Natural Frequencies of Levodopa‐Induced Dyskinesia in Parkinson's Disease

OBJECTIVES: Abnormal involuntary movements, known as dyskinesias, are common complications of levodopa treatment in patients with Parkinson's disease and can significantly impair quality of life. The underlying pathophysiology remains unclear, and current therapeutic options are limited. This study aimed to investigate the oscillatory dynamics of the supplementary motor area during levodopa administration and the emergence of dyskinesias. METHODS: We applied transcranial magnetic stimulation to directly perturb the supplementary motor area and used high-density electroencephalography to measure its natural oscillatory frequency during levodopa administration and the emergence of dyskinesias. RESULTS: Levodopa intake increased cortical excitability in both dyskinetic and non-dyskinetic parkinsonian patients. Transcranial magnetic stimulation consistently evoked dominant beta-gamma oscillations in both groups. Notably, dyskinetic patients exhibited a shift of event-related spectral perturbation toward beta low frequencies, paralleling the clinical manifestation of peak-of-dose dyskinesias. INTERPRETATION: These findings support the view of dyskinesias as disorders of oscillatory local and network activity and suggest that targeted neuromodulation strategies could be developed to mitigate these motor complications.