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The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response

The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response characteristics, inter-subject variability, consistency of effect across outcome measures, and day-to-day variability. Eight subjects with PD and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS) and at three reduced amplitude conditions: approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively). Overall symptom severity and performance on a battery of motor tasks - gait, postural control, single-joint flexion-extension, postural tremor, and tapping - were assessed at each condition using the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and quantitative measures. Data were analyzed to determine whether subjects demonstrated a threshold response (one decrement in stimulation resulted in ≥ 70% of the maximum change) or a graded response to reduced stimulation. Day-to-day variability was assessed using the CDS data from the three testing sessions. Although the cohort as a whole demonstrated a graded response on several measures, there was high variability across subjects, with subsets exhibiting graded, threshold, or minimal responses. Some subjects experienced greater variability in their CDS performance across the three days than the change induced by reducing stimulation. For several tasks, a subset of subjects exhibited improved performance at one or more of the reduced conditions. Reducing stimulation did not affect all subjects equally, nor did it uniformly affect each subject's performance across tasks. These results indicate that altered recruitment of neural structures can differentially affect motor capabilities and demonstrate the need for clinical consideration of the effects on multiple symptoms across several days when selecting DBS parameters.
ContributorsConovaloff, Alison (Author) / Abbas, James (Thesis advisor) / Krishnamurthi, Narayanan (Committee member) / Mahant, Padma (Committee member) / Jung, Ranu (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the

Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the desired skill level. It would result in more reliable and adaptive neural interfaces that could record optimal neural activity 24/7 with high fidelity signals, high yield and increased throughput. The main contribution here is validating adaptive strategies to overcome challenges in autonomous navigation of microelectrodes inside the brain. The following issues pose significant challenges as brain tissue is both functionally and structurally dynamic: a) time varying mechanical properties of the brain tissue-microelectrode interface due to the hyperelastic, viscoelastic nature of brain tissue b) non-stationarities in the neural signal caused by mechanical and physiological events in the interface and c) the lack of visual feedback of microelectrode position in brain tissue. A closed loop control algorithm is proposed here for autonomous navigation of microelectrodes in brain tissue while optimizing the signal-to-noise ratio of multi-unit neural recordings. The algorithm incorporates a quantitative understanding of constitutive mechanical properties of soft viscoelastic tissue like the brain and is guided by models that predict stresses developed in brain tissue during movement of the microelectrode. An optimal movement strategy is developed that achieves precise positioning of microelectrodes in the brain by minimizing the stresses developed in the surrounding tissue during navigation and maximizing the speed of movement. Results of testing the closed-loop control paradigm in short-term rodent experiments validated that it was possible to achieve a consistently high quality SNR throughout the duration of the experiment. At the systems level, new generation of MEMS actuators for movable microelectrode array are characterized and the MEMS device operation parameters are optimized for improved performance and reliability. Further, recommendations for packaging to minimize the form factor of the implant; design of device mounting and implantation techniques of MEMS microelectrode array to enhance the longevity of the implant are also included in a top-down approach to achieve a reliable brain interface.
ContributorsAnand, Sindhu (Author) / Muthuswamy, Jitendran (Thesis advisor) / Tillery, Stephen H (Committee member) / Buneo, Christopher (Committee member) / Abbas, James (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control

Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control from the brain. In the case of incomplete paraplegia, locomotion is impaired and often results in increased incidence of foot drag and decreased postural stability after injury. The overall goal of this work is to understand how changes in kinematics of movement and neural control of muscles effect locomotor coordination following SCI. Toward this end, we examined musculoskeletal parameters and kinematics of gait in rats with and without incomplete SCI (iSCI) and used an empirically developed computational model to test related hypotheses. The first study tested the hypothesis that iSCI causes a decrease in locomotor and joint angle movement complexity. A rat model was used to measure musculoskeletal properties and gait kinematics following mild iSCI. The data indicated joint-specific changes in kinematics in the absence of measurable muscle atrophy, particularly at the ankle as a result of the injury. Kinematic changes manifested as a decrease in complexity of ankle motion as indicated by measures of permutation entropy. In the second study, a new 2-dimensional computational model of the rat ankle combining forward and inverse dynamics was developed using the previously collected data. This model was used to test the hypothesis that altered coordination of flexor and extensor muscles (specifically alteration in burst shape and timing) acting at the ankle joint could be responsible for increases in incidence of foot drag following injury. Simulation results suggest a time course for changes in neural control following injury that begins with foot drag and decreased delay between antagonistic muscle activations. Following this, beneficial adaptations in muscle activation profile and ankle kinematics counteract the decreased delay to allow foot swing. In both studies, small changes in neural control caused large changes in behavior, particularly at the ankle. Future work will further examine the role of neural control of hindlimb in rat locomotion following iSCI.
ContributorsHillen, Brian (Author) / Jung, Ranu (Thesis advisor) / Abbas, James (Committee member) / Muthuswamy, Jit (Committee member) / Jindrich, Devin (Committee member) / Yamaguchi, Gary (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Lower-limb prosthesis users have commonly-recognized deficits in gait and posture control. However, existing methods in balance and mobility analysis fail to provide sufficient sensitivity to detect changes in prosthesis users' postural control and mobility in response to clinical intervention or experimental manipulations and often fail to detect differences between prosthesis

