Site-specific stimulation imperative: Lessons from a failed auricular-cervical transcutaneous vagus nerve stimulation comparison using closely matched parameters

The inability to activate the cervical vagus nullifies direct comparison, illustrates a critical methodological consideration for cross-site comparisons: anatomical depth necessitates site-specific stimulation protocols. We therefore propose that future cross-site tVNS comparisons adopt a "verify-first" framework, where target engagement is validated (e.g., via modeling or neuroimaging) prior to physiological comparison. The pronounced sAA response to cervical stimulation, which we demonstrate can be elicited independently of vagal engagement, questions the specificity of sAA as a vagus biomarker and underscores the necessity of rigorous active controls to isolate vagus-specific effects.