Subthalamic modulation of sequential working memory in Parkinson’s disease

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Maintaining the ability to arrange working memory representations in an appropriate serial order is crucial for complex behavior. Serial ordering within working memory constitutes one core aspect of mental manipulation, yet this aspect has been largely neglected in previous research. In previous studies, we have defined a neural network that underlies serial ordering including the dorsolateral and ventrolateral prefrontal cortex, posterior parietal cortex, globus pallidus, thalamus, substantia nigra, cerebellum and importantly, the subthalamic nucleus (STN). Moreover, we have demonstrated an impairment of serial ordering in working memory in patients with Parkinson’s disease (PD). The STN is the target of deep brain stimulation (DBS) in PD. Patients with STN-DBS will be used in the current project to causally modulate the serial ordering network by performing an ordering task with stimulator switched on and off. A subset of patients will be tested with running stimulator in an fMRI-version of the task. Moreover, in a group of patients with externalized electrode leads after the operation we will record directly from the STN with the expectation to find neural signatures of different error categories during serial ordering. Finally, we will modulate core cortical nodes of the serial ordering network by robot-navigated theta-burst transcranial magnetic stimulation in healthy participants.The current work will deliver crucial novel knowledge on a largely neglected cognitive process, serial ordering within working memory, and the underlying neural processes. In particular, it will provide causal evidence by interfering with subcortical (STN) and cortical (dorsolateral and ventrolateral PFC, posterior parietal cortex) nodes of the serial ordering network.