In this talk, I will present recent studies in our lab, where new tools are pushing the boundaries of sleep research.In a first line of studies, we are investigating how sleep promotes memory consolidation in humans. To this end, we developed a novel ecological paradigm to study episodic memory without report; upon repeated viewing of special movies ,eye gaze patterns can quantify memory for specific events. Next, we show that deep brain closed-loop intracranial electrical stimulation during human sleep enhances hippocampus-cortex synchrony and memory performance. Finally, we examine how sleep and memory are disrupted in amnestic mild cognitive impairment (aMCI) representing early Alzheimer’s disease (AD). To this end, we developed a novelmachine learning-based method to non-invasively detect interictal spikes occurring in the medial temporal lobe during sleep. This approach can help identify disruptions in hippocampus-cortex synchrony and memory consolidation during sleep.In the second line of studies, we investigate how reduced locus coeruleus-noradrenaline (LC-NE) activity during sleep mediates sensory disconnection. In rodents, the level of ongoing tonic LC activity during sleep anticipates sound-evoked awakenings, while minimal optogenetic LC activation or silencing increases and decreases such awakenings, respectively. Projection-specific investigation in mice indicates that an early surge of brainstem NE is particularly important for mediating sensory-evoked awakenings. These findings may shift how we view arousal- promoting neuromodulation; rather than acting in a diffuse hormonal-like manner, the LC-NE system may in fact operate through specific projection pathways, in a circuit-like manner. Finally, I will describe a novel method for monitoring gaze direction and pupil size through closed eyes in humans via short-wave infrared (SWIR) imaging in combination with video analysis algorithms. This technology has potential to enable touchless and continuous monitoring of depth of anesthesia, pain, and detection of intraoperative awareness.
