A common symptom of Idiopathic Parkinson’s disease (IPD) is decreased trunk and balance control. These deficits in patients with IPD are not treatable, and their underlying mechanisms are not well understood. Additionally, it is not known to what extent decreased trunk control contributes to postural instability in patients with IPD. Previous work by Martin (1965) observed that patients with post-encephalitatic Parkinson’s disease would fall in the direction of the tilt when perturbed while seated. In order to better understand the underlying causes of these observed trunk deficits and attempt to replicate Martins findings, this study investigated postural corrective movement of the trunk while seated in patients with IPD and age-matched healthy controls. Participants’ range of motion (ROM) was tested actively and passively while lying supine, following which, bilateral electromyography (EMG) (rectus abdominis (RA), external oblique (EO), and erector spinae (EST9, L3)) and 3-D kinematic measures were recorded while participants were seated on a modified chair and received unexpected perturbations, 7° at 40°/sec, in four different directions (forward, backward, left, and right). EMG responses were normalized to participant’s maximum voluntary contractions. We observed patients with IPD to have decreased active and passive ROM only in the frontal plane relative to controls. Patterning of muscle responses to rotational perturbations did not vary between groups in any direction, except backward, and trends toward significantly greater EST9 activity were observed during backward and left tilts in patients with IPD. Despite this both patients with IPD and controls were able to make appropriate trunk corrective movements opposite the direction of the tilt. However, two patients, who were most severely affected, did make incorrect trunk movements in the direction of the tilt during left and right tilting perturbations which, upon visual inspection, appear to be due to improperly modulated and timed muscle responses. Thus, our data counters the findings of Martin, and suggests the trunk is posturally stable in IPD. Therefore, balance instabilities during stance are likely due to improper responses of the lower limbs. However, as disease severity increases, the contributing influence of an improperly responding trunk may add to their postural deficits.

This thesis provides new insight into how learned skilled movements are affected in a disease with basal ganglia damage, within what task demands these deficits can be detected, and how this detection can occur within the constraints of primary motor symptoms. Hence the purpose of this thesis was threefold. Firstly, the aim was to take a model-based approach to apraxia in PD, in order to determine the nature of the errors in reference to other populations that experience apraxia. Apraxia by definition cannot be the product of primary motor deficits, weakness, sensory loss, or lack of comprehension, therefore the second objective of the study was to detect apraxia while remaining true to these prerequisites. The third objective was to extend the examination of apraxia beyond the upper limbs, and investigate the relationship between upper limb and lower limb apraxia, as well as the relationship between freezing (which shares similarities with gait apraxia) and upper limb and lower apraxia. Overall, the most common pattern of apraxia identified in this PD group was impairment at both pantomime and imitation, suggesting issues with executive function. However, there are other results that suggest an issue with visuomotor transformation may be superimposed on this executive function deficit, including a higher frequency of participants impaired at imitation and a very pronounced impairment at meaningless gestures. To ensure that these deficits are not the product of primary motor symptoms, correlation analyses were conducted between gestural impairment and total motor impairment, cardinal symptom impairment, and degree of asymmetry of these symptoms. While there was a significant correlation of total motor severity and gestural impairment, there were no significant correlations between cardinal motor symptoms and total gestural impairment, or limb specific gestural impairment and the degree of motor asymmetry. These results indicate that the outward manifestation of primary motor symptoms does not necessarily correspond with gestural impairment, however the overall relationship (total UPDRS) hints to an indirect influence of the basal ganglia on healthy praxis. With regards to the third objective, the lower limb assessment turned out to be very consistent with the results yielded in the upper limb assessment. While there were similar frequencies of impairment in both pantomime and imitation, the upper limb and lower limbs assessments were found to correlate very strongly. This is a promising result, because the lower limb battery is easy to administer, there are typically less motor symptoms to deal with, and preliminary analyses show a high inter-rater reliability established. Furthermore, there was a higher proportion of freezers with apraxia compared to non-freezers, and this is the first study to reveal this. All these results taken together are evidence of similar underlying mechanisms for these impairments (upper limb apraxia, lower limb apraxia, and freezing). The model-based approach to studying apraxia in both the upper and lower limbs of PD, enables us to determine the frequencies, patterns and severities of apraxia, and better equips us to predict which systems are more susceptible to deterioration. This thesis project has hopefully created a framework for determining coping strategies and future interventions for apraxia, specifically in basal ganglia disordered populations.

