0468 Enhancement of Sleep Slow Waves Using Transcranial Electrical Stimulation with Temporal Interference (TES-TI)

Abstract Introduction Slow waves are a key feature of high-quality, restorative sleep that occur during non-rapid eye movement (NREM) sleep, which comprises 75–80% of total time spent in sleep. Left ventromedial prefrontal cortex (vmPFC) regions have been shown to be a prominent “hot spot” where slow waves are generated. Slow-wave activity (SWA) is homeostatically regulated, which is believed to reflect the renormalization of synaptic strength that counteracts synaptic potentiation and cellular stress during wake. Disrupted SWA has been implicated in poor cognitive performance. Conversely, enhancement of slow waves has been shown to improve performance. Here, we used a novel neuromodulatory tool called Transcranial Electrical Stimulation with Temporal Interference (TES-TI) to enhance SWA. Methods Twenty-eight healthy participants (µ=30.5±10.0 years, 18 Female) received TES-TI interventions (STIM or SHAM) targeting left vmPFC during NREM sleep overnight for one (STIM-LOW) or two (STIM-HIGH) nights a week for four weeks. Simultaneous 256-channel high-density electroencephalography recordings were performed. TES-TI parameters were: 15,000Hz carrier frequency, 5mA, 15-second ramp, 3-minute stimulations repeated up to 10 times during NREM sleep. Difference frequencies were 1Hz for STIM and 0Hz for SHAM. Data were preprocessed and analyzed using MATLAB and EEGLAB. SWA (spectral power 0.5–4Hz) was quantified before (PRE), during (STIM), and after (POST) stimulations. Percent changes in SWA during (STIM-PRE) and after (POST-PRE) stimulation were calculated and evaluated for statistical significance using paired-samples t-tests with Bonferroni correction. Independent samples t-tests were used to compare STIM-HIGH and STIM-LOW. Results On combined first and last nights, twenty-one STIM participants (µ=31.5±10.0 years, 12 Female) showed a significant increase in SWA during (t=6.65, p=3.56x10-6) and after (t=7.11, p=1.38x10-6) TES-TI stimulation; whereas seven SHAM participants (µ=27.4±9.8 years, 5 Female) showed no significant changes in SWA (during: t=2.24, p=0.148; after: t=2.47, p=0.098). STIM-HIGH participants (N=10, µ=32.9±11.2 years, 7 Female) had greater increases in SWA during stimulation on the last night as compared to the first night when compared to STIM-LOW participants (N=7, µ=31.6±10.4 years, 2 Female) (t=1.89, p=0.039). Conclusion This study is the first to provide evidence supporting the ability of TES-TI to enhance SWA during NREM sleep overnight. Support (if any) DARPA STRENGTHEN (HR00112320033)