Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
Displaying 1 - 10 of 79
Description
When surgical resection becomes necessary to alleviate a patient's epileptiform activity, that patient is monitored by video synchronized with electrocorticography (ECoG) to determine the type and location of seizure focus. This provides a unique opportunity for researchers to gather neurophysiological data with high temporal and spatial resolution; these data are assessed prior to surgical resection to ensure the preservation of the patient's quality of life, e.g. avoid the removal of brain tissue required for speech processing. Currently considered the "gold standard" for the mapping of cortex, electrical cortical stimulation (ECS) involves the systematic activation of pairs of electrodes to localize functionally specific brain regions. This method has distinct limitations, which often includes pain experienced by the patient. Even in the best cases, the technique suffers from subjective assessments on the parts of both patients and physicians, and high inter- and intra-observer variability. Recent advances have been made as researchers have reported the localization of language areas through several signal processing methodologies, all necessitating patient participation in a controlled experiment. The development of a quantification tool to localize speech areas in which a patient is engaged in an unconstrained interpersonal conversation would eliminate the dependence of biased patient and reviewer input, as well as unnecessary discomfort to the patient. Post-hoc ECoG data were gathered from five patients with intractable epilepsy while each was engaged in a conversation with family members or clinicians. After the data were separated into different speech conditions, the power of each was compared to baseline to determine statistically significant activated electrodes. The results of several analytical methods are presented here. The algorithms did not yield language-specific areas exclusively, as broad activation of statistically significant electrodes was apparent across cortical areas. For one patient, 15 adjacent contacts along superior temporal gyrus (STG) and posterior part of the temporal lobe were determined language-significant through a controlled experiment. The task involved a patient lying in bed listening to repeated words, and yielded statistically significant activations that aligned with those of clinical evaluation. The results of this study do not support the hypothesis that unconstrained conversation may be used to localize areas required for receptive and productive speech, yet suggests a simple listening task may be an adequate alternative to direct cortical stimulation.
ContributorsLingo VanGilder, Jennapher (Author) / Helms Tillery, Stephen I (Thesis advisor) / Wahnoun, Remy (Thesis advisor) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2013
Description
Intracortical microstimulation (ICMS) within somatosensory cortex can produce artificial sensations including touch, pressure, and vibration. There is significant interest in using ICMS to provide sensory feedback for a prosthetic limb. In such a system, information recorded from sensors on the prosthetic would be translated into electrical stimulation and delivered directly to the brain, providing feedback about features of objects in contact with the prosthetic. To achieve this goal, multiple simultaneous streams of information will need to be encoded by ICMS in a manner that produces robust, reliable, and discriminable sensations. The first segment of this work focuses on the discriminability of sensations elicited by ICMS within somatosensory cortex. Stimulation on multiple single electrodes and near-simultaneous stimulation across multiple electrodes, driven by a multimodal tactile sensor, were both used in these experiments. A SynTouch BioTac sensor was moved across a flat surface in several directions, and a subset of the sensor's electrode impedance channels were used to drive multichannel ICMS in the somatosensory cortex of a non-human primate. The animal performed a behavioral task during this stimulation to indicate the discriminability of sensations evoked by the electrical stimulation. The animal's responses to ICMS were somewhat inconsistent across experimental sessions but indicated that discriminable sensations were evoked by both single and multichannel ICMS. The factors that affect the discriminability of stimulation-induced sensations are not well understood, in part because the relationship between ICMS and the neural activity it induces is poorly defined. The second component of this work was to develop computational models that describe the populations of neurons likely to be activated by ICMS. Models of several neurons were constructed, and their responses to ICMS were calculated. A three-dimensional cortical model was constructed using these cell models and used to identify the populations of neurons likely to be recruited by ICMS. Stimulation activated neurons in a sparse and discontinuous fashion; additionally, the type, number, and location of neurons likely to be activated by stimulation varied with electrode depth.
ContributorsOverstreet, Cynthia K (Author) / Helms Tillery, Stephen I (Thesis advisor) / Santos, Veronica (Committee member) / Buneo, Christopher (Committee member) / Otto, Kevin (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
Description
Humans' ability to perform fine object and tool manipulation is a defining feature of their sensorimotor repertoire. How the central nervous system builds and maintains internal representations of such skilled hand-object interactions has attracted significant attention over the past three decades. Nevertheless, two major gaps exist: a) how digit positions and forces are coordinated during natural manipulation tasks, and b) what mechanisms underlie the formation and retention of internal representations of dexterous manipulation. This dissertation addresses these two questions through five experiments that are based on novel grip devices and experimental protocols. It was found that high-level representation of manipulation tasks can be learned in an effector-independent fashion. Specifically, when challenged by trial-to-trial variability in finger positions or using digits that were not previously engaged in learning the task, subjects could adjust finger forces to compensate for this variability, thus leading to consistent task performance. The results from a follow-up experiment conducted in a virtual reality environment indicate that haptic feedback is sufficient to implement the above coordination between digit position and forces. However, it was also found that the generalizability of a learned manipulation is limited across tasks. Specifically, when subjects learned to manipulate the same object across different contexts that require different motor output, interference was found at the time of switching contexts. Data from additional studies provide evidence for parallel learning processes, which are characterized by different rates of decay and learning. These experiments have provided important insight into the neural mechanisms underlying learning and control of object manipulation. The present findings have potential biomedical applications including brain-machine interfaces, rehabilitation of hand function, and prosthetics.
