Interaction between Fatigue, Dopamine and Plasticity in Health and Parkinson$S Disease

Fatigue and learning commonly coexist. However, the influence of fatigue on learning has been controversy. In the past few years, we have noticed that voluntary contraction can modulate motor plasticity happening near the contraction moment. The duration and force level of voluntary contraction, which may involve different amount of muscle fatigue, are noticed as critical factors of the modulation effect on motor plasticity. Therefore, it would be helpful to understand the influence of muscle fatigue on motor learning from the viewpoint of physiology and behavior by studying how different levels of fatigue interact with subsequent motor plasticity and learning. Furthermore, dopamine is known as a critical transmitter for both fatigue and plasticity. Hence, we are also interested in the role of dopamine in the interaction between fatigue and plasticity. In contrast to give levodopa to healthy subjects to explore the effect of increasing dopamine level in the brain, the study on patients with Parkinsons disease (PD) will provide the knowledge about the effect of dopamine depletion. In this project, we shall first explore the fatigue component of three fatigue tasks, including strong and short voluntary contraction, moderate and shot voluntary contraction and moderate and prolonged voluntary contraction in healthy subjects and later in PD patients. Then, we will evaluate the influence of the different fatigue conditions on subsequence motor plasticity using repetitive transcranial magnetic stimulation (rTMS) and on the motor learning with the behavioral investigation. Moreover, the modulation effect of dopamine on the interaction between fatigue and plasticity will be assessed in both the physiological and behavioral aspects. Healthy subjects pretreated with levodopa will be studied as the condition of dopamine elevation, while patients with PD provide the opportunity to know the effect of dopamine depletion. This is a rather complex and time consuming study. rTMS-induced plasticity effects take almost one week to washout; while the motor learning effect may need a month or so to forget, so that experiments have to be done 1 week or even 1 months apart from each other to avoid the carryover effect. Moreover, since we would like to know the effects of different kinds of fatigue on both long-term potentiation and depression types of plasticity and motor learning, multi-sessional investigation is therefore required. However, we consider this a very interesting and practical topic that deserves a careful study. The results of the project are expected to be helpful for designing training protocols, improving learning strategies, coping with fatigue in healthy and patients and many other relevant issues, e.g. rehabilitation. On the other hand, the data will also provide insights for improving the delivery of rTMS for plasticity induction.

Project ID:PC10701-0276
External Project ID:MOST105-2314-B182-004-MY3