Deep brain stimulation of the subthalamic nucleus (STN) restores spatial reversal learning in patients with Parkinson’s disease
Isabel Schneider, Robby Schönfeld, Annika Hanert, Sarah Philippen, Inken Tödt, Oliver Granert, Maximilian Mehdorn, Jos Becktepe, Günther Deuschl, Daniela Berg, Steffen Paschen, Thorsten Bartsch- Neurology
- Cellular and Molecular Neuroscience
- Biological Psychiatry
- Psychiatry and Mental health
Abstract
Spatial learning and navigation are supported by distinct memory systems in the human brain such as the hippocampus based navigational system and the striatum-cortex based system involved in motor sequence, habit and reversal learning. Here, we studied the role of subthalamic circuits in hippocampus-associated spatial memory and striatal-associated spatial reversal learning formation in patients with Parkinson's disease (PD), who underwent a deep brain stimulation (DBS) of the subthalamic nucleus (STN).
DBS patients (PD-STN: n = 26) and healthy subjects (n = 15) were tested in a novel experimental spatial memory task based on the Morris water maze that assesses both hippocampal place memory as well as spatial reversal learning. All subjects were trained to navigate to a distinct spatial location hidden within the virtual environment during 16 learning trials in a STN Stim-On condition. Patients were then randomized into two groups with either a DBS On- or Off-condition. Four hours later, subjects were retested in a delayed recall and reversal learning condition. The reversal learning was realized with a new hidden location that should be memorized during six consecutive trials. The performance was measured by means of an index indicating the improvement during the reversal learning.
In the delayed recall condition, neither patients, healthy subjects nor the DBS On- vs. Off-groups showed a difference in place memory performance of the former trained location. In the reversal learning condition, healthy subjects (reversal index 2.0) and patients in the DBS On-condition (reversal index 1.6) showed a significant improvement. However, patients in the DBS Off-condition (reversal index 1.1) performed significantly worse and did not improve. There were no differences between all groups in a final visual guided navigation task with a visible target.
These results suggest that DBS of subthalamic nucleus restores spatial reversal learning in a virtual navigation task in patients with Parkinson’s disease and gives insight into the neuromodulation effects on cognition of subthalamic circuits in Parkinson’s disease.