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A current thrust in neurorehabilitation research involves exogenous neuromodulation of peripheral nerves to enhance neuroplasticity and maximize recovery of function. This dissertation presents the results of four experiments aimed at assessing the effects of trigeminal nerve stimulation (TNS) and occipital nerve stimulation (ONS) on motor learning, which was behaviorally characterized

A current thrust in neurorehabilitation research involves exogenous neuromodulation of peripheral nerves to enhance neuroplasticity and maximize recovery of function. This dissertation presents the results of four experiments aimed at assessing the effects of trigeminal nerve stimulation (TNS) and occipital nerve stimulation (ONS) on motor learning, which was behaviorally characterized using an upper extremity visuomotor adaptation paradigm. In Aim 1a, the effects of offline TNS using clinically tested frequencies (120 and 60 Hz) were characterized. Sixty-three participants (22.75±4.6 y/o), performed a visuomotor rotation task and received TNS before encountering rotation of hand visual feedback. In Aim 1b, TNS at 3 kHz, which has been shown to be more tolerable at higher current intensities, was evaluated in 42 additional subjects (23.4±4.6 y/o). Results indicated that 3 kHz stimulation accelerated learning while 60 Hz stimulation slowed learning, suggesting a frequency-dependent effect on learning. In Aim 2, the effect of online TNS using 120 and 60 Hz were characterized to determine if this protocol would deliver better outcomes. Sixty-three participants (23.2±3.9 y/o) received either TNS or sham concurrently with perturbed visual feedback. Results showed no significant differences among groups. However, a cross-study comparison of results obtained with 60 Hz offline TNS showed a statistically significant improvement in learning rates with online stimulation relative to offline, suggesting a timing-dependent effect on learning. In Aim 3, TNS and ONS were compared using the best protocol from previous aims (offline 3 kHz). Additionally, concurrent stimulation of both nerves was explored to look for potential synergistic effects. Eighty-four participants (22.9±3.2 y/o) were assigned to one of four groups: TNS, ONS, TNS+ONS, and sham. Visual inspection of learning curves revealed that the ONS group demonstrated the fastest learning among groups. However, statistical analyses did not confirm this observation. In addition, the TNS+ONS group appeared to learn faster than the sham and TNS groups but slower than the ONS only group, suggesting no synergistic effects using this protocol, as initially hypothesized. The results provide new information on the potential use of TNS and ONS in neurorehabilitation and performance enhancement in the motor domain.
ContributorsArias, Diego (Author) / Buneo, Christopher (Thesis advisor) / Schaefer, Sydney (Committee member) / Helms-Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2023
Description

Neuromodulation is an emerging field of research that has a proven therapeutic benefit on a number of neurological disorders, including epilepsy and stroke. It is characterized by using exogenous stimulation to modify neural activity. Prior studies have shown the positive effect of non-invasive trigeminal nerve stimulation (TNS) on motor learning.

Neuromodulation is an emerging field of research that has a proven therapeutic benefit on a number of neurological disorders, including epilepsy and stroke. It is characterized by using exogenous stimulation to modify neural activity. Prior studies have shown the positive effect of non-invasive trigeminal nerve stimulation (TNS) on motor learning. However, few studies have explored the effect of this specific neuromodulatory method on the underlying physiological processes, including heart rate variability (HRV), facial skin temperatures, skin conductance level, and respiratory rate. Here we present preliminary results of the effects of 3kHz supraorbital TNS on HRV using non-linear (Poincaré plot descriptors) and time-domain (SDNN) measures of analysis. Twenty-one (21) healthy adult subjects were randomly assigned to 2 groups: 3kHz Active stimulation (n=11) and Sham (n=10). Participants’ physiological markers were monitored continuously across three blocks: one ten-minute baseline block, one twenty-minute treatment block, and one ten-minute recovery block. TNS targeting the ophthalmic branches of the trigeminal nerve was delivered during the treatment block for twenty minutes in 30 sec. ON/OFF cycles. The active stimulation group exhibited larger values of all Poincaré descriptors and SDNN during blocks two and three, signifying increased HRV and autonomic nervous system activity.

