Subthalamic neuromodulation improves short-term motor learning in Parkinson’s disease

Abstract

The basal ganglia and cerebellum are implicated in both motor learning and Parkinson’s disease. Deep brain stimulation (DBS) is an established treatment for advanced Parkinson’s disease that leads to motor and non-motor effects by modulating specific neural pathways. Recently, a disynaptic projection from the subthalamic nucleus (STN) to cerebellar hemispheres was discovered. To investigate the functional significance of this pathway in motor learning, short-term improvement in motor execution in 20 patients with Parkinson’s disease on and off STN-DBS and 20 age-matched healthy controls was studied in a visuomotor task combined with whole-brain connectomics. Motor learning was impaired in Parkinson’s disease off stimulation but was partially restored through DBS. Connectivity between active DBS contacts and a distributed network of brain regions correlated with improvement in motor learning. Region of interest analysis revealed connectivity from active contact to cerebellar hemisphere ipsilateral to hand movement as the strongest predictor for change in motor learning. Peak predictive voxels in the cerebellum localized to Crus II of lobule VII, which also showed higher STN than motor cortex connectivity, suggestive of a connection surpassing motor cortex. Our findings provide new insight into the circuit nature of Parkinson’s disease and the distributed network effects of DBS in motor learning.

Motor training strengthens corticospinal suppression during movement preparation

“…For instance, disruption of the prefrontal cortex prevents training-related RT gains (Filmer et al, 2013). Besides, motor learning deficits in Parkinson’s disease patients are partly reversed by deep brain stimulation of the subthalamic nucleus (which is part of the BG; Carbon and Eidelberg, 2006; Mure et al, 2012; de Almeida Marcelino et al, 2019). Hence, one may hypothesize that plasticity in the fronto-BG network mediated the strengthening of preparatory suppression we observed with practice.…”

Editorial: The Role of the Basal Ganglia in Somatosensory-Motor Interactions: Evidence From Neurophysiology and Behavior

“…Furthermore, the evidence for functional significance of the basal ganglia-cerebellar connections, and how these connections facilitate co-operation is growing and opens an entirely new perspective on the pathophysiology of movement disorders, like dystonia (Darby et al, 2019;Fung and Peall, 2019). Finally, these basal-ganglia cerebellar connections can now be functionally restored using DBS of the subthalamic nucleus (STN), leading to improved (sensori) motor learning (de Almeida Marcelino et al, 2019).…”

Deep Brain Stimulation: Imaging on a group level

“…. De Almeida showed that functional connectivity between STN-DBS electrodes and a specific site in the ipsilateral cerebellum was associated with partly restoring motor learning in PD patients (de Almeida Marcelino et al, 2019). Finally, focusing on localized instead of connectivity-mediated effects, Irmen et al showed that modulating specific subregions of the STN could restore risk-taking behavior to a level observed in healthy controls (Irmen et al, 2019a).…”

“…Aside from its clinical value, DBS opens an invaluable window to the human brain and it is increasingly adopted to probe causal relationships between stimulated targets and certain behavioral effects, such as risk control (Irmen et al, 2019a;Nachev et al, 2015), movement speed (W.-J. , memory learning (de Almeida Marcelino et al, 2019) or verbal fluency (Ehlen et al, 2017;Mikos et al, 2011).…”

“…Various publications could demonstrate that electrode reconstructions in such common spaces remain informative and may be used to predict outcomes or behavioral measures across cohorts and DBS centers (Al-Fatly et al, 2019;Baldermann et al, 2019;de Almeida Marcelino et al, 2019;Horn et al, 2019a;W.-J. Neumann et al, 2018).…”