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- All Subjects: Biomedical Engineering
- All Subjects: Biomechanics
- All Subjects: Startle-evoked Movements
- Creators: Brafman, David
- Member of: Theses and Dissertations
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Status: Published
Description
Most daily living tasks consist of pairing a series of sequential movements, e.g., reaching to a cup, grabbing the cup, lifting and returning the cup to your mouth. The process by which we control and mediate the smooth progression of these tasks is not well understood. One method which we can use to further evaluate these motions is known as Startle Evoked Movements (SEM). SEM is an established technique to probe the motor learning and planning processes by detecting muscle activation of the sternocleidomastoid muscles of the neck prior to 120ms after a startling stimulus is presented. If activation of these muscles was detected following a stimulus in the 120ms window, the movement is classified as Startle+ whereas if no sternocleidomastoid activation is detected after a stimulus in the allotted time the movement is considered Startle-. For a movement to be considered SEM, the activation of movements for Startle+ trials must be faster than the activation of Startle- trials. The objective of this study was to evaluate the effect that expertise has on sequential movements as well as determining if startle can distinguish when the consolidation of actions, known as chunking, has occurred. We hypothesized that SEM could distinguish words that were solidified or chunked. Specifically, SEM would be present when expert typists were asked to type a common word but not during uncommon letter combinations. The results from this study indicated that the only word that was susceptible to SEM, where Startle+ trials were initiated faster than Startle-, was an uncommon task "HET" while the common words "AND" and "THE" were not. Additionally, the evaluation of the differences between each keystroke for common and uncommon words showed that Startle was unable to distinguish differences in motor chunking between Startle+ and Startle- trials. Explanations into why these results were observed could be related to hand dominance in expert typists. No proper research has been conducted to evaluate the susceptibility of the non-dominant hand's fingers to SEM, and the results of future studies into this as well as the results from this study can impact our understanding of sequential movements.
ContributorsMieth, Justin Richard (Author) / Honeycutt, Claire (Thesis director) / Santello, Marco (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Previous research has shown that a loud acoustic stimulus can trigger an individual's prepared movement plan. This movement response is referred to as a startle-evoked movement (SEM). SEM has been observed in the stroke survivor population where results have shown that SEM enhances single joint movements that are usually performed with difficulty. While the presence of SEM in the stroke survivor population advances scientific understanding of movement capabilities following a stroke, published studies using the SEM phenomenon only examined one joint. The ability of SEM to generate multi-jointed movements is understudied and consequently limits SEM as a potential therapy tool. In order to apply SEM as a therapy tool however, the biomechanics of the arm in multi-jointed movement planning and execution must be better understood. Thus, the objective of our study was to evaluate if SEM could elicit multi-joint reaching movements that were accurate in an unrestrained, two-dimensional workspace. Data was collected from ten subjects with no previous neck, arm, or brain injury. Each subject performed a reaching task to five Targets that were equally spaced in a semi-circle to create a two-dimensional workspace. The subject reached to each Target following a sequence of two non-startling acoustic stimuli cues: "Get Ready" and "Go". A loud acoustic stimuli was randomly substituted for the "Go" cue. We hypothesized that SEM is accessible and accurate for unrestricted multi-jointed reaching tasks in a functional workspace and is therefore independent of movement direction. Our results found that SEM is possible in all five Target directions. The probability of evoking SEM and the movement kinematics (i.e. total movement time, linear deviation, average velocity) to each Target are not statistically different. Thus, we conclude that SEM is possible in a functional workspace and is not dependent on where arm stability is maximized. Moreover, coordinated preparation and storage of a multi-jointed movement is indeed possible.
ContributorsOssanna, Meilin Ryan (Author) / Honeycutt, Claire (Thesis director) / Schaefer, Sydney (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Startle-evoked-movement (SEM), the involuntary release of a planned movement via a startling stimulus, has gained significant attention recently for its ability to probe motor planning as well as enhance movement of the upper extremity following stroke. We recently showed that hand movements are susceptible to SEM. Interestingly, only coordinated movements of the hand (grasp) but not individuated movements of the finger (finger abduction) were susceptible. It was suggested that this resulted from different neural mechanisms involved in each task; however it is possible this was the result of task familiarity. The objective of this study was to evaluate a more familiar individuated finger movement, typing, to determine if this task was susceptible to SEM. We hypothesized that typing movements will be susceptible to SEM in all fingers. These results indicate that individuated movements of the fingers are susceptible to SEM when the task involves a more familiar task, since the electromyogram (EMG) latency is faster in SCM+ trials compared to SCM- trials. However, the middle finger does not show a difference in terms of the keystroke voltage signal, suggesting the middle finger is less susceptible to SEM. Given that SEM is thought to be mediated by the brainstem, specifically the reticulospinal tract, this suggest that the brainstem may play a role in movements of the distal limb when those movements are very familiar, and the independence of each finger might also have a significant on the effect of SEM. Further research includes understanding SEM in fingers in the stroke population. The implications of this research can impact the way upper extremity rehabilitation is delivered.
