No abstract

Evidence indicates that sleep after learning is critical for the subsequent consolidation of human memory. Whether sleep before learning is equally essential for the initial formation of new memories, however, remains an open question. We report that a single night of sleep deprivation produces a significant deficit in hippocampal activity during episodic memory encoding, resulting in worse subsequent retention. Furthermore, these hippocampal impairments instantiate a different pattern of functional connectivity in basic alertness networks of the brainstem and thalamus. We also find that unique prefrontal regions predict the success of encoding for sleep-deprived individuals relative to those who have slept normally. These results demonstrate that an absence of prior sleep substantially compromises the neural and behavioral capacity for committing new experiences to memory. It therefore appears that sleep before learning is critical in preparing the human brain for next-day memory formation-a worrying finding considering society's increasing erosion of sleep time.

Relational memory, the flexible ability to generalize across existing stores of information, is a fundamental property of human cognition. Little is known, however, about how and when this inferential knowledge emerges. Here, we test the hypothesis that human relational memory develops during offline time periods. Fifty-six participants initially learned five ''premise pairs'' (A>B, B>C, C>D, D>E, and E>F). Unknown to subjects, the pairs contained an embedded hierarchy (A>B>C>D>E>F). Following an offline delay of either 20 min, 12 hr (wake or sleep), or 24 hr, knowledge of the hierarchy was tested by examining inferential judgments for novel ''inference pairs'' (B>D, C>E, and B>E). Despite all groups achieving near-identical premise pair retention after the offline delay (all groups, >85%; the building blocks of the hierarchy), a striking dissociation was evident in the ability to make relational inference judgments: the 20-min group showed no evidence of inferential ability (52%), whereas the 12-and 24-hr groups displayed highly significant relational memory developments (inference ability of both groups, >75%; P < 0.001). Moreover, if the 12-hr period contained sleep, an additional boost to relational memory was seen for the most distant inferential judgment (the B>E pair; sleep ‫؍‬ 93%, wake ‫؍‬ 69%, P ‫؍‬ 0.03). Interestingly, despite this increase in performance, the sleep benefit was not associated with an increase in subjective confidence for these judgments. Together, these findings demonstrate that human relational memory develops during offline time delays. Furthermore, sleep appears to preferentially facilitate this process by enhancing hierarchical memory binding, thereby allowing superior performance for the more distant inferential judgments, a benefit that may operate below the level of conscious awareness.association ͉ inference ͉ learning ͉ offline

Appropriate interpretation of pleasurable, rewarding experiences favors decisions that enhance survival. Conversely, dysfunctional affective brain processing can lead to life-threatening risk behaviors (e.g. addiction) and emotion imbalance (e.g. mood disorders). The state of sleep deprivation continues to be associated with maladaptive emotional regulation, leading to exaggerated neural and behavioral reactivity to negative, aversive experiences. However, such detrimental consequences are paradoxically aligned with the perplexing antidepressant benefit of sleep deprivation, elevating mood in a proportion of patients with major depression. Nevertheless, it remains unknown how sleep loss alters the dynamics of brain and behavioral reactivity to rewarding, positive emotional experiences. Using fMRI, here we demonstrate that sleep deprivation amplifies reactivity throughout human mesolimbic reward brain networks in response to pleasure-evoking stimuli. In addition, this amplified reactivity was associated with enhanced connectivity in early primary visual processing pathways and extended limbic regions, yet with a reduction in coupling with medial- and orbito-frontal regions. These neural changes were accompanied by a biased increase in the number of emotional stimuli judged as pleasant in the sleep-deprived group, the extent of which exclusively correlated with activity in mesolimbic regions. Together, these data support a view that sleep deprivation is not only associated with enhanced reactivity towards negative stimuli, but imposes a bi-directional nature of affective imbalance, associated with amplified reward-relevant reactivity towards pleasure-evoking stimuli also. Such findings may offer a neural foundation on which to consider interactions between sleep loss and emotional reactivity in a variety of clinical mood disorders.