Rapid Profiling of EEG Responses to Non-Invasive Brain Stimulation in Parkinson's Disease: A Biomarker-Driven Screening Framework.

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Background/Objectives: Parkinson's disease (PD) is associated with alterations in resting-state Electroencephalogram (EEG) biomarkers. Identifying stimulation protocols that reliably shift these biomarkers toward healthy-like patterns is essential for developing personalized neuromodulation strategies. This study introduces a rapid, biomarker-driven framework for screening the EEG effects of diverse Galvanic Vestibular Stimulation (GVS) waveforms in PD. Methods: More than 300 subthreshold GVS stimuli were delivered during resting-state EEG to PD (n = 5) subjects and Healthy Controls (n = 5). A composite biomarker score that included spectral, cross-frequency, aperiodic, and complexity measures quantified stimulation-related changes. A linear classifier and multi-criteria decision analysis were used to evaluate and rank stimuli. Results: Stimulation produced consistent improvements in the composite biomarker score, with the strongest effects observed for beta-range sinusoids, multisine waveforms, frequency-modulated stimuli with a 75 Hz carrier, and PAC-modulated signals. No significant post-stimulation carryover effects were detected. Conclusions: While preliminary, this exploratory framework enables rapid, interpretable profiling of EEG responses to non-invasive stimulation in PD. By prioritizing candidate GVS protocols based on biomarker shifts rather than behavioural endpoints, the approach provides a practical foundation for future personalized neuromodulation strategies.

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