Transcranial temporal interference stimulation (tTIS) has recently emerged as a non-invasive method for modulating neural activity using interfering high-frequency electric fields. Although behavioral and neuroimaging effects of tTIS have been reported, evidence for electrophysiological modulation remains inconsistent, and it is unclear whether observed effects are attributable to temporal interference itself or to other components of the signal, e.g. high-frequency carrier signals. We therefore investigated whether tTIS at to the individual alpha frequency (IAF) modulates occipital alpha power compared with both sham stimulation and an active high-frequency carrier control. Eighteen healthy participants were enrolled in a randomized, double-blind, within-subject crossover study; 17 participants were included in the final analysis. Each participant completed three stimulation sessions consisting of three conditions (tTIS, carrier control, sham stimulation). tTIS was delivered for 20 minutes using two high-frequency signals at 1000 Hz and 1000 Hz + IAF, whereas the carrier control used two 1000-Hz signals without an envelope modulation. EEG was recorded before and after stimulation during a visual vigilance task. Individual electric-field distributions in the occipital cortex were estimated using structural MRI-based finite-element simulations. A significant main effect of stimulation condition on the change in occipital alpha power was observed (F(2,32) = 5.69, p = .008, eta2p = .26). Post-hoc comparisons showed a significantly greater increase in alpha power following tTIS compared with both the carrier control (mean difference = 0.30, adjusted p = .036, Cohens d = 0.686) and sham stimulation (mean difference = 0.31, adjusted p = .037, Cohens d = 0.683). Carrier and sham conditions did not differ (adjusted p = 1.000). No behavioral effects were observed. The magnitude of the alpha-power change was not significantly associated with simulated electric-field strength in the occipital target region. tTIS was well tolerated, with no stimulation-related study discontinuations. tTIS targeting the occipital cortex therefore produced significant post-stimulation enhancement of alpha power beyond both sham and high-frequency carrier stimulation. The absence of an effect in the carrier condition supports the interpretation that the electrophysiological aftereffect depends on temporal interference rather than high-frequency stimulation components alone. These findings provide evidence for frequency-specific modulation of cortical oscillations by tTIS and support further investigation of its underlying mechanisms and stimulation parameters.
Stalter, J., Stecher, H. I., Aleman, A., Herrmann, C., Witt, K.
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