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An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space

An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space and the consequences of misestimation of limb position on movements. Two independent but related studies were performed. The first involved characterizing the neural mechanisms of limb position estimation in the non-human primate brain. Single unit recordings were obtained in area 5 of the posterior parietal cortex in order to examine the role of this area in estimating limb position based on visual and somatic signals (proprioceptive, efference copy). When examined individually, many area 5 neurons were tuned to the position of the limb in the workspace but very few neurons were modulated by visual feedback. At the population level however decoding of limb position was somewhat more accurate when visual feedback was provided. These findings support a role for area 5 in limb position estimation but also suggest that visual signals regarding limb position are only weakly represented in this area, and only at the population level. The second part of this dissertation focused on the consequences of misestimation of limb position for movement production. It is well known that limb movements are inherently variable. This variability could be the result of noise arising at one or more stages of movement production. Here we used biomechanical modeling and simulation techniques to characterize movement variability resulting from noise in estimating limb position ('sensing noise') and in planning required movement vectors ('planning noise'), and compared that to the variability expected due to noise in movement execution. We found that the effects of sensing and planning related noise on movement variability were dependent upon both the planned movement direction and the initial configuration of the arm and were different in many respects from the effects of execution noise.
ContributorsShi, Ying (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / He, Jiping (Committee member) / Santos, Veronica (Committee member) / Arizona State University (Publisher)
Created2011
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Description
In order to successfully implement a neural prosthetic system, it is necessary to understand the control of limb movements and the representation of body position in the nervous system. As this development process continues, it is becoming increasingly important to understand the way multiple sensory modalities are used in limb

In order to successfully implement a neural prosthetic system, it is necessary to understand the control of limb movements and the representation of body position in the nervous system. As this development process continues, it is becoming increasingly important to understand the way multiple sensory modalities are used in limb representation. In a previous study, Shi et al. (2013) examined the multimodal basis of limb position in the superior parietal lobule (SPL) as monkeys reached to and held their arm at various target locations in a frontal plane. Visual feedback was withheld in half the trials, though non-visual (i.e. somatic) feedback was available in all trials. Previous analysis showed that some of the neurons were tuned to limb position and that some neurons had their response modulated by the presence or absence of visual feedback. This modulation manifested in decreases in firing rate variability in the vision condition as compared to nonvision. The decreases in firing rate variability, as shown through decreases in both the Fano factor of spike counts and the coefficient of variation of the inter-spike intervals, suggested that changes were taking place in both trial-by-trial and intra-trial variability. I sought to further probe the source of the change in intra-trial variability through spectral analysis. It was hypothesized that the presence of temporal structure in the vision condition would account for a regularity in firing that would have decreased intra-trial variability. While no peaks were apparent in the spectra, differences in spectral power between visual conditions were found. These differences are suggestive of unique temporal spiking patterns at the individual neuron level that may be influential at the population level.
ContributorsDyson, Keith (Author) / Buneo, Christopher A (Thesis advisor) / Helms-Tillery, Stephen I (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Our ability to estimate the position of our body parts in space, a fundamentally proprioceptive process, is crucial for interacting with the environment and movement control. For proprioception to support these actions, the Central Nervous System has to rely on a stored internal representation of the body parts in space.

