This dissertation aimed to evaluate the effectiveness and drawbacks of promising fall prevention strategies in individuals with stroke by rigorously analyzing the biomechanics of laboratory falls and compensatory movements required to prevent a fall. Ankle-foot-orthoses (AFOs) and functional electrical stimulators (FESs) are commonly prescribed to treat foot drop. Despite well-established positive impacts of AFOs and FES devices on balance and gait, AFO and FES users fall at a high rate. In chapter 2 (as a preliminary study), solely mechanical impacts of a semi-rigid AFO on the compensatory stepping response of young healthy individuals following trip-like treadmill perturbations were evaluated. It was found that a semi-rigid AFO on the stepping leg diminished the propulsive impulse of the compensatory step which led to decreased trunk movement control, shorter step length, and reduced center of mass (COM) stability. These results highlight the critical role of plantarflexors in generating an effective compensatory stepping response. In chapter 3, the underlying biomechanical mechanisms leading to high fall risk in long-term AFO and FES users with chronic stroke were studied. It was found that AFO and FES users fall more than Non-users because they have a more impaired lower limb that is not fully addressed by AFO/FES, therefore leading to a more impaired compensatory stepping response characterized by increased inability to generate a compensatory step with paretic leg and decreased trunk movement control. An ideal future AFO that provides dorsiflexion assistance during the swing phase and plantarflexion assistance during the push-off phase of gait is suggested to enhance the compensatory stepping response and reduce more falls. In chapter 4, the effects of a single-session trip-specific training on the compensatory stepping response of individuals with stroke were evaluated. Trunk movement control was improved after a single session of training suggesting that this type of training is a viable option to enhance compensatory stepping response and reduce falls in individuals with stroke. Finally, a future powered AFO with plantarflexion assistance complemented by a trip-specific training program is suggested to enhance the compensatory stepping response and decrease falls in individuals with stroke.

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.

Electrical stimulation can be used to activate peripheral nerve fibers to restore sensation to individuals with amputation and the technique is also being investigated as a means of treating a wide range of diseases. Longitudinal intrafascicular electrodes (LIFEs) are one of several types of electrodes that have been used to activate peripheral nerves. LIFEs can be used to activate small groups of fibers within a peripheral nerve fascicle, but the degree of their selectivity is uncertain. To investigate the effects of intrafascicular stimulation on nerve fiber activation, a mathematical, conductance-based model of an axon drawn from the literature was implemented and used to simulate the firing response of sensory nerve fibers in the presence of an applied monopolar electric field. Several axons were simulated to represent axons of different size, conductivity, spatial composition and location with respect to the electrode. Electric field profiles produced by pulses of different pulse widths and pulse amplitudes were created. Each fiber was placed within each resulting electric field and the firing threshold was determined. The effects of changes in pulse width, pulse amplitude, and distance on firing patterns were shown; all of these results were consistent with published experimental findings. The models showed lower firing threshold for smaller fibers than larger fibers and for fibers that were farther from the stimulating electrode than those that were closer. Firing threshold was also lower for stimuli of greater pulse width. Analysis of axon recruitment upon increases in pulse amplitude showed that the effects of fiber distance may be more pronounced than the effects of fiber size. This model can serve as a basis for further development to more accurately represent the effects of LIFEs and eventually may assist in the design of stimulation paradigms and waveforms to improve selectivity of axon activation when using LIFEs.

Intracellular voltage recordings from single neurons in vitro and in vivo have been fundamental to our understanding of neuronal function. Conventional electrodes and associated positioning systems for intracellular recording in vivo are large and bulky, which has largely restricted their use to single-channel recording from anesthetized animals. Further, intracellular recordings are very cumbersome, requiring a high degree of skill not readily achieved in a typical laboratory. This dissertation presents a robotic, head-mountable, MEMS (Micro-Electro-Mechanical Systems) based intracellular recording system to overcome the above limitations associated with form-factor, scalability and highly skilled and tedious manual operations required for intracellular recordings. This system combines three distinct technologies: 1) novel microscale, polycrystalline silicon-based electrode for intracellular recording, 2) electrothermal microactuators for precise microscale navigation of the electrode and 3) closed-loop control algorithm for autonomous movement and positioning of electrode inside single neurons. First, two distinct designs of polysilicon-based microscale electrodes were fabricated and tested for intracellular recordings. In the first approach, tips of polysilicon microelectrodes were milled to nanoscale dimensions (<300 nm) using focused ion beam (FIB) to develop polysilicon nanoelectrodes. Polysilicon nanoelectrodes recorded >1.5 mV amplitude, positive-going action potentials and synaptic potentials from neurons in the abdominal ganglion of Aplysia Californica. In the second approach, polysilicon microelectrodes were integrated with miniaturized glass micropipettes filled with electrolyte to fabricate glass-polysilicon microelectrodes. These electrodes consistently recorded high fidelity intracellular potentials from neurons in the abdominal ganglion of Aplysia Californica (Resting Potentials < -35 mV, Action Potentials > 60 mV) as well as the rat motor cortex (Resting Potentials < -50 mV). Next, glass-polysilicon microelectrodes were coupled with microscale electrothermal actuators and controller for autonomous intracellular recordings from single neurons in the abdominal ganglion. Consistent resting potentials (< -35 mV) and action potentials (> 60 mV) were recorded after each successful penetration attempt with the controller and microactuated glass-polysilicon microelectrodes. The success rate of penetration and quality of recordings achieved using electrothermal microactuators were comparable to that of conventional positioning systems. Finally, the feasibility of this miniaturized system to obtain intracellular recordings from single neurons in the motor cortex of rats in vivo is also demonstrated. The MEMS-based system offers significant advantages: 1) reduction in overall size for potential use in behaving animals, 2) scalable approach to potentially realize multi-channel recordings and 3) a viable method to fully automate measurement of intracellular recordings.