Lower-limb prosthesis users have commonly-recognized deficits in gait and posture control. However, existing methods in balance and mobility analysis fail to provide sufficient sensitivity to detect changes in prosthesis users' postural control and mobility in response to clinical intervention or experimental manipulations and often fail to detect differences between prosthesis users and non-amputee control subjects. This lack of sensitivity limits the ability of clinicians to make informed clinical decisions and presents challenges with insurance reimbursement for comprehensive clinical care and advanced prosthetic devices. These issues have directly impacted clinical care by restricting device options, increasing financial burden on clinics, and limiting support for research and development. This work aims to establish experimental methods and outcome measures that are more sensitive than traditional methods to balance and mobility changes in prosthesis users. Methods and analysis techniques were developed to probe aspects of balance and mobility control that may be specifically impacted by use of a prosthesis and present challenges similar to those experienced in daily life that could improve the detection of balance and mobility changes. Using the framework of cognitive resource allocation and dual-tasking, this work identified unique characteristics of prosthesis users’ postural control and developed sensitive measures of gait variability. The results also provide broader insight into dual-task analysis and the motor-cognitive response to demanding conditions. Specifically, this work identified altered motor behavior in prosthesis users and high cognitive demand of using a prosthesis. The residual standard deviation method was developed and demonstrated to be more effective than traditional gait variability measures at detecting the impact of dual-tasking. Additionally, spectral analysis of the center of pressure while standing identified altered somatosensory control in prosthesis users. These findings provide a new understanding of prosthetic use and new, highly sensitive techniques to assess balance and mobility in prosthesis users.
ContributorsHoward, Charla Lindley (Author) / Abbas, James (Thesis advisor) / Buneo, Christopher (Committee member) / Lynskey, Jim (Committee member) / Santello, Marco (Committee member) / Artemiadis, Panagiotis (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Injuries and death associated with fall incidences pose a significant burden to society, both in terms of human suffering and economic losses. The main aim of this dissertation is to study approaches that can reduce the risk of falls. One major subset of falls is falls due to neurodegenerative disorders

Injuries and death associated with fall incidences pose a significant burden to society, both in terms of human suffering and economic losses. The main aim of this dissertation is to study approaches that can reduce the risk of falls. One major subset of falls is falls due to neurodegenerative disorders such as Parkinson’s disease (PD). Freezing of gait (FOG) is a major cause of falls in this population. Therefore, a new FOG detection method using wavelet transform technique employing optimal sampling window size, update time, and sensor placements for identification of FOG events is created and validated in this dissertation. Another approach to reduce the risk of falls in PD patients is to correctly diagnose PD motor subtypes. PD can be further divided into two subtypes based on clinical features: tremor dominant (TD), and postural instability and gait difficulty (PIGD). PIGD subtype can place PD patients at a higher risk for falls compared to TD patients and, they have worse postural control in comparison to TD patients. Accordingly, correctly diagnosing subtypes can help caregivers to initiate early amenable interventions to reduce the risk of falls in PIGD patients. As such, a method using the standing center-of-pressure time series data has been developed to identify PD motor subtypes in this dissertation. Finally, an intervention method to improve dynamic stability was tested and validated. Unexpected perturbation-based training (PBT) is an intervention method which has shown promising results in regard to improving balance and reducing falls. Although PBT has shown promising results, the efficacy of such interventions is not well understood and evaluated. In other words, there is paucity of data revealing the effects of PBT on improving dynamic stability of walking and flexible gait adaptability. Therefore, the effects

