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- Genre: Doctoral Dissertation
Description
Neurostimulation methods currently include deep brain stimulation (DBS), optogenetic, transcranial direct-current stimulation (tDCS), and transcranial magnetic stimulation (TMS). TMS and tDCS are noninvasive techniques whereas DBS and optogenetic require surgical implantation of electrodes or light emitting devices. All approaches, except for optogenetic, have been implemented in clinical settings because they have demonstrated therapeutic utility and clinical efficacy for neurological and psychiatric disorders. When applied for therapeutic applications, these techniques suffer from limitations that hinder the progression of its intended use to treat compromised brain function. DBS requires an invasive surgical procedure that surfaces complications from infection, longevity of electrical components, and immune responses to foreign materials. Both TMS and tDCS circumvent the problems seen with DBS as they are noninvasive procedures, but they fail to produce the spatial resolution required to target specific brain structures. Realizing these restrictions, we sought out to use ultrasound as a neurostimulation modality. Ultrasound is capable of achieving greater resolution than TMS and tDCS, as we have demonstrated a ~2mm lateral resolution, which can be delivered noninvasively. These characteristics place ultrasound superior to current neurostimulation methods. For these reasons, this dissertation provides a developed protocol to use transcranial pulsed ultrasound (TPU) as a neurostimulation technique. These investigations implement electrophysiological, optophysiological, immunohistological, and behavioral methods to elucidate the effects of ultrasound on the central nervous system and raise questions about the functional consequences. Intriguingly, we showed that TPU was also capable of stimulating intact sub-cortical circuits in the anesthetized mouse. These data reveal that TPU can evoke synchronous oscillations in the hippocampus in addition to increasing expression of brain-derived neurotrophic factor (BDNF). Considering these observations, and the ability to noninvasively stimulate neuronal activity on a mesoscale resolution, reveals a potential avenue to be effective in clinical settings where current brain stimulation techniques have shown to be beneficial. Thus, the results explained by this dissertation help to pronounce the significance for these protocols to gain translational recognition.
ContributorsTufail, Yusuf Zahid (Author) / Tyler, William J (Thesis advisor) / Duch, Carsten (Committee member) / Muthuswamy, Jitendran (Committee member) / Santello, Marco (Committee member) / Tillery, Stephen H (Committee member) / Arizona State University (Publisher)
Created2011
Description
An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space and the consequences of misestimation of limb position on movements. Two independent but related studies were performed. The first involved characterizing the neural mechanisms of limb position estimation in the non-human primate brain. Single unit recordings were obtained in area 5 of the posterior parietal cortex in order to examine the role of this area in estimating limb position based on visual and somatic signals (proprioceptive, efference copy). When examined individually, many area 5 neurons were tuned to the position of the limb in the workspace but very few neurons were modulated by visual feedback. At the population level however decoding of limb position was somewhat more accurate when visual feedback was provided. These findings support a role for area 5 in limb position estimation but also suggest that visual signals regarding limb position are only weakly represented in this area, and only at the population level. The second part of this dissertation focused on the consequences of misestimation of limb position for movement production. It is well known that limb movements are inherently variable. This variability could be the result of noise arising at one or more stages of movement production. Here we used biomechanical modeling and simulation techniques to characterize movement variability resulting from noise in estimating limb position ('sensing noise') and in planning required movement vectors ('planning noise'), and compared that to the variability expected due to noise in movement execution. We found that the effects of sensing and planning related noise on movement variability were dependent upon both the planned movement direction and the initial configuration of the arm and were different in many respects from the effects of execution noise.
