Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in Parkinson disease

Background: The neural mechanisms and the circuitry involved in levodopa-induced dyskinesia (LID) are still partially obscure. LID can be considered the consequence of an abnormal pattern or code of activity that originates and is conveyed from the basal ganglia to the thalamus and the cortical motor areas. However, not only striatothalamocortical motor circuits but also other interconnected pathways could be implicated in its pathogenesis. Methods: In a series of experiments, we applied repetitive transcranial magnetic stimulation (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson disease, to investigate whether modulation of cerebellothalamocortical circuits by means of rTMS may result in a modification of a dyskinetic state induced by levodopa ingestion. Results: We found that a single session of cerebellar continuous theta burst stimulation (cTBS) was capable of transiently reducing LID. In the same patients, we observed that cerebellar cTBS changed the profile of activation of intracortical circuits in the contralateral primary motor cortex. Cerebellar cTBS reduced short intracortical inhibition and increased long intracortical inhibition, inducing a cortical reorganization that is associated with a reduction of LID. Furthermore, in another experiment, we observed that a 2-week course of bilateral cerebellar cTBS induced persistent clinical beneficial effects, reducing peak-dose LID for up to 4 weeks after the end of the daily stimulation period. Conclusions: Our study demonstrates that cerebellar continuous theta burst stimulation has an antidyskinetic effect in Parkinson disease patients with levodopa-induced dyskinesia, possibly due to modulation of cerebellothalamocortical pathways.