ContributorsFu, Qiushi (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Santos, Veronica (Committee member) / Artemiadis, Panagiotis (Committee member) / Arizona State University (Publisher)
Created2013
Description
Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the desired skill level. It would result in more reliable and adaptive neural interfaces that could record optimal neural activity 24/7 with high fidelity signals, high yield and increased throughput. The main contribution here is validating adaptive strategies to overcome challenges in autonomous navigation of microelectrodes inside the brain. The following issues pose significant challenges as brain tissue is both functionally and structurally dynamic: a) time varying mechanical properties of the brain tissue-microelectrode interface due to the hyperelastic, viscoelastic nature of brain tissue b) non-stationarities in the neural signal caused by mechanical and physiological events in the interface and c) the lack of visual feedback of microelectrode position in brain tissue. A closed loop control algorithm is proposed here for autonomous navigation of microelectrodes in brain tissue while optimizing the signal-to-noise ratio of multi-unit neural recordings. The algorithm incorporates a quantitative understanding of constitutive mechanical properties of soft viscoelastic tissue like the brain and is guided by models that predict stresses developed in brain tissue during movement of the microelectrode. An optimal movement strategy is developed that achieves precise positioning of microelectrodes in the brain by minimizing the stresses developed in the surrounding tissue during navigation and maximizing the speed of movement. Results of testing the closed-loop control paradigm in short-term rodent experiments validated that it was possible to achieve a consistently high quality SNR throughout the duration of the experiment. At the systems level, new generation of MEMS actuators for movable microelectrode array are characterized and the MEMS device operation parameters are optimized for improved performance and reliability. Further, recommendations for packaging to minimize the form factor of the implant; design of device mounting and implantation techniques of MEMS microelectrode array to enhance the longevity of the implant are also included in a top-down approach to achieve a reliable brain interface.
ContributorsAnand, Sindhu (Author) / Muthuswamy, Jitendran (Thesis advisor) / Tillery, Stephen H (Committee member) / Buneo, Christopher (Committee member) / Abbas, James (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
Description
Gait and balance disorders are the second leading cause of falls in the elderly. Investigating the changes in static and dynamic balance due to aging may provide a better understanding of the effects of aging on postural control system. Static and dynamic balance were evaluated in a total of 21 young (21-35 years) and 22 elderly (50-75 years) healthy subjects while they performed three different tasks: quiet standing, dynamic weight shifts, and over ground walking. During the quiet standing task, the subjects stood with their eyes open and eyes closed. When performing dynamic weight shifts task, subjects shifted their Center of Pressure (CoP) from the center target to outward targets and vice versa while following real-time feedback of their CoP. For over ground walking tasks, subjects performed Timed Up and Go test, tandem walking, and regular walking at their self-selected speed. Various quantitative balance and gait measures were obtained to evaluate the above respective balance and walking tasks. Total excursion, sway area, and mean frequency of CoP during quiet standing were found to be the most reliable and showed significant increase with age and absence of visual input. During dynamic shifts, elderly subjects exhibited higher initiation time, initiation path length, movement time, movement path length, and inaccuracy indicating deterioration in performance. Furthermore, the elderly walked with a shorter stride length, increased stride variability, with a greater turn and turn-to-sit duration. Significant correlations were also observed between measures derived from the different balance and gait tasks. Thus, it can be concluded that aging deteriorates the postural control system affecting static and dynamic balance and some of the alterations in CoP and gait measures may be considered as protective mechanisms to prevent loss of balance.
