Dopamine-Deficiency-Related Reorganization of the Somatomotor Network in Prodromal and Early Parkinson's Disease.

INTRODUCTION Network attack tolerance (NAT) measures the brain's ability to sustain information flow despite the loss of critical brain regions. In Parkinson's disease (PD), NAT has been linked to cognitive and motor function. However, it remains unclear how dopaminergic degeneration shapes NAT, and whether it relates to motor symptom progression.

Objective

To examine dopamine deficiency-related changes in NAT across the early PD disease continuum and its association with longitudinal motor outcomes.

Methods

We used cross-sectional resting-state functional magnetic resonance imaging of 28 healthy controls, 60 prodromal, and 94 clinical PD patients to create graph-theoretical networks. NAT was assessed at the global and subnetwork levels by calculating the global efficiency upon iterative node removal at different network densities. Using linear mixed-effects models, we assessed how putaminal dopamine transporter (DaT) binding or disease status affected NAT, controlling for network density, age, sex, and education. Baseline somatomotor (SMN) NAT was examined as a predictor of motor symptom progression in 145 patients.

Results

Lower putaminal DaT signal was associated with higher SMN NAT across groups. PD patients exhibited elevated SMN NAT relative to controls. Neither global nor other subnetworks showed effects. While the effect of baseline SMN NAT on motor progression was not significant, an exploratory analysis (Johnson-Neyman) suggested that higher SMN NAT may associate with slower motor decline across most of the observed NAT range.

Conclusions

Dopaminergic depletion is associated with a targeted SMN reorganization, potentially maintaining network information flow despite progressive hub loss. Whether this reorganization represents compensation or a consequence of progressive pathology requires further longitudinal assessment. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.