitating or inhibiting spontaneous neural activity. tDCS applied to the dorsolateral prefrontal cortex (DLPFC) increases dopamine release in the striatum, an area of the brain involved in the reward–motivation pathways. I propose that a repeated intervention, consisting of tDCS applied to the DLPFC followed by a short walking exercise stimulus, enhances motivation for PA and daily PA levels in healthy adults. Results showed that using tDCS followed by short-duration walking exercise may enhance daily PA levels in low-physically active participants but may not have similar effects on those with higher levels of daily PA. Moreover, there was a significant effect on increasing intrinsic motivation for PA in males, but there were no sex-related differences in PA. These effects were not observed during a 2-week follow-up period of the study after the intervention was discontinued. Further research is needed to confirm and continue exploring the effects of tDCS on motivation for PA in larger cohorts of sedentary populations. This novel research will lead to a cascade of new evidence-based technological applications that increase PA by employing approaches rooted in biology.
ContributorsRuiz Tejada, Anaissa (Author) / Katsanos, Christos (Thesis advisor) / Neisewander, Janet (Committee member) / Sadleir, Rosalind (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2023
Description
Non-invasive visualization of the trigeminal nerve through advanced MR sequences and methods like tractography is important for studying anatomical and microstructural changes due to pathology like trigeminal neuralgia (TN), facial dystonia, multiple sclerosis, and for surgical pre-planning. The use of specific anatomical markers from CT, MPRAGE and cranial nerve imaging (CRANI) sequences, enabled successful tractography of patient-specific trajectory of the frontal, nasociliary, infraorbital, and mandibular nerve branches extending beyond the cisternal brain stem region and leading to the face. Performance of MPRAGE sequence together with the advanced T2-weighted CRANI sequence with and without a gadolinium contrast agent, was studied to characterize identification efficiency in smaller nerve structures in the extremities. A large FOV nerve visualization exam inclusive of the anatomy of all trigeminal nerve distal branches can be obtained within an acquisition time of 20 minutes using pre-contrast CRANI and MPRAGE. Post-processing with MPR and MIP images improved nerve visualization.Transcranial electrical stimulation techniques (TES) have been used for the treatment of multiple neurodegenerative diseases. These techniques involve placing electrodes on the scalp with multiple peripheral branches of the trigeminal nerve crossing directly under that may be stimulated. This was studied through hybrid computational realistic axon models. These models also facilitated studying the effects of electrode drift during experiments on the recruitment of peripheral nerves. An optimal point of lowest threshold was found while displacing the nerve horizontally i.e., the activation thresholds of both myelinated and unmyelinated axons increased when the electrodes were displaced medially and decreased to a certain extend when the electrodes were displaced laterally, after which further lateral displacement led to increase of thresholds. Inclusion of unmyelinated axons in the modeling provided the capability of finding maximum stimulation amplitude below which side effects like pain sensation may be avoided. In the case of F3 – F4 electrode montage the maximum amplitude was 2.39 mA and in case of RS – LS montage the maximum amplitude was 2.44 mA. Such modeling studies may be useful for personalization of TES devices for finding optimal positioning of electrodes with respect to target and stimulation amplitude range that minimizes side effects.
ContributorsSahu, Sulagna (Author) / Sadleir, Rosalind (Thesis advisor) / Tillery, Stephen H (Committee member) / Crook, Sharon (Committee member) / Beeman, Scott (Committee member) / Abbas, James (Committee member) / Arizona State University (Publisher)
Created2023