Recent research has found that perceptual deficits exist in Parkinson???s disease (PD), yet the link between perception and movement impairments is not well understood. Inaccurate estimation of distance has the potential to be an underlying cause of movement impairments. Alternatively, those with PD may not be able to perceive their own movements accurately. The main objective of this thesis was to evaluate (1) whether distance estimation is influenced by static perception compared to perception during movement in PD, (2) how visual motion processing contributes to distance estimation during movement, and (3) how dopaminergic medication contributes to these distance estimation deficits. Thirty-seven participants (19 individuals with PD, 18 age-matched healthy control participants (HC) estimated distance to a remembered target in a total of 48 trials, in 4 randomized blocks. Estimation conditions included: (i) no motion: participants pointed with a laser, (ii) motion: participants walked to the estimated position, (iii) visual motion (wheelchair): participants were pushed in a wheelchair while they gave their estimate, (iv) visual motion (VR): participants completed their distance estimate while seated and viewed themselves (as if they were walking) in VR. PD patients completed this protocol twice; once OFF and once ON dopaminergic medication. Participants were matched for age, distance acuity, Modified Mini Mental State Exam (3MS), spatial working memory and motor planning ability. In Study 1 (no motion vs. motion), individuals with PD and healthy control participants did not differ in judgment accuracy during the no motion condition. However, those with PD did have greater amounts of error compared to healthy control participants while estimating distance during the motion condition. Similarly, those with PD significantly underestimated the target position compared to healthy control participants during the motion condition only. Individuals with PD demonstrated greater variability overall. In Study 2, error did not differ between PD and HC groups during visual motion perception (wheelchair). Interestingly, the HC group tended to perform significantly worse than those with PD in the VR condition. Overall, across both studies there was no significant influence of dopaminergic medication in any of the conditions. Individuals with PD demonstrated distance estimation deficits only when required to move through their environment. In contrast to estimations made with movement, neither static estimation nor estimations made with visual motion revealed significant differences between the two groups. Thus perceptual estimation deficits appear to occur only during movement, which may be suggestive of an underlying sensory processing deficit which leads to a problem integrating vision and self-motion information.

Thesis (Ph. D.)--Northeastern University, 2008. / Title from title page (viewed March 3, 2009). Graduate School of Arts and Sciences, Dept. of Psychology. Includes bibliographical references (p. 148-156).

Thesis (Ph.D.) - University of St Andrews, April 2008.

Thesis (Ph. D.)--Auburn University. / Abstract. Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Chicago, Committee on Neurobiology, August 1999. / Includes bibliographical references. Also available on the Internet.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Restricted until October 2005. Bibliography: leaves 71-94.

Thesis (Ph. D. in Molecular Physiology and Biophysics)--Vanderbilt University, Aug. 2007. / Title from title screen. Includes bibliographical references.

No description available.

Parkinson's disease (PD) is characterised by the loss of dopaminergic neurons in the Substantia Nigra pars compacta in the midbrain and the presence of intracellular aggregates, known as Lewy bodies (LBs), in the surviving neurons. The aetiology of PD is unknown but a causative role for α-Synuclein (SNCA) has been proposed. Although the function of αSyn is not well understood, a number of pathological mechanisms associated with αSyn toxicity have been proposed. In this study, nine induced pluripotent stem cells (iPSCs) lines from healthy individuals and PD patients carrying the A53T SNCA mutation or a triplication of SNCA were differentiated to dopaminergic neurons (iDAn). All iPSC lines differentiated with similar efficiency to iDAn, indicating that they could be used for phenotypic analysis. Quantification of αSyn expression showed increased αSyn intracellular staining and the novel detection of increased αSyn oligomerization in PD iDAn. Analysis of mitochondrial respiration found a decrease in basal respiration, maximal respiration, ATP production and spare capacity in PD iDAn, but not in undifferentiated iPSCs, indicating the cell-type specificity of these defects. Decreased phosphorylation of dynamin-1-like protein at Ser616 (DRP1^Ser616) and increased levels of Peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) in A53T SNCA iDAn suggest a new pathological mechanism linking αSyn to the imbalance in mitochondria homeostasis. Markers of endoplasmic reticulum (ER) stress were found to be up-regulated, along with increased β- Glucocerebrosidase (GBA) activity, perturbation of autophagy and decreased expression of fatty acids binding protein 7 (FAPB7) in PD iDAn. Lastly, lentiviral vectors for RNAi-mediated knockdown of αSyn were developed and these reduced αSyn protein levels in iDAn, resulting in increased expression of FABP7. These results describe a novel functional link between αSyn and FABP7. This work demonstrates that iDAn are a promising and relevant in vitro cell model for studying cellular dysfunctions in PD pathology, and the phenotypic analysis of A53T SNCA and SNCA triplication iDAn enabled the detection of novel pathological mechanisms associated with PD.

No description available.