ContributorsShi, Ying (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / He, Jiping (Committee member) / Santos, Veronica (Committee member) / Arizona State University (Publisher)
Created2011
Description
The health benefits of physical activity are widely accepted. Emerging research also indicates that sedentary behaviors can carry negative health consequences regardless of physical activity level. This dissertation explored four projects that examined measurement properties of physical activity and sedentary behavior monitors. Project one identified the oxygen costs of four other care activities in seventeen adults. Pushing a wheelchair and pushing a stroller were identified as moderate-intensity activities. Minutes spent engaged in these activities contribute towards meeting the 2008 Physical Activity Guidelines. Project two identified the oxygen costs of common cleaning activities in sixteen adults. Mopping a floor was identified as moderate-intensity physical activity, while cleaning a kitchen and cleaning a bathtub were identified as light-intensity physical activity. Minutes spent engaged in mopping a floor contributes towards meeting the 2008 Physical Activity Guidelines. Project three evaluated the differences in number of minutes spent in activity levels when utilizing different epoch lengths in accelerometry. A shorter epoch length (1-second, 5-seconds) accumulated significantly more minutes of sedentary behaviors than a longer epoch length (60-seconds). The longer epoch length also identified significantly more time engaged in light-intensity activities than the shorter epoch lengths. Future research needs to account for epoch length selection when conducting physical activity and sedentary behavior assessment. Project four investigated the accuracy of four activity monitors in assessing activities that were either sedentary behaviors or light-intensity physical activities. The ActiGraph GT3X+ assessed the activities least accurately, while the SenseWear Armband and ActivPAL assessed activities equally accurately. The monitor used to assess physical activity and sedentary behaviors may influence the accuracy of the measurement of a construct.
ContributorsMeckes, Nathanael (Author) / Ainsworth, Barbara E (Thesis advisor) / Belyea, Michael (Committee member) / Buman, Matthew (Committee member) / Gaesser, Glenn (Committee member) / Wharton, Christopher (Christopher Mack), 1977- (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.
ContributorsSawyer, Brandon J (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Lee, Chong (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2013
Description
Purpose: The purpose of this study was to examine the acute effects of two novel intermittent exercise prescriptions on glucose regulation and ambulatory blood pressure. Methods: Ten subjects (5 men and 5 women, ages 31.5 ± 5.42 yr, height 170.38 ± 9.69 cm and weight 88.59 ± 18.91 kg) participated in this four-treatment crossover trial. All subjects participated in four trials, each taking place over three days. On the evening of the first day, subjects were fitted with a continuous glucose monitor (CGM). On the second day, subjects were fitted with an ambulatory blood pressure monitor (ABP) and underwent one of the following four conditions in a randomized order: 1) 30-min: 30 minutes of continuous exercise at 60 - 70% VO2peak; 2) Mod 2-min: twenty-one 2-min bouts of walking at 3 mph performed once every 20 minutes; 3) HI 2-min: eight 2-min bouts of walking at maximal incline performed once every hour; 4) Control: a no exercise control condition. On the morning of the third day, the CGM and ABP devices were removed. All meals were standardized during the study visits. Linear mixed models were used to compare mean differences in glucose and blood pressure regulation between the four trials. Results: Glucose concentrations were significantly lower following the 30-min (91.1 ± 14.9 mg/dl), Mod 2-min (93.7 ± 19.8 mg/dl) and HI 2-min (96.1 ± 16.4 mg/dl) trials as compared to the Control (101.1 ± 20 mg/dl) (P < 0.001 for all three comparisons). The 30-min trial was superior to the Mod 2-min, which was superior to the HI 2-min trial in lowering blood glucose levels (P < 0.001 and P = 0.003 respectively). Only the 30-min trial was effective in lowering systolic ABP (124 ± 12 mmHg) as compared to the Control trial (127 ± 14 mmHg; P < 0.001) for up to 11 hours post exercise. Conclusion: Performing frequent short (i.e., 2 minutes) bouts of moderate or high intensity exercise may be a viable alternative to traditional continuous exercise in improving glucose regulation. However, 2-min bouts of exercise are not effective in reducing ambulatory blood pressure in healthy adults.
