Objective: Paired associative stimumlation (PAS)-induced plasticity, a form of spike-time dependent plasticity (STDP), is deficient in PD. We tested whether (1) PAS-induced plasticity could be restored by chronic levodopa therapy or by increasing the cerebellar output and then depotentiated and (2) the response depended on the dyskinetic status of the patients.

Background: Patient’s with Parkinson’s disease (PD) have deficient plastic responsiveness of the motor cortex (M1) to theta burst stimulation (TBS). TBS-induced plasticity is a form of homosynaptic plasticity. Long term potentiation (LTP)-like plasticity after TBS can be partly restored by chronic levodopa therapy. The restored plasticity can be depotentiated only in patients without levodopa induced dyskinesias (LID). Lack of depotentiation has been considered a hallmark of LID so far.

Method: We recruited 11 PD patients with peak-dose LID and 11 patients who were non dyskinetic on levodopa treatment. The 2 groups were similar in age and the UPDRS total and subset III motor scores. The daily equivalent dose of levodopa was higher in the dyskinetic group (863.6 ± 247.8 mg) than in the non -dyskinetic group (579.5 ± 244.9 mg; P = 0.01). We tested in the 2 groups (1) the responsiveness of left M1 to PAS, (2) whether cTBS applied to cerebellum before the PAS (CB-PAS) restored the responsiveness of M1 to PAS and (3) whether PAS-induced plasticity could be depotentiated by a cTBS150 protocol applied to M1 just after PAS or CB-PAS. Patients were tested in ON (1 hour after morning dose of medications).

Results: PAS-induced plasticity was present in ON, albeit limited, and to a similar extent in both dyskinetic and non-dyskinetic groups. In both groups, cerebellar stimulation applied before the PAS intervention led to a dramatic and significant enhancement of PAS-induced plasticity. The depotentiation protocol erased both the PAS and the CB-PAS-induced plasticity.

Conclusion: Long term dopa therapy or cerebellar stimulation potentiated the PAS-induced effects to a similar extent in non dyskinetic and dyskinetic patients. In contrast to homosynaptic plasticity, STDP-like plasticity can be depotentiated in dyskinetic patients while on their regular doses of dopaminergic drugs.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/lack-of-depotentiation-may-not-be-a-hallmark-of-levodopa-induced-dyskinesias/