Matching Items (25)
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- All Subjects: Biomedical Engineering
- Genre: Academic theses
- Creators: Greger, Bradley
- Member of: Theses and Dissertations
- Status: Published
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 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
Description
Multisensory integration is the process by which information from different sensory modalities is integrated by the nervous system. This process is important not only from a basic science perspective but also for translational reasons, e.g., for the development of closed-loop neural prosthetic systems. A mixed virtual reality platform was developed to study the neural mechanisms of multisensory integration for the upper limb during motor planning. The platform allows for selection of different arms and manipulation of the locations of physical and virtual target cues in the environment. The system was tested with two non-human primates (NHP) trained to reach to multiple virtual targets. Arm kinematic data as well as neural spiking data from primary motor (M1) and dorsal premotor cortex (PMd) were collected. The task involved manipulating visual information about initial arm position by rendering the virtual avatar arm in either its actual position (veridical (V) condition) or in a different shifted (e.g., small vs large shifts) position (perturbed (P) condition) prior to movement. Tactile feedback was modulated in blocks by placing or removing the physical start cue on the table (tactile (T), and no-tactile (NT) conditions, respectively). Behaviorally, errors in initial movement direction were larger when the physical start cue was absent. Slightly larger directional errors were found in the P condition compared to the V condition for some movement directions. Both effects were consistent with the idea that erroneous or reduced information about initial hand location led to movement direction-dependent reach planning errors. Neural correlates of these behavioral effects were probed using population decoding techniques. For small shifts in the visual position of the arm, no differences in decoding accuracy between the T and NT conditions were observed in either M1 or PMd. However, for larger visual shifts, decoding accuracy decreased in the NT condition, but only in PMd. Thus, activity in PMd, but not M1, may reflect the uncertainty in reach planning that results when sensory cues regarding initial hand position are erroneous or absent.
ContributorsPhataraphruk, Preyaporn Kris (Author) / Buneo, Christopher A (Thesis advisor) / Zhou, Yi (Committee member) / Helms Tillery, Steve (Committee member) / Greger, Bradley (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2023
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 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
Description
Studies using transcranial direct current stimulation (tDCS) to enhance motor training areoften irreproducible. This may be partly due to differences in stimulation parameters across
studies, but it is also plausible that uncontrolled placebo effects may interact with the true
‘treatment’ effect of tDCS. Thus, the purpose of this study was to test whether there was a
placebo effect of tDCS on motor training and to identify possible mechanisms of such an effect.
Fifty-one participants (age: 22.2 ± 4.16; 26 F) were randomly assigned to one of three groups:
active anodal tDCS (n=18), sham tDCS (n=18), or no stimulation control (n=15). Participant
expectations about how much tDCS could enhance motor function and their general suggestibility
were assessed. Participants then completed 30 trials of functional upper extremity motor training
with or without online tDCS. Stimulation (20-min, 2mA) was applied to the right primary motor
cortex (C4) in a double-blind, sham-controlled fashion, while the control group was unblinded and
not exposed to any stimulation. Following motor training, expectations about how much tDCS
could enhance motor function were assessed again for participants in the sham and active tDCS
groups only. Results showed no effect of active tDCS on motor training (p=.67). However, there
was a significant placebo effect, such that the collapsed sham and active tDCS groups improved
more during motor training than the control group (p=.02). This placebo effect was significantly
influenced by post-training expectations about tDCS (p=.0004). Thus, this exploratory study
showed that there is a measurable placebo effect of tDCS on motor training, likely driven by
participants’ perceptions of whether they received stimulation. Future studies should consider
placebo effects of tDCS and identify their underlying mechanisms in order to leverage them in
clinical care.
ContributorsHAIKALIS, NICOLE (Author) / Schaefer, Sydney Y (Thesis advisor) / Honeycutt, Claire (Committee member) / Daliri, Ayoub (Committee member) / Arizona State University (Publisher)
Created2022
Description
Information processing in the brain is mediated by network interactions between anatomically distant (centimeters apart) regions of cortex and network action is fundamental to human behavior. Disruptive activity of these networks may allow a variety of diseases to develop. Degradation or loss of network function in the brain can affect many aspects of the human experience; motor disorder, language difficulties, memory loss, mood swings, and more. The cortico-basal ganglia loop is a system of networks in the brain between the cortex, basal ganglia, the thalamus, and back to the cortex. It is not one singular circuit, but rather a series of parallel circuits that are relevant towards motor output, motor planning, and motivation and reward. Studying the relationship between basal ganglia neurons and cortical local field potentials may lead to insights about neurodegenerative diseases and how these diseases change the cortico-basal ganglia circuit. Speech and language are uniquely human and require the coactivation of several brain regions. The various aspects of language are spread over the temporal lobe and parts of the occipital, parietal, and frontal lobe. However, the core network for speech production involves collaboration between phonologic retrieval (encoding ideas into syllabic representations) from Wernicke’s area, and phonemic encoding (translating syllables into motor articulations) from Broca’s area. Studying the coactivation of these brain regions during a repetitive speech production task may lead to a greater understanding of their electrophysiological functional connectivity. The primary purpose of the work presented in this document is to validate the use of subdural microelectrodes in electrophysiological functional connectivity research as these devices best match the spatial and temporal scales of brain activity. Neuron populations in the cortex are organized into functional units called cortical columns. These cortical columns operate on the sub-millisecond temporal and millimeter spatial scale. The study of brain networks, both in healthy and unwell individuals, may reveal new methodologies of treatment or management for disease and injury, as well as contribute to our scientific understanding of how the brain works.
