A consistent vigor network in Parkinson's disease: a potential target for brain stimulation effects

Abstract

In motor tasks with repetitive trials, motor vigor varies substantially from trial to trial in people with Parkinson's disease (PD). A key question is whether neural variability reflects behavioral variability or whether additional variability emerges as the neural signal is translated into movement. We aimed to identify a vigor-related neural network that could provide a candidate target for brain stimulation. We analyzed individual-trial fMRI data from 18 participants with PD who performed an overlearned ballistic hand-squeeze task in OFF- and ON-medication sessions while receiving subthreshold galvanic vestibular stimulation (GVS) with different stimulus waveforms. Single-trial fMRI responses were estimated using GLMsingle and entered into a constrained optimisation framework designed to identify a network that was task-active, encoded behavior, showed low trial-to-trial variability, and was spatially coherent. The analysis identified a distributed vigor network whose activity remained related to behavioral vigor while showing lower variability than behavior itself. The network included motor, striatal, cerebellar, thalamic, parietal, temporal-limbic, and orbitofrontal regions and showed limited overlap with the standard task-activation map. GVS waveforms associated with faster responses were accompanied by corresponding changes in vigor-network activity, but not in the broader task-activation network. Dopaminergic medication was also associated with stronger local functional connectivity within the vigor network. These findings suggest that movement variability in PD may arise partly when a relatively stable central vigor-related command is translated downstream into movement. The identified network may therefore provide a potential target for neuromodulation approaches aimed at increasing motor vigor in people with PD. Independent validation and future causal testing are needed.