Abstract
Motor learning is defined as an improvement in performance through practice. The ability to learn new motor skills may be particularly challenged in patients with Parkinson's disease, in whom motor execution is impaired by the disease-defining motor symptoms such as bradykinesia. Subthalamic deep brain stimulation is an effective treatment in advanced Parkinson's disease, and its beneficial effects on Parkinsonian motor symptoms and motor execution have been widely demonstrated. Much less is known about whether deep brain stimulation directly interacts with motor learning independent of modulation of motor execution. We investigated motor sequence learning in 19 patients with Parkinson's disease treated with subthalamic deep brain stimulation and 19 age-matched controls. In a cross-over design, patients performed an initial motor sequence training session with active and inactive stimulation, respectively (experiments separated by ≥14 days). Performance was retested after 5 min and after a 6 h consolidation interval with active stimulation. Healthy controls performed a similar experiment once. We further investigated neural correlates underlying stimulation-related effects on motor learning by exploring the association of normative subthalamic deep brain stimulation functional connectivity profiles with stimulation-related differences in performance gains during training. Pausing deep brain stimulation during initial training resulted in the inhibition of performance gains that could have been indicative of learning at the behavioural level. Task performance improved significantly during training with active deep brain stimulation, but did not reach the level of learning dynamics of healthy controls. Importantly, task performance after the 6 h consolidation interval was similar across patients with Parkinson's disease independent of whether the initial training session had been performed with active or inactive deep brain stimulation. This indicates that early learning and subsequent consolidation were relatively intact despite severe impairments of motor execution during training with inactive deep brain stimulation. Normative connectivity analyses revealed plausible and significant connectivity of volumes of tissue activated by deep brain stimulation with several cortical areas. However, no specific connectivity profiles were associated with stimulation-dependent differences in learning during initial training. Our results show that motor learning in Parkinson's disease is independent of modulation of motor execution by subthalamic deep brain stimulation. This indicates an important role of the subthalamic nucleus in regulating general motor execution, whereas its role in motor learning appears negligible. Because longer-term outcomes were independent of performance gains during initial training, patients with Parkinson's disease may not need to wait for an optimal motor state to practice new motor skills.