When bi-lateral movements of differing difficulty are performed as rapidly as possible the "easier" of the two limbs slows down and is attracted to the temporal structure of the more difficult movement. Simultaneous movements are expected to be severely compromised in Parkinson's Disease (PD). The purpose of this study was to investigate whether Parkinsonians elicit temporal assimilations in the belief that an assimilatory response may facilitate simultaneous bi-lateral control in PD. / Temporal attractions were elicited by the non-impaired subjects during the bi-lateral task. The increased movement duration of the "easy" limb was the consequence of a contralateral motor command interference. The Parkinsonians failed to generate sufficient contralateral shoulder torque to interfere with the metrical structure of the "easier" task comprising the bi-lateral movements. These observations suggest that temporal assimilations elicited by this class of movements are the result of a motor command interference and not the effect of a restructuring of the movements metrics.

No description available.

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1.8% of the population over 65 years of age. It is characterized by three cardinal symptoms: bradykinesia, muscle rigidity and resting tremor. Symptoms are presented following 50% loss of dopaminergic neurons within the substantia nigra pars compacta (SNc). Neurodegeneration is associated with reactive oxygen species (ROS) production, protein aggregation, mitochondrial dysfunction, ubiquitin-proteasome system (UPS) inhibition and lysosomal malfunction; however it is unclear if a single mechanism or multiple mechanisms lead to disease onset. The primary aim of the studies described in this thesis was to elucidate the interactions between various pathological mechanisms underlying PD pathology. An examination of organelle function during exposure of SH-SY5Y neuroblastoma to a variety of toxins which mimic purported pathological processes in PD reveal mitochondrial membrane potential becomes depolarized, not only following mitochondrial impairment, but also after the UPS and lysosome are inhibited. Given that mitochondrial dysfunction appeared to be central to PD pathology, mitochondrial dysfunction was studied in more detail. Mitochondrial fission and fusion maintains mitochondrial integrity, which is critical to neuronal health. Thus, we examined mitochondrial dynamics in a common genetic variant linked with familial PD, known as leucine-rich repeat kinase 2 (LRRK2). Upon the expression of wild-type and mutant LRRK2, mitochondrial fusion was inhibited causing fragmentation of mitochondria. This inhibition of fusion may be the initial step leading to mitochondrial dysfunction, since inhibition of fusion occurs prior to the induction of cell stress. The findings that mitochondrial dysfunction appears to be central to PD pathology, suggest that mitochondria may be an excellent therapeutic target for PD. Thus, the potential neuroprotective function of a regulator of mitochondrial function, known as SIRT3 was examined. In SH-SY5Y cells, over-expression of SIRT3 protected neurons from degeneration associated with LRRK2 over-expression. The studies described in this thesis provide evidence that multiple sub-cellular mechanisms converge to inhibit mitochondrial function. Furthermore, mitochondrial dynamics which regulate mitochondrial function could be a key mediator in the pathology associated with PD. The work herein suggests therapies which target the mitochondria are likely to be successful in the treatment of PD.

