Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder that primarily affects the motor system. Prominent motor symptoms in the disease include unilateral tremor, rigidity, and bradykinesia. For the clinical standardization of disease severity, the motor scores from the Unified Parkinson’s Disease Rating Scale (UPDRS-III) have long been used but recent evidence suggests there can be significant inter-rater variability in these scores that can be influenced by experience level. Our project therefore aims to identify a resting state functional magnetic resonance imaging (rsfMRI) biomarker that provides a more objective determination of disease severity.

Methods: Seven patients (3 female) with advanced PD underwent a preoperative MRI under anesthesia in preparation for DBS surgery. Motor scores (UPDRS-III) were collected before and after DBS (mean follow-up of 5.9 months). Scans were performed in a 3T Achieva Philips MR scanner, including rsfMRI (TR=2000ms, TE=25ms, FOV=68×68mm, flip angle=90o, spatial resolution=1.87×1.87×3.5mm, matrix size=128×128). Images were preprocessed to correct for spatial and temporal artifacts. Regions of interest (ROIs) were defined using the Harvard-Oxford atlas and the ATAG-MNI04 basal ganglia atlas. Functional connectivity was calculated using the MatLab-based CONN toolbox via two-tailed bivariate correlations. Significant connectivity differences were evaluated in a linear fashion based on UPDRS-III scores with both a ROI-to-voxel and ROI-to-ROI analysis (FDR-corrected p<0.05).

Results: Patients were 66.1±8.9 years old with disease duration of 7.2±1.8 years. Preoperative UPDRS-III was 26.6±8.5 and postoperative UPDRS-III was 22.3±9.5. Individuals with higher UPDRS-III scores demonstrated increased resting state connectivity within the basal ganglia (STN, pallidum, thalamus, striatum) (p=0.006).

Conclusions: Our findings demonstrate that Parkinson’s disease severity is associated with increased resting state connectivity between the various nuclei of the basal ganglia, which have long been hypothesized to be key players in disease progression. In the future, rsfMRI may be beneficial in offering a more objective measurement of disease severity in PD.

Patient Care: Our research shows promise in the ability for rsfMRI to offer a more objective measurement of disease severity in PD.

Learning Objectives: By the conclusion of this session, participants should be able to: 1. Describe the use of UPDRS-III scores in Parkinson’s disease to clinically standardize disease severity 2. Understand the limitations of UPDRS-III scores 3. Identify the role for resting state functional magnetic resonance imaging as a method to objectively quantify disease severity

References: Post B, Merkus MP, De bie RM, De haan RJ, Speelman JD. Unified Parkinson's disease rating scale motor examination: are ratings of nurses, residents in neurology, and movement disorders specialists interchangeable?. Mov Disord. 2005;20(12):1577-84.