External Trigeminal Nerve Stimulation Evokes Bilateral Electroencephalography Responses and Modulates Spectral Power in Healthy Adults.

BACKGROUND

External trigeminal nerve stimulation (eTNS) is a noninvasive neuromodulation method approved for treating migraines and pediatric attention deficit hyperactivity disorder, and is under investigation for a variety of disorders. Despite the manifest therapeutic potential of eTNS, substantial variability remains across studies, and the mechanisms underlying eTNS effects remain poorly understood.

OBJECTIVES

We aimed to investigate the effect of eTNS on cortical activity and ways specific stimulation parameters modulate these responses in healthy adults using electroencephalography (EEG).

MATERIALS AND

METHODS

In 24 participants, EEG was recorded during unilateral application of either eTNS or median nerve stimulation (MNS; control). Time-domain evoked potentials (EPs) and short-term and sustained power spectral density (PSD) were analyzed. Additional eTNS blocks varied stimulation frequency and burst duration to assess parameter-specific effects.

RESULTS

eTNS elicited bilateral EPs with maximal responses in frontal regions, contrasting the lateralized somatosensory responses observed with MNS (p < 0.001). eTNS induced greater increases in PSD across all frequency bands than did MNS (p < 0.001), with effects persisting after stimulation (p < 0.015). Longer eTNS bursts (30 milliseconds) and lower frequencies (500 Hz) increased PSD (p < 0.001), whereas higher frequencies (1500 Hz) and longer bursts (30 milliseconds) yielded the largest EP amplitudes (p = 0.003).

CONCLUSIONS

eTNS evoked bilateral cortical responses and greater spectral power increases than did MNS. These effects depended on the stimulation parameters, highlighting the importance of protocol optimization. Our findings provide new insights into ways eTNS modulates cortical activity, contribute to a better understanding of its underlying mechanisms, and may help guide the development of more effective therapeutic protocols.

CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT04577677.