Objective: To characterize the pattern and temporal evolution of iTBS-induced LTP-like cortical plasticity in drug-naïve patients with early Parkinson’s disease (PD).

Background: Long-term potentiation (LTP)-like plasticity induced by intermittent theta burst stimulation (iTBS) is a well-established neurophysiological marker of cortical synaptic plasticity. Increasing evidence suggests that synaptic plasticity mechanisms may be altered in Parkinson’s disease (PD), but their characteristics in the earliest, untreated stages remain insufficiently defined

Method: This pilot study included 15 drug-naïve patients with early PD and 10 healthy controls. PD diagnosis was based on clinical criteria and supported by positive 123I-ioflupane SPECT

imaging. iTBS was delivered over the primary motor cortex. Motor evoked potentials (MEPs) were recorded at baseline and at 1, 6, 11, 16, and 21 minutes after stimulation. Given the limited sample size, between-group comparisons at each post-stimulation time point were performed using Mann–Whitney U tests.

Results: Healthy controls showed a robust and sustained increase in MEP amplitudes following iTBS, consistent with LTP-like facilitation. In contrast, PD patients exhibited a paradoxical reduction in MEP amplitudes, indicating a Long-Term Depression (LTD)-like response. Compared with healthy controls, PD patients showed significantly lower MEP amplitudes at all post-stimulation time points: T1 (1.50 vs 0.92; p=0.008), T6 (1.44 vs 0.92; p=0.037), T11 (1.43 vs 0.86; p=0.0017), T16 (1.62 vs 0.87; p=0.0017), and T21 (1.60 vs 0.87; p=0.0003). Group differences increased over time, reflecting a progressive divergence in the expression of both early and late phases of plasticity.

Conclusion: In early, drug-naïve Parkinson’s disease, iTBS reveals a marked alteration in cortical plasticity dynamics, with a shift toward LTD-like responses. This abnormal plasticity pattern appears to be an intrinsic pathophysiological feature of the disease, present before dopaminergic treatment. Further studies are needed to explore the potential modulatory role of dopaminergic therapy on cortical plasticity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-impairment-in-itbs-induced-cortical-plasticity-in-drug-naive-parkinsons-disease-a-rtms-pilot-study/