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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

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
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Description
Noninvasive neuromodulation could help treat many neurological disorders, but existing techniques have low resolution and weak penetration. Ultrasound (US) shows promise for stimulation of smaller areas and subcortical structures. However, the mechanism and parameter design are not understood. US can stimulate tail and hindlimb movements in rats, but not forelimb,

Noninvasive neuromodulation could help treat many neurological disorders, but existing techniques have low resolution and weak penetration. Ultrasound (US) shows promise for stimulation of smaller areas and subcortical structures. However, the mechanism and parameter design are not understood. US can stimulate tail and hindlimb movements in rats, but not forelimb, for unknown reasons. Potentially, US could also stimulate peripheral or enteric neurons for control of blood glucose.

To better understand the inconsistent effects across rat motor cortex, US modulation of electrically-evoked movements was tested. A stimulation array was implanted on the cortical surface and US (200 kHz, 30-60 W/cm2 peak) was applied while measuring changes in the evoked forelimb and hindlimb movements. Direct US stimulation of the hindlimb was also studied. To test peripheral effects, rat blood glucose levels were measured while applying US near the liver.

No short-term motor modulation was visible (95% confidence interval: -3.5% to +5.1% forelimb, -3.8% to +5.5% hindlimb). There was significant long-term (minutes-order) suppression (95% confidence interval: -3.7% to -10.8% forelimb, -3.8% to -11.9% hindlimb). This suppression may be due to the considerable heating (+1.8°C between US
on-US conditions); effects of heat and US were not separable in this experiment. US directly evoked hindlimb and scrotum movements in some sessions. This required a long interval, at least 3 seconds between US bursts. Movement could be evoked with much shorter pulses than used in literature (3 ms). The EMG latency (10 ms) was compatible with activation of corticospinal neurons. The glucose modulation test showed a strong increase in a few trials, but across all trials found no significant effect.

The single motor response and the long refractory period together suggest that only the beginning of the US burst had a stimulatory effect. This would explain the lack of short-term modulation, and suggests future work with shorter pulses could better explore the missing forelimb response. During the refractory period there was no change in the electrically-evoked response, which suggests the US stimulation mechanism is independent of normal brain activity. These results challenge the literature-standard protocols and provide new insights on the unknown mechanism.
ContributorsGulick, Daniel Withers (Author) / Kleim, Jeffrey (Thesis advisor) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Herman, Richard (Committee member) / Helms Tillery, Steven (Committee member) / Arizona State University (Publisher)
Created2015
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Description
There is a strong medical need and important therapeutic applications for improved wireless bioelectric interfaces to the nervous system. Multichannel devices are desired for neural control of robotic prosthetics that interface to remaining nerves in limb stumps of amputees and as alternatives to traditional wired arrays used in for some

There is a strong medical need and important therapeutic applications for improved wireless bioelectric interfaces to the nervous system. Multichannel devices are desired for neural control of robotic prosthetics that interface to remaining nerves in limb stumps of amputees and as alternatives to traditional wired arrays used in for some types of brain stimulation. This present work investigates a new approach to ultrasound-powering of implantable microelectronic devices within the tissue that may better support such applications. These devices are of ultra-miniature size that is enabled by a wireless technique. This study investigates two types of ultrasound-powered neural interfaces for multichannel sensory feedback in neurostimulation. The piezoceramics lead zirconate titanate (PZT) ceramic and polyvinylidene fluoride (PVDF) polymer were the primary materials used to build the devices. They convert ultrasound to electricity that when rectified by a diode produce a current output that is neuro stimulatory to peripheral nerve or the neurons in the brain. Multichannel devices employ a form of spatial multiplexing that directs focused ultrasound towards localized and segmented regions of PVDF or PZT that allows independent channels of nerve actuation. Different frequencies of ultrasound were evaluated for best results. Firstly, a 2.25 MHz frequency signal that is reasonably penetrating through body tissue to an implant several centimeters deep and also a 5 MHz frequency more suited to application for actuation of devices within a less than a centimeter of nerve. Results show multichannel device performance to have a complex inter-relationship with frequency, size and thickness, angular incidence, channel separations, and number of folds (layers connected in series and parallel). The output electrical port impedances of PVDF devices were examined in relationship to that of stimulating electrodes and tissue interfaces. Miniature multichannel devices were constructed using an unreported method of employing state of the art laser cutting systems. The results show that PVDF based devices have advantages over PZT, because of better acoustic coupling with tissue, known better biocompatibility, and better separation between multiple channels. However, the PZT devices proved to be better overall in terms of compactness and higher outputs for a given ultrasound power level.
ContributorsNanda Kumar, Yashwanth (Author) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2015
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Description
The purpose of this study was to examine swallowing patterns using ultrasound technology subsequent to the implementation of two therapeutic interventions. Baseline swallow patterns were compared to swallows after implementation of therapeutic interventions common in both feeding therapy (FT) and orofacial myofunctional therapy (OMT). The interventions consist of stimulation of