of three types of perturbation methods on improving dynamics stability was assessed. Treadmill delivered translational perturbations training improved dynamic stability, and adaptability of locomotor system in resisting perturbations while walking.
ContributorsRezvanian, Saba (Author) / Lockhart, Thurmon (Thesis advisor) / Buneo, Christopher (Committee member) / Lieberman, Abraham (Committee member) / Abbas, James (Committee member) / Deep, Aman (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Presented below is the design and fabrication of prosthetic components consisting of an attachment, tactile sensing, and actuator systems with Fused Filament Fabrication (FFF) technique. The attachment system is a thermoplastic osseointegrated upper limb prosthesis for average adult trans-humeral amputation with mechanical properties greater than upper limb skeletal bone. The

Presented below is the design and fabrication of prosthetic components consisting of an attachment, tactile sensing, and actuator systems with Fused Filament Fabrication (FFF) technique. The attachment system is a thermoplastic osseointegrated upper limb prosthesis for average adult trans-humeral amputation with mechanical properties greater than upper limb skeletal bone. The prosthetic designed has: a one-step surgical process, large cavities for bone tissue ingrowth, uses a material that has an elastic modulus less than skeletal bone, and can be fabricated on one system.

FFF osseointegration screw is an improvement upon the current two-part osseointegrated prosthetics that are composed of a fixture and abutment. The current prosthetic design requires two invasive surgeries for implantation and are made of titanium, which has an elastic modulus greater than bone. An elastic modulus greater than bone causes stress shielding and overtime can cause loosening of the prosthetic.

The tactile sensor is a thermoplastic piezo-resistive sensor for daily activities for a prosthetic’s feedback system. The tactile sensor is manufactured from a low elastic modulus composite comprising of a compressible thermoplastic elastomer and conductive carbon. Carbon is in graphite form and added in high filler ratios. The printed sensors were compared to sensors that were fabricated in a gravity mold to highlight the difference in FFF sensors to molded sensors. The 3D printed tactile sensor has a thickness and feel similar to human skin, has a simple fabrication technique, can detect forces needed for daily activities, and can be manufactured in to user specific geometries.

Lastly, a biomimicking skeletal muscle actuator for prosthetics was developed. The actuator developed is manufactured with Fuse Filament Fabrication using a shape memory polymer composite that has non-linear contractile and passive forces, contractile forces and strains comparable to mammalian skeletal muscle, reaction time under one second, low operating temperature, and has a low mass, volume, and material costs. The actuator improves upon current prosthetic actuators that provide rigid, linear force with high weight, cost, and noise.
ContributorsLathers, Steven (Author) / La Belle, Jeffrey (Thesis advisor) / Vowels, David (Committee member) / Lockhart, Thurmon (Committee member) / Abbas, James (Committee member) / McDaniel, Troy (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Transcranial electrical stimulation (tES) is a non-invasive brain stimulation therapy that has shown potential in improving motor, physiological and cognitive functions in healthy and diseased population. Typical tES procedures involve application of weak current (< 2 mA) to the brain via a pair of large electrodes placed on the scalp.

