Functional Reorganization of the Somatomotor Network in Prodromal and Early Parkinson's Disease

Abstract

In Parkinsons disease (PD), higher network attack tolerance (NAT) may contribute to compensation of motor deficits. However, it is unclear whether NAT is lost due to disease progression or actively increased as a compensatory response. We used cross-sectional resting state functional MRI data of 28 healthy controls (HC), 60 prodromal PD patients, 94 clinical PD patients to create graph theoretical networks. NAT was assessed at global and subnetwork level by calculating global efficiency upon iterative node removal. Using linear mixed-effects models we assessed how putaminal dopamine terminal (DaT) binding, or disease status affected NAT, controlling for density, age, sex and education. Finally, we compared the node degree distribution specifically for the somatomotor network (SMN) across groups. Lower putaminal DaT predicted higher SMN NAT. Patients with PD showed elevated SMN NAT versus controls. Neither global nor other networks showed an effect. Compared to HCs subcortical/cerebellar SMN nodes appeared more connected in PD and prodromal patients. Dopaminergic depletion appears to drive targeted reorganization of the SMN. This reorganization may involve additional recruitment of subcortical and cerebellar regions to sustain the information flow inside the SMN. Concomitantly, this active adaptation motivates further investigations regarding SMN NAT as potential compensation mechanism in early PD.