The purpose of this study was to examine swallowing patterns using ultrasound technology subsequent to the implementation of two therapeutic interventions. Baseline swallow patterns were compared to swallows after implementation of therapeutic interventions common in both feeding therapy (FT) and orofacial myofunctional therapy (OMT). The interventions consist of stimulation of the tongue by z-vibe and tongue pops. Changes in swallowing patterns are described, and similarities of interventions across the two professions are discussed. Ultrasound research in the realm of swallowing is sparse despite having potential clinical application in both professions. In using ultrasound, this study outlines a protocol for utilization of a hand-held probe and reinforces a particular protocol described in the literature. Real-time ultrasound recordings of swallows for 19 adult female subjects were made. Participants with orofacial myofunctional disorder are compared to a group with typical swallowing and differences in swallowing patterns are described. Three stages of the oral phase of the swallow were assigned based on ultrasonic observation of the tongue shape. Analysis involves total duration of the swallow, duration of the three stages in relation to the total duration of the swallow, and the number of swallows required for the bolus to be cleared from the oral cavity. No significant effects of either intervention were found. Swallowing patterns showed a general trend to become faster in total duration subsequent to each intervention. An unexpected finding showed significant changes in the relationship between the bolus preparation stage and the bolus transportation stage when comparing the group classified as having a single swallow and the group classified as having multiple swallows.
ContributorsMckay, Michelle Diane (Author) / Weinhold, Juliet (Thesis director) / Scherer, Nancy (Committee member) / Department of Speech and Hearing Science (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
In this study, the Bark transform and Lobanov method were used to normalize vowel formants in speech produced by persons with dysarthria. The computer classification accuracy of these normalized data were then compared to the results of human perceptual classification accuracy of the actual vowels. These results were then analyzed

In this study, the Bark transform and Lobanov method were used to normalize vowel formants in speech produced by persons with dysarthria. The computer classification accuracy of these normalized data were then compared to the results of human perceptual classification accuracy of the actual vowels. These results were then analyzed to determine if these techniques correlated with the human data.
ContributorsJones, Hanna Vanessa (Author) / Liss, Julie (Thesis director) / Dorman, Michael (Committee member) / Borrie, Stephanie (Committee member) / Barrett, The Honors College (Contributor) / Department of Speech and Hearing Science (Contributor) / Department of English (Contributor) / Speech and Hearing Science (Contributor)
Created2013-05
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Description
Research on /r/ production previously used formant analysis as the primary acoustic analysis, with particular focus on the low third formant in the speech signal. Prior imaging of speech used X-Ray, MRI, and electromagnetic midsagittal articulometer systems. More recently, the signal processing technique of Mel-log spectral plots has been used

