Enhancing Motor Learning with a Single Dose of Levodopa

Motor impairments are the most common deficits caused by stroke. Although
standard revalidation rehabilitation efforts are used to facilitate recovery
after stroke, additional interventions are necessary to further improve/regain
motor function and avoid limitation in mobility. Improving motor learning
capacity could aid the rehabilitation process. Motor learning is in the brain
mainly regulated by the olivo-cerebellar system. The Granule cell (GC) layer is
one of the major information gateways that relay sensory signals to the
cerebellar cortex. The GC layer has very intriguing properties; they receive
sensory information (from the body) and express many modulatory receptors. They
integrate and filter the sensory information from the body before sending it to
the cerebellar cortex. The GC layer can theoretically be manipulated in order
to facilitate motor learning by using pharmacological modulators. Activation of
modulatory receptors in the GC layer can alter the information flow towards the
cerebellar cortex. In the GC layer dopamine receptors are present. Enhanced
levels of dopamine in the GC layer might facilitate the information flow to the
cerebellar cortex and consequently accelerate the process of motor learning.
Currently, it is still unknown what the exact role is of dopamine in the human
cerebellum. Levodopa/carbidopa can be used as a tool to enhance the levels of
dopamine in the GC layer and allow us to investigate which elements of the
motor learning process are regulated by dopamine. Although the drug intervene
on other receptors in the brain, it could potentially shorten the revalidation
time and help to achieve higher levels of motor performances. Furthermore,
manipulating the GC layer in this ways will also give us more insight in the
functional capacity of the GC layer during motor performance and learning.
In this study, we will investigate the role of dopamine transmission (via
pharmacological manipulation of the GC layer using levodopa/carbidopa) on motor
learning in healthy individuals during cerebellar specific motor adaptation
tasks.

To identify the role of dopamine transmission in the GC layer on motor learning
in healthy individuals during cerebellar specific motor adaptation tasks.

Double-blind randomized placebo-controlled cross-over design study

Each participant receives once a dose of Levodopa / Carbidopa (100mg / 25mg)
and once a placebo. The two intake moments are separated for at least a week.

The subjects have to visit the Erasmus MC for 2 times and for a total of 4
hours. They have to fill in two questionnaires, do five motor tasks and one
cognitive task. Subjects have to wait (in the relax room) for 30 minutes before
the start of the motor- and cognitive tasks. The total duration of all tasks
will be around 1 hour. Neither the behavioural tasks nor the single-dose of
levodopa/carbidopa does cause a significant discomfort or risk for the subject.
The subject*s receive a financial compensation for expenses made due to
participation.