Subthalamic stimulation modulates working memory-related cortical dynamics in Parkinson's disease

The dynamic modulation of large-scale network activity, which is inherent to cognitive processes, is disrupted in Parkinson's disease. Subthalamic deep brain stimulation can either improve or deteriorate cognition, particularly executive function, with these effects often going unnoticed during acute parameter optimization. This highlights the need for longer stimulation periods and more focused research on the underlying cortical mechanisms, which remain underexplored. This study was a prospective clinical trial involving nineteen people with Parkinson's disease, who were evaluated off their medication at preoperative baseline and 6 months after deep brain stimulation implantation. Brain activity related to verbal and visuospatial working memory tasks was recorded using electroencephalography at both baseline and during follow-up evaluations conducted under stimulation. The follow-up assessments were carried out following 3-week periods of either omnidirectional or directional stimulation, applied in a randomized, double-blind, crossover design. Average postoperative working memory performance remained stable at the group level regardless of the stimulation condition for both verbal and visuospatial working memory tasks. However, at the individual level, higher alpha and beta power at baseline was associated with slower visuospatial working memory reaction time at follow-up. Additionally, reductions in theta and beta power during stimulation at follow-up correlated with better verbal working memory accuracy during the task and compared with baseline, respectively. These findings suggest that task-related electroencephalography may provide candidate physiological markers of individual working memory trajectories after subthalamic deep brain stimulation. Oscillatory brain activity may help to characterize stimulation-related cognitive variability beyond motor outcomes, but these exploratory findings require validation in larger cohorts before they can inform stimulation programming or closed-loop treatment strategies. Registration: ClinicalTrials.gov: NCT03548506.