The inception of the human-powered water pump began during my trip to Maasailand in Kenya over the Summer of 2017. Being one of the few Broadening the Reach of Engineering through Community Engagement (BRECE) Scholars at Arizona State University, I was given the opportunity to join Prescott College (PC) on their annual trip to the Maasai Education, Research, and Conservation (MERC) Institute in rural Kenya. The ASU BRECE scholars that choose to travel were asked to collaborate with the local Maasai community to help develop functional and sustainable engineering solutions to problems identified alongside community members using rudimentary technology and tools that were available in this resource-constrained setting. This initiative evolved into multiple projects from the installation of GravityLights (a local invention that powers LEDs with falling sandbags), the construction/installation of smokeless stoves, and development of a much-needed solution to move water from the rainwater collection tanks around camp to other locations. This last project listed was prototyped once in camp, and this report details subsequent iterations of this human-powered pump.

Skin and muscle receptors in the leg and foot provide able-bodied humans with force and position information that is crucial for balance and movement control. In lower-limb amputees however, this vital information is either missing or incomplete. Amputees typically compensate for the loss of sensory information by relying on haptic feedback from the stump-socket interface. Unfortunately, this is not an adequate substitute. Areas of the stump that directly interface with the socket are also prone to painful irritation, which further degrades haptic feedback. The lack of somatosensory feedback from prosthetic legs causes several problems for lower-limb amputees. Previous studies have established that the lack of adequate sensory feedback from prosthetic limbs contributes to poor balance and abnormal gait kinematics. These improper gait kinematics can, in turn, lead to the development of musculoskeletal diseases. Finally, the absence of sensory information has been shown to lead to steeper learning curves and increased rehabilitation times, which hampers amputees from recovering from the trauma. In this study, a novel haptic feedback system for lower-limb amputees was develped, and studies were performed to verify that information presented was sufficiently accurate and precise in comparison to a Bertec 4060-NC force plate. The prototype device consisted of a sensorized insole, a belt-mounted microcontroller, and a linear array of four vibrotactile motors worn on the thigh. The prototype worked by calculating the center of pressure in the anteroposterior plane, and applying a time-discrete vibrotactile stimulus based on the location of the center of pressure.

This study was conducted to examine the potential effects of exercise training on partial spinal cord injury on locomotor recovery in juvenile rats. Three groups were tested, where three female Long-Evans rats 10-12 weeks of age were studied for their locomotion. All animals underwent a T8-T9 laminectomy and two of the three in each group received a dorsal, partial spinal cord injury. Locomotion was then analyzed every week, over 8-10 weeks. One of the two injured animals was given open access to a wheel after 2 weeks for voluntary exercise training. The results of this study suggested that injured animals displayed more irregular stepping patterns, larger hindlimb bases of support, greater and more variable interpaw distances, slower hindlimb speed, and increased dependency of swing-phase duty cycle on hindlimb speed. Trained animals displayed quicker recovery of stepping patterns, stepping of the hindpaw in relation to the preceding ipsilateral forepaw, and higher swing-duty cycle dependency on hindlimb speed in comparison to injured animals that did not receive exercise training. Due to a small sample size, there was a large amount of variation between individual animals in most parameters. These results are considered to be potential effects that may be seen in further study with a larger sample size. The research team will continue the research project to examine changes in neural pathways in the spinal cord and the effects of exercise on recovery after injury.

Progressive gait disorder in Parkinson's disease (PD) is usually exhibited as reduced step/stride length and gait speed. People with PD also exhibit stooped posture, which can contribute to reduced step length and arm swing. Since gait and posture deficits in people with PD do not respond well to pharmaceutical and surgical treatments, novel rehabilitative therapies to alleviate these impairments are necessary. Many studies have confirmed that people with PD can improve their walking patterns when external cues are presented. Only a few studies have provided explicit real-time feedback on performance, but they did not report how well people with PD can follow the cues on a step-by-step basis. In a single-session study using a novel-treadmill based paradigm, our group had previously demonstrated that people with PD could follow step-length and back angle feedback and improve their gait and posture during treadmill walking. This study investigated whether a long-term (6-week, 3 sessions/week) real-time feedback training (RTFT) program can improve overground gait, upright posture, balance, and quality of life. Three subjects (mean age 70 ± 2 years) with mild to moderate PD (Hoehn and Yahr stage III or below) were enrolled and participated in the program. The RTFT sessions involved walking on a treadmill while following visual feedback of step length and posture (one at any given time) displayed on a monitor placed in front of the subject at eye-level. The target step length was set between 110-120% of the step length obtained during a baseline non-feedback walking trial and the target back angle was set at the maximum upright posture exhibited during a quiet standing task. Two subjects were found to significantly improve their posture and overground walking at post-training and these changes were retained six weeks after RTFT (follow-up) and the third subject improved his upright posture and gait rhythmicity. Furthermore, the magnitude of the improvements observed in these subjects was greater than the improvements observed in reports on other neuromotor interventions. These results provide preliminary evidence that real-time feedback training can be used as an effective rehabilitative strategy to improve gait and upright posture in people with PD.

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.

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.