Biomedical Physiology and Kinesiology - Theses, Dissertations, and other Required Graduate Degree Essays

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Electrophysiological correlates of performance monitoring and error detection in response to augmented feedback

Date created: 
2005
Abstract: 

The ability to monitor performance and detect errors is essential for intelligent behaviour. Motor behaviourists have long been interested in how information about the performance of motor skills is used to facilitate learning. Recently, cognitive neuroscientists have also been interested in studying performance monitoring, particularly after the discovery of an event-related potential (ERP) component linked to error processing. This ERP component, aptly termed the error-related negativity (ERN), is observed in response to physical errors and also upon presentation of augmented feedback indicating performance errors or monetary losses. The neural generator of the ERN is thought to be located in the anterior cingulate cortex (ACC), a structure situated in the medial frontal wall of the human frontal lobe. ERN studies along with functional imaging experiments have suggested that ACC acts as part of an error detection system. In this thesis I challenge the notion that ACC activity, as measured by feedback ERN (f-ERN), is in fact related to errors. Experiment 1 measured participants' expectation of feedback by asking them to estimate their performance on each trial of an anticipation-timing task. The results show that f-ERN is elicited by feedback indicating both correct performance and errors, so long as expected feedback does not match the actual feedback. Experiment 2 replicated the results of Experiment 1 without asking participants to estimate their performance. This was accomplished by presenting false correct feedback in situations in which participants made errors. Taken together, the results of Experiments 1 and 2 suggest that ACC might not be selectively activated by errors, and that f-ERN might not be elicited exclusively by feedback indicating performance errors and monetary losses. I propose that f-ERN is the outcome of a more general system that searches the environment for violations of expectancy.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Retrograde transport rates in the G93A mouse model of amyotrophic lateral sclerosis

Date created: 
2005
Abstract: 

Amyotrophic Lateral Sclerosis is a late-onset, progressive neuromuscular disease involving degeneration of corticospinal tracts and motor neurons in the brain stem and spinal cord. Recently, it has been suggested that ALS results from a "dying back" axonopathy as opposed to originating in the motor neuron cell body. This is supported by a reduction of neuromuscular junctions in skeletal muscle prior to symptom onset and motor neuron death. It is known that there is a slowing of retrograde transport when comparing presymptomatic and end-stage mice; however, when during disease progression this occurs has not been clarified. By using a retrograde tracer, I sought to observe retrograde transport rates during disease progression in the G93A mouse, a murine model of ALS. Results indicate that retrograde transport is attenuated before symptom onset, loss of motor neurons, and precedes alterations in anterograde transport indicating this is one of the earliest pathological events in ALS.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Neural mechanisms of incorporating prior knowledge of movement experience into feedforward motor commands

Date created: 
2008
Abstract: 

The central nervous system (CNS) predicts the amount of force needed so that the hands can grasp and hold objects securely. How does the CNS compute the dynamics and produce the appropriate forces required to perform tasks like holding a cup or a needle? It has been proposed that the CNS combines a priori information about the properties of a movement with sensory information from the peripheral sensory receptors, to obtain optimal force estimation. We propose a novel task that requires the subjects to experience the magnitude of a first torque pulse and subsequently estimate and compensate a second torque pulse that is equal in magnitude. By varying the magnitude of the torque pulses according to a normal probability distribution with a large standard deviation, we investigate the neural mechanisms of how the CNS combines prior knowledge of movement experience with sensory feedback, to produce accurate feedforward motor commands.

Document type: 
Thesis
File(s): 
Senior supervisor: 
T
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

The influence of voluntary movement dynamics on postural stability borders and balance recovery strategies

Date created: 
2008
Abstract: 

Falls are the number one cause of unintentional injury, and often occur during tasks such as bending and reaching. My thesis examined how the dynamic features of an ongoing task influenced one’s ability to maintain and recover balance. In study one, I conducted experiments and mathematical modeling to show there was a tradeoff between the frequency and amplitude of heel-toe rocking movements that can be performed without losing balance. The central nervous system (CNS) must account for this tradeoff in planning stable movements. In study two, I conducted experiments to perturb participants’ balance at different phases of the rocking cycle, and found that, when the initial position was constant, the velocity at the time of the perturbation influenced the kinematics and muscle activities associated with the recovery response. This indicated an ability of the CNS to adapt the postural response to the nature of the ongoing task.

