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Description
Humans are capable of transferring learning for anticipatory control of dexterous object manipulation despite changes in degrees-of-freedom (DoF), i.e., switching from lifting an object with two fingers to lifting the same object with three fingers. However, the role that tactile information plays in this transfer of learning is unknown. In

Humans are capable of transferring learning for anticipatory control of dexterous object manipulation despite changes in degrees-of-freedom (DoF), i.e., switching from lifting an object with two fingers to lifting the same object with three fingers. However, the role that tactile information plays in this transfer of learning is unknown. In this study, subjects lifted an L-shaped object with two fingers (2-DoF), and then lifted the object with three fingers (3-DoF). The subjects were divided into two groups--one group performed the task wearing a glove (to reduce tactile sensibility) upon the switch to 3-DoF (glove group), while the other group did not wear the glove (control group). Compensatory moment (torque) was used as a measure to determine how well the subject could minimize the tilt of the object following the switch from 2-DoF to 3-DoF. Upon the switch to 3-DoF, subjects wearing the glove generated a compensatory moment (Mcom) that had a significantly higher error than the average of the last five trials at the end of the 3-DoF block (p = 0.012), while the control subjects did not demonstrate a significant difference in Mcom. Additional effects of the reduction in tactile sensibility were: (1) the grip force for the group of subjects wearing the glove was significantly higher in the 3-DoF trials compared to the 2-DoF trials (p = 0.014), while the grip force of the control subjects was not significantly different; (2) the difference in centers of pressure between the thumb and fingers (ΔCoP) significantly increased in the 3-DoF block for the group of subjects wearing the glove, while the ΔCoP of the control subjects was not significantly different; (3) lastly, the control subjects demonstrated a greater increase in lift force than the group of subjects wearing the glove (though results were not significant). Combined together, these results suggest different force modulation strategies are used depending on the amount of tactile feedback that is available to the subject. Therefore, reduction of tactile sensibility has important effects on subjects' ability to transfer learned manipulation across different DoF contexts.
ContributorsGaw, Nathan (Author) / Helms Tillery, Stephen (Thesis advisor) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Dexterous manipulation is a representative task that involves sensorimotor integration underlying a fine control of movements. Over the past 30 years, research has provided significant insight, including the control mechanisms of force coordination during manipulation tasks. Successful dexterous manipulation is thought to rely on the ability to integrate the sense

Dexterous manipulation is a representative task that involves sensorimotor integration underlying a fine control of movements. Over the past 30 years, research has provided significant insight, including the control mechanisms of force coordination during manipulation tasks. Successful dexterous manipulation is thought to rely on the ability to integrate the sense of digit position with motor commands responsible for generating digit forces and placement. However, the mechanisms underlying the phenomenon of digit position-force coordination are not well understood. This dissertation addresses this question through three experiments that are based on psychophysics and object lifting tasks. It was found in psychophysics tasks that sensed relative digit position was accurately reproduced when sensorimotor transformations occurred with larger vertical fingertip separations, within the same hand, and at the same hand posture. The results from a follow-up experiment conducted in the same digit position-matching task while generating forces in different directions reveal a biased relative digit position toward the direction of force production. Specifically, subjects reproduced the thumb CoP higher than the index finger CoP when vertical digit forces were directed upward and downward, respectively, and vice versa. It was also found in lifting tasks that the ability to discriminate the relative digit position prior to lifting an object and modulate digit forces to minimize object roll as a function of digit position are robust regardless of whether motor commands for positioning the digits on the object are involved. These results indicate that the erroneous sensorimotor transformations of relative digit position reported here must be compensated during dexterous manipulation by other mechanisms, e.g., visual feedback of fingertip position. Furthermore, predicted sensory consequences derived from the efference copy of voluntary motor commands to generate vertical digit forces may override haptic sensory feedback for the estimation of relative digit position. Lastly, the sensorimotor transformations from haptic feedback to digit force modulation to position appear to be facilitated by motor commands for active digit placement in manipulation.
ContributorsShibata, Daisuke (Author) / Santello, Marco (Thesis advisor) / Dounskaia, Natalia (Committee member) / Kleim, Jeffrey (Committee member) / Helms Tillery, Stephen (Committee member) / McBeath, Michael (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Understanding where our bodies are in space is imperative for motor control, particularly for actions such as goal-directed reaching. Multisensory integration is crucial for reducing uncertainty in arm position estimates. This dissertation examines time and frequency-domain correlates of visual-proprioceptive integration during an arm-position maintenance task. Neural recordings

Understanding where our bodies are in space is imperative for motor control, particularly for actions such as goal-directed reaching. Multisensory integration is crucial for reducing uncertainty in arm position estimates. This dissertation examines time and frequency-domain correlates of visual-proprioceptive integration during an arm-position maintenance task. Neural recordings were obtained from two different cortical areas as non-human primates performed a center-out reaching task in a virtual reality environment. Following a reach, animals maintained the end-point position of their arm under unimodal (proprioception only) and bimodal (proprioception and vision) conditions. In both areas, time domain and multi-taper spectral analysis methods were used to quantify changes in the spiking, local field potential (LFP), and spike-field coherence during arm-position maintenance.

