Abstract
Abstract
Objective: 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.