Transcranial electrical stimulation (tES) is a non-invasive brain stimulation therapy that has shown potential in improving motor, physiological and cognitive functions in healthy and diseased population. Typical tES procedures involve application of weak current (< 2 mA) to the brain via a pair of large electrodes placed on the scalp. While the therapeutic benefits of tES are promising, the efficacy of tES treatments is limited by the knowledge of how current travels in the brain. It has been assumed that the current density and electric fields are the largest, and thus have the most effect, in brain structures nearby the electrodes. Recent studies using finite element modeling (FEM) have suggested that current patterns in the brain are diffuse and not concentrated in any particular brain structure. Although current flow modeling is useful means of informing tES target optimization, few studies have validated tES FEM models against experimental measurements. MREIT-CDI can be used to recover magnetic flux density caused by current flow in a conducting object. This dissertation reports the first comparisons between experimental data from in-vivo human MREIT-CDI during tES and results from tES FEM using head models derived from the same subjects. First, tES FEM pipelines were verified by confirming FEM predictions agreed with analytic results at the mesh sizes used and that a sufficiently large head extent was modeled to approximate results on human subjects. Second, models were used to predict magnetic flux density, and predicted and MREIT-CDI results were compared to validate and refine modeling outcomes. Finally, models were used to investigate inter-subject variability and biological side effects reported by tES subjects. The study demonstrated good agreements in patterns between magnetic flux distributions from experimental and simulation data. However, the discrepancy in scales between simulation and experimental data suggested that tissue conductivities typically used in tES FEM might be incorrect, and thus performing in-vivo conductivity measurements in humans is desirable. Overall, in-vivo MREIT-CDI in human heads has been established as a validation tool for tES predictions and to study the underlying mechanisms of tES therapies.
ContributorsIndahlastari, Aprinda (Author) / Sadleir, Rosalind J (Thesis advisor) / Abbas, James (Committee member) / Frakes, David (Committee member) / Kleim, Jeffrey (Committee member) / Kodibagkar, Vikram (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Nearly one percent of the population over 65 years of age is living with Parkinson’s disease (PD) and this population worldwide is projected to be approximately nine million by 2030. PD is a progressive neurological disease characterized by both motor and cognitive impairments. One of the most serious challenges for

Nearly one percent of the population over 65 years of age is living with Parkinson’s disease (PD) and this population worldwide is projected to be approximately nine million by 2030. PD is a progressive neurological disease characterized by both motor and cognitive impairments. One of the most serious challenges for an individual as the disease progresses is the increasing severity of gait and posture impairments since they result in debilitating conditions such as freezing of gait, increased likelihood of falls, and poor quality of life. Although dopaminergic therapy and deep brain stimulation are generally effective, they often fail to improve gait and posture deficits. Several recent studies have employed real-time feedback (RTF) of gait parameters to improve walking patterns in PD. In earlier work, results from the investigation of the effects of RTF of step length and back angle during treadmill walking demonstrated that people with PD could follow the feedback and utilize it to modulate movements favorably in a manner that transferred, at least acutely, to overground walking. In this work, recent advances in wearable technologies were leveraged to develop a wearable real-time feedback (WRTF) system that can monitor and evaluate movements and provide feedback during daily activities that involve overground walking. Specifically, this work addressed the challenges of obtaining accurate gait and posture measures from wearable sensors in real-time and providing auditory feedback on the calculated real-time measures for rehabilitation. An algorithm was developed to calculate gait and posture variables from wearable sensor measurements, which were then validated against gold-standard measurements. The WRTF system calculates these measures and provides auditory feedback in real-time. The WRTF system was evaluated as a potential rehabilitation tool for use by people with mild to moderate PD. Results from the study indicated that the system can accurately measure step length and back angle, and that subjects could respond to real-time auditory feedback in a manner that improved their step length and uprightness. These improvements were exhibited while using the system that provided feedback and were sustained in subsequent trials immediately thereafter in which subjects walked without receiving feedback from the system.
ContributorsMuthukrishnan, Niveditha (Author) / Abbas, James (Thesis advisor) / Krishnamurthi, Narayanan (Thesis advisor) / Shill, Holly A (Committee member) / Honeycutt, Claire (Committee member) / Turaga, Pavan (Committee member) / Ingalls, Todd (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Safety and efficacy of neuromodulation are influenced by abiotic factors like failure of implants, biotic factors like tissue damage, and molecular and cellular mechanisms of neuromodulation. Accelerated lifetime test (ALT) predict lifetime of implants by accelerating failure modes in controlled bench-top conditions. Current ALT models do not capture failure modes