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1.8% of the population over 65 years of age. It is characterized by three cardinal symptoms: bradykinesia, muscle rigidity and resting tremor. Symptoms are presented following 50% loss of dopaminergic neurons within the substantia nigra pars compacta (SNc). Neurodegeneration is associated with reactive oxygen species (ROS) production, protein aggregation, mitochondrial dysfunction, ubiquitin-proteasome system (UPS) inhibition and lysosomal malfunction; however it is unclear if a single mechanism or multiple mechanisms lead to disease onset. The primary aim of the studies described in this thesis was to elucidate the interactions between various pathological mechanisms underlying PD pathology. An examination of organelle function during exposure of SH-SY5Y neuroblastoma to a variety of toxins which mimic purported pathological processes in PD reveal mitochondrial membrane potential becomes depolarized, not only following mitochondrial impairment, but also after the UPS and lysosome are inhibited. Given that mitochondrial dysfunction appeared to be central to PD pathology, mitochondrial dysfunction was studied in more detail. Mitochondrial fission and fusion maintains mitochondrial integrity, which is critical to neuronal health. Thus, we examined mitochondrial dynamics in a common genetic variant linked with familial PD, known as leucine-rich repeat kinase 2 (LRRK2). Upon the expression of wild-type and mutant LRRK2, mitochondrial fusion was inhibited causing fragmentation of mitochondria. This inhibition of fusion may be the initial step leading to mitochondrial dysfunction, since inhibition of fusion occurs prior to the induction of cell stress. The findings that mitochondrial dysfunction appears to be central to PD pathology, suggest that mitochondria may be an excellent therapeutic target for PD. Thus, the potential neuroprotective function of a regulator of mitochondrial function, known as SIRT3 was examined. In SH-SY5Y cells, over-expression of SIRT3 protected neurons from degeneration associated with LRRK2 over-expression. The studies described in this thesis provide evidence that multiple sub-cellular mechanisms converge to inhibit mitochondrial function. Furthermore, mitochondrial dynamics which regulate mitochondrial function could be a key mediator in the pathology associated with PD. The work herein suggests therapies which target the mitochondria are likely to be successful in the treatment of PD.

Thesis (Ph. D.)--University of Hawaii at Manoa, 1994. / Includes bibliographical references (leaves 89-106). / Microfiche. / xi, 106 leaves, bound ill. 29 cm

A common symptom of Idiopathic Parkinson’s disease (IPD) is decreased trunk and balance control. These deficits in patients with IPD are not treatable, and their underlying mechanisms are not well understood. Additionally, it is not known to what extent decreased trunk control contributes to postural instability in patients with IPD. Previous work by Martin (1965) observed that patients with post-encephalitatic Parkinson’s disease would fall in the direction of the tilt when perturbed while seated. In order to better understand the underlying causes of these observed trunk deficits and attempt to replicate Martins findings, this study investigated postural corrective movement of the trunk while seated in patients with IPD and age-matched healthy controls. Participants’ range of motion (ROM) was tested actively and passively while lying supine, following which, bilateral electromyography (EMG) (rectus abdominis (RA), external oblique (EO), and erector spinae (EST9, L3)) and 3-D kinematic measures were recorded while participants were seated on a modified chair and received unexpected perturbations, 7° at 40°/sec, in four different directions (forward, backward, left, and right). EMG responses were normalized to participant’s maximum voluntary contractions. We observed patients with IPD to have decreased active and passive ROM only in the frontal plane relative to controls. Patterning of muscle responses to rotational perturbations did not vary between groups in any direction, except backward, and trends toward significantly greater EST9 activity were observed during backward and left tilts in patients with IPD. Despite this both patients with IPD and controls were able to make appropriate trunk corrective movements opposite the direction of the tilt. However, two patients, who were most severely affected, did make incorrect trunk movements in the direction of the tilt during left and right tilting perturbations which, upon visual inspection, appear to be due to improperly modulated and timed muscle responses. Thus, our data counters the findings of Martin, and suggests the trunk is posturally stable in IPD. Therefore, balance instabilities during stance are likely due to improper responses of the lower limbs. However, as disease severity increases, the contributing influence of an improperly responding trunk may add to their postural deficits.

Thesis (Ph.D.)--Texas Christian University, 2007. / Title from dissertation title page (viewed Apr. 29, 2008). Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.