Our ability to estimate the position of our body parts in space, a fundamentally proprioceptive process, is crucial for interacting with the environment and movement control. For proprioception to support these actions, the Central Nervous System has to rely on a stored internal representation of the body parts in space. However, relatively little is known about this internal representation of arm position. To this end, I developed a method to map proprioceptive estimates of hand location across a 2-d workspace. In this task, I moved each subject's hand to a target location while the subject's eyes were closed. After returning the hand, subjects opened their eyes to verbally report the location of where their fingertip had been. Then, I reconstructed and analyzed the spatial structure of the pattern of estimation errors. In the first couple of experiments I probed the structure and stability of the pattern of errors by manipulating the hand used and tactile feedback provided when the hand was at each target location. I found that the resulting pattern of errors was systematically stable across conditions for each subject, subject-specific, and not uniform across the workspace. These findings suggest that the observed structure of pattern of errors has been constructed through experience, which has resulted in a systematically stable internal representation of arm location. Moreover, this representation is continuously being calibrated across the workspace. In the next two experiments, I aimed to probe the calibration of this structure. To this end, I used two different perturbation paradigms: 1) a virtual reality visuomotor adaptation to induce a local perturbation, 2) and a standard prism adaptation paradigm to induce a global perturbation. I found that the magnitude of the errors significantly increased to a similar extent after each perturbation. This small effect indicates that proprioception is recalibrated to a similar extent regardless of how the perturbation is introduced, suggesting that sensory and motor changes may be two independent processes arising from the perturbation. Moreover, I propose that the internal representation of arm location might be constructed with a global solution and not capable of local changes.
ContributorsRincon Gonzalez, Liliana (Author) / Helms Tillery, Stephen I (Thesis advisor) / Buneo, Christopher A (Thesis advisor) / Santello, Marco (Committee member) / Santos, Veronica (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Reaching movements are subject to noise in both the planning and execution phases of movement production. Although the effects of these noise sources in estimating and/or controlling endpoint position have been examined in many studies, the independent effects of limb configuration on endpoint variability have been largely ignored. The present

Reaching movements are subject to noise in both the planning and execution phases of movement production. Although the effects of these noise sources in estimating and/or controlling endpoint position have been examined in many studies, the independent effects of limb configuration on endpoint variability have been largely ignored. The present study investigated the effects of arm configuration on the interaction between planning noise and execution noise. Subjects performed reaching movements to three targets located in a frontal plane. At the starting position, subjects matched one of two desired arm configuration 'templates' namely "adducted" and "abducted". These arm configurations were obtained by rotations along the shoulder-hand axis, thereby maintaining endpoint position. Visual feedback of the hand was varied from trial to trial, thereby increasing uncertainty in movement planning and execution. It was hypothesized that 1) pattern of endpoint variability would be dependent on arm configuration and 2) that these differences would be most apparent in conditions without visual feedback. It was found that there were differences in endpoint variability between arm configurations in both visual conditions, but these differences were much larger when visual feedback was withheld. The overall results suggest that patterns of endpoint variability are highly dependent on arm configuration, particularly in the absence of visual feedback. This suggests that in the presence of vision, movement planning in 3D space is performed using coordinates that are largely arm configuration independent (i.e. extrinsic coordinates). In contrast, in the absence of vision, movement planning in 3D space reflects a substantial contribution of intrinsic coordinates.
ContributorsLakshmi Narayanan, Kishor (Author) / Buneo, Christopher (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Situations of sensory overload are steadily becoming more frequent as the ubiquity of technology approaches reality--particularly with the advent of socio-communicative smartphone applications, and pervasive, high speed wireless networks. Although the ease of accessing information has improved our communication effectiveness and efficiency, our visual and auditory modalities--those modalities that today's

Situations of sensory overload are steadily becoming more frequent as the ubiquity of technology approaches reality--particularly with the advent of socio-communicative smartphone applications, and pervasive, high speed wireless networks. Although the ease of accessing information has improved our communication effectiveness and efficiency, our visual and auditory modalities--those modalities that today's computerized devices and displays largely engage--have become overloaded, creating possibilities for distractions, delays and high cognitive load; which in turn can lead to a loss of situational awareness, increasing chances for life threatening situations such as texting while driving. Surprisingly, alternative modalities for information delivery have seen little exploration. Touch, in particular, is a promising candidate given that it is our largest sensory organ with impressive spatial and temporal acuity. Although some approaches have been proposed for touch-based information delivery, they are not without limitations including high learning curves, limited applicability and/or limited expression. This is largely due to the lack of a versatile, comprehensive design theory--specifically, a theory that addresses the design of touch-based building blocks for expandable, efficient, rich and robust touch languages that are easy to learn and use. Moreover, beyond design, there is a lack of implementation and evaluation theories for such languages. To overcome these limitations, a unified, theoretical framework, inspired by natural, spoken language, is proposed called Somatic ABC's for Articulating (designing), Building (developing) and Confirming (evaluating) touch-based languages. To evaluate the usefulness of Somatic ABC's, its design, implementation and evaluation theories were applied to create communication languages for two very unique application areas: audio described movies and motor learning. These applications were chosen as they presented opportunities for complementing communication by offloading information, typically conveyed visually and/or aurally, to the skin. For both studies, it was found that Somatic ABC's aided the design, development and evaluation of rich somatic languages with distinct and natural communication units.
ContributorsMcDaniel, Troy Lee (Author) / Panchanathan, Sethuraman (Thesis advisor) / Davulcu, Hasan (Committee member) / Li, Baoxin (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Rasopathies are a family of developmental syndromes that exhibit craniofacial abnormalities, cognitive disabilities, developmental delay and increased risk of cancer. However, little is known about the pathogenesis of developmental defects in the nervous system. Frequently, gain-of-function mutations in the Ras/Raf/MEK/ERK cascade (aka ERK/MAPK) are associated with the observed pathogenesis. My

