The Impact of the Basal Ganglia on Working Memory: Evidence from Parkinson's Disease

In our everyday life we rearrange numerous motor and cognitive sequences for goal-driven behavior, such as skillfully sequencing tasks to prepare a meal, arranging the correct order of ingredients in our working memory, and adding them in a certain sequence to create a tasty meal. Here, the critical feature of motor behavior is the selection of motor acts, that is, the facilitation and inhibition of predefined motional elements to arrange a temporal sequence of movements to practice a goal-oriented motor behavior. Animal and human studies favor the concept of competitive queuing to structure parallel representations of motional elements in a sequential order. In the phase of movement preparation, each motional act is linked with the probability of its execution in a temporal order (Fig. 1). The sequential position of a motional element within a sequence is decoded in a temporal context of when the appropriate movement is planned and executed to establish an ordinal position code of desired motional elements. These motional elements are the result of a selection driven by cortical intrinsic mechanisms (the temporal content and a planning layer) and a subcortical contribution of the basal ganglia that are participating in the process of movement selection. The corticobasal ganglia-thalamo-cortical loops, support this selection process. The subthalamic nucleus (STN), in a central position of these loops, has a powerful position. It receives information from a motor program via the indirect pathway of the basal ganglia loop, has access to cortical information via the hyperdirectional pathway, and can dynamically regulate motor and nonmotor output. Working memory enables us to store information temporally and actively manipulate and rearrange the order of information. Hence it shares some similarities with the motor system in the sequential selection of items. Indeed, electrophysiological recordings during deep brain stimulation (DBS) surgery in patients with Parkinson’s disease (PD) showed changes in the STN and prefrontal activity when patients were asked to memorize task-relevant information in their working memory. To solve the question of the impact of the basal ganglia and their influence on working memory performance, it would seem to be easy to investigate patients with PD treated with STN-DBS. The activity of the STN can be manipulated using electrical stimulation. Consequently, a comparison of working memory performance in ONand OFF-stimulation settings should provide clarity. However, these studies give us no conclusive answer to this question, given their heterogeneous results. Although some studies show no effect of DBS on working memory, others suggest mild improvement or a decline in working memory performance. These contradictory results can be explained by varying lead trajectory or placement of the STN electrodes that may influence motor and associative areas of the STN. Moreover, STN-DBS is performed in patients with PD in an advanced disease stage where a spread of Lewy body pathology is seen, compared with patients with de novo PD where the Lewy body pathology is more focused in the brain stem nuclei, such as the locus ceruleus and the substantia nigra. A study by Ye et al published in this issue of Movement Disorders brings us closer to understanding more precisely the impact of PD on working memory in general and the role of the STN in working memory function in more detail. The authors selected patients with de novo PD who had not been treated with antiparkinsonian medication. Using functional magnetic resonance imaging, the authors compare the brain © 2020 International Parkinson and Movement Disorder Society