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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- All Subjects: Neurosciences
Description
Neurostimulation methods currently include deep brain stimulation (DBS), optogenetic, transcranial direct-current stimulation (tDCS), and transcranial magnetic stimulation (TMS). TMS and tDCS are noninvasive techniques whereas DBS and optogenetic require surgical implantation of electrodes or light emitting devices. All approaches, except for optogenetic, have been implemented in clinical settings because they have demonstrated therapeutic utility and clinical efficacy for neurological and psychiatric disorders. When applied for therapeutic applications, these techniques suffer from limitations that hinder the progression of its intended use to treat compromised brain function. DBS requires an invasive surgical procedure that surfaces complications from infection, longevity of electrical components, and immune responses to foreign materials. Both TMS and tDCS circumvent the problems seen with DBS as they are noninvasive procedures, but they fail to produce the spatial resolution required to target specific brain structures. Realizing these restrictions, we sought out to use ultrasound as a neurostimulation modality. Ultrasound is capable of achieving greater resolution than TMS and tDCS, as we have demonstrated a ~2mm lateral resolution, which can be delivered noninvasively. These characteristics place ultrasound superior to current neurostimulation methods. For these reasons, this dissertation provides a developed protocol to use transcranial pulsed ultrasound (TPU) as a neurostimulation technique. These investigations implement electrophysiological, optophysiological, immunohistological, and behavioral methods to elucidate the effects of ultrasound on the central nervous system and raise questions about the functional consequences. Intriguingly, we showed that TPU was also capable of stimulating intact sub-cortical circuits in the anesthetized mouse. These data reveal that TPU can evoke synchronous oscillations in the hippocampus in addition to increasing expression of brain-derived neurotrophic factor (BDNF). Considering these observations, and the ability to noninvasively stimulate neuronal activity on a mesoscale resolution, reveals a potential avenue to be effective in clinical settings where current brain stimulation techniques have shown to be beneficial. Thus, the results explained by this dissertation help to pronounce the significance for these protocols to gain translational recognition.
ContributorsTufail, Yusuf Zahid (Author) / Tyler, William J (Thesis advisor) / Duch, Carsten (Committee member) / Muthuswamy, Jitendran (Committee member) / Santello, Marco (Committee member) / Tillery, Stephen H (Committee member) / Arizona State University (Publisher)
Created2011
Description
Neural tissue is a delicate system comprised of neurons and their synapses, glial cells for support, and vasculature for oxygen and nutrient delivery. This complexity ultimately gives rise to the human brain, a system researchers have become increasingly interested in replicating for artificial intelligence purposes. Some have even gone so far as to use neuronal cultures as computing hardware, but utilizing an environment closer to a living brain means having to grapple with the same issues faced by clinicians and researchers trying to treat brain disorders. Most outstanding among these are the problems that arise with invasive interfaces. Optical techniques that use fluorescent dyes and proteins have emerged as a solution for noninvasive imaging with single-cell resolution in vitro and in vivo, but feeding in information in the form of neuromodulation still requires implanted electrodes. The implantation process of these electrodes damages nearby neurons and their connections, causes hemorrhaging, and leads to scarring and gliosis that diminish efficacy. Here, a new approach for noninvasive neuromodulation with high spatial precision is described. It makes use of a combination of ultrasound, high frequency acoustic energy that can be focused to submillimeter regions at significant depths, and electric fields, an effective tool for neuromodulation that lacks spatial precision when used in a noninvasive manner. The hypothesis is that, when combined in a specific manner, these will lead to nonlinear effects at neuronal membranes that cause cells only in the region of overlap to be stimulated. Computational modeling confirmed this combination to be uniquely stimulating, contingent on certain physical effects of ultrasound on cell membranes. Subsequent in vitro experiments led to inconclusive results, however, leaving the door open for future experimentation with modified configurations and approaches. The specific combination explored here is also not the only untested technique that may achieve a similar goal.
