Redefining the hypotheses driving Parkinson’s diseases research

Journal article

Parkinson's disease (PD) is a progressive multi-system neurodegenerative disease that affects approximately 2% of the population over the age of 80. The accelerated increase in prevalence with age, combined with the rapid aging population in Europe and other Western regions, is leading to a dramatic increase in the (social, economic and personal) burden of PD. Accordingly, there is an urgent need for a better understanding of the disease. So far, almost 200 years of research have yielded significant insights into the pathophysiology of PD. While the precise mechanisms between pathology and clinical presentation are incompletely understood, recent evidence points to a motivational influence on PD motor symptoms. This cumulative thesis aims to investigate the importance of the motivational brain in PD and its associations with PD motor symptoms. To address this aim, this thesis is comprised of three individual research projects, each guided by a different perspective, ultimately addressing the overall research question. The objective of the first project is to provide an overview of the current literature on neuropathological changes in motivational brain regions and their associated clinical manifestations in PD. The study showed that pathological changes can be observed early on, with some alterations being related to PD motor symptoms. The second project aims to further elucidate the underlying mechanism of motivational contributions to PD motor symptoms. Interestingly, this project showed that the loss of effortful movements may be based on a reduced implicit motivation to move, suggesting that PD motor symptoms may not be a purely motoric issue. Finally, in the third project, it is investigated whether patients can be divided into subtypes based on their observed neurodegeneration in the motivational brain, more specifically the amygdala. However, although the motivational brain seems to play a role in PD motor symptoms, the results of this project suggest that it does not seem to aid classification. Taken together, the research projects included in this thesis provide an in-depth understanding of the role of motivational brain regions in PD. Collectively, they highlight the far-reaching consequences of neurodegenerative changes that go beyond non-motor symptoms and also contribute to the cardinal motor impairments. In doing so, this work highlights the importance of including motivational brain regions in the scientific discourse and encourages further investigation to promote a better understanding of the disease. Finally, the knowledge gained may contribute to the development of novel therapeutic strategies with the ultimate goal of alleviating the burden of PD

Authors: Farrow, SL; Cooper, AA; O'Sullivan, JM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: npj Parkinson's Disease
• Volume: 8
• Issue: 1
• Pages: 45-45
• Publication date: 2022-04-19
• DOI: 10.1038/s41531-022-00307-w
• EISSN: 2373-8057
• ISSN: 2373-8057
• Language: English
• Keywords: Disease; Biomarker discovery; Pathology; Neuroscience; Biomarker; Precision medicine; Identification (biology); Genetics; Biology; Medicine; Bioinformatics; Gene; Clinical phenotype; Phenotype; Parkinson's disease