In both areas, individual neurons were classified based on the spectrum of their spiking patterns. A large proportion of cells in the SPL that exhibited sensory condition-specific oscillatory spiking in the beta (13-30Hz) frequency band. Cells in the IPL typically had a more diverse mix of oscillatory and refractory spiking patterns during the task in response to changing sensory condition. Contrary to the assumptions made in many modelling studies, none of the cells exhibited Poisson-spiking statistics in SPL or IPL.

Evoked LFPs in both areas exhibited greater effects of target location than visual condition, though the evoked responses in the preferred reach direction were generally suppressed in the bimodal condition relative to the unimodal condition. Significant effects of target location on evoked responses were observed during the movement period of the task well.

In the frequency domain, LFP power in both cortical areas was enhanced in the beta band during the position estimation epoch of the task, indicating that LFP beta oscillations may be important for maintaining the ongoing state. This was particularly evident at the population level, with clear increase in alpha and beta power. Differences in spectral power between conditions also became apparent at the population level, with power during bimodal trials being suppressed relative to unimodal. The spike-field coherence showed confounding results in both the SPL and IPL, with no clear correlation between incidence of beta oscillations and significant beta coherence.
ContributorsVanGilder, Paul (Author) / Buneo, Christopher A (Thesis advisor) / Helms-Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Muthuswamy, Jit (Committee member) / Foldes, Stephen (Committee member) / Arizona State University (Publisher)
Created2017
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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

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.
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
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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
Proprioception is the sense of body position, movement, force, and effort. Loss of proprioception can affect planning and control of limb and body movements, negatively impacting activities of daily living and quality of life. Assessments employing planar robots have shown that proprioceptive sensitivity is directionally dependent within the horizontal plane

Proprioception is the sense of body position, movement, force, and effort. Loss of proprioception can affect planning and control of limb and body movements, negatively impacting activities of daily living and quality of life. Assessments employing planar robots have shown that proprioceptive sensitivity is directionally dependent within the horizontal plane however, few studies have looked at proprioceptive sensitivity in 3d space. In addition, the extent to which proprioceptive sensitivity is modifiable by factors such as exogenous neuromodulation is unclear. To investigate proprioceptive sensitivity in 3d we developed a novel experimental paradigm employing a 7-DoF robot arm, which enables reliable testing of arm proprioception along arbitrary paths in 3d space, including vertical motion which has previously been neglected. A participant’s right arm was coupled to a trough held by the robot that stabilized the wrist and forearm, allowing for changes in configuration only at the elbow and shoulder. Sensitivity to imposed displacements of the endpoint of the arm were evaluated using a “same/different” task, where participant’s hands were moved 1-4 cm from a previously visited reference position. A measure of sensitivity (d’) was compared across 6 movement directions and between 2 postures. For all directions, sensitivity increased monotonically as the distance from the reference location increased. Sensitivity was also shown to be anisotropic (directionally dependent) which has implications for our understanding of the planning and control of reaching movements in 3d space.

The effect of neuromodulation on proprioceptive sensitivity was assessed using transcutaneous electrical nerve stimulation (TENS), which has been shown to have beneficial effects on human cognitive and sensorimotor performance in other contexts. In this pilot study the effects of two frequencies (30hz and 300hz) and three electrode configurations were examined. No effect of electrode configuration was found, however sensitivity with 30hz stimulation was significantly lower than with 300hz stimulation (which was similar to sensitivity without stimulation). Although TENS was shown to modulate proprioceptive sensitivity, additional experiments are required to determine if TENS can produce enhancement rather than depression of sensitivity which would have positive implications for rehabilitation of proprioceptive deficits arising from stroke and other disorders.
ContributorsKlein, Joshua (Author) / Buneo, Christopher (Thesis advisor) / Helms-Tillery, Stephen (Committee member) / Kleim, Jeffrey (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Brain-machine interfaces (BMIs) were first imagined as a technology that would allow subjects to have direct communication with prosthetics and external devices (e.g. control over a computer cursor or robotic arm movement). Operation of these devices was not automatic, and subjects needed calibration and training in order to master this