ContributorsParmar, Romir (Author) / Buneo, Christopher (Thesis director) / Helms Tillery, Stephen (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor)
Created2023-05
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Description
Vagus nerve stimulation (VNS) has shown benefits beyond its original therapeutic application, though there is a lack of research into these benefits in healthy and athletic populations. To address this gap in the VNS literature, the present study addresses the feasibility and possible efficacy of transcutaneous VNS (tVNS) in improving

Vagus nerve stimulation (VNS) has shown benefits beyond its original therapeutic application, though there is a lack of research into these benefits in healthy and athletic populations. To address this gap in the VNS literature, the present study addresses the feasibility and possible efficacy of transcutaneous VNS (tVNS) in improving performance and various biometrics during two athletic tasks: golf tee shots and baseball pitching. Performance, cortical dynamics, anxiety measures, muscle excitation, and heart rate characteristics were assessed before and after stimulation using electroencephalography (EEG), the State-Trait Anxiety Inventory (STAI), and electrocardiography (ECG) during the baseball and golf tasks as well as electromyography (EMG) for muscle excitation in the golf participants. Golfers exhibited increased perceived quality of each repetition (independent from outcome) and an improvement in state and trait anxiety after stimulation. Golfers in the active stimulation group also showed a greater reduction in right upper trapezius muscle excitation when compared to the sham stimulation group. Baseball pitchers exhibited an increase in perceived quality of each repetition (independent from outcome) after active stimulation but not an improvement of state and trait anxiety. No significant effects of stimulation Priming, stimulation Type, or the Priming×Type interaction were seen in heart rate, EEG, or performance in the golf or baseball tasks. The present study supports the feasibility of tVNS in sports and athletic tasks and suggests the need for future research to investigate further into the effects of tVNS on the performance, psychologic, and physiologic attributes of athletes during competition.
ContributorsLindley, Kyle (Author) / Tyler, William J (Thesis advisor) / Wyckoff, Sarah (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Sleep is an essential human function. Modern day society has made it so that sleep is prioritized less and less. Professionals in critical positions such as doctors, nurses, and emergency medical technicians can often have hectic schedules that are unforgiving toward sleep due to the increase in shift work that

Sleep is an essential human function. Modern day society has made it so that sleep is prioritized less and less. Professionals in critical positions such as doctors, nurses, and emergency medical technicians can often have hectic schedules that are unforgiving toward sleep due to the increase in shift work that dominates these fields. Sleep deficits can have detrimental effects on one’s psyche and mood. Depression and anxiety both have high comorbidity rates with insomnia because of sleeping deficits. Transdermal Electrical Nerve Stimulation (TENS) offers a potential solution to improving sleep quality and mood by modulating the ascending reticular activating system (RAS). This system starts in the anterior portion of the head with trigeminal nerve branches and is stimulated using a 500-550 Hz waveform.

In this experiment Positive Affect and Negative Affect Schedule (PANAS) scores are recorded daily to monitor mood differences between pre and post treatment (TENS vs Sham). PANAS scores were found to be insignificant between groups. Pittsburgh Sleep Quality Index (PSQI), and Fitbit were chosen to study perceived sleep, and objective sleep. Both PSQI, and Fitbit found insignificant differences between TENS and Sham. Finally, the Beck Depression and Beck Anxiety Inventories were administered weekly to determine if there are immediate changes to depressive and anxiety symptom, after a week of treatment (TENS vs Sham). A significant difference was found between the pre and post of the TENS treatment group. The TENS group was not found to be significantly different from Sham, potentially the result of a placebo effect. These results were found with n=10 participants in the TENS treatment group and n=6 in the sham group.
ContributorsUdave, Ceasar (Author) / Tyler, William J (Thesis advisor) / Buneo, Christopher (Committee member) / Wyckoff, Sarah (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Intracellular voltage recordings from single neurons in vitro and in vivo have been fundamental to our understanding of neuronal function. Conventional electrodes and associated positioning systems for intracellular recording in vivo are large and bulky, which has largely restricted their use to single-channel recording from anesthetized animals. Further, intracellular recordings