ContributorsNester, Elliot (Author) / Wang, Yalin (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Towe, Bruce (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
Neurological disorders are the leading cause of physical and cognitive declineglobally and affect nearly 15% of the current worldwide population. These disorders
include, but are not limited to, epilepsy, Alzheimer’s disease, Parkinson’s disease,
and multiple sclerosis. With the aging population, an increase in the prevalence of
neurodegenerative disorders is expected. Electrophysiological monitoring of neural
signals has been the gold standard for clinicians in diagnosing and treating neurological
disorders. However, advances in detection and stimulation techniques have paved the
way for relevant information not seen by standard procedures to be captured and
used in patient treatment. Amongst these advances have been improved analysis of
higher frequency activity and the increased concentration of alternative biomarkers,
specifically pH change, during states of increased neural activity. The design and
fabrication of devices with the ability to reliably interface with the brain on multiple
scales and modalities has been a significant challenge.
This dissertation introduces a novel, concentric, multi-scale micro-ECoG array
for neural applications specifically designed for seizure detection in epileptic patients.
This work investigates simultaneous detection and recording of adjacent neural tissue
using electrodes of different sizes during neural events. Signal fidelity from electrodes
of different sizes during in vivo experimentation are explored and analyzed to highlight
the advantages and disadvantages of using varying electrode sizes. Furthermore, the
novel multi-scale array was modified to perform multi-analyte detection experiments
of pH change and electrophysiological activity on the cortical surface during epileptic
events. This device highlights the ability to accurately monitor relevant information
from multiple electrode sizes and concurrently monitor multiple biomarkers during
clinical periods in one procedure that typically requires multiple surgeries.
ContributorsAkamine, Ian (Author) / Blain Christen, Jennifer (Thesis advisor) / Abbas, Jimmy (Committee member) / Muthuswamy, Jitendran (Committee member) / Goryll, Michael (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2024
Description
A direct Magnetic Resonance (MR)-based neural activity mapping technique with high spatial and temporal resolution may accelerate studies of brain functional organization.
The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging.
Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise.
Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.
The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging.
Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise.
Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.
ContributorsFu, Fanrui (Author) / Sadleir, Rosalind (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Kleim, Jeffrey (Committee member) / Muthuswamy, Jitendran (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2019
Description
Vagal Nerve Stimulation (VNS) has been shown to be a promising therapeutic technique in treating many neurological diseases, including epilepsy, stroke, traumatic brain injury, and migraine headache. The mechanisms by which VNS acts, however, are not fully understood but may involve changes in cerebral blood flow. The vagus nerve plays a significant role in the regulation of heart rate and cerebral blood flow that are altered during VNS. Here, the effects of acute vagal nerve stimulation using varying stimulation parameters on both heart rate and cerebral blood flow were examined. Laser Speckle Contrast Analysis (LASCA) was used to analyze the cerebral blood flow of male Long–Evans rats. In the first experiment, results showed two distinct patterns of responses to 0.8mA of stimulation whereby animals either experienced a mild or severe decrease in heart rate. Further, animals that displayed mild heart rate decreases showed an increase in cerebral blood flow that persisted beyond VNS. Animals that displayed severe decreases showed a transient decrease in cerebral blood flow followed by an increase that was greater than that observed in mild animals but progressively decreased after VNS. The results suggest two distinct patterns of changes in both heart rate and blood flow that may be related to the intensity of VNS. To investigate the effects of lower levels of stimulation, an additional group of animals were stimulated at 0.4mA. The results showed moderate changes in heart rate but no significant changes in cerebral blood flow in these animals. The results demonstrate that VNS alters both heart rate and cerebral blood flow and that these effects are dependent on current intensity.
