Theta frequency deep brain stimulation in the subthalamic nucleus improves working memory in Parkinson's disease

Most research in Parkinson's disease focuses on improving motor symptoms. Yet, up to 80% of patients present with non-motor symptoms that often have a large impact on patients' quality of life. Impairment in working memory, a fundamental cognitive process, is common in Parkinson's disease. While deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in Parkinson's disease, its impact on cognitive functions is less well studied. Here, we examine the effect of DBS in the theta, beta, low and high gamma frequency on working memory in 20 Parkinson's disease patients with bilateral STN-DBS. A linear mixed effects model demonstrates that STN-DBS in the theta frequency improves working memory performance. This effect is frequency-specific and was absent for beta and gamma frequency stimulation. Further, this effect is specific to cognitive performance, as theta frequency DBS did not affect motor function. A non-parametric cluster-based permutation analysis of whole-brain normative structural connectivity shows that working memory enhancement by theta frequency stimulation is associated with higher connectivity between the stimulated subthalamic area and the right middle frontal gyrus. Again, this association is frequency- and task-specific. These findings highlight the potential of theta frequency STN-DBS as a targeted intervention to improve working memory in patients with Parkinson's disease. Up to 80% of patients with Parkinson's disease present with non-motor symptoms that often have a large impact on quality of life. Salehi et al. show that deep brain stimulation at specific frequencies can improve working memory in patients. The effect is independent of motor performance, and is mediated by subthalamic nucleus-prefrontal pathways.