Mapping unintended trigeminal nerve activation during transcranial alternating current stimulation (tACS): A...

To systematically characterize activation thresholds for peripheral trigeminal nerve branches under clinical tACS parameters using a computational modelling approach. Approach: An MRI-derived finite element head model was coupled with multicompartment NEURON cable models of myelinated sensory axons (4-14 µm diameter). Seven trigeminal branches were manually delineated. Activation thresholds were computed across eight sinusoidal frequencies (5-100 Hz) for two electrode montages (F3-F4 and Fp1-Fp2). A 60 Hz biphasic pulse enabled direct comparison with established transcutaneous nerve stimulation devices. Sensitivity analyses assessed robustness to nerve orientation and depth, and electrode displacement. Main results: Threshold decreased non-linearly with increasing frequency, plateauing above 40 Hz. Under F3-F4, the auriculotemporal and zygomaticotemporal nerves, and under Fp1-Fp2, the supraorbital and supratrochlear nerves fell below 2 mA threshold at ≥40 Hz. Thresholds were largely independent of axon diameter above 40 Hz. Thresholds for 60 Hz sinusoidal waveforms were consistently lower than 60 Hz biphasic pulse condition. Sensitivity analyses confirmed sub-2 mA thresholds were preserved for tested perturbations. Significance: Select trigeminal branches are activated below the standard 2 mA clinical dose across both montages. This study provides preliminary indication that peripheral trigeminal recruitment is a predictable, montage-dependent, and mechanistically plausible contributor to tACS effects that warrants explicit consideration in trial design and result interpretation. .