Research on /r/ production previously used formant analysis as the primary acoustic analysis, with particular focus on the low third formant in the speech signal. Prior imaging of speech used X-Ray, MRI, and electromagnetic midsagittal articulometer systems. More recently, the signal processing technique of Mel-log spectral plots has been used to study /r/ production in children and female adults. Ultrasound imaging of the tongue also has been used to image the tongue during speech production in both clinical and research settings. The current study attempts to describe /r/ production in three different allophonic contexts; vocalic, prevocalic, and postvocalic positions. Ultrasound analysis, formant analysis, Mel-log spectral plots, and /r/ duration were measured for /r/ production in 29 adult speakers (10 male, 19 female). A possible relationship between these variables was also explored. Results showed that the amount of superior constriction in the postvocalic /r/ allophone was significantly lower than the other /r/ allophones. Formant two was significantly lower and the distance between formant two and three was significantly higher for the prevocalic /r/ allophone. Vocalic /r/ had the longest average duration, while prevocalic /r/ had the shortest duration. Signal processing results revealed candidate Mel-bin values for accurate /r/ production for each allophone of /r/. The results indicate that allophones of /r/ can be distinguished based the different analyses. However, relationships between these analyses are still unclear. Future research is needed in order to gather more data on /r/ acoustics and articulation in order to find possible relationships between the analyses for /r/ production.
ContributorsHirsch, Megan Elizabeth (Author) / Weinhold, Juliet (Thesis director) / Gardner, Joshua (Committee member) / Department of Speech and Hearing Science (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
Student to Student: A Guide to Anatomy is an anatomy guide written by students, for students. Its focus is on teaching the anatomy of the heart, lungs, nose, ears and throat in a manner that isn't overpowering or stress inducing. Daniel and I have taken numerous anatomy courses, and fully

Student to Student: A Guide to Anatomy is an anatomy guide written by students, for students. Its focus is on teaching the anatomy of the heart, lungs, nose, ears and throat in a manner that isn't overpowering or stress inducing. Daniel and I have taken numerous anatomy courses, and fully comprehend what it takes to have success in these classes. We found that the anatomy books recommended for these courses are often completely overwhelming, offering way more information than what is needed. This renders them near useless for a college student who just wants to learn the essentials. Why would a student even pick it up if they can't find what they need to learn? With that in mind, our goal was to create a comprehensive, easy to understand, and easy to follow guide to the heart, lungs and ENT (ear nose throat). We know what information is vital for test day, and wanted to highlight these key concepts and ideas in our guide. Spending just 60 to 90 minutes studying our guide should help any student with their studying needs. Whether the student has medical school aspirations, or if they simply just want to pass the class, our guide is there for them. We aren't experts, but we know what strategies and methods can help even the most confused students learn. Our guide can also be used as an introductory resource to our respective majors (Daniel-Biology, Charles-Speech and Hearing) for students who are undecided on what they want to do. In the future Daniel and I would like to see more students creating similar guides, and adding onto the "Student to Student' title with their own works... After all, who better to teach students than the students who know what it takes?
ContributorsKennedy, Charles (Co-author) / McDermand, Daniel (Co-author) / Kingsbury, Jeffrey (Thesis director) / Washo-Krupps, Delon (Committee member) / Department of Speech and Hearing Science (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
An improved system for wireless neurostimulation was investigated through the design and development of sub-millimeter piezoelectric devices. The devices build on prior work in the lab, which was limited by device size and required surgical implantation. A method of manufacturing sub-mm devices was developed, and utilized to construct this new

An improved system for wireless neurostimulation was investigated through the design and development of sub-millimeter piezoelectric devices. The devices build on prior work in the lab, which was limited by device size and required surgical implantation. A method of manufacturing sub-mm devices was developed, and utilized to construct this new design. The device frequency response was characterized and its resonant modes and output voltages determined through a Fast Fourier Transform. The fundamental thickness mode frequency was found to be 15.4MHz with a corresponding 10.25mV amplitude, and a longitudinal resonant frequency of 3.1Mhz with a corresponding 2.2mV amplitude across a 50Ω resistor. The high miniaturization of the device holds promise for future work for creating an injectable, wireless system for the treatment of neurological disorders.
ContributorsCatchings, Michael Thomas (Author) / Towe, Bruce (Thesis director) / Muthuswamy, Jitendran (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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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

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.
ContributorsChirania, Sanchit (Author) / Towe, Bruce (Thesis advisor) / Abbas, James (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2016
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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

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