Neurophysiological effects of targeting sleep spindles with closed-loop auditory stimulation.

Sleep spindles are neural events unique to nonrapid eye movement sleep that play key roles in memory reactivation and consolidation. However, much of the evidence for their function remains correlational rather than causal. Closed-loop brain stimulation uses real-time monitoring of neural events (often via electroencephalography; EEG) to deliver precise auditory, magnetic, or electrical stimulation for research or therapeutic purposes. Automated online algorithms to detect and stimulate sleep spindles have recently been validated, but the time- and frequency-resolved physiological responses generated by them have not yet been documented. Building on the recent findings that sleep spindles do not block the transmission of sound to cortex, the present work investigates the neurophysiological responses to closed-loop auditory stimulation of sleep spindles. EEG data were collected from 10 healthy human adults (6 nights each), whilst sleep spindles were detected and in half the nights, targeted with auditory stimulation. Spindles were successfully stimulated before their offset in 97.6% of detections and did not disturb sleep. Comparing stimulation with sham, we observed that stimulation resulted in increased sigma activity (11-16 Hz) at about 1 second poststimulation but that stimulation occurring at the beginning of the spindle also resulted in early termination of the spindle. Finally, we observed that stimulating an evoked spindle did not elicit additional sigma activity. Our results validate the use of closed-loop auditory stimulation targeting sleep spindles, and document its neural effects, as a basis for future causal investigations concerning spindles' roles in memory consolidation.