Functional Near-Infrared Spectroscopy-Guided Frequency Mapping of Auricular Vagus Nerve Stimulation in Depression.

Major depressive disorder (MDD) is associated with alterations in large-scale brain networks, and variability in transcutaneous auricular vagus nerve stimulation (taVNS) parameters, particularly stimulation frequency, limits reproducibility and comparability across studies. Standardized strategies for systematic parameter selection are therefore needed. This protocol presents a reproducible, neuroimaging-guided workflow for mapping individual cortical responses to multiple taVNS frequencies using functional near-infrared spectroscopy (fNIRS). The approach combines continuous fNIRS acquisition with within-session delivery of multiple stimulation frequencies and network-level analysis of default mode network activity. Frequency-specific responses are quantified using distance-based metrics, followed by algorithmic ranking to identify candidate stimulation parameters within each participant. The workflow enables direct within-subject comparison of stimulation conditions and provides a structured framework for exploratory parameter mapping based on network-level responses rather than fixed-frequency designs. Representative results demonstrate the feasibility of acquiring stable fNIRS signals across conditions and generating interpretable participant-specific frequency rankings. Although demonstrated in MDD, this protocol is adaptable to other neuromodulation paradigms and disorders involving network-level dysfunction and may support future studies aimed at individualized parameter selection.