ContributorsBhammar, Dharini Mukeshkumar (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Buman, Matthew (Committee member) / Swan, Pamela (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2013
Description
Our ability to estimate the position of our body parts in space, a fundamentally proprioceptive process, is crucial for interacting with the environment and movement control. For proprioception to support these actions, the Central Nervous System has to rely on a stored internal representation of the body parts in space. However, relatively little is known about this internal representation of arm position. To this end, I developed a method to map proprioceptive estimates of hand location across a 2-d workspace. In this task, I moved each subject's hand to a target location while the subject's eyes were closed. After returning the hand, subjects opened their eyes to verbally report the location of where their fingertip had been. Then, I reconstructed and analyzed the spatial structure of the pattern of estimation errors. In the first couple of experiments I probed the structure and stability of the pattern of errors by manipulating the hand used and tactile feedback provided when the hand was at each target location. I found that the resulting pattern of errors was systematically stable across conditions for each subject, subject-specific, and not uniform across the workspace. These findings suggest that the observed structure of pattern of errors has been constructed through experience, which has resulted in a systematically stable internal representation of arm location. Moreover, this representation is continuously being calibrated across the workspace. In the next two experiments, I aimed to probe the calibration of this structure. To this end, I used two different perturbation paradigms: 1) a virtual reality visuomotor adaptation to induce a local perturbation, 2) and a standard prism adaptation paradigm to induce a global perturbation. I found that the magnitude of the errors significantly increased to a similar extent after each perturbation. This small effect indicates that proprioception is recalibrated to a similar extent regardless of how the perturbation is introduced, suggesting that sensory and motor changes may be two independent processes arising from the perturbation. Moreover, I propose that the internal representation of arm location might be constructed with a global solution and not capable of local changes.
ContributorsRincon Gonzalez, Liliana (Author) / Helms Tillery, Stephen I (Thesis advisor) / Buneo, Christopher A (Thesis advisor) / Santello, Marco (Committee member) / Santos, Veronica (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2012
Description
In recent years, machine learning and data mining technologies have received growing attention in several areas such as recommendation systems, natural language processing, speech and handwriting recognition, image processing and biomedical domain. Many of these applications which deal with physiological and biomedical data require person specific or person adaptive systems. The greatest challenge in developing such systems is the subject-dependent data variations or subject-based variability in physiological and biomedical data, which leads to difference in data distributions making the task of modeling these data, using traditional machine learning algorithms, complex and challenging. As a result, despite the wide application of machine learning, efficient deployment of its principles to model real-world data is still a challenge. This dissertation addresses the problem of subject based variability in physiological and biomedical data and proposes person adaptive prediction models based on novel transfer and active learning algorithms, an emerging field in machine learning. One of the significant contributions of this dissertation is a person adaptive method, for early detection of muscle fatigue using Surface Electromyogram signals, based on a new multi-source transfer learning algorithm. This dissertation also proposes a subject-independent algorithm for grading the progression of muscle fatigue from 0 to 1 level in a test subject, during isometric or dynamic contractions, at real-time. Besides subject based variability, biomedical image data also varies due to variations in their imaging techniques, leading to distribution differences between the image databases. Hence a classifier learned on one database may perform poorly on the other database. Another significant contribution of this dissertation has been the design and development of an efficient biomedical image data annotation framework, based on a novel combination of transfer learning and a new batch-mode active learning method, capable of addressing the distribution differences across databases. The methodologies developed in this dissertation are relevant and applicable to a large set of computing problems where there is a high variation of data between subjects or sources, such as face detection, pose detection and speech recognition. From a broader perspective, these frameworks can be viewed as a first step towards design of automated adaptive systems for real world data.
ContributorsChattopadhyay, Rita (Author) / Panchanathan, Sethuraman (Thesis advisor) / Ye, Jieping (Thesis advisor) / Li, Baoxin (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
Description
Humans' ability to perform fine object and tool manipulation is a defining feature of their sensorimotor repertoire. How the central nervous system builds and maintains internal representations of such skilled hand-object interactions has attracted significant attention over the past three decades. Nevertheless, two major gaps exist: a) how digit positions and forces are coordinated during natural manipulation tasks, and b) what mechanisms underlie the formation and retention of internal representations of dexterous manipulation. This dissertation addresses these two questions through five experiments that are based on novel grip devices and experimental protocols. It was found that high-level representation of manipulation tasks can be learned in an effector-independent fashion. Specifically, when challenged by trial-to-trial variability in finger positions or using digits that were not previously engaged in learning the task, subjects could adjust finger forces to compensate for this variability, thus leading to consistent task performance. The results from a follow-up experiment conducted in a virtual reality environment indicate that haptic feedback is sufficient to implement the above coordination between digit position and forces. However, it was also found that the generalizability of a learned manipulation is limited across tasks. Specifically, when subjects learned to manipulate the same object across different contexts that require different motor output, interference was found at the time of switching contexts. Data from additional studies provide evidence for parallel learning processes, which are characterized by different rates of decay and learning. These experiments have provided important insight into the neural mechanisms underlying learning and control of object manipulation. The present findings have potential biomedical applications including brain-machine interfaces, rehabilitation of hand function, and prosthetics.
