Neuroplasticity of Ipsilateral Cortical Motor Representations, Training Effects and Role in Stroke Recovery

This thesis examines the contribution of the ipsilateral hemisphere to motor control with the aim of evaluating the potential of the contralesional hemisphere to contribute to motor recovery after stroke. Predictive algorithms based on neurobiological principles emphasize integrity of the ipsilesional corticospinal tract as the strongest prognostic indicator of good motor recovery. In contrast, extensive lesions placing reliance on alternative contralesional ipsilateral motor pathways are associated with poor recovery. Within the predictive algorithms are elements of motor control that rely on contributions from ipsilateral motor pathways, suggesting that balanced, parallel contralesional contributions can be beneficial. Current therapeutic approaches have focussed on the maladaptive potential of the contralesional hemisphere and sought to inhibit its activity with neuromodulation. Using Transcranial Magnetic Stimulation I seek examples of beneficial plasticity in ipsilateral cortical motor representations of expert performers, who have accumulated vast amounts of deliberate practise training skilled bilateral activation of muscles habitually under ipsilateral control. I demonstrate that ipsilateral cortical motor representations reorganize in response to training to acquisition of skilled motor performance. Features of this reorganization are compatible with evidence suggesting ipsilateral importance in synergy representations, controlled through corticoreticulopropriospinal pathways. I demonstrate that ipsilateral plasticity can associate positively with motor recovery after stroke. Features of plastic change in ipsilateral cortical representations are shown in response to robotic training of chronic stroke patients. These findings have implications for the individualization of motor rehabilitation after stroke, and prompt reappraisal of the approach to therapeutic intervention in the chronic phase of stroke

Effect of abdominal binding on cardiorespiratory function in paralympic athletes with cervical spinal cord injury

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University on 4 July 2011.Spinal cord injury (SCI) causes a lesion-dependent impairment in cardiorespiratory function that may limit exercise capacity. The aims of this thesis were to describe cardiorespiratory function in highly-trained athletes with low-cervical SCI, and to investigate whether abdominal binding enhances cardiorespiratory function at rest and during exercise in this population. Using body plethysmography, bilateral phrenic nerve stimulation and transthoracic ultrasound, it was demonstrated that Paralympic athletes with cervical SCI exhibit a restrictive pulmonary defect, impaired diaphragm and expiratory muscle function, and low left ventricular mass and ejection fraction compared to able-bodied controls. Using the same methods, it was shown that abdominal binding improves resting cardiorespiratory function by reducing operating lung volumes, and increasing vital capacity, twitch transdiaphragmatic pressure, expiratory muscle strength and cardiac output. A further finding was a positive relationship between binder tightness and cardiorespiratory function. During a field-based assessment of fitness, abdominal binding reduced the time taken to complete an acceleration/deceleration test and increased the distance covered during a repeated maximal 4-min push test. During laboratory-based incremental wheelchair propulsion, abdominal binding altered breathing mechanics by reducing operating lung volumes and attenuating the rise in the pressure-time index of the diaphragm. Furthermore, abdominal binding increased peak oxygen uptake and reduced peak blood lactate concentration, despite no change in peak work rate. Peak oxygen uptake in the laboratory was related to the distance covered during the maximal 4-min push, suggesting that the improvement in field-based performance with binding was due to an improvement in aerobic capacity. In conclusion, this thesis demonstrates that abdominal binding significantly enhances cardiorespiratory function at rest, improves exercise performance in the field, and improves operating lung volumes, breathing mechanics and peak oxygen uptake during incremental treadmill exercise. Thus, abdominal binding provides a simple, easy-to-use tool that can be used to enhance cardiorespiratory function at rest and during exercise in highly-trained athletes with cervical SCI

Respiratory mechanics during upper body exercise in healthy humans

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonThe physiological responses to upper-body exercise (UBE) are well established. Few published studies, however, have attempted to elucidate the mechanical ventilatory responses to UBE. There is empirical evidence that respiratory function may be compromised by UBE during which the ventilatory and postural functions of the ‘respiratory’ muscles may be exacerbated. Therefore, the aims of this thesis were: 1) to characterise the mechanical-ventilatory responses to UBE in healthy subjects; 2) to explore the putative mechanisms that underpin the respiratory responses to UBE; and 3) to assess whether the mechanical-ventilatory stress imposed by UBE induces contractile fatigue of the respiratory muscles. Compared to lower-body exercise (LBE; leg cycling) at ventilation-matched work rates, UBE (arm-cranking) resulted in constraint of tidal volume, higher respiratory frequency, and greater neural drive to the respiratory muscles. Furthermore, end-expiratory lung volume was significantly elevated during peak UBE compared to LBE (39 ± 8 vs. 29 ± 8% vital capacity, p 0.05). In conclusion, mechanical-ventilatory function may be compromised during UBE due to complex interactions between thoracic muscle recruitment, central neural drive and thoracic volume displacement. This thesis presents novel findings which may have important functional implications for clinical populations who report breathlessness during activities of daily living that involve the upper-body, as well a

