Alterations in functional brain connection may be apparent even before the onset of brain atrophy, indicating their potential as early indicators of disease processes. Researchers used resting-state functional magnetic resonance imaging to establish the whole-brain network topology architecture of the functional connectome in a large cohort of drug-free patients and wanted to see if baseline connectivity alterations predicted clinical progression. At the start of the trial, 147 drug-free, cognitively unimpaired patients with PD were compared to 38 age- and gender-matched controls. A non-hierarchical cluster analysis of motor and non-motor data was used to divide patients with PD patients into two subtypes: 77 early/mild and 70 early/severe. At the outset, graph theory analysis and connectomics were employed to analyze global and local topological network features, as well as regional functional connections. A stepwise multivariate regression analysis was used to determine if baseline functional imaging data were predictive of clinical development over a 2 year period.

When PD patients were compared to controls, broad functional connectivity impairments were found in the basal ganglia, sensorimotor, frontal, and occipital networks. Reduced regional functional connectivity, primarily involving striate-frontal, temporal, occipital, and limbic connections, distinguished early/mild from early/severe patients with PD. At a 2-year follow-up, connectivity alterations were shown to be independent predictors of cognitive advancement.

Findings show that functional remodeling of the brain connectome starts early in PD and is responsible for the critical involvement of striatal projections. Connectomic measurements may be useful in identifying a distinct PD patient subtype, which is characterized by severe motor and non-motor clinical load as well as broad functional connectivity impairments.