Intracellular voltage recordings from single neurons in vitro and in vivo have been fundamental to our understanding of neuronal function. Conventional electrodes and associated positioning systems for intracellular recording in vivo are large and bulky, which has largely restricted their use to single-channel recording from anesthetized animals. Further, intracellular recordings are very cumbersome, requiring a high degree of skill not readily achieved in a typical laboratory. This dissertation presents a robotic, head-mountable, MEMS (Micro-Electro-Mechanical Systems) based intracellular recording system to overcome the above limitations associated with form-factor, scalability and highly skilled and tedious manual operations required for intracellular recordings. This system combines three distinct technologies: 1) novel microscale, polycrystalline silicon-based electrode for intracellular recording, 2) electrothermal microactuators for precise microscale navigation of the electrode and 3) closed-loop control algorithm for autonomous movement and positioning of electrode inside single neurons. First, two distinct designs of polysilicon-based microscale electrodes were fabricated and tested for intracellular recordings. In the first approach, tips of polysilicon microelectrodes were milled to nanoscale dimensions (<300 nm) using focused ion beam (FIB) to develop polysilicon nanoelectrodes. Polysilicon nanoelectrodes recorded >1.5 mV amplitude, positive-going action potentials and synaptic potentials from neurons in the abdominal ganglion of Aplysia Californica. In the second approach, polysilicon microelectrodes were integrated with miniaturized glass micropipettes filled with electrolyte to fabricate glass-polysilicon microelectrodes. These electrodes consistently recorded high fidelity intracellular potentials from neurons in the abdominal ganglion of Aplysia Californica (Resting Potentials < -35 mV, Action Potentials > 60 mV) as well as the rat motor cortex (Resting Potentials < -50 mV). Next, glass-polysilicon microelectrodes were coupled with microscale electrothermal actuators and controller for autonomous intracellular recordings from single neurons in the abdominal ganglion. Consistent resting potentials (< -35 mV) and action potentials (> 60 mV) were recorded after each successful penetration attempt with the controller and microactuated glass-polysilicon microelectrodes. The success rate of penetration and quality of recordings achieved using electrothermal microactuators were comparable to that of conventional positioning systems. Finally, the feasibility of this miniaturized system to obtain intracellular recordings from single neurons in the motor cortex of rats in vivo is also demonstrated. The MEMS-based system offers significant advantages: 1) reduction in overall size for potential use in behaving animals, 2) scalable approach to potentially realize multi-channel recordings and 3) a viable method to fully automate measurement of intracellular recordings.
ContributorsSampath Kumar, Swathy (Author) / Muthuswamy, Jit (Thesis advisor) / Abbas, James (Committee member) / Hamm, Thomas (Committee member) / Christen, Jennifer Blain (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Neural interfacing applications have advanced in complexity, with needs for increasingly high degrees of freedom in prosthetic device control, sharper discrimination in sensory percepts in bidirectional interfaces, and more precise localization of functional connectivity in the brain. As such, there is a growing need for reliable neurophysiological recordings at a

Neural interfacing applications have advanced in complexity, with needs for increasingly high degrees of freedom in prosthetic device control, sharper discrimination in sensory percepts in bidirectional interfaces, and more precise localization of functional connectivity in the brain. As such, there is a growing need for reliable neurophysiological recordings at a fine spatial scale matching that of cortical columnar processing. Penetrating microelectrodes provide localization sufficient to isolate action potential (AP) waveforms, but often suffer from recorded signal deterioration linked to foreign body response. Micro-Electrocorticography (μECoG) surface electrodes elicit lower foreign body response and show greater chronic stability of recorded signals, though they typically lack the signal localization necessary to isolate individual APs. This dissertation validates the recording capacity of a novel, flexible, large area μECoG array with bilayer routing in a feline implant, and explores the ability of conventional μECoG arrays to detect features of neuronal activity in a very high frequency band associated with AP waveforms.