Inspiratory resistances facilitate the diaphragm response to transcranial stimulation in humans

BACKGROUND: Breathing in humans is dually controlled for metabolic (brainstem commands) and behavioral purposes (suprapontine commands) with reciprocal modulation through spinal integration. Whereas the ventilatory response to chemical stimuli arises from the brainstem, the compensation of mechanical loads in awake humans is thought to involve suprapontine mechanisms. The aim of this study was to test this hypothesis by examining the effects of inspiratory resistive loading on the response of the diaphragm to transcranial magnetic stimulation. RESULTS: Six healthy volunteers breathed room air without load (R0) and then against inspiratory resistances (5 and 20 cmH(2)O/L/s, R5 and R20). Ventilatory variables were recorded. Transcranial magnetic stimulation (TMS) was performed during early inspiration (I) or late expiration (E), giving rise to motor evoked potentials (MEPs) in the diaphragm (Di) and abductor pollicis brevis (APB). Breathing frequency significantly decreased during R20 without any other change. Resistive breathing had no effect on the amplitude of Di MEPs, but shortened their latency (R20: -0.903 ms, p = 0.03) when TMS was superimposed on inspiration. There was no change in APB MEPs. CONCLUSION: Inspiratory resistive breathing facilitates the diaphragm response to TMS while it does not increase the automatic drive to breathe. We interpret these findings as a neurophysiological substratum of the suprapontine nature of inspiratory load compensation in awake humans

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

<p>Abstract</p> <p>Background</p> <p>Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.</p> <p>Methods</p> <p>Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂= 80%) and hyperoxic (FiO₂= 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.</p> <p>Results</p> <p>Hypoxia enhanced hyperpnoea-induced P_di,twand P_ga,twreductions both immediately after hyperpnoea (P_di,tw: normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw: normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all <it>P </it>< 0.05) and after 30 min of recovery (P_di,tw: normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw: normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all <it>P </it>< 0.05). No significant difference in P_di,twor P_ga,twreductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.</p> <p>Conclusions</p> <p>These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂transport as during exercise in altitude or in hypoxemic patients.</p

Efficacy of Functional Magnetic Stimulation in Neurogenic Bowel Dysfunction after Spinal Cord Injury

[[abstract]]Objective: The aims of this study were to assess the usefulness of functional magnetic stimulation in controlling neurogenic bowel dysfunction in spinal cord injured patients with supraconal and conal/caudal lesions, and to investigate the efficacy of this regimen with a 3-month follow-up. Design: A longitudinal, prospective before-after trial. Subjects: A total of 22 patients with chronic spinal cord injured and intractable neurogenic bowel dysfunction. They were divided into group 1 (supraconal lesion) and group 2 (conal/caudal lesion). Methods: The colonic transit time assessment and Knowles-Eccersley-Scott Symptom Questionnaire were carried out for each patient before they received a 3-week functional magnetic stimulation protocol and on the day following the treatment. Results and conclusion: Following functional magnetic stimulation, the mean colonic transit time for all patients decreased from 62.6 to 50.4 h (p < 0.001). The patients’ Knowles-Eccersley-Scott Symptom scores decreased from 24.5 to 19.2 points (p < 0.001). The colonic transit time decrement in both group 1 (p = 0.003) and group 2 (p = 0.043) showed significant differences, as did the Knowles-Eccersley-Scott Symptom score in both groups following stimulation and in the 3-month follow-up results (p < 0.01). The improvements in bowel function indicate that functional magnetic stimulation, featuring broad-spectrum application, can be incorporated successfully into other therapies as an optimal adjuvant treatment for neurogenic bowel dysfunction resulting from spinal cord injury.[[journaltype]]國外[[incitationindex]]SCI[[booktype]]紙本[[countrycodes]]SW

Effect of abdominal binding on cardiorespiratory function in paralympic athletes with cervical spinal cord injury