ContributorsO'Neill, Kevin John (Author) / Greger, Bradley (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen (Committee member) / Papandreou-Suppapola, Antonia (Committee member) / Kleim, Jeffery (Committee member) / Arizona State University (Publisher)
Created2021
Description
Low back pain (LBP) is the most common symptom leading to hospitalization and medical assistance. In the US, LBP is the fifth most prevalent case for visiting hospitals. Approximately 2.06 million LBP incidents were reported during the timeline between 2004 and 2008. Globally, LBP occurrence increased by almost 200 million from 1990 to 2017. This problem is further implicated by physical and financial constraints that impact the individual’s quality of life. The medical cost exceeded $87.6 billion, and the lifetime prevalence was 84%. This indicates that the majority of people in the US will experience this symptom. Also, LBP limits Activities of Daily Living (ADL) and possibly affects the gait and postural stability. Prior studies indicated that LBP patients have slower gait speed and postural instability. To alleviate this symptom, the epidural injection is prescribed to treat pain and improve mobility function. To evaluate the effectiveness of LBP epidural injection intervention, gait and posture stability was investigated before and after the injection. While these factors are the fundamental indicator of LBP improvement, ADL is an element that needs to be significantly considered. The physical activity level depicts a person’s dynamic movement during the day, it is essential to gather activity level that supports monitoring chronic conditions, such as LBP, osteoporosis, and falls. The objective of this study was to assess the effects of Epidural Steroid Injection (ESI) on LBP and related gait and postural stability in the pre and post-intervention status. As such, the second objective was to assess the influence of ESI on LBP, and how it influences the participant’s ADL physical activity level. The results indicated that post-ESI intervention has significantly improved LBP patient’s gait and posture stability, however, there was insufficient evidence to determine the significant disparity in the physical activity levels. In conclusion, ESI depicts significant positive effects on LBP patients’ gait and postural parameters, however, more verification is required to indicate a significant effect on ADL physical activity levels.
ContributorsMoon, Seong Hyun (Author) / Lockhart, Thurmon (Thesis advisor) / Honeycutt, Claire (Committee member) / Peterson, Daniel (Committee member) / Lee, Hyunglae (Committee member) / Soangra, Rahul (Committee member) / Arizona State University (Publisher)
Created2023
Description
Adapting to one novel condition of a motor task has been shown to generalize to other naïve conditions (i.e., motor generalization). In contrast, learning one task affects the proficiency of another task that is altogether different (i.e. motor transfer). Much more is known about motor generalization than about motor transfer, despite of decades of behavioral evidence. Moreover, motor generalization is studied as a probe to understanding how movements in any novel situations are affected by previous experiences. Thus, one could assume that mechanisms underlying transfer from trained to untrained tasks may be same as the ones known to be underlying motor generalization. However, the direct relationship between transfer and generalization has not yet been shown, thereby limiting the assumption that transfer and generalization rely on the same mechanisms. The purpose of this study was to test whether there is a relationship between motor generalization and motor transfer. To date, ten healthy young adult subjects were scored on their motor generalization ability and motor transfer ability on various upper extremity tasks. Although our current sample size is too small to clearly identify whether there is a relationship between generalization and transfer, Pearson product-moment correlation results and a priori power analysis suggest that a significant relationship will be observed with an increased sample size by 30%. If so, this would suggest that the mechanisms of transfer may be similar to those of motor generalization.
ContributorsSohani, Priyanka (Author) / Schaefer, Sydney (Thesis advisor) / Daliri, Ayoub (Committee member) / Honeycutt, Claire (Committee member) / Arizona State University (Publisher)
Created2018
Description
In medical imaging, a wide variety of methods are used to interrogate structural and physiological differences between soft tissues. One of the most ubiquitous methods in clinical practice is Magnetic Resonance Imaging (MRI), which has the advantage of limited invasiveness, soft tissue discrimination, and adequate volumetric resolution. A myriad of advanced MRI methods exists to investigate the microstructural, physiologic and metabolic characteristics of tissue. For example, Dynamic Contrast Enhanced (DCE) and Dynamic Susceptibility Contrast (DSC) MRI non-invasively interrogates the dynamic passage of an exogenously administered MRI contrast agent through tissue to quantify local tracer kinetic properties like blood flow, vascular permeability and tissue compartmental volume fractions. Recently, an improved understanding of the biophysical basis of DSC-MRI signals in brain tumors revealed a new approach to derive multiple quantitative biomarkers that identify intrinsic sub-voxel cellular and vascular microstructure that can be used differentiate tumor sub-types. One of these characteristic biomarkers called Transverse Relaxivity at Tracer Equilibrium (TRATE), utilizes a combination of DCE and DSC techniques to compute a steady-state metric which is particularly sensitive to cell size, density, and packing properties. This work seeks to investigate the sensitivity and potential utility of TRATE in a range of disease states including Glioblastomas, Amyotrophic Lateral Sclerosis (ALS), and Duchenne’s Muscular Dystrophy (DMD). The MRC measures of TRATE showed the most promise in mouse models of ALS where TRATE values decreased with disease progression, a finding that correlated with reductions in myofiber size and area, as quantified by immunohistochemistry. In the animal models of cancer and DMD, TRATE results were more inconclusive, due to marked heterogeneity across animals and treatment state. Overall, TRATE seems to be a promising new biomarker but still needs further methodological refinement due to its sensitivity to contrast to noise and further characterization owing to its non-specificity with respect to multiple cellular features (e.g. size, density, heterogeneity) that complicate interpretation.
ContributorsFuentes, Alberto (Author) / Quarles, Chad C (Thesis advisor) / Kodibagkar, Vikram (Thesis advisor) / Greger, Bradley (Committee member) / Arizona State University (Publisher)
Created2018
Description
Bioimpedance measurements have been long used for monitoring tissue ischemia and blood flow. This research employs implantable microelectronic devices to measure impedance chronically as a potential way to monitor the progress of peripheral vascular disease (PVD). Ultrasonically powered implantable microdevices previously developed for the purposes of neuroelectric vasodilation for therapeutic treatment of PVD were found to also allow a secondary function of tissue bioimpedance monitoring. Having no structural differences between devices used for neurostimulation and impedance measurements, there is a potential for double functionality and closed loop control of the neurostimulation performed by these types of microimplants. The proposed technique involves actuation of the implantable microdevices using a frequency-swept amplitude modulated continuous waveform ultrasound and remote monitoring of induced tissue current. The design has been investigated using simulations, ex vivo testing, and preliminary animal experiments. Obtained results have demonstrated the ability of ultrasonically powered neurostimulators to be sensitive to the impedance changes of tissue surrounding the device and wirelessly report impedance spectra. Present work suggests the potential feasibility of wireless tissue impedance measurements for PVD applications as a complement to neurostimulation.
ContributorsCelinskis, Dmitrijs (Author) / Towe, Bruce (Thesis advisor) / Greger, Bradley (Committee member) / Sadleir, Rosalind (Committee member) / Arizona State University (Publisher)
Created2015
Description
According to the CDC in 2010, there were 2.8 million emergency room visits costing $7.9 billion dollars for treatment of nonfatal falling injuries in emergency departments across the country. Falls are a recognized risk factor for unintentional injuries among older adults, accounting for a large proportion of fractures, emergency department visits, and urgent hospitalizations. The objective of this research was to identify and learn more about what factors affect balance using analysis techniques from nonlinear dynamics. Human balance and gait research traditionally uses linear or qualitative tests to assess and describe human motion; however, it is growing more apparent that human motion is neither a simple nor a linear task. In the 1990s Collins, first started applying stochastic processes to analyze human postural control system. Recently, Zakynthinaki et al. modeled human balance using the idea that humans will remain erect when perturbed until some boundary, or physical limit, is passed. This boundary is similar to the notion of basins of attraction in nonlinear dynamics and is referred to as the basin of stability. Human balance data was collected using dual force plates and Vicon marker position data for leans using only ankle movements and leans that were unrestricted. With this dataset, Zakynthinaki’s work was extended by comparing different algorithms used to create the critical curve (basin of stability boundary) that encloses the experimental data points as well as comparing the differences between the two leaning conditions.
ContributorsSmith, Victoria (Author) / Spano, Mark L (Thesis advisor) / Lockhart, Thurmon E (Thesis advisor) / Honeycutt, Claire (Committee member) / Arizona State University (Publisher)
Created2016