ContributorsBalasubramanian, Shruthi (Author) / Krishnamurthi, Narayanan (Thesis advisor) / Abbas, James (Thesis advisor) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2014
Description
Learning by trial-and-error requires retrospective information that whether a past action resulted in a rewarded outcome. Previous outcome in turn may provide information to guide future behavioral adjustment. But the specific contribution of this information to learning a task and the neural representations during the trial-and-error learning process is not well understood. In this dissertation, such learning is analyzed by means of single unit neural recordings in the rats' motor agranular medial (AGm) and agranular lateral (AGl) while the rats learned to perform a directional choice task. Multichannel chronic recordings using implanted microelectrodes in the rat's brain were essential to this study. Also for fundamental scientific investigations in general and for some applications such as brain machine interface, the recorded neural waveforms need to be analyzed first to identify neural action potentials as basic computing units. Prior to analyzing and modeling the recorded neural signals, this dissertation proposes an advanced spike sorting system, the M-Sorter, to extract the action potentials from raw neural waveforms. The M-Sorter shows better or comparable performance compared with two other popular spike sorters under automatic mode. With the sorted action potentials in place, neuronal activity in the AGm and AGl areas in rats during learning of a directional choice task is examined. Systematic analyses suggest that rat's neural activity in AGm and AGl was modulated by previous trial outcomes during learning. Single unit based neural dynamics during task learning are described in detail in the dissertation. Furthermore, the differences in neural modulation between fast and slow learning rats were compared. The results show that the level of neural modulation of previous trial outcome is different in fast and slow learning rats which may in turn suggest an important role of previous trial outcome encoding in learning.
ContributorsYuan, Yu'an (Author) / Si, Jennie (Thesis advisor) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Chae, Junseok (Committee member) / Arizona State University (Publisher)
Created2014
Description
Animals learn to choose a proper action among alternatives according to the circumstance. Through trial-and-error, animals improve their odds by making correct association between their behavioral choices and external stimuli. While there has been an extensive literature on the theory of learning, it is still unclear how individual neurons and a neural network adapt as learning progresses. In this dissertation, single units in the medial and lateral agranular (AGm and AGl) cortices were recorded as rats learned a directional choice task. The task required the rat to make a left/right side lever press if a light cue appeared on the left/right side of the interface panel. Behavior analysis showed that rat's movement parameters during performance of directional choices became stereotyped very quickly (2-3 days) while learning to solve the directional choice problem took weeks to occur. The entire learning process was further broken down to 3 stages, each having similar number of recording sessions (days). Single unit based firing rate analysis revealed that 1) directional rate modulation was observed in both cortices; 2) the averaged mean rate between left and right trials in the neural ensemble each day did not change significantly among the three learning stages; 3) the rate difference between left and right trials of the ensemble did not change significantly either. Besides, for either left or right trials, the trial-to-trial firing variability of single neurons did not change significantly over the three stages. To explore the spatiotemporal neural pattern of the recorded ensemble, support vector machines (SVMs) were constructed each day to decode the direction of choice in single trials. Improved classification accuracy indicated enhanced discriminability between neural patterns of left and right choices as learning progressed. When using a restricted Boltzmann machine (RBM) model to extract features from neural activity patterns, results further supported the idea that neural firing patterns adapted during the three learning stages to facilitate the neural codes of directional choices. Put together, these findings suggest a spatiotemporal neural coding scheme in a rat AGl and AGm neural ensemble that may be responsible for and contributing to learning the directional choice task.
ContributorsMao, Hongwei (Author) / Si, Jennie (Thesis advisor) / Buneo, Christopher (Committee member) / Cao, Yu (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2014
Description
Membrane proteins are a vital part of cellular structure. They are directly involved in many important cellular functions, such as uptake, signaling, respiration, and photosynthesis, among others. Despite their importance, however, less than 500 unique membrane protein structures have been determined to date. This is due to several difficulties with macromolecular crystallography, primarily the difficulty of growing large, well-ordered protein crystals. Since the first proof of concept for femtosecond nanocrystallography showing that diffraction patterns can be collected on extremely small crystals, thus negating the need to grow larger crystals, there have been many exciting advancements in the field. The technique has been proven to show high spatial resolution, thus making it a viable method for structural biology. However, due to the ultrafast nature of the technique, which allows for a lack of radiation damage in imaging, even more interesting experiments are possible, and the first temporal and spatial images of an undamaged structure could be acquired. This concept was denoted as time-resolved femtosecond nanocrystallography.
This dissertation presents on the first time-resolved data set of Photosystem II where structural changes can actually be seen without radiation damage. In order to accomplish this, new crystallization techniques had to be developed so that enough crystals could be made for the liquid jet to deliver a fully hydrated stream of crystals to the high-powered X-ray source. These changes are still in the preliminary stages due to the slightly lower resolution data obtained, but they are still a promising show of the power of this new technique. With further optimization of crystal growth methods and quality, injection technique, and continued development of data analysis software, it is only a matter of time before the ability to make movies of molecules in motion from X-ray diffraction snapshots in time exists. The work presented here is the first step in that process.