Document type: 
Thesis
File(s): 
Senior supervisor: 
S
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Biomechanics of Postural Stability in the Elderly

Author: 
Date created: 
2004
Abstract: 

Falls cause substantial death and morbidity in the elderly. Fall risk depends on ability to maintain balance during daily activities and ability to recover balance following a perturbation such as a slip or trip. To guide the design of fall prevention programs, we need an improved understanding of the biomechanical variables that govern ability to recover balance. The aims of this thesis were to determine (1) the relative importance of strength versus speed-of-response variables in explaining age differences in balance recovery performance with the ankle strategy, and (2) the association between variables related to ability to recover balance and variables related to ability to maintain balance. To address Aim 1, young and elderly women were supported in a forward leaning position by a horizontal tether and instructed to recover an upright vertical stance by contracting their ankle muscles. The maximum initial lean angle where they could recover balance without release of the tether (which depends primarily on strength) was 19.6% smaller for elderly than young. The maximum initial lean angle where they could recover balance after the tether was suddenly released (which depends on strength and speed-of-response) was 36.1% smaller for elderly. Moreover, between-group differences in performance were related to both strength and speed-of-response. Peak ankle torque was 7.7% smaller in elderly than young during tether release trials, reaction time was 27% slower in elderly, due to a lengthened muscle response latency, and rate of ankle torque generation was 15.6% slower in elderly. These results suggest that exercise-based fall prevention programs should include balance and agility training, in addition to strength training. To address Aim 2, the same elderly subjects participated in postural steadiness experiments, where the amplitude, velocity, and frequency of their centre-of-pressure displacement were measured during quiet stance. Postural steadiness during quiet stance and ability to recover balance with the ankle strategy were not associated, perhaps because postural steadiness during quiet stance is controlled partly by anticipatory strategies, while balance recovery following a perturbation is governed by reactive strategies. These results support the need to measure both balance recovery and postural steadiness in balance assessments of the elderly.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
Thesis (M.Sc.)

Adaptive control of goal-oriented human arm movement

Author: 
Date created: 
2003
Document type: 
Thesis
File(s): 
Department: 
Theses (School of Kinesiology) / Simon Fraser University
Thesis type: 
Thesis (M.Sc. (Kinesiology))

Abnormal Protein Phosphorylation in Human Amyotrophic Lateral Sclerosis

Author: 
Date created: 
2003
Abstract: 

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of neurons in cortex, brain stem and spinal cord. Currently, ALS is believed to be triggered by a number of distinct factors including glutamate excitotoxicity and mutations in the sod1 gene (mSOD). To explore the role of protein kinase C (PKC) in N-methyl-D-aspartate (NMDA)- mediated cytotoxicity, cell death assays were performed in NR 1 AINR2A-transfected human embryonic kidney (HEK) cells. NMDA-mediated cell death was potentiated by the activation of ca2+- and lipid-dependent isoforms of PKC, specifically PKCP 1. A discrete segment of the C-terminus of NR2A subunit contributed to this potentiation by PKC. These data demonstrate that the elevation of PKC activity increases cell death induced by NMDA receptor activation. To examine the involvement of abnormal protein phosphorylation in ALS, the expression of over 130 proteins were evaluated in postmortem spinal cord tissues from patients having sporadic ALS and controls. There was increased expression of protein kinases and phosphoproteins in ALS tissue such as PKCaIP, protein kinase B a (PKBa) and phospho-PKCalP. This suggests that both pro- and anti-apoptotic signaling pathways are up-regulated in ALS. It is possible that the final outcome for each individual cell is determined by which pathway dominates over the other. Transgenic mice over-expressing mSOD have been used extensively as a model of familial ALS. Comparative studies have revealed a striking similarity in pathology between mSOD mouse and human ALS. The morphological analogy between these two was investigated and we found that in G93A mSOD mice, the spinal nucleus of bulbocavernosus (SNB) is spared from degeneration, paralleling the survival of its functional and anatomical homologue, Onuf s nucleus. This provides evidence that mSOD mice may suitably models ALS. However, a distinct profile of changes in protein expression were observed in the CNS tissues of G93A mSOD mice compared with their control littermates, which was dissimilar to that between ALS patients and controls. This observation indicates that the activation of protein kinases is different with neuron loss in mSOD mouse compared with that seen in patients with sporadic ALS. These findings suggest an important role for abnormal protein phosphorylation in ALS.