Rasopathies are a family of developmental syndromes that exhibit craniofacial abnormalities, cognitive disabilities, developmental delay and increased risk of cancer. However, little is known about the pathogenesis of developmental defects in the nervous system. Frequently, gain-of-function mutations in the Ras/Raf/MEK/ERK cascade (aka ERK/MAPK) are associated with the observed pathogenesis. My research focuses on defining the relationship between increased ERK/MAPK signaling and its effects on the nervous system, specifically in the context of motor learning. Motor function depends on several neuroanatomically distinct regions, especially the spinal cord, cerebellum, striatum, and cerebral cortex. We tested whether hyperactivation of ERK/MAPK specifically in the cortex was sufficient to drive changes in motor function. We used a series of genetically modified mouse models and cre-lox technology to hyperactivate ERK/MAPK in the cerebral cortex. Nex:Cre/NeuroD6:Cre was employed to express a constitutively active MEK mutation throughout all layers of the cerebral cortex from an early stage of development. RBP4:Cre, caMEK only exhibited hyper activation in cortical glutamatergic neurons responsible for cortical output (neurons in layer V of the cerebral cortex). First, the two mouse strains were tested in an open field paradigm to assess global locomotor abilities and overall fitness for fine motor tasks. Next, a skilled motor reaching task was used to evaluate motor learning capabilities. The results show that Nex:Cre/NeuroD6:Cre, caMEK mutants do not learn the motor reaching task, although they performed normally on the open field task. Preliminary results suggest RBP4:Cre, caMEK mutants exhibit normal locomotor capabilities and a partial lack of learning. The difference in motor learning capabilities might be explained by the extent of altered connectivity in different regions of the corticospinal tract. Once we have identified the neuropathological effects of various layers in the cortex we will be able to determine whether therapeutic interventions are sufficient to reverse these learning defects.
ContributorsRoose, Cassandra Ann (Author) / Newbern, Jason M. (Thesis director) / Olive, Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for

The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for the differentiation of Embryonic Stem Cells (ESC) into neuronal precursors (Li z et al, 2006). ERK signaling has also shown to mediate Schwann cell myelination of the peripheral nervous system (PNS) as well as oligodendrocyte proliferation (Newbern et al, 2011). The class of developmental disorders that result in the dysregulation of RAS signaling are known as RASopathies. The molecular and cell-specific consequences of these various pathway mutations remain to be elucidated. While there is evidence for altered DNA transcription in RASopathies, there is little work examining the effects of the RASopathy-linked mutations on protein translation and post-translational modifications in vivo. RASopathies have phenotypic and molecular similarities to other disorders such as Fragile X Syndrome (FXS) and Tuberous Sclerosis (TSC) that show evidence of aberrant protein synthesis and affect related pathways. There are also well-defined downstream RAS pathway elements involved in translation. Additionally, aberrant corticospinal axon outgrowth has been observed in disease models of RASopathies (Xing et al, 2016). For these reasons, this present study examines a subset of proteins involved in translation and translational regulation in the context of RASopathy disease states. Results indicate that in both of the tested RASopathy model systems, there is altered mTOR expression. Additionally the loss of function model showed a decrease in rps6 activation. This data supports a role for the selective dysregulation of translational control elements in RASopathy models. This data also indicates that the primary candidate mechanism for control of altered translation in these modes is through the altered expression of mTOR.
ContributorsHilbert, Alexander Robert (Author) / Newbern, Jason (Thesis director) / Olive, M. Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
This dissertation focuses on reinforcement learning (RL) controller design aiming for real-life applications in continuous state and control problems. It involves three major research investigations in the aspect of design, analysis, implementation, and evaluation. The application case addresses automatically configuring robotic prosthesis impedance parameters. Major contributions of the dissertation include