Spinal cord injury (SCI) causes a lesion-dependent impairment in cardiorespiratory function that may limit exercise capacity. The aims of this thesis were to describe cardiorespiratory function in highly-trained athletes with low-cervical SCI, and to investigate whether abdominal binding enhances cardiorespiratory function at rest and during exercise in this population. Using body plethysmography, bilateral phrenic nerve stimulation and transthoracic ultrasound, it was demonstrated that Paralympic athletes with cervical SCI exhibit a restrictive pulmonary defect, impaired diaphragm and expiratory muscle function, and low left ventricular mass and ejection fraction compared to able-bodied controls. Using the same methods, it was shown that abdominal binding improves resting cardiorespiratory function by reducing operating lung volumes, and increasing vital capacity, twitch transdiaphragmatic pressure, expiratory muscle strength and cardiac output. A further finding was a positive relationship between binder tightness and cardiorespiratory function. During a field-based assessment of fitness, abdominal binding reduced the time taken to complete an acceleration/deceleration test and increased the distance covered during a repeated maximal 4-min push test. During laboratory-based incremental wheelchair propulsion, abdominal binding altered breathing mechanics by reducing operating lung volumes and attenuating the rise in the pressure-time index of the diaphragm. Furthermore, abdominal binding increased peak oxygen uptake and reduced peak blood lactate concentration, despite no change in peak work rate. Peak oxygen uptake in the laboratory was related to the distance covered during the maximal 4-min push, suggesting that the improvement in field-based performance with binding was due to an improvement in aerobic capacity. In conclusion, this thesis demonstrates that abdominal binding significantly enhances cardiorespiratory function at rest, improves exercise performance in the field, and improves operating lung volumes, breathing mechanics and peak oxygen uptake during incremental treadmill exercise. Thus, abdominal binding provides a simple, easy-to-use tool that can be used to enhance cardiorespiratory function at rest and during exercise in highly-trained athletes with cervical SCI.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Influence of inspiratory resistive loading on expiratory muscle fatigue in healthy humans

Expiratory resistive loading elicits inspiratory as well as expiratory muscle fatigue, suggesting parallel co-activation of the inspiratory muscles during expiration. It is unknown whether the expiratorymuscles are similarly co-activated to the point of fatigue during inspiratory resistive loading (IRL).The purpose of this study was to determine whether IRL elicits expiratory as well as inspiratory muscle fatigue. Healthy male subjects (n=9) underwent isocapnic IRL (60% maximal inspiratory pressure, 15 breaths∙min-1, 0.7 inspiratory duty cycle) to task failure. Abdominal and diaphragm contractile function was assessed at baseline and at 3, 15 and 30 min post-IRL by measuring gastric twitch pressure (Pga,tw) and transdiaphragmatic twitch pressure (Pdi,tw) in response to potentiated magnetic stimulation of the thoracic and phrenic nerves, respectively. Fatigue was defined as a significant reduction from baseline in Pga,tw or Pdi,tw. Throughout IRL, there was a time-dependent increase in cardiac frequency and mean arterial blood pressure, suggesting activation of the respiratory muscle metaboreflex. Pdi,tw was significantly lower than baseline (34.3 9.6 cmH2O) at 3min (23.2 5.7 cmH2O, P<0.001), 15 min (24.2 5.1 cmH2O, P<0.001) and 30 min post-IRL (26.3 6.0 cmH2O, P<0.001). Pga,tw was not significantly different from baseline (37.6 17.1 cmH2O) at 3min (36.5 14.6 cmH2O), 15 min (33.7 12.4 cmH2O) and 30 min post-IRL (32.9 11.3 cmH2O). IRL elicits objective evidence of diaphragm, but not abdominal, muscle fatigue. Agonist-antagonist interactions for the respiratory muscles appear to be more important during expiratory versus inspiratory loading.The Natural Sciences and Engineering Research Council (NSERC) of Canada supported this study. C.M. Peters, P.B. Dominelli, and Y. Molgat-Seon were supported by NSERC postgraduate scholarships. J.F Welch was supported by a University of British Columbia graduate fellowship

Functional Imaging of Autonomic Regulation: Methods and Key Findings.

Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI). The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: (1) describe the fMRI neuroimaging methodology for assessment of autonomic neural control, (2) outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, (3) illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and (4) highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure, and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory, and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with brain regions mediating postural and motoric actions, including respiration, and cardiac output. The study of pathological processes associated with autonomic disruption shows susceptibilities of different brain structures to altered timing of neural function, notably in sleep disordered breathing, such as obstructive sleep apnea and congenital central hypoventilation syndrome. The cerebellum, in particular, serves coordination roles for vestibular stimuli and blood pressure changes, and shows both injury and substantially altered timing of responses to pressor challenges in sleep-disordered breathing conditions. The insights into central autonomic processing provided by neuroimaging have assisted understanding of such regulation, and may lead to new treatment options for conditions with disrupted autonomic function