Structural connectivity and brain network analyses in Parkinson's disease: A cross-sectional and longitudinal study

Maurizio Bergamino; Elizabeth G Keeling; Nicola J Ray; Antonella Macerollo; Monty Silverdale; Ashley M Stokes

doi:10.3389/fneur.2023.1137780

Structural connectivity and brain network analyses in Parkinson's disease: A cross-sectional and longitudinal study

Front Neurol. 2023 Mar 23:14:1137780. doi: 10.3389/fneur.2023.1137780. eCollection 2023.

Authors

Maurizio Bergamino¹, Elizabeth G Keeling^{1

2}, Nicola J Ray³, Antonella Macerollo^{4

5}, Monty Silverdale⁶, Ashley M Stokes¹

Affiliations

¹ Barrow Neuroimaging Innovation Center, Barrow Neurological Institute, Phoenix, AZ, United States.
² School of Life Sciences, Arizona State University, Tempe, AZ, United States.
³ Health, Psychology and Communities Research Centre, Department of Psychology, Manchester Metropolitan University, Manchester, United Kingdom.
⁴ Neurology Department, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.
⁵ Institute of Systems, Molecular and Integrative Biology, School of Life Sciences, University of Liverpool, Liverpool, United Kingdom.
⁶ Manchester Centre for Clinical Neurosciences, University of Manchester, Manchester, United Kingdom.

Abstract

Introduction: Parkinson's disease (PD) is an idiopathic disease of the central nervous system characterized by both motor and non-motor symptoms. It is the second most common neurodegenerative disease. Magnetic resonance imaging (MRI) can reveal underlying brain changes associated with PD.

Objective: In this study, structural connectivity and white matter networks were analyzed by diffusion MRI and graph theory in a cohort of patients with PD and a cohort of healthy controls (HC) obtained from the Parkinson's Progression Markers Initiative (PPMI) database in a cross-sectional analysis. Furthermore, we investigated longitudinal changes in the PD cohort over 36 months.

Result: Compared with the control group, participants with PD showed lower structural connectivity in several brain areas, including the corpus callosum, fornix, and uncinate fasciculus, which were also confirmed by a large effect-size. Additionally, altered connectivity between baseline and after 36 months was found in different network paths inside the white matter with a medium effect-size. Network analysis showed trends toward lower network density in PD compared with HC at baseline and after 36 months, though not significant after correction. Significant differences were observed in nodal degree and strength in several nodes.

Conclusion: In conclusion, altered structural and network metrics in several brain regions, such as corpus callosum, fornix, and cingulum were found in PD, compared to HC. We also report altered connectivity in the PD group after 36 months, reflecting the impact of both PD pathology and aging processes. These results indicate that structural and network metrics might yield insight into network reorganization that occurs in PD.

Keywords: Parkinson's Progression Markers Initiative; Parkinson's disease; diffusion magnetic resonance imaging; network analysis; structural connectivity.

Grants and funding

Data used in the preparation of this article were obtained from the Parkinson's Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). PPMI—a public-private partnership—is funded by the Michael J. Fox Foundation for Parkinson's Research funding partners 4D Pharma, Abbvie, Acurex Therapeutics, Allergan, Amathus Therapeutics, ASAP, Avid Radiopharmaceuticals, BlueRock Therapeutics, Bial Biotech, Biogen, BioLegend, Bristol-Myers Squibb, Calico, Celgene, Dacapo Brain Science, Denali, The Edmond J. Safra Foundaiton, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Pfizer, Piramal, Prevail, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics. This work was supported by the Barrow Neurological Foundation, Sam and Peggy Grossman Family Foundation, and Samuel P. Mandell Foundation.