ContributorsFu, Qiushi (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Santos, Veronica (Committee member) / Artemiadis, Panagiotis (Committee member) / Arizona State University (Publisher)
Created2013
Description
Eccentric muscle action (ECC) occurs when the force exerted by a working muscle is less than that of an outside resistance. This is characterized by muscle lengthening, despite actin-myosin crossbridge formation. Research has indicated that muscles acting eccentrically are capable of producing more force when compared to muscles acting concentrically. Further, research has shown ECC muscle actions may have different fatigue patterns that CON actions. The purpose of this study was to determine if a) ECC bench press yields greater strength than concentric (CON) as measured by one-repetition maximum (1RM), b) there is a difference between the number of repetitions that can be completed concentrically and eccentrically under the same relative intensities of 1RM (90%, 80%, 70%, 60%), c) a prediction model may be able to predict ECC 1RM from CON 1RM or CON repetitions to fatigue. For this study, 30 healthy males (age = 24.63 + 5.6 years) were tested for 1RM in CON and ECC bench press, as well as the number of repetitions they were able to complete at various intensities of mode-specific 1RM. A mechanical hoist was affixed to a gantry crane and placed over a standard weightlifting bench. The hoist was connected to 45lb plates that were loaded on a standard barbell, which allowed for mechanical raising and lowering of the barbell. For CON repetitions, the weight was mechanically lowered to the chest and the participant pressed it up. For ECC repetitions, the weight was mechanically raised and the participant lowered it. Paired t-tests showed that ECC 1RM was significantly (p < 0.05) greater than CON 1RM (ECC =255.17 + 68.37lbs, CON = 205.83 + 58.43lbs). There was a significant difference (p < 0.05) between the number of repetitions completed at 90% 1RM (CON = 4.57 + 2.21 repetitions, ECC = 7.67 + 3.24 repetitions). There were no differences in repetitions completed at any other intensity 1RM. CON 1RM and the number of repetitions completed with two different absolute loads (130-150lbs and 155-175lbs) concentrically and eccentrically were valid predictors of ECC 1RM. These data indicate that ECC actions yield increased force capabilities than CON actions, there is no difference in the rate of the fatigue, and ECC 1RM may be predicted from various CON tests.
ContributorsKelly, Stephen B., Jr (Author) / Hooker, Steven (Thesis advisor) / Brown, Lee (Committee member) / Buman, Matthew (Committee member) / Gaesser, Glenn (Committee member) / Swan, Pamela (Committee member) / Arizona State University (Publisher)
Created2013
Description
Stroke remains the leading cause of adult disability in developed countries. Most survivors live with residual motor impairments that severely diminish independence and quality of life. After stroke, the only accepted treatment for these patients is motor rehabilitation. However, the amount and kind of rehabilitation required to induce clinically significant improvements in motor function is rarely given due to the constraints of our current health care system. Research reported in this dissertation contributes towards developing adjuvant therapies that may augment the impact of motor rehabilitation and improve functional outcome. These studies have demonstrated reorganization of maps within motor cortex as a function of experience in both healthy and brain-injured animals by using intracortical microstimulation technique. Furthermore, synaptic plasticity has been identified as a key neural mechanism in directing motor map plasticity, evidenced by restoration of movement representations within the spared cortical tissue accompanied by increase in synapse number translating into motor improvement after stroke. There is increasing evidence that brain-derived neurotrophic factor (BDNF) modulates synaptic and morphological plasticity in the developing and mature nervous system. Unfortunately, BDNF itself is a poor candidate because of its short half-life, low penetration through the blood brain barrier, and activating multiple receptor units, p75 and TrkB on the neuronal membrane. In order to circumvent this problem efficacy of two recently developed novel TrkB agonists, LM22A-4 and 7,8-dihydroxyflavone, that actively penetrate the blood brain barrier and enhance functional recovery. Findings from these dissertation studies indicate that administration of these pharmacological compounds, accompanied by motor rehabilitation provide a powerful therapeutic tool for stroke recovery.
ContributorsWarraich, Zuha (Author) / Kleim, Jeffrey A (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Tillery, Stephen-Helms (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013