Safety and efficacy of neuromodulation are influenced by abiotic factors like failure of implants, biotic factors like tissue damage, and molecular and cellular mechanisms of neuromodulation. Accelerated lifetime test (ALT) predict lifetime of implants by accelerating failure modes in controlled bench-top conditions. Current ALT models do not capture failure modes involving biological mechanisms. First part of this dissertation is focused on developing ALTs for predicting failure of chronically implanted tungsten stimulation electrodes. Three factors used in ALT are temperature, H2O2 concentration, and amount of charge delivered through electrode to develop a predictive model of lifetime for stimulation electrodes. Second part of this dissertation is focused on developing a novel method for evaluating tissue response to implants and electrical stimulation. Current methods to evaluate tissue damage in the brain require invasive and terminal procedures that have poor clinical translation. I report a novel non-invasive method that sampled peripheral blood monocytes (PBMCs) and used enzyme-linked immunoassay (ELISA) to assess level of glial fibrillary acidic protein (GFAP) expression and fluorescence-activated cell sorting (FACS) to quantify number of GFAP expressing PBMCs. Using this method, I was able to detect and quantify GFAP expression in PBMCs. However, there was no statistically significant difference in GFAP expression between stimulatory and non-stimulatory implants. Final part of this dissertation assessed molecular and cellular mechanisms of non-invasive ultrasound neuromodulation approach. Unlike electrical stimulation, cellular mechanisms of ultrasound-based neuromodulation are not fully known. Final part of this dissertation assessed role of mechanosensitive ion channels and neuronal nitric oxide production in cell cultures under ultrasound excitation. I used fluorescent imaging to quantify expression of nitric oxide in neuronal cell cultures in response to ultrasound stimulation. Results from these experiments indicate that neuronal nitric oxide production increased in response to ultrasound stimulation compared to control and decreased when mechanosensitive ion channels were suppressed. Two novel methods developed in this dissertation enable assessment of lifetime and safety of neuromodulation techniques that use electrical stimulation through implants. The final part of this dissertation concludes that non-invasive ultrasound neuromodulation may be mediated through neuronal nitric oxide even in absence of activation of mechanosensitive ion channels.
ContributorsVoziyanov, Vladislav (Author) / Muthuswamy, Jitendran (Thesis advisor) / Smith, Barbara (Committee member) / Greger, Bradley (Committee member) / Abbas, James (Committee member) / Okandan, Murat (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Finite element models (FEMs) of spine segments validated in their intact states are often used to make predictions following structural modifications simulating surgical procedures, including posterior fusion with pedicle screws and rods (PSR) and laminectomy (removal of posterior column bone to decompress the spinal cord). The gold standard for spine

Finite element models (FEMs) of spine segments validated in their intact states are often used to make predictions following structural modifications simulating surgical procedures, including posterior fusion with pedicle screws and rods (PSR) and laminectomy (removal of posterior column bone to decompress the spinal cord). The gold standard for spine FEM validation compares predicted vs. experimental intervertebral ranges of motion (ROM). Given that muscle co-contraction compresses the spine, validation that considers compression may produce a more robust FEM. One research goal was to evaluate an experimental method of compressing a lumbar spine segment through its sagittal plane balance (pivot) point (BP) using a 6DOF robotic test system. Experimental data supported the hypothesis that structural modifications, such as PSR and laminectomy alter the segment’s BP location and its compressive stiffness. However, evaluation showed that the experimental BP method is sensitive to specimen posture in the robotic test frame; slight flexion or extension produced shear loads during compression that affect BP location and should be included in specimen-specific FEMs to ensure similar load conditions. Another goal was to develop a uniquely calibrated specimen-specific FEM of an intact L4-5 motion segment using the experimental BP data. A specimen-specific FEM was created and calibrated using experimental BP compressive stiffness data, however matching experimental BP location data was unsuccessful. The BP-compression calibrated FEM was evaluated by comparing predicted responses to loads following simulated PSR and laminectomy to specimen-specific experimental data. Predictions using the BP-calibrated and ROM-calibrated FEMs were compared. The BP-calibration process helped identify an unrealistic FEM disc geometry (nucleus pulposus size and location). Both BP-compression and ROM-calibrated FEMs predicted effects of PSR on stiffness (compressive and flexural) that were greater than experimental, which helped identify a problem with simplified representations of bone in the posterior column and at the anterior column interface. The BP-compression calibrated FEMs predicted relative shifts in BP locations and bone surface strains during compression that were closer to experimental data than similarly modified ROM-calibrated FEMs. Collectively, these results support the use of BP measures in experimental and model-based investigations of surgical modifications of the spine.
ContributorsSawa, Anna Genowefa Ulrika (Author) / Abbas, James (Thesis advisor) / Crawford, Neil R (Thesis advisor) / Kelly, Brian P (Committee member) / Helms-Tillery, Stephen (Committee member) / Sadleir, Rosalind (Committee member) / Arizona State University (Publisher)
Created2023