Objective: To evaluate the clinical and resting-state functional connectivity effects of bilateral M1-iTBS in patients with de novo Parkinson’s disease.

Background: Dopaminergic neurodegeneration in Parkinson’s disease (PD) disrupts cortico-basal ganglia-thalamo-cortical circuits from the earliest stages, resulting in motor and non-motor symptoms. De novo PD patients represent a critical window to investigate disease mechanisms before compensatory adaptations or chronic medications confound findings. Intermittent theta-burst stimulation (iTBS) of bilateral primary motor cortex (M1) induces synaptic plasticity, modulates network dynamics and facilitates endogenous dopamine release—yet its clinical and neuroplastic effects remain largely untested in early untreated PD.

Method: Randomized, double-blind, sham-controlled trial in 19 de novo PD patients (mean age 61.1±8.2 years; disease duration 0.38±0.55 years), randomized 1:1 to five daily sessions of real vs sham neuronavigated bilateral M1-iTBS (80% active motor threshold). Clinical assessments included UPDRS motor scores and a neuropsychiatric battery for mood, cognition, and quality of life. Resting-state fMRI (rs-fMRI) was acquired pre- and post-intervention to assess functional connectivity changes.

Results: Real iTBS produced greater motor improvement than sham, sustained at one and two weeks post-stimulation (mean UPDRS-III reduction 6.4±5.7 points from baseline). Quality of life improved significantly in mobility, emotional well-being, cognition and PDQ-39 total score. rs-fMRI showed increased connectivity within cortico-basal ganglia-thalamic networks (supplementary motor area, M1, putamen, globus pallidus, VPL/pulvinar thalamic nuclei) and in associative/limbic regions (anterior cingulate, orbitofrontal cortex).

Conclusion: Bilateral M1-iTBS enhances motor function, quality of life and induces network reorganization in de novo PD. These results suggest neuromodulation restores circuit efficiency in early disease and supports M1-iTBS as a promising strategy for larger trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/therapeutic-effects-of-intermittent-theta-burst-stimulation-on-motor-non-motor-symptoms-and-functional-connectivity-in-de-novo-parkinsons-disease/