This dissertation presents on the first time-resolved data set of Photosystem II where structural changes can actually be seen without radiation damage. In order to accomplish this, new crystallization techniques had to be developed so that enough crystals could be made for the liquid jet to deliver a fully hydrated stream of crystals to the high-powered X-ray source. These changes are still in the preliminary stages due to the slightly lower resolution data obtained, but they are still a promising show of the power of this new technique. With further optimization of crystal growth methods and quality, injection technique, and continued development of data analysis software, it is only a matter of time before the ability to make movies of molecules in motion from X-ray diffraction snapshots in time exists. The work presented here is the first step in that process.
ContributorsKupitz, Christopher (Author) / Fromme, Petra (Thesis advisor) / Spence, John C. (Thesis advisor) / Redding, Kevin (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2014
Description
The utilization of solar energy requires an efficient means of its storage as fuel. In bio-inspired artificial photosynthesis, light energy can be used to drive water oxidation, but catalysts that produce molecular oxygen from water are required. This dissertation demonstrates a novel complex utilizing earth-abundant Ni in combination with glycine as an efficient catalyst with a modest overpotential of 0.475 ± 0.005 V for a current density of 1 mA/cm2 at pH 11. The production of molecular oxygen at a high potential was verified by measurement of the change in oxygen concentration, yielding a Faradaic efficiency of 60 ± 5%. This Ni species can achieve a current density of 4 mA/cm2 that persists for at least 10 hours. Based upon the observed pH dependence of the current amplitude and oxidation/reduction peaks, the catalysis is an electron-proton coupled process. In addition, to investigate the binding of divalent metals to proteins, four peptides were designed and synthesized with carboxylate and histidine ligands. The binding of the metals was characterized by monitoring the metal-induced changes in circular dichroism spectra. Cyclic voltammetry demonstrated that bound copper underwent a Cu(I)/Cu(II) oxidation/reduction change at a potential of approximately 0.32 V in a quasi-reversible process. The relative binding affinity of Mn(II), Fe(II), Co(II), Ni(II) and Cu(II) to the peptides is correlated with the stability constants of the Irving-Williams series for divalent metal ions. A potential application of these complexes of transition metals with amino acids or peptides is in the development of artificial photosynthetic cells.
ContributorsWang, Dong (Author) / Allen, James P. (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Redding, Kevin (Committee member) / Arizona State University (Publisher)
Created2014
Description
Cyanovirin-N (CVN) is a cyanobacterial lectin with potent anti-HIV activity, mediated by binding to the N-linked oligosaccharide moiety of the envelope protein gp120. CVN offers a scaffold to develop multivalent carbohydrate-binding proteins with tunable specificities and affinities. I present here biophysical calculations completed on a monomeric-stabilized mutant of cyanovirin-N, P51G-m4-CVN, in which domain A binding activity is abolished by four mutations; with comparisons made to CVNmutDB, in which domain B binding activity is abolished. Using Monte Carlo calculations and docking simulations, mutations in CVNmutDB were considered singularly, and the mutations E41A/G and T57A were found to impact the affinity towards dimannose the greatest. 15N-labeled proteins were titrated with Manα(1-2)Manα, while following chemical shift perturbations in NMR spectra. The mutants, E41A/G and T57A, had a larger Kd than P51G-m4-CVN, matching the trends predicted by the calculations. We also observed that the N42A mutation affects the local fold of the binding pocket, thus removing all binding to dimannose. Characterization of the mutant N53S showed similar binding affinity to P51G-m4-CVN. Using biophysical calculations allows us to study future iterations of models to explore affinities and specificities. In order to further elucidate the role of multivalency, I report here a designed covalent dimer of CVN, Nested cyanovirin-N (Nested CVN), which has four binding sites. Nested CVN was found to have comparable binding affinity to gp120 and antiviral activity to wt CVN. These results demonstrate the ability to create a multivalent, covalent dimer that has comparable results to that of wt CVN.
WW domains are small modules consisting of 32-40 amino acids that recognize proline-rich peptides and are found in many signaling pathways. We use WW domain sequences to explore protein folding by simulations using Zipping and Assembly Method. We identified five crucial contacts that enabled us to predict the folding of WW domain sequences based on those contacts. We then designed a folded WW domain peptide from an unfolded WW domain sequence by introducing native contacts at those critical positions.
WW domains are small modules consisting of 32-40 amino acids that recognize proline-rich peptides and are found in many signaling pathways. We use WW domain sequences to explore protein folding by simulations using Zipping and Assembly Method. We identified five crucial contacts that enabled us to predict the folding of WW domain sequences based on those contacts. We then designed a folded WW domain peptide from an unfolded WW domain sequence by introducing native contacts at those critical positions.
ContributorsWoodrum, Brian William (Author) / Ghirlanda, Giovanna (Thesis advisor) / Redding, Kevin (Committee member) / Wang, Xu (Committee member) / Arizona State University (Publisher)
Created2014