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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
Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on

Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on bulk cell analysis, which results in averaging out the results acquired from a group of cells and hence missing important information about individual cells and their behavior. Understanding the cellular behavior at the single-cell level can help in obtaining a complete profile of the cell and to get a more in-depth knowledge of cellular processes. For example, measuring transmembrane fluxes oxygen can provide a direct readout of the cell metabolism.

The goal of this thesis is to design, optimize and implement a device that can measure the oxygen consumption rate (OCR) of live single cells. A microfluidic device has been designed with the ability to rapidly seal and unseal microchambers containing individual cells and an extracellular optical oxygen sensor for measuring the OCR of live single cells. The device consists of two parts, one with the sensor in microwells (top half) and the other with channels and cells trapped in Pachinko-type micro-traps (bottom half). When the two parts of the device are placed together the wells enclose each cell. Oil is flown in through the channels of the device to produce isolated and sealed microchamber around each cell. Different fluids can be flowed in and out of the device, alternating with oil, to rapidly switch between sealed and unsealed microenvironment around each cell. A fluorescent ratiometric dual pH and oxygen sensor is placed in each well. The thesis focuses on measuring changes in the oxygen consumption rate of each cell within a well. Live and dead cells are identified using a fluorescent live/dead cell assay. Finally, the technology is designed to be scalable for high-throughput applications by controlling the flow rate of the system and increasing the cell array density.
ContributorsRodrigues, Meryl (Author) / Meldrum, Deirdre (Thesis advisor) / Kelbauskas, Laimonas (Committee member) / LaBelle, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of

Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of single cells. Yet to date, no live-cell compatible version of the technology exists. In this thesis, a microfluidic chip with the ability to rotate live single cells in hydrodynamic microvortices about an axis parallel to the optical focal plane has been demonstrated. The chip utilizes a novel 3D microchamber design arranged beneath a main channel creating flow detachment into the chamber, producing recirculating flow conditions. Single cells are flowed through the main channel, held in the center of the microvortex by an optical trap, and rotated by the forces induced by the recirculating fluid flow. Computational fluid dynamics (CFD) was employed to optimize the geometry of the microchamber. Two methods for the fabrication of the 3D microchamber were devised: anisotropic etching of silicon and backside diffuser photolithography (BDPL). First, the optimization of the silicon etching conditions was demonstrated through design of experiment (DOE). In addition, a non-conventional method of soft-lithography was demonstrated which incorporates the use of two positive molds, one of the main channel and the other of the microchambers, compressed together during replication to produce a single ultra-thin (<200 µm) negative used for device assembly. Second, methods for using thick negative photoresists such as SU-8 with BDPL have been developed which include a new simple and effective method for promoting the adhesion of SU-8 to glass. An assembly method that bonds two individual ultra-thin (<100 µm) replications of the channel and the microfeatures has also been demonstrated. Finally, a pressure driven pumping system with nanoliter per minute flow rate regulation, sub-second response times, and < 3% flow variability has been designed and characterized. The fabrication and assembly of this device is inexpensive and utilizes simple variants of conventional microfluidic fabrication techniques, making it easily accessible to the single cell analysis community.
ContributorsMyers, Jakrey R (Author) / Meldrum, Deirdre (Thesis advisor) / Johnson, Roger (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2012
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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
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
Traumatic brain injury (TBI) is a leading cause of disability worldwide with 1.7 million TBIs reported annually in the United States. Broadly, TBI can be classified into focal injury, associated with cerebral contusion, and diffuse injury, a widespread injury pathology. TBI results in a host of pathological alterations and may

Traumatic brain injury (TBI) is a leading cause of disability worldwide with 1.7 million TBIs reported annually in the United States. Broadly, TBI can be classified into focal injury, associated with cerebral contusion, and diffuse injury, a widespread injury pathology. TBI results in a host of pathological alterations and may lead to a transient blood-brain-barrier (BBB) breakdown. Although the BBB dysfunction after TBI may provide a window for therapeutic delivery, the current drug delivery approaches remains largely inefficient due to rapid clearance, inactivation and degradation. One potential strategy to address the current therapeutic limitations is to employ nanoparticle (NP)-based technology to archive greater efficacy and reduced clearance compared to standard drug administration. However, NP application for TBI is challenging not only due to the transient temporal resolution of the BBB breakdown, but also due to the heterogeneous (focal/diffuse) aspect of the disease itself. Furthermore, recent literature suggests sex of the animal influences neuroinflammation/outcome after TBI; yet, the influence of sex on BBB integrity following TBI and subsequent NP delivery has not been previously investigated. The overarching hypothesis for this thesis is that TBI-induced compromised BBB and leaky vasculature will enable delivery of systemically injected NPs to the injury penumbra. This study specifically explored the feasibility and the temporal accumulation of NPs in preclinical mouse models of focal and diffuse TBI. Key findings from these studies include the following. (1) After focal TBI, NPs ranging from 20-500nm exhibited peak accumulation within the injury penumbra acutely (1h) post-injury. (2) A smaller delayed peak of NP accumulation (40nm) was observed sub-acutely (3d) after focal brain injury. (3) Mild diffuse TBI simulated with a mild closed head injury model did not display any measurable NP accumulation after 1h post-injury. (4) In contrast, a moderate diffuse model (fluid percussion injury) demonstrated peak accumulation at 3h post-injury with up to 500 nm size NPs accumulating in cortical tissue. (5) Robust NP accumulation (40nm) was found in female mice compared to the males at 24h and 3d following focal brain injury. Taken together, these results demonstrate the potential for NP delivery at acute and sub-acute time points after TBI by exploiting the compromised BBB. Results also reveal a potential sex dependent component of BBB disruption leading to altered NP accumulation. The applications of this research are far-reaching ranging from theranostic delivery to personalized NP delivery for effective therapeutic outcome.
ContributorsBharadwaj, Vimala Nagabhushana (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Kodibagkar, Vikram D (Thesis advisor) / Kleim, Jeffrey (Committee member) / Tian, Yanqing (Committee member) / Lifshitz, Jonathan (Committee member) / Anderson, Trent R (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
Spasticity is a neurological disorder in which a target group of muscles remain in a contracted state. In addition to interfering with the function of these muscles, spasticity causes chronic pain and discomfort. Often found in patients with cerebral palsy, multiple sclerosis, or stroke history, spasticity affects an estimated twelve

