Involvement of the Cerebellothalamocortical Pathway in Parkinson Disease

Objective: Lesioning or stimulation of the cerebellar thalamus is an established treatment for rest and postural tremors in Parkinson disease (PD). The cerebellothalamocortical (CTC) pathway can be assessed by transcranial magnetic stimulation (TMS) of the cerebellum, which suppresses the contralateral primary motor cortex (M1), a phenomenon termed cerebellar inhibition (CBI). Tremor reset can be used to assess whether the stimulated brain area is involved in the generation or transmission of tremor. We tested whether M1 or cerebellar stimulation can reset PD tremor, and investigated the excitability of the CTC pathway in PD. Methods: Ten mild to moderate PD patients in the OFF medication state and 10 healthy controls were studied. Tremor reset was tested with TMS delivered to the cerebellum or M1. CBI was assessed by cerebellar stimulation followed by M1 stimulation at interstimulus intervals of 3 to 8 milliseconds. Subjects were tested both at rest and during arm extension. Results: Rest tremor in PD was reset by M1 stimulation but not by cerebellar stimulation. Postural tremor was reset by both types of stimulation. At rest, CBI was reduced in PD patients compared to controls. Arm extension decreased CBI in controls and turned the inhibition into facilitation in patients. CBI correlated with the degree of tremor reset caused by the cerebellar stimulation. Interpretation: The excitability of CTC pathway is decreased in PD. Rest and postural tremors in PD are mediated by different neuronal pathways, and the CTC pathway is involved in the generation or transmission of postural tremor. ANN NEUROL 2010;68:816-824