Enhancement of Sleep Slow Wave Activity using Transcranial Electrical Stimulation with Temporal Interference

Abstract Slow waves mediate restorative functions of non-rapid eye movement (NREM) sleep. To enhance slow wave activity (SWA, 0.5-4 Hz) non-invasively, we employed a novel neuromodulatory tool, Transcranial Electrical Stimulation with Temporal Interference (TES-TI). Healthy participants (n=21) received TES-TI during NREM sleep over several nights (∼10 stimulation periods, 3min each, first half of night, 4-week protocol), targeting left ventromedial prefrontal cortex—a “hot spot” of slow wave generation. Two high frequency carriers with 1Hz difference (TES 15kHz -TI 1Hz ) produced amplitude modulated temporal interference at 1Hz. SWA, measured with simultaneous high-density electroencephalography (hd-EEG), was increased by TES 15kHz -TI 1Hz , with the effect outlasting the stimulation period. Higher frequencies (sigma and beta) decreased. Pure TES 15kHz did not have comparable effects. The incremental effects of TES 15kHz -TI 1Hz on SWA between first and last intervention night were positively correlated with subjective ratings of restorative sleep. This is the first study demonstrating that TES-TI can enhance sleep and its restorative function.