Document type: 
Thesis
File(s): 
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
Thesis (Ph.D.)

Pulmonary ventilation following acclimation to a hot environment

Date created: 
2007
Abstract: 

Human pulmonary ventilation and the hyperoxic-centrally mediated ventilatory response to CO2 were studied before and after a 10-day passive heat acclimation (HA). It was hypothesized pulmonary ventilation during a passively- or actively-induced hyperthermia would adapt similarily to thermolytic heat loss responses and that chemosensitivity would be increased following HA. Following HA, onset of increased cutaneous vasodilatation, eccrine sweating and ventilation in both passively- and actively-induced hyperthermia were at significantly lower esophageal temperature thresholds (p<0.05). Addtitionally, following HA the breathing pattern during passively-induced hyperthermia adapted to promote respiratory heat loss and actively-induced hyperthermia gave a significantly (p<0.05) greater ventilation. Irrespective of acclimation state, hyperthermia significantly increased chemosensitivity (p=0.027) across all levels of end-tidal partial pressure of CO2. HA did not modify the normo- or hyperthermic ventilatory recruitment thresholds (VRT) or the supra-VRT chemosensitivity. In conclusion, pulmonary ventilation adapted similarly to thermolytic heat loss responses and chemosensitivity was unmodified following HA.

Document type: 
Thesis
File(s): 
Senior supervisor: 
M
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Numerical and structural abnormalities of centrosomes in oral cancer and premalignancy

Author: 
Date created: 
2007
Abstract: 

Centrosomes play a critical role in cell division. Recent findings that both numerical and structural alterations to centrosomes occur in cancers support the possibility that such change may be a driving force for cancer development. However, little is known about centrosome alteration in oral cancers and premalignancies. The objective of this study was to assess the frequency of centrosome abnormalities in oral cancers and precancers utilizing immunofluorescence with antibodies to £^-tubulin, a well-characterized centrosomal component, and ƒÑ/ƒÒ-tubulin, the main component of centrioles. Fifty paraffin samples (13 oral cancers; 21 oral premalignancies; 16 nondysplastic controls) were used. The results showed a strong association of centrosome abnormalities and histology (cancer or presence/degree of dysplasia): size abnormalities: P<0.001; cluster formation: P=0.001, and more than 2 centrosomes in each cell: P<0.001. More than 90% of amplified centrosomes lacked centrioles. The results support a role for structural and numerical abnormalities of centrosomes in early carcinogenesis.

Document type: 
Thesis
File(s): 
Senior supervisor: 
M
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)

Extracellular release of high mobility group box1 protein from necrotic beta-cells in the pathogenesis of type 1 diabetes mellitus

Author: 
Date created: 
2007
Abstract: 

Nonobese diabetic (NOD) mice, an animal model of human type 1 diabetes mellitus (T1DM), exhibit impaired phagocytosis of apoptotic cells. In addition to phagocytosis, degradation of apoptotic cells determines the level of dead cells in tissues. Therefore, the work examined the kinetics of apoptotic cell degradation in vitro. The work revealed that macrophages from NOD mice digested internalised apoptotic thymocytes at a reduced rate compared to macrophages from control mice. How defective clearance leads to the development of T1DM is unclear. Necrosis is associated with inflammation, and high mobility group box 1 protein (HMGB1) released from necrotic cells induce inflammation. The relationship between beta-cell death and HMGB1 release was investigated. The results showed that HMGB1 was released from necrotic beta-cells in a dose-dependent manner. If impaired, clearance of apoptotic beta-cells results in an increased population of necrotic beta-cells. HMGB1 release could initiate or exacerbate an inflammatory response in NOD mice.

Document type: 
Thesis
File(s): 
Senior supervisor: 
D
Department: 
School of Kinesiology - Simon Fraser University
Thesis type: 
(Kinesiology) Thesis (M.Sc.)