Brain-machine interfaces (BMIs) were first imagined as a technology that would allow subjects to have direct communication with prosthetics and external devices (e.g. control over a computer cursor or robotic arm movement). Operation of these devices was not automatic, and subjects needed calibration and training in order to master this control. In short, learning became a key component in controlling these systems. As a result, BMIs have become ideal tools to probe and explore brain activity, since they allow the isolation of neural inputs and systematic altering of the relationships between the neural signals and output. I have used BMIs to explore the process of brain adaptability in a motor-like task. To this end, I trained non-human primates to control a 3D cursor and adapt to two different perturbations: a visuomotor rotation, uniform across the neural ensemble, and a decorrelation task, which non-uniformly altered the relationship between the activity of particular neurons in an ensemble and movement output. I measured individual and population level changes in the neural ensemble as subjects honed their skills over the span of several days. I found some similarities in the adaptation process elicited by these two tasks. On one hand, individual neurons displayed tuning changes across the entire ensemble after task adaptation: most neurons displayed transient changes in their preferred directions, and most neuron pairs showed changes in their cross-correlations during the learning process. On the other hand, I also measured population level adaptation in the neural ensemble: the underlying neural manifolds that control these neural signals also had dynamic changes during adaptation. I have found that the neural circuits seem to apply an exploratory strategy when adapting to new tasks. Our results suggest that information and trajectories in the neural space increase after initially introducing the perturbations, and before the subject settles into workable solutions. These results provide new insights into both the underlying population level processes in motor learning, and the changes in neural coding which are necessary for subjects to learn to control neuroprosthetics. Understanding of these mechanisms can help us create better control algorithms, and design training paradigms that will take advantage of these processes.
ContributorsArmenta Salas, Michelle (Author) / Helms Tillery, Stephen I (Thesis advisor) / Si, Jennie (Committee member) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2015
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Description
For two centuries, electrical stimulation has been the conventional method for interfacing with the nervous system. As interfaces with the peripheral nervous system become more refined and higher-resolution, several challenges appear, including immune responses to invasive electrode application, large-to-small axon recruitment order, and electrode size-dependent spatial selectivity. Optogenetics offers a

For two centuries, electrical stimulation has been the conventional method for interfacing with the nervous system. As interfaces with the peripheral nervous system become more refined and higher-resolution, several challenges appear, including immune responses to invasive electrode application, large-to-small axon recruitment order, and electrode size-dependent spatial selectivity. Optogenetics offers a solution that is less invasive, more tissue-selective, and has small-to-large axon recruitment order. By adding genes to express photosensitive proteins optogenetics provides neuroscientists the ability to genetically select cell populations to stimulate with simple illumination. However, optogenetic stimulation of peripheral nerves uses diffuse light to activate the photosensitive neural cell lines. To increase the specificity of stimulus response, research was conducted to test the hypothesis that multiple, focused light emissions placed around the circumference of optogenetic mouse sciatic nerve could be driven to produce differential responses in hindlimb motor movement depending on the pattern of light presented. A Monte Carlo computer simulation was created to model the number of emitters, the light emission size, and the focal power of accompanying micro-lenses to provide targeted stimulation to select regions within the sciatic nerve. The computer simulation results were used to parameterize the design of micro-lenses. By modeling multiple focused beams, only fascicles within a nerve diameter less than 1 mm are expected to be fully accessible to focused optical stimulation; a minimum of 4 light sources is required to generate a photon intensity at a point in a nerve over the initial contact along its surface. To elicit the same effect in larger nerves, focusing lenses would require a numerical aperture > 1. Microlenses which met the simulation requirements were fabricated and deployed on a flexible nerve cuff which was used to stimulate the sciatic nerve in optogenetic mice. Motor neuron responses from this stimulation were compared to global illumination; stimulation using the optical cuff resulted in fine motor movement of the extensor muscles of the digits in the hindlimb. Increasing optical power resulted in a shift to gross motor movement of hindlimb. Finally, varying illumination intensity across the cuff showed changes in the extension of individual digits.
ContributorsFritz, Nicholas (Author) / Blain Christen, Jennifer (Thesis advisor) / Abbas, James (Committee member) / Goryll, Michael (Committee member) / Sadleir, Rosalind (Committee member) / Helms-Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2021
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Description
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
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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