ContributorsHillebrand, Peter (M.S.) (Author) / Kleim, Jeffrey A (Thesis advisor) / Helms Tillery, Stephen I (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2019
Description
There is a critical need for creating an implantable microscale neural interface that can chronically monitor neural activity and oxygenation. These are key aspects for understating the development of impaired neural circuits and their functions. A technology with such capability would foster new insights in the studies of brain diseases and disorders. The propose is that MR-PISTOL (Proton imaging of Siloxane to Map Tissue Oxygenation Levels) imaging technique can be used for direct measurements of oxygen partial pressure at microelectrode-tissue interface. The strategy consists of coating microelectrodes with soft-silicone, a ultra-soft conductive PDMS (polydimethylsiloxane), as a carrier for liquid siloxanes MR-PISTOL contrast agents. This work presents a proof-of-concept of an injection molding technique for batch fabricate microelectrodes with such coating. Also, reports stability studies of soft-silicone loaded with liquid polydimethylsiloxane (PDMSO) in rodent brains. A batch of thirty coated carbon electrodes was achieved using candy molds. Coating uniformity was evaluated in twelve probes. They were randomly chosen and imaged with a custom image setup that allows 90o rotation of the probes. The total average coating thickness before and after rotation were 0.397 millimeters with standard deviation of 0.070 millimeters and 0.442 millimeters with standard deviation of 0.062 millimeters. Therefore, data confirms that this technique yields uniform coating. Stability of fabricated coated carbon electrodes unloaded (n= 3) and loaded with PDMSO (n= 3) was assessed. 3D X-ray imaging using Zeiss Xradia 520 machine was chosen for studying coatings mechanical stability in ex-vivo rat brain. Transmission electron microscopy (TEM) and scanning electron microscope (SEM) with an energy dispersive x-ray microanalysis (EDS) detector were used to investigate their chemical stability in in vivo mouse brain. Initial EDS analysis from TEM and SEM of acute (6 hours) and chronic (2 weeks) brain slices suggest that PDMSO does not leach into brain. More experiments should be done to confirm and endorse this finding. The mechanical study shows that coating loaded with PDMSO delaminated during insertion. This was not observed with electrodes used in the chemical stability studies. Further experiments need to be done to identify possible causes of mechanical failures.
Contributorsde Mesquita Teixeira, Livia (Author) / Muthuswamy, Jitendran (Thesis advisor, Committee member) / Kodibagkar, Vikram (Thesis advisor, Committee member) / Sridharan, Arati (Committee member) / Arizona State University (Publisher)
Created2018
Description
The basal ganglia are four sub-cortical nuclei associated with motor control and reward learning. They are part of numerous larger mostly segregated loops where the basal ganglia receive inputs from specific regions of cortex. Converging on these inputs are dopaminergic neurons that alter their firing based on received and/or predicted rewarding outcomes of a behavior. The basal ganglia's output feeds through the thalamus back to the areas of the cortex where the loop originated. Understanding the dynamic interactions between the various parts of these loops is critical to understanding the basal ganglia's role in motor control and reward based learning. This work developed several experimental techniques that can be applied to further study basal ganglia function. The first technique used micro-volume injections of low concentration muscimol to decrease the firing rates of recorded neurons in a limited area of cortex in rats. Afterwards, an artificial cerebrospinal fluid flush was injected to rapidly eliminate the muscimol's effects. This technique was able to contain the effects of muscimol to approximately a 1 mm radius volume and limited the duration of the drug effect to less than one hour. This technique could be used to temporarily perturb a small portion of the loops involving the basal ganglia and then observe how these effects propagate in other connected regions. The second part applied self-organizing maps (SOM) to find temporal patterns in neural firing rate that are independent of behavior. The distribution of detected patterns frequency on these maps can then be used to determine if changes in neural activity are occurring over time. The final technique focused on the role of the basal ganglia in reward learning. A new conditioning technique was created to increase the occurrence of selected patterns of neural activity without utilizing any external reward or behavior. A pattern of neural activity in the cortex of rats was selected using an SOM. The pattern was then reinforced by being paired with electrical stimulation of the medial forebrain bundle triggering dopamine release in the basal ganglia. Ultimately, this technique proved unsuccessful possibly due to poor selection of the patterns being reinforced.
ContributorsBaldwin, Nathan Aaron (Author) / Helms Tillery, Stephen I (Thesis advisor) / Castaneda, Edward (Committee member) / Buneo, Christopher A (Committee member) / Muthuswamy, Jitendran (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2014
Description
Electrical nerve stimulation is a promising drug-free technology that could treat a variety of ailments and disorders. Methods like Vagus Nerve Stimulation have been used for decades to treat disorders like epilepsy, and research with non-invasive vagus nerve stimulation has shown similar effects as its invasive counterpart. Non-invasive nerve stimulation methods like vagus nerve stimulation could help millions of people treat and manage various disorders.
