Subthalamic deep brain stimulation identifies frontal networks supporting initiation, inhibition and strategy use in Parkinson's disease

Abstract

Initiation and inhibition are executive functions whose disruption in Parkinson's disease impacts substantially on everyday activities. Management of Parkinson's disease with subthalamic deep brain stimulation (DBS) modifies initiation and inhibition, with prior work suggesting that these effects may be mediated via the connectivity of the subthalamic nucleus (STN) with the frontal cortex. Here, we employed high-resolution structural neuroimaging to investigate the variability in initiation, inhibition and strategy use in a cohort of twenty-five (ten females, mean age 62.5, mean Hoehn and Yahr stage 2.5) participants undertaking subthalamic DBS for Parkinson's disease. Neuropsychological assessment of initiation and inhibition was performed preoperatively and at six months postoperatively. We first reconstructed the preoperative connectivity of the STN with a frontal network of anterior and superior medial cortical regions. We then modelled the postoperative site of subthalamic stimulation and reconstructed the connectivity of the stimulation field within this same network. We found that, at both pre- and postoperative intervals, inter-individual variability in inhibition and initiation were strongly associated with structural network connectivity. Measures of subcortical atrophy and local stimulation effects did not play a significant role. Preoperatively, we replicated prior work, including a role for the right inferior frontal gyrus in inhibition and strategy use, as well as the left inferior frontal gyrus in tasks requiring selection under conditions of maintained inhibition. Postoperatively, greater connectivity of the stimulation field with right anterior cortical regions was associated with greater rule violations and suppression errors, supporting prior work implicating right-hemispheric STN stimulation in disinhibition. Our findings suggest that, in Parkinson's disease, connectivity of the frontal cortex with the STN is an important mediator of individual variability in initiation and inhibition,. Personalised information on brain network architecture could guide individualised brain circuit manipulation to minimise neuropsychological disruption after STN-DBS.