Potential modulation of cortical oscillations by temporal interference stimulation in the primary somatosensory cortex

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Abstract Background Temporal interference stimulation (TIS) is a promising non-invasive technique for reaching deep brain regions that are difficult to modulate with conventional transcranial electrical stimulation. A critical question is whether TIS can reliably induce neural modulation at its envelope frequency in humans. Objective As an initial step toward applications targeting deeper structures, we investigated whether TIS can modulate cortical oscillations at the envelope frequency within the primary somatosensory cortex (S1). We also examined how electric fields in off-target regions contribute to interindividual variability in stimulation efficacy using individualized simulations based on each participant’s magnetic resonance imaging (MRI). Methods Forty-nine healthy participants were enrolled (24 TIS, 25 active sham without envelope modulation). TIS was applied over the left S1 hand area using a stimulation protocol designed to generate a 10 Hz envelope frequency. Brain activity was recorded with magnetoencephalography (MEG) before and after stimulation. Electric field simulations were conducted using individualized head models reconstructed from each participant’s structural MRI. Results The primary mixed two-way ANOVA revealed no significant group-by-time interaction for alpha-band power, with a sensitivity analysis indicating that the study was slightly underpowered to detect this interaction effect. Subsequent exploratory within-group analyses showed a post-stimulation increase in alpha band power around 10 Hz in the targeted S1 in the TIS group (Cohen’s d = 0.570), whereas no significant change was observed in the active sham group. No clear changes were observed in the beta or gamma bands, and the increase was descriptively largest in the alpha band, although a direct statistical comparison across frequency bands did not reach significance. Furthermore, exploratory analyses based on individualized electric field simulations suggested that off-target electric fields may attenuate the relationship between local field strength in S1 and changes in alpha-band oscillations. Conclusions These findings provide preliminary evidence suggesting that TIS may modulate cortical oscillations in humans in accordance with the envelope frequency, although the evidence remains limited. Furthermore, its effectiveness may be influenced by off-target electric fields.