This study observed the effects of three different non-invasive nerve stimulation paradigms in human participants. The first study analyzed the safety and efficacy of transcutaneous auricular vagal nerve stimulation in healthy humans using a bilateral stimulation protocol with uniquely designed dry-hydrogel electrodes. Results demonstrate bilateral auricular vagal nerve stimulation has significant effects on specific parameters of autonomic activity and is safe and well tolerated. The second study analyzed the effects of non-invasive electrical stimulation of a region on the side of the neck that contains the Great Auricular Nerve and the Auricular Branch of the Vagus Nerve called the tympanomastoid fissure on golf hitting performance in healthy golfers. Results did not show significant effects on hitting performance or physiological activity, but the nerve stimulation had significant effects on reducing state-anxiety and improving the quality of feel of each shot. The third study analyzed the effects of non-invasive nerve stimulation of cervical nerves on the back of the neck on putting performance of yips-affected golfers. Results demonstrated that cervical nerve stimulation had significant effects on improving putting performance but did not have significant effects on physiological activity. Data from these studies show there are potential applications for non-invasive electrical nerve stimulation for healthy and athletic populations. Future research should also examine the effects of these stimulation methods in clinical populations.
This study observed the effects of three different non-invasive nerve stimulation paradigms in human participants. The first study analyzed the safety and efficacy of transcutaneous auricular vagal nerve stimulation in healthy humans using a bilateral stimulation protocol with uniquely designed dry-hydrogel electrodes. Results demonstrate bilateral auricular vagal nerve stimulation has significant effects on specific parameters of autonomic activity and is safe and well tolerated. The second study analyzed the effects of non-invasive electrical stimulation of a region on the side of the neck that contains the Great Auricular Nerve and the Auricular Branch of the Vagus Nerve called the tympanomastoid fissure on golf hitting performance in healthy golfers. Results did not show significant effects on hitting performance or physiological activity, but the nerve stimulation had significant effects on reducing state-anxiety and improving the quality of feel of each shot. The third study analyzed the effects of non-invasive nerve stimulation of cervical nerves on the back of the neck on putting performance of yips-affected golfers. Results demonstrated that cervical nerve stimulation had significant effects on improving putting performance but did not have significant effects on physiological activity. Data from these studies show there are potential applications for non-invasive electrical nerve stimulation for healthy and athletic populations. Future research should also examine the effects of these stimulation methods in clinical populations.
ContributorsHool, Nicholas (Author) / Tyler, William J (Thesis advisor) / Crews, Debbie (Committee member) / Muthuswamy, Jitendran (Committee member) / Helms Tillery, Stephen (Committee member) / Sebold, Brent (Committee member) / Arizona State University (Publisher)
Created2020
Description
The use of a non-invasive form of energy to modulate neural structures has gained wide spread attention because of its ability to remotely control neural excitation. This study investigates the ability of focused high frequency ultrasound to modulate the excitability the peripheral nerve of an amphibian. A 5MHz ultrasound transducer is used for the study with the pulse characteristics of 57msec long train burst and duty cycle of 8% followed by an interrogative electrical stimulus varying from 30μsecs to 2msecs in pulse duration. The nerve excitability is determined by the compound action potential (CAP) amplitude evoked by a constant electrical stimulus. We observe that ultrasound's immediate effect on axons is to reduce the electrically evoked CAP amplitude and thereby suppressive in effect. However, a subsequent time delayed increased excitability was observed as reflected in the CAP amplitude of the nerve several tens of milliseconds later. This subsequent change from ultrasound induced nerve inhibition to increased excitability as a function of delay from ultrasound pulse application is unexpected and not predicted by typical nerve ion channel kinetic models. The recruitment curve of the sciatic nerve modified by ultrasound suggests the possibility of a fiber specific response where the ultrasound inhibits the faster fibers more than the slower ones. Also, changes in the shape of the CAP waveform when the nerve is under the inhibitive effect of ultrasound was observed. It is postulated that these effects can be a result of activation of stretch activation channels, mechanical sensitivity of the nerve to acoustic radiation pressure and modulation of ion channels by ultrasound.
The neuromodulatory capabilities of ultrasound in tandem with electrical stimulation has a significant potential for development of neural interfaces to peripheral nerve.
The neuromodulatory capabilities of ultrasound in tandem with electrical stimulation has a significant potential for development of neural interfaces to peripheral nerve.
ContributorsChirania, Sanchit (Author) / Towe, Bruce (Thesis advisor) / Abbas, James (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2016