Recordings from both layers of the flexible μECoG array showed frequency features typical of cortical local field potentials (LFP) and were shown to be stable in amplitude over time. Recordings from both layers also showed consistent, frequency-dependent modulation after induction of general anesthesia, with large increases in beta and gamma band and decreases in theta band observed over three experiments. Recordings from conventional μECoG arrays over human cortex showed robust modulation in a high frequency (250-2000 Hz) band upon production of spoken words. Modulation in this band was used to predict spoken words with over 90% accuracy. Basal Ganglia neuronal AP firing was also shown to significantly correlate with various cortical μECoG recordings in this frequency band. Results indicate that μECoG surface electrodes may detect high frequency neuronal activity potentially associated with AP firing, a source of information previously unutilized by these devices.
ContributorsBarton, Cody David (Author) / Greger, Bradley (Thesis advisor, Committee member) / Santello, Marco (Committee member) / Buneo, Christopher (Committee member) / Graudejus, Oliver (Committee member) / Artemiadis, Panagiotis (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Previously accomplished research examined sensory integration between upper limb proprioception and tactile sensation. The active proprioceptive-tactile relationship points towards an opportunity to examine neuromodulation effects on sensory integration with respect to proprioceptive error magnitude and direction. Efforts to improve focus and attention during upper limb proprioceptive tasks results in a

Previously accomplished research examined sensory integration between upper limb proprioception and tactile sensation. The active proprioceptive-tactile relationship points towards an opportunity to examine neuromodulation effects on sensory integration with respect to proprioceptive error magnitude and direction. Efforts to improve focus and attention during upper limb proprioceptive tasks results in a decrease of proprioceptive error magnitudes and greater endpoint accuracy. Increased focus and attention can also be correlated to neurophysiological activity in the Locus Coeruleus (LC) during a variety of mental tasks. Through non-invasive trigeminal nerve stimulation, it may be possible to affect the activity of the LC and induce improvements in arousal and attention that would assist in proprioceptive estimation. The trigeminal nerve projects to the LC through the mesencephalic nucleus of the trigeminal complex, providing a pathway similar to the effects seen from vagus nerve stimulation. In this experiment, the effect of trigeminal nerve stimulation (TNS) on proprioceptive ability is evaluated by the proprioceptive estimation error magnitude and direction, while LC activation via autonomic pathways is indirectly measured using pupil diameter, pupil recovery time, and pupil velocity. TNS decreases proprioceptive error magnitude in 59% of subjects, while having no measurable impact on proprioceptive strategy. Autonomic nervous system changes were observed in 88% of subjects, with mostly parasympathetic activation and a mixed sympathetic effect.
ContributorsOrthlieb, Gerrit Chi Luk (Author) / Helms-Tillery, Stephen (Thesis advisor) / Tanner, Justin (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Growing understanding of the neural code and how to speak it has allowed for notable advancements in neural prosthetics. With commercially-available implantable systems with bi- directional neural communication on the horizon, there is an increasing imperative to develop high resolution interfaces that can survive the environment and be well tolerated

Growing understanding of the neural code and how to speak it has allowed for notable advancements in neural prosthetics. With commercially-available implantable systems with bi- directional neural communication on the horizon, there is an increasing imperative to develop high resolution interfaces that can survive the environment and be well tolerated by the nervous system under chronic use. The sensory encoding aspect optimally interfaces at a scale sufficient to evoke perception but focal in nature to maximize resolution and evoke more complex and nuanced sensations. Microelectrode arrays can maintain high spatial density, operating on the scale of cortical columns, and can be either penetrating or non-penetrating. The non-penetrating subset sits on the tissue surface without puncturing the parenchyma and is known to engender minimal tissue response and less damage than the penetrating counterpart, improving long term viability in vivo. Provided non-penetrating microelectrodes can consistently evoke perception and maintain a localized region of activation, non-penetrating micro-electrodes may provide an ideal platform for a high performing neural prosthesis; this dissertation explores their functional capacity.