Spasticity is a neurological disorder in which a target group of muscles remain in a contracted state. In addition to interfering with the function of these muscles, spasticity causes chronic pain and discomfort. Often found in patients with cerebral palsy, multiple sclerosis, or stroke history, spasticity affects an estimated twelve million people worldwide. Not only does spasticity cause discomfort and loss of function, but the condition can lead to contractures, or permanent shortenings of the muscle and connective tissue, if left untreated. Current treatments for spasticity are primarily different forms of muscle relaxant pharmaceuticals. Almost all of these drugs, however, carry unwanted side effects, including total muscle weakness, liver toxicity, and possible dependence. Additionally, kinesiotherapy, conducted by physical therapists at rehabilitation clinics, is often prescribed to people suffering from spasticity. Since kinesiotherapy requires frequent practice to be effective, proper treatment requires constant professional care and clinic appointments, discouraging patient compliance. Consequently, a medical device that could automate relief for spasticity outside of a clinic is desired in the market. While a number of different dynamic splints for hand spasticity are currently on the market, research has shown that these devices, which simply brace the hand in an extended position, do not work through any mechanism to decrease spastic tension over time. Two methods of temporarily reducing spasticity that have been observed in clinical studies are cryotherapy, or the decrease of temperature on a target area, and electrotherapy, which is the delivery of regulated electrical pulses to a target area. It is possible that either of these mechanisms could be incorporated into a medical device aimed toward spastic relief. In fact, electrotherapy is used in a current market device called the SaeboStim, which is advertised to help stroke recovery and spastic reduction. The purpose of this paper is to evaluate the viability of a potential spastic relief device that utilizes cryotherapy to a current and closest competitor, the SaeboStim. The effectiveness of each device in relieving spasticity is reviewed. The two devices are also compared on their ability to address primary customer needs, such as convenience, ease of use, durability, and price. Overall, it is concluded that the cryotherapy device more effectively relieves hand spasticity in users, although the SaeboStim's smaller size and better convenience gives it market appeal, and reveals some of the shortcomings in the preliminary design of the cryotherapy device.
ContributorsWiedeman, Christopher Blaise (Author) / Kleim, Jeffrey (Thesis director) / Buneo, Christopher (Committee member) / W.P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
This is a report of a study that investigated the thinking of a high-achieving precalculus student when responding to tasks that required him to define linear formulas to relate covarying quantities. Two interviews were conducted for analysis. A team of us in the mathematics education department at Arizona State University

This is a report of a study that investigated the thinking of a high-achieving precalculus student when responding to tasks that required him to define linear formulas to relate covarying quantities. Two interviews were conducted for analysis. A team of us in the mathematics education department at Arizona State University initially identified mental actions that we conjectured were needed for constructing meaningful linear formulas. This guided the development of tasks for the sequence of clinical interviews with one high-performing precalculus student. Analysis of the interview data revealed that in instances when the subject engaged in meaning making that led to him imagining and identifying the relevant quantities and how they change together, he was able to give accurate definitions of variables and was usually able to define a formula to relate the two quantities of interest. However, we found that the student sometimes had difficulty imagining how the two quantities of interest were changing together. At other times he exhibited a weak understanding of the operation of subtraction and the idea of constant rate of change. He did not appear to conceptualize subtraction as a quantitative comparison. His inability to conceptualize a constant rate of change as a proportional relationship between the changes in two quantities also presented an obstacle in his developing a meaningful formula that relied on this understanding. The results further stress the need to develop a student's ability to engage in mental operations that involve covarying quantities and a more robust understanding of constant rate of change since these abilities and understanding are critical for student success in future courses in mathematics.
ContributorsKlinger, Tana Paige (Author) / Carlson, Marilyn (Thesis director) / Thompson, Pat (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2014-05