Consolidation of Motor Learning of Writing Skills and Its Related Brain Activity Changes in Parkinson's Disease

This translational study is a monocentric Randomized Controlled Trial (RCT). The investigators will recruit 40 PD patients from the early Hoehn & Yahr stages. Patients will be randomly allocated to an experimental group (writing training) and a control group (stretch- and relaxation training). All patients will receive the same frequency and duration of intervention. After the training period, patients will be followed up for another 6 weeks. Patients will be tested in the ON-phase of the medication cycle at 3 occasions: before (T1) and after training (T2) and after a 6-week retention period (T3). At T1 & T2 participants will be tested at the behavioral & neural level. At T3 participants will only be tested at the behavioral level.

Motor performance will be measured using MRI-compatible touch sensitive tablets and pencils. This system allows registration and translation of writing movements into online-cursor movements on screen in and outside a scanner environment. Both patient groups will be compared during a behavioral test battery consisting of (i) a trained sequence with and without visual cues; (ii) an untrained sequence with and without visual cues to test transfer; and (iii) a trained dual task to test automatization. Visual cues will consist of differently colored target zones of different band widths, indicating the scale and accuracy of writing.

Functional MRI measurements will take place in a 3T MR Philips Intera scanner. Before scanning, subjects will undergo a training session in a dummy scanner to familiarize them with the scanner environment and task instructions. During the fMRI sessions, participants will perform a trained and untrained sequence, both with and without visual cues. To control for differences in movement speed, all participants will perform the tasks at the same frequency, defined by an auditory pace. In addition to the fMRI measurements, resting state fMRI and DTI will also be performed to reveal alterations of the structural and functional connectivity between critical regions.

Behavioral data will be recorded as xy-coordinates and pressure values at a sampling rate of 200Hz and with a spatial resolution of 32.5µm. Statistical analysis of the behavioral data will have a between-subject factor of group (experimental and placebo group) and a within-subject factor of time (before training, after training and after the retention period).

Image analysis will be performed with Statistical Parametric Mapping (SPM) software. The investigators will contrast for either decreased or increased activation, as different regions may show divergent changes related to learning and transfer, with group as a between-subject factor and time (before and after training) and task condition (trained with cues, trained without cues, untrained with cues and untrained without cues) as within-subject factors.

Inclusion criteria

• Diagnosis of PD based on the UK Brain Bank criteria
• Hoehn & Yahr stage I (with impairments on the right side) and II in the on-phase
• Without cognitive impairment (MMSE >24)
• On stable medication
• Right handed

Exclusion criteria

• Deep Brain Stimulator
• Other contra-indications for MR scanning
• Colorblind