Consolidation of Motor Learning of Writing Skills and Its Related Brain Activity Changes in Parkinson's Disease
Consolidation of Motor Learning of Writing Skills and Its Related Brain Activity Changes in Parkinson's Disease
The basal ganglia play an important role in motor learning, especially during the
 consolidation phase of motor learning. This raises the question whether it is possible to
 sustain learning increments in a neurodegenerative condition such as Parkinson's disease
 (PD). The aim of this study is to gain knowledge on whether it is possible to relearn skills
 which are actually affected by PD, such as writing, and determine whether neuroplasticity is
 possible. In this randomized controlled study, PD patients will either follow intensive
 writing training or a placebo treatment (stretch and relaxation training) during 6 weeks. The
 writing training will focus on automatization (withstanding dual task interference), transfer
 to an untrained task and retention. The placebo program is aimed to reduce stiffness in the
 upper limbs and has been shown to be ineffective in PD. To date, it is unknown how neural
 networks change as a result of consolidation after a prolonged period of motor learning in
 PD. Therefore the second arm of this study will investigate, for the first time, changes in
 neural connectivity using brain imaging data to elucidate which neuroanatomical regions are
 involved in consolidation of learning in PD. Finally, DTI and resting state fMRI-analysis
 will complement insights into the neural changes as a result of learning.
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