This dissertation focuses on reinforcement learning (RL) controller design aiming for real-life applications in continuous state and control problems. It involves three major research investigations in the aspect of design, analysis, implementation, and evaluation. The application case addresses automatically configuring robotic prosthesis impedance parameters. Major contributions of the dissertation include the following. 1) An “echo control” using the intact knee profile as target is designed to overcome the limitation of a designer prescribed robotic knee profile. 2) Collaborative multiagent reinforcement learning (cMARL) is proposed to directly take into account human influence in the robot control design. 3) A phased actor in actor-critic (PAAC) reinforcement learning method is developed to reduce learning variance in RL. The design of an “echo control” is based on a new formulation of direct heuristic dynamic programming (dHDP) for tracking control of a robotic knee prosthesis to mimic the intact knee profile. A systematic simulation of the proposed control is provided using a human-robot system simulation in OpenSim. The tracking controller is then tested on able-bodied and amputee subjects. This is the first real-time human testing of RL tracking control of a robotic knee to mirror the profile of an intact knee. The cMARL is a new solution framework for the human-prosthesis collaboration (HPC) problem. This is the first attempt at considering human influence on human-robot walking with the presence of a reinforcement learning controlled lower limb prosthesis. Results show that treating the human and robot as coupled and collaborating agents and using an estimated human adaptation in robot control design help improve human walking performance. The above studies have demonstrated great potential of RL control in solving continuous problems. To solve more complex real-life tasks with multiple control inputs and high dimensional state space, high variance, low data efficiency, slow learning or even instability are major roadblocks to be addressed. A novel PAAC method is proposed to improve learning performance in policy gradient RL by accounting for both Q value and TD error in actor updates. Systematical and comprehensive demonstrations show its effectiveness by qualitative analysis and quantitative evaluation in DeepMind Control Suite.
ContributorsWu, Ruofan (Author) / Si, Jennie (Thesis advisor) / Huang, He (Committee member) / Santello, Marco (Committee member) / Papandreou- Suppappola, Antonia (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Humans constantly rely on a complex interaction of a variety of sensory modalities in order to complete even the simplest of daily tasks. For reaching and grasping to interact with objects, the visual, tactile, and proprioceptive senses provide the majority of the information used. While vision is often relied on

Humans constantly rely on a complex interaction of a variety of sensory modalities in order to complete even the simplest of daily tasks. For reaching and grasping to interact with objects, the visual, tactile, and proprioceptive senses provide the majority of the information used. While vision is often relied on for many tasks, most people are able to accomplish common daily rituals without constant visual attention, instead relying mainly on tactile and proprioceptive cues. However, amputees using prosthetic arms do not have access to these cues, making tasks impossible without vision. Even tasks with vision can be incredibly difficult as prosthesis users are unable to modify grip force using touch, and thus tend to grip objects excessively hard to make sure they don’t slip.

Methods such as vibratory sensory substitution have shown promise for providing prosthesis users with a sense of contact and have proved helpful in completing motor tasks. In this thesis, two experiments were conducted to determine whether vibratory cues could be useful in discriminating between sizes. In the first experiment, subjects were asked to grasp a series of hidden virtual blocks of varying sizes with vibrations on the fingertips as indication of contact and compare the size of consecutive boxes. Vibratory haptic feedback significantly increased the accuracy of size discrimination over objects with only visual indication of contact, though accuracy was not as great as for typical grasping tasks with physical blocks. In the second, subjects were asked to adjust their virtual finger position around a series of virtual boxes with vibratory feedback on the fingertips using either finger movement or EMG. It was found that EMG control allowed for significantly less accuracy in size discrimination, implying that, while proprioceptive feedback alone is not enough to determine size, direct kinesthetic information about finger position is still needed.
ContributorsOlson, Markey (Author) / Helms-Tillery, Stephen (Thesis advisor) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2016
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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