2.1. Participants

We recruited 57 Parkinson's disease and 20 HC participants from the Stanford Movement Disorders Clinic and from the surrounding community for our classification cohort. All patients were diagnosed with Parkinson's disease by a board-certified neurologist with specialty training in movement disorders (KLP) based on UK Parkinson's Disease Society Brain Bank criteria (Litvan et al., 2003) and meet the more recent criteria for ‘Clinically Probable Parkinson's disease’ (Postuma et al., 2015). Parkinson's disease participants underwent a comprehensive neurological screening exam and the Movement Disorders Society-Unified Parkinson's disease Rating Scale motor assessment (MDS-UPDRS part III) (Goetz et al., 2008) both OFF and ON dopaminergic medications. The MDS-UPDRS part III was performed just prior to the MRI scan. According to published protocols (Poston et al., 2016), the ‘practical’ off medication state (Parkinson's disease OFF) for both clinical and imaging assessments was defined as ≥ 72 h off extended release dopamine agonists, selective MAO-inhibitors, and long-acting levodopa, and ≥ 12 h off short acting dopamine agonists and levodopa. The on medication state (Parkinson's disease ON) for both clinical and imaging assessments was defined as the patients taking their normal daily medications in the optimally medicated state, as determined by both the patient and the movement disorders neurologist. To maximize diagnostic specificity, we only included subjects with at least two years of a Parkinson's disease diagnosis and at least 20% improvement in the MDS-UPDRS part III score when ON medications. Further inclusion criteria for all Parkinson's disease and HC participants were as follows: 1) age between 45 and 90 years, 2) no contraindications to MRI, 3) no history of significant neurological disease (other than Parkinson's disease), hospitalization for psychiatric illness, or current substance abuse, and 4) no history of severe cognitive impairment during phone screening. In addition, all HC were evaluated as healthy in a neurological screening exam, and obtained a score on the Mini Mental State Exam (MMSE) ≥ 27 (Folstein et al., 1975). We further subdivided the MDS-UPDRS part III into a Tremor Subscore (items 3.15–3.18) and a Bradykinesia/Rigidity Subscore (items 3.3–3.8).

We recruited a second, independent cohort of 14 Parkinson's disease for the motor severity analysis and 14 HC for base correlation matrix estimation (see Methods: connectivity-based classification). Inclusion criteria, exclusion criteria, and all analysis were identical to the original classification cohort.

The Stanford University Institutional Review Board approved all study protocols. All study participants provided written consent according to the Declaration of Helsinki.