"An identical sensory stimulus might lead to a different chain of neuronal responses and perceptual experience, depending on the behavioral state of the organism and on cognitive factors such as vigilance, attention and intention. Perhaps the most dramatic illustration of this phenomenon is provided by sleep, where perceptual awareness is strikingly ""disconnected"" from the external world. This disconnection, which we all experience every night, remains a major puzzle since it can occur along with robust early neuronal responses to external stimuli, and while we are conscious – but in the form of dreams – that are rarely affected by external stimuli. While cortical electrophysiology and metabolism can be grossly similar across wakefulness (when we are ‘connected’ to the external world) and sleep (when we are largely ‘disconnected’), the neuromodulatory milieu is fundamentally altered. Therefore, we reasoned that neuromodulation might play a key role in determining the neural and perceptual fate of sensory events. In particular, several lines of evidence suggest that noradrenaline (NE) may play a key role in sensory processing, and that its reduced activity throughout sleep may mediate disconnection from the external environment. Thus we hypothesized that even during wakefulness, reducing NE levels will impair sensory perception, i.e. lead to a mild form of “waking sensory disconnection” and conversely, that boosting NE signaling may lead to improved sensory perception. While previous human NE studies focused on high-level cognition including memory, emotion, attention, motivation, decision-making and metacognition, studies investigating the causal role of NE in basic sensory processing are still missing. In the course of this project, we investigated this by pharmacologically and bi-directionally manipulating NE levels in healthy volunteers, while they were performing simple visual detection and discrimination tasks. We measured how reduced or enhanced NE signaling affected behavior, EEG, fMRI, pupil size, as well as peripheral and subjective measures of arousal, thereby taking advantages of the full-range of neuroscientific methods available to study human cognition and brain activity. We found that while reduced NE signaling impaired detection and discrimination abilities and lead to delayed and reduced late neural response, enhanced NE signaling lead to the opposite results. These results establish that NE indeed has a causal role in modulating sensory perception, and its reduced signaling in sleep likely plays a key role in mediating the “sensory disconnection” that we experience throughout sleep. The results have been presented in several conferences and are now summarized in a manuscript entitled “Noradrenaline causally modulates visual perception and late visually-evoked activity”, that we plan to submit within the next month."
