Final Report Summary - STATEDEPENDENTPROCES (Markers and mechanisms of sensory disconnection) With the help of the EU CIG grant, I used a combined approach of animal models and human studies to reveal the markers and mechanisms of sensory disconnection during sleep and related states. Together with my research team, we revealed that cognitive lapses after sleep deprivation in humans involve attenuated and delayed neuronal responses in the medial temporal lobe co-occurring with local sleep-like slow/theta waves (Nature Medicine 2017). In the auditory domain, we show in both rodents and humans that responses in sleep and light anesthesia are preserved up to the primary auditory cortex, but robust attenuation occurs later in high-level cortical regions. By comparing auditory responses at the level of individual neurons in animals and in neurosurgical patients across wakefulness, sleep, and anesthesia, we are revealing the stage at which sensory disconnection affects brain processing of external events. In addition, by using steady-state visual stimulation (Cerebral Cortex 2017) and hierarchical speech (Journal of Neuroscience 2017) paradigms, we show that sleep affects more strongly responses that require integration over long time intervals, and responses to high-frequency content. Finally, we tested the potential role of locus coeruleus-noradrenaline (LC-NE) system in sensory disconnection in awake humans (Current Biology 2018). Pharmacologically manipulating NE levels in double-blind placebo-controlled experiments, we found that NE modulates sensitivity and accuracy of visual perception without significant effects on decision-making. In addition, NE improved late visual responses as evident by EEG and fMRI measurements, suggesting that NE plays an enabling causal role in visual awareness by affecting late visual processing. Overall, our research is revealing how the brain responds different to the external environment in disconnected states such as sleep, anesthesia, and cognitive lapses, thereby addressing a fundamental open question in system neuroscience and sleep research, with implications for sleep disorders, consciousness research, anesthesia, and neuropsychiatric disorders. In terms of career development and reintegration, the EU CIG grant has been indispensable for my integration into an independent research position. Thanks to CIG support, I have built my own successful laboratory (http://medicine.mytau.org/nir/) . By attending international conferences, I established strong collaborations with fellow scientists who are experts in sensory physiology, sleep, functional imaging and optogenetics. I have secured tenure at Tel Aviv University and am currently in the process of being evaluated for Assistant Professor academic rank. This career progress is based on research publications, teaching, fund recruitment, and successful mentoring of graduate students - all of which have been made possible by the CIG grant.
