Thalamic transcranial electrical stimulation with temporal interference enhances sleep spindle activity during a daytime nap

Study objectives Sleep spindles are electroencephalographic elements characteristic of non-rapid eye movement sleep (NREM) generated by thalamo-cortical interactions. Spindles have been linked to some of the cognitive benefits afforded by sleep and increased arousal threshold. This proof-of-concept study demonstrates that targeting the thalamus with Transcranial Electrical Stimulation with Temporal Interference (TES-TI) can enhance spindle activity. Methods 46 participants (24 ± 9.5 years; 58.7% F) underwent thalamic TES-TI stimulation during daytime naps. Three stimulation protocols with 15 kHz carrier frequency were tested during stage NREM 2: fixed difference frequency of 10 Hz (TES15kHz-TI10Hz), difference frequency matched to individual spindle peak, and no difference frequency. Spindle (sigma) band power and integrated spindle activity (ISA) were compared before and during the stimulation, and across stimulation protocols. Results TES15kHz-TI10Hz stimulation was associated with increased sigma power (∆x~STIM-PRE = 0.46 log10μV2, p = .0042) and ISA (∆x~STIM-PRE = 4.064 μV/s, p = .030). Cluster-based analysis localized the increase in sigma power across the entire scalp (p = .008). Linear mixed effects models showed that both sigma power and ISA during stimulation increased significantly more in TES15kHz-TI10Hz compared to the other stimulation protocols. Conclusions This study provides evidence supporting the successful use of TES-TI targeting the thalamus to enhance sleep spindle activity. Stimulation at a fixed difference frequency of 10 Hz increased sigma band power and ISA, whereas neither stimulation matched to individual sigma band peak nor TES alone produced comparable effects. These promising results warrant further investigations into the cognitive and clinical impact of TES-TI.