Modulating autonomic nervous system activity with transcutaneous auricular vagus nerve stimulation in Parkinson’s disease: a proof of concept study

Figures

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  Figure 1. Randomized, sham-controlled, crossover study design and intra-visit protocol. Flowchart detailing the experimental design for evaluating the acute autonomic effects of transcutaneous auricular Vagus Nerve Stimulation (taVNS) in an idiopathic Parkinson’s disease cohort (N = 8). Following baseline phenotyping, participants were randomized into one of two crossover sequences, receiving either active taVNS or sham stimulation during their first interventional visit, and crossing over to the alternate condition during the subsequent visit. A minimum 48-h washout period was observed between visits. The lower panel illustrates the standardized intra-visit testing timeline. Continuous autonomic monitoring (electrocardiography and hemodynamics) was maintained throughout four sequential epochs: a 1-min pre-treatment baseline, a 15-min stimulation phase, a 1-min post-treatment washout, and the dynamic Ewing autonomic test battery (comprising the Valsalva maneuver, deep breathing, and a lying-to-standing orthostatic challenge). Active taVNS was delivered at 30 Hz with a 250 μs pulse width, titrated to each individual participant’s sub-perceptual sensory threshold; sham stimulation was…

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  Figure 2. Responder profiles: Baseline autonomic symptom burden predicts acute chronotropic response to taVNS. Scatter plot demonstrating the relationship between baseline autonomic symptom severity and the magnitude of physiological response to active transcutaneous auricular Vagus Nerve Stimulation (taVNS) in individuals with Parkinson’s disease (N = 5). The x-axis represents the baseline Composite Autonomic Symptom Score (COMPASS-31) total score. The y-axis displays the change (delta) in mean heart rate (bpm) from the 1-min pre-treatment baseline epoch to the 15-min active stimulation phase. Individual patient values are represented by black circles, and the solid red line indicates the linear line of best fit. Statistical analysis utilized Spearman’s rank correlation, which suggests that individuals with a higher baseline autonomic burden exhibited a greater chronotropic response to active taVNS.

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  Figure 3. Longitudinal trajectories of heart rate variability metrics across study phases. A comparison of raw median values for six different cardiovascular autonomic indices between Active taVNS (green circles/lines) and Sham (gray circles/lines) conditions. Continuous HR data were acquired from eight individuals with Parkinson’s disease across three sequential epochs: 1. Baseline, 2. Treatment (15 min), and 3. Post-Tx washout. The six facets display distinct standard heart rate variability metrics: (A) Mean Heart Rate (bpm); (B) SDNN (ms); (C) RMSSD (ms); (D) HF Power (ms2); (E) LF Power (ms2); and (F) LF/HF Ratio. Individual data points are plotted as circles, and solid lines indicate the group trajectory. The blue lines represent active 30 Hz taVNS, and the gray lines represent sham (0 mA) stimulation. For detailed statistical analysis, please refer to Supplementary Materials.