The scale at which non-penetrating electrode arrays can interface with cortex is evaluated in the context of extracting useful information. Articulate movements were decoded from surface microelectrode electrodes, and additional spatial analysis revealed unique signal content despite dense electrode spacing. With a basis for data extraction established, the focus shifts towards the information encoding half of neural interfaces. Finite element modeling was used to compare tissue recruitment under surface stimulation across electrode scales. Results indicated charge density-based metrics provide a reasonable approximation for current levels required to evoke a visual sensation and showed tissue recruitment increases exponentially with electrode diameter. Micro-scale electrodes (0.1 – 0.3 mm diameter) could sufficiently activate layers II/III in a model tuned to striate cortex while maintaining focal radii of activated tissue.

In vivo testing proceeded in a nonhuman primate model. Stimulation consistently evoked visual percepts at safe current thresholds. Tracking perception thresholds across one year reflected stable values within minimal fluctuation. Modulating waveform parameters was found useful in reducing charge requirements to evoke perception. Pulse frequency and phase asymmetry were each used to reduce thresholds, improve charge efficiency, lower charge per phase – charge density metrics associated with tissue damage. No impairments to photic perception were observed during the course of the study, suggesting limited tissue damage from array implantation or electrically induced neurotoxicity. The subject consistently identified stimulation on closely spaced electrodes (2 mm center-to-center) as separate percepts, indicating sub-visual degree discrete resolution may be feasible with this platform. Although continued testing is necessary, preliminary results supports epicortical microelectrode arrays as a stable platform for interfacing with neural tissue and a viable option for bi-directional BCI applications.
ContributorsOswalt, Denise (Author) / Greger, Bradley (Thesis advisor) / Buneo, Christopher (Committee member) / Helms-Tillery, Stephen (Committee member) / Mirzadeh, Zaman (Committee member) / Papandreou-Suppappola, Antonia (Committee member) / Arizona State University (Publisher)
Created2018
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Description
The ultimate goal of human movement control research is to understand how natural movements performed in daily reaching activities, are controlled. Natural movements require coordination of multiple degrees of freedom (DOF) of the arm. Patterns of arm joint control were studied during daily functional tasks, which were performed through the

The ultimate goal of human movement control research is to understand how natural movements performed in daily reaching activities, are controlled. Natural movements require coordination of multiple degrees of freedom (DOF) of the arm. Patterns of arm joint control were studied during daily functional tasks, which were performed through the rotation of seven DOF in the arm. Analyzed movements which imitated the following 3 activities of daily living: moving an empty soda can from a table and placing it on a further position; placing the empty soda can from initial position at table to a position at shoulder level on a shelf; and placing the empty soda can from initial position at table to a position at eye level on a shelf. Kinematic and kinetic analyses were conducted for these three movements. The studied kinematic characteristics were: hand trajectory in the sagittal plane, displacements of the 7 DOF, and contribution of each DOF to hand velocity. The kinetic analysis involved computation of 3-dimensional vectors of muscle torque (MT), interaction torque (IT), gravity torque (GT), and net torque (NT) at the shoulder, elbow, and wrist. Using the relationship NT = MT + GT + IT, the role of active control and passive factors (gravitation and inter-segmental dynamics) in rotation of each joint by computing MT contribution (MTC) to NT was assessed. MTC was computed using the ratio of the signed MT projection on NT to NT magnitude. Despite a variety of joint movements available across the different tasks, 3 patterns of shoulder and elbow coordination prevailed in each movement: 1) active rotation of the shoulder and predominantly passive rotation of the elbow; 2) active rotation of the elbow and predominantly passive rotation of the shoulder; and 3) passive rotation of both joints. Analysis of wrist control suggested that MT mainly compensates for passive torque and provides adjustment of wrist motion according to requirements of each task. In conclusion, it was observed that the 3 shoulder-elbow coordination patterns (during which at least one joint moved) passively represented joint control primitives, underlying the performance of well-learned arm movements, although these patterns may be less prevalent during non-habitual movements.
ContributorsSansgiri, Dattaraj (Author) / Dounskaia, Natalia (Thesis advisor) / Schaefer, Sydney (Thesis advisor) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2018