A Personalized Closed-Loop Brain Stimulation Protocol for Difficulty Falling Asleep

Insomnia, a common mental health issue, is characterized by brain hyperarousal and difficulties in transitioning between sleep stages. Pharmacological interventions often come with adverse effects and variable efficacy, while non-invasive brain stimulation holds potential but lacks in providing tailored, dynamic, and precisely targeted solutions. A novel online closed-loop individualized frequency transcranial alternating current stimulation protocol (IF-tACS) was developed to dynamically adjust the stimulation sites and parameters in sync with sleep states. Specifically, the frequency of the stimulation signal is synchronized with the predominant individualized neural oscillation frequency specific to each state: the alpha rhythm in the parietal-occipital region during Wake, theta in the central parietal region during stage N1, and delta in the frontal region during the early stage N2. This approach was evaluated in 30 subjects with insomnia. The application of IF-tACS showed preliminary improvements for those with insomnia, significantly reducing deep sleep latency by an average of 8.6 minutes. The stimulation also restore the cortical connectivity that is disrupted at sleep onset. Furthermore, IF-tACS decreased the instability in transitioning from N3 to N1 stages by approximately 46.4% and modulated spindle density towards healthier levels. The findings support the hypothesis that personalized, state-dependent, oscillation-synchronized tES can effectively normalize sleep in individuals with insomnia. This immediate intervention of may enhance sleep-promoting neural networks, thereby increasing excitatory inhibition, as well as stabilizing sleep homeostasis throughout the night.