ContributorsQuezada Valladares, Maria Jose (Author) / Honeycutt, Claire (Thesis director) / Santello, Marco (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Cardiovascular disease (CVD) remains the leading cause of mortality, resulting in 1 out of 4 deaths in the United States at the alarming rate of 1 death every 36 seconds, despite great efforts in ongoing research. In vitro research to study CVDs has had limited success, due to lack of biomimicry and structural complexity of 2D models. As such, there is a critical need to develop a 3D, biomimetic human cardiac tissue within precisely engineered in vitro platforms. This PhD dissertation involved development of an innovative anisotropic 3D human stem cell-derived cardiac tissue on-a-chip model (i.e., heart on-a-chip), with an enhanced maturation tissue state, as demonstrated through extensive biological assessments. To demonstrate the potential of the platform to study cardiac-specific diseases, the developed heart on-a-chip was used to model myocardial infarction (MI) due to exposure to hypoxia. The successful induction of MI on-a-chip (heart attack-on-a-chip) was evidenced through fibrotic tissue response, contractile dysregulation, and transcriptomic regulation of key pathways.This dissertation also described incorporation of CRISPR/Cas9 gene-editing to create a human induced pluripotent stem cell line (hiPSC) with a mutation in KCNH2, the gene implicated in Long QT Syndrome Type 2 (LQTS2). This novel stem cell line, combined with the developed heart on-a-chip technology, led to creation of a 3D human cardiac on-chip tissue model of LQTS2 disease.. Extensive mechanistic biological and electrophysiological characterizations were performed to elucidate the mechanism of R531W mutation in KCNH2, significantly adding to existing knowledge about LQTS2. In summary, this thesis described creation of a LQTS2 cardiac on-a-chip model, incorporated with gene-edited hiPSC-cardiomyocytes and hiPSC-cardiac fibroblasts, to study mechanisms of LQTS2.
Overall, this dissertation provides broad impact for fundamental studies toward cardiac biological studies as well as drug screening applications. Specifically, the developed heart on-a-chip from this dissertation provides a unique alternative platform to animal testing and 2D studies that recapitulates the human myocardium, with capabilities to model critical CVDs to study disease mechanisms, and/or ultimately lead to development of future therapeutic strategies.
ContributorsVeldhuizen, Jaimeson (Author) / Nikkhah, Mehdi (Thesis advisor) / Brafman, David (Committee member) / Ebrahimkhani, Mo (Committee member) / Migrino, Raymond Q (Committee member) / Plaisier, Christopher (Committee member) / Arizona State University (Publisher)
Created2021
Description
Skin wounds can be caused by traumatic lacerations or incisions which disrupt the structural and functional integrity of the skin. Wound closure and primary intention treatment of the wound as soon as possible is crucial to avoid or minimize the risk of infection that can result in a compromised healing rate or advanced functional intricacy. The gold standard treatment for skin wound healing is suturing. Light-activated tissue sealing is an appealing alternative to sutures as it seals the wound edges minimizing the risk of infection and scarring, especially when utilized along with biodegradable polymeric biomaterials in the wound bed. Silk fibroins can be used as a biodegradable biomaterial that possesses properties supporting cell migration and proliferation in the tissue it interacts with. In addition, histamine treatment is shown to have extensive effects on cellular functions promoting wound healing. Here, the evaluation of Laser-activated Sealants (LASE) consisting of silk fibroin films induced with Indocyanine Green dye in a wound sealed with laser in the presence of Histamine receptor agonists H1R, H2R and H4R take place. The results were evaluated using Trans-epidermal Water Loss (TEWL), histological and analytical techniques where immune cell biomarkers Arginase-1, Ly6G, iNOS, Alpha-SMA, Proliferating Cell Nuclear Antigen (PCNA), and E-Cadherin were used to study the activity of specific cells such as macrophages, neutrophils, and myofibroblasts that aid in wound healing. PBS was used as a control for histamine receptor agonists. It was found that TEWL increased when treated with H1 receptor agonists while decreasing significantly in H2R and H4R-treated wounds. Arginase-1 activity improved, while it displayed an inverse relationship compared to iNOS. H4R agonist escalated Alpha-SMA cells, while others did not have any significant difference. Ly6G activity depleted in all histamine agonists significantly, while PCNA and E-Cadherin failed to show a positive or negative effect.
