Bilateral intermittent theta-burst stimulation as a priming strategy to enhance action observation and imitation training in early parkinson's disease: a proof-of-concept study.

BACKGROUND

Action observation and imitation training (AOIT) is an evidence-based cognitive-motor rehabilitation strategy for Parkinson's disease (PD), particularly for the postural instability and gait disorder (PIGD) subtype. However, its effectiveness may decline with disease-related impairments in neuroplasticity. Intermittent theta burst stimulation (iTBS), a patterned repetitive transcranial magnetic stimulation protocol, can induce LTP-like plasticity and may enhance responsiveness to rehabilitation. This study investigated whether iTBS priming augments AOIT effects on gait and cognition in early-stage PIGD and explored underlying neurophysiological mechanisms.

METHODS

Fifteen patients with early-stage PIGD participated in a randomized, double-blind, sham-controlled crossover trial. Each phase included five consecutive days of AOIT preceded by either real or sham iTBS applied over the bilateral leg region of the primary motor cortex, separated by a washout period of more than four weeks. Pre- and post-intervention assessments included dual-task gait analysis, cognitive tests, clinical scales, neurophysiological measures (motor evoked potentials, cortical silent period), and resting-state EEG power spectral density.

RESULTS

Both conditions improved balance and gait measures. However, real iTBS significantly enhanced dual-task gait automaticity (F = 5.558, P = 0.026) and global cognition (F = 5.294, P = 0.026) compared to sham. Real iTBS also increased cortical silent period (F = 4.655, P = 0.040) and MEP-based cortical plasticity response (F = 6.131, P = 0.020). Improvements in cortical plasticity were significantly correlated with better gait performance (r = - 0.429, P = 0.020) and motor scores (r = - 0.463, P = 0.011). No adverse events were reported.

CONCLUSIONS

Bilateral iTBS targeting the leg representation of the primary motor cortex can potentiate AOIT effects in early-stage PIGD by enhancing cortical plasticity and motor learning. These findings support the integration of iTBS as a priming strategy within cognitive-motor rehabilitation protocols for PD. Trial registration Chinese Clinical Trial Registry, ChiCTR2300067657. Registered January 17, 2023.