An identical sensory stimulus may or may not be incorporated into perceptual experience, depending on the behavioral and cognitive state of the organism. What determines whether a sensory stimulus will be perceived? While different behavioral and cognitive states may share a similar profile of electrophysiology, metabolism, and early sensory responses, neuromodulation is often different and therefore may constitute a key mechanism enabling perceptual awareness. Specifically, noradrenaline improves sensory responses, correlates with orienting toward behaviorally relevant stimuli, and is markedly reduced during sleep, while experience is largely "disconnected" from external events. Despite correlative evidence hinting at a relationship between noradrenaline and perception, causal evidence remains absent. Here, we pharmacologically down- and upregulated noradrenaline signaling in healthy volunteers using clonidine and reboxetine in double-blind placebo-controlled experiments, testing the effects on perceptual abilities and visually evoked electroencephalography (EEG) and fMRI responses. We found that detection sensitivity, discrimination accuracy, and subjective visibility change in accordance with noradrenaline (NE) levels, whereas decision bias (criterion) is not affected. Similarly, noradrenaline increases the consistency of EEG visually evoked potentials, while lower noradrenaline levels delay response components around 200 ms. Furthermore, blood-oxygen-level-dependent (BOLD) fMRI activations in high-order visual cortex selectively vary along with noradrenaline signaling. Taken together, these results point to noradrenaline as a key factor causally linking visual awareness to external world events. VIDEO ABSTRACT.

Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive-emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality.

Introduction: Post-Traumatic Stress Disorder (PTSD) is a prevalent, severe and tenacious psychopathological consequence of traumatic events. Neurobehavioral mechanisms underlying PTSD pathogenesis have been identified, and may serve as risk-resilience factors during the early aftermath of trauma exposure. Longitudinally documenting the neurobehavioral dimensions of early responses to trauma may help characterize survivors at risk and inform mechanism-based interventions. We present two independent longitudinal studies that repeatedly probed clinical symptoms and neurocognitive domains in recent trauma survivors. We hypothesized that better neurocognitive functioning shortly after trauma will be associated with less severe PTSD symptoms a year later, and that an early neurocognitive intervention will improve cognitive functioning and reduce PTSD symptoms.Methods: Participants in both studies were adult survivors of traumatic events admitted to two general hospitals’ emergency departments (EDs) in Israel. The studies used identical clinical and neurocognitive tools, which included assessment of PTSD symptoms and diagnosis, and a battery of neurocognitive tests. The first study evaluated 181 trauma-exposed individuals one-, six-, and 14 months following trauma exposure. The second study evaluated 97 trauma survivors 1 month after trauma exposure, randomly allocated to 30 days of web-based neurocognitive intervention (n = 50) or control tasks (n = 47), and re-evaluated all subjects three- and 6 months after trauma exposure.Results: In the first study, individuals with better cognitive flexibility at 1 month post-trauma showed significantly less severe PTSD symptoms after 13 months (p = 0.002). In the second study, the neurocognitive training group showed more improvement in cognitive flexibility post-intervention (p = 0.019), and lower PTSD symptoms 6 months post-trauma (p = 0.017), compared with controls. Intervention- induced improvement in cognitive flexibility positively correlated with clinical improvement (p = 0.002).Discussion: Cognitive flexibility, shortly after trauma exposure, emerged as a significant predictor of PTSD symptom severity. It was also ameliorated by a neurocognitive intervention and associated with a better treatment outcome. These findings support further research into the implementation of mechanism-driven neurocognitive preventive interventions for PTSD.

These results suggest that the ACC and DLPFC, 2 major cognitive-emotional modulation areas, and their connections to somatosensory areas, are functionally involved in the analgesic effect of THC in chronic pain. This effect may therefore be mediated through induction of functional disconnection between regulatory high-order affective regions and the sensorimotor cortex. Moreover, baseline functional connectivity between these brain areas may serve as a predictor for the extent of pain relief induced by THC.