ContributorsPatel, Dirghau Manishbhai (Author) / Rege, Kaushal (Thesis advisor) / Massia, Stephen (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2022
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
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
Annually, approximately 1.7 million people suffer a traumatic brain injury (TBI) in the United States. After initial insult, a TBI persists as a series of molecular and cellular events that lead to cognitive and motor deficits which have no treatment. In addition, the injured brain activates the regenerative niches of the adult brain presumably to reduce damage. The subventricular zone (SVZ) niche contains neural progenitor cells (NPCs) that generate astrocytes, oligodendrocyte, and neuroblasts. Following TBI, the injury microenvironment secretes signaling molecules like stromal cell derived factor-1a (SDF-1a). SDF-1a gradients from the injury contribute to the redirection of neuroblasts from the SVZ towards the lesion which may differentiate into neurons and integrate into existing circuitry. This repair mechanism is transient and does not lead to complete recovery of damaged tissue. Further, the mechanism by which SDF-1a gradients reach SVZ cells is not fully understood. To prolong NPC recruitment to the injured brain, exogenous SDF-1a delivery strategies have been employed. Increases in cell recruitment following stroke, spinal cord injury, and TBI have been demonstrated following SDF-1a delivery. Exogenous delivery of SDF-1a is limited by its 28-minute half-life and clearance from the injury microenvironment. Biomaterials-based delivery improves stability of molecules like SDF-1a and offer control of its release.
This dissertation investigates SDF-1a delivery strategies for neural regeneration in three ways: 1) elucidating the mechanisms of spatiotemporal SDF-1a signaling across the brain, 2) developing a tunable biomaterials system for SDF-1a delivery to the brain, 3) investigating SDF-1a delivery on SVZ-derived cell migration following TBI. Using in vitro, in vivo, and in silico analyses, autocrine/paracrine signaling was necessary to produce SDF-1a gradients in the brain. Native cell types engaged in autocrine/paracrine signaling. A microfluidics device generated injectable hyaluronic-based microgels that released SDF-1a peptide via enzymatic cleavage. Microgels (±SDF-1a peptide) were injected 7 days post-TBI in a mouse model and evaluated for NPC migration 7 days later using immunohistochemistry. Initial staining suggested complex presence of astrocytes, NPCs, and neuroblasts throughout the frontoparietal cortex.
Advancement of chemokine delivery was demonstrated by uncovering endogenous chemokine propagation in the brain, generating new approaches to maximize chemokine-based neural regeneration.
ContributorsHickey, Kassondra (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Holloway, Julianne (Committee member) / Caplan, Michael (Committee member) / Brafman, David (Committee member) / Newbern, Jason (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
Mechanical impedance is a concept that is used to model biomechanical propertiesof human joints. These models can then be utilized to provide insight into the inner
workings of the human neuromuscular system or to provide insight into how to best
design controllers for robotic applications that either attempt to mimic capabilities of
the human neuromuscular system or physically interact with it. To further elucidate
patterns and properties of how the human neuromuscular system modulates mechanical
impedance at the human ankle joint, multiple studies were conducted. The first
study was to assess the ability of linear regression models to characterize the change
in stiffness - a component of mechanical impedance - seen at the human ankle during
the stance phase of walking in the Dorsiflexion-Plantarflexion (DP) direction. A
collection of biomechanical variables were used as input variables. The R^2 value of
the best performing model was 0.71. The second and third studies were performed to
showcase the ability of a newly developed twin dual-axis platform, which goes beyond
the limits of a single dual-axis platform, to quantify bilateral stiffness properties. The
second study quantified the bilateral mechanical stiffness of the human ankle joint
for healthy able-bodied subjects during the stance phase of walking and during quiet
standing in both the DP and inversion-eversion directions. Subjects showed a high
level of subject specific symmetry. Lastly, a similar bilateral ankle characterization
study was conducted on a set of subjects with multiple sclerosis, but only during
quiet standing and in the DP direction. Results showed a high level of discrepancy
between the subject’s most-affected and least-affected limbs with a larger range and
variance than in the healthy population.
ContributorsRussell, Joshua (Author) / Lee, Hyunglae (Thesis advisor) / Honeycutt, Claire (Committee member) / Marvi, Hamid (Committee member) / Arizona State University (Publisher)
Created2022