Neural consequences of sleep loss and sleep recovery on the human reward system

描述(由申请人提供)：对愉快、有益的体验的最佳解释有利于做出提高生存能力的决定。然而，寻欢作乐也会导致有害和危及生命的行为，例如滥用药物成瘾、冲动寻求刺激和承担不利风险。这些奖赏机制在一定程度上是由大脑多巴胺通路的活动支持的，包括腹侧被盖核和纹状体。与多巴胺能大脑奖赏敏感度改变越来越相关的一种情况是睡眠不足。睡眠不足可触发大鼠脑内多巴胺能网络的放大反应 对愉悦体验的反应，提高这些回路中的多巴胺水平，并进一步增强这些网络中的多巴胺受体敏感性。尽管有这些新出现的证据，但睡眠不足对人类大脑奖励过程和相关行为的影响在很大程度上仍然没有定论。此外，这些神经和行为过程在多大程度上可以通过剥夺后的恢复睡眠来恢复，同样是未知的。考虑到已知的与奖赏大脑活动改变相关的许多成瘾障碍的睡眠中断，表征这种潜在的因果相互作用的需要值得关注。确定这种相互作用将意味着睡眠不足是导致响应性增强的诱因风险因素，从而可能导致对奖励刺激药物的上瘾。这将进一步表明睡眠中断在维持成瘾习惯方面的作用，特别是在试图戒断期间。在这里，我们建议使用功能磁共振扫描结合既定的奖励范例和睡眠生理记录来检验以下中心假设：(I)睡眠剥夺放大了人类多巴胺系统对奖励激励的敏感性，这另外(Ii)使大脑偏向不成比例的海马区奖励驱动学习，以及(Iii)在剥夺之后的一晚恢复睡眠，足以恢复这些神经和行为奖励过程的最佳功能。因此，这项R21建议代表了对睡眠减少和睡眠恢复如何因果地放大人类大脑的奖励敏感性、改变相关行为以及这种功能障碍是否被恢复睡眠逆转的系统评估。考虑到成瘾障碍中睡眠障碍的高患病率和共患性，拟议的研究具有实质性和直接的临床影响以及广泛的公共健康分支，并具有合理的下一步翻译目标。 与公共健康相关：这项建议代表了一项系统的评估，评估了睡眠不足可能会如何因果地放大人类大脑的奖励敏感度；不适应地改变相关行为，以及这种功能障碍是否会被恢复睡眠逆转。考虑到成瘾障碍中睡眠障碍的高患病率和共患性，拟议的研究具有实质性和直接的临床影响以及广泛的公共健康分支，并具有合理的下一步翻译目标。此外，考虑到整个社会睡眠时间的持续减少，特别是在更容易受到奖励和成瘾困难影响的年轻人中，这些研究的适用性进一步提高了相关性。

DESCRIPTION (provided by applicant): Optimal interpretation of pleasurable, rewarding experiences favors decisions that enhance survival. However, pleasure seeking can also lead to deleterious and life- threatening behaviors, exemplified by abusive drug addiction, impulsive thrill seeking and adverse risk taking. These reward mechanisms are supported, in part, by activity in dopamine pathways of the brain, including the ventral tegmental nuclei and striatum. One circumstance increasingly related to altered dopaminergic brain reward sensitivity is the state of sleep deprivation. Sleep loss can trigger amplified reactivity in dopaminergic networks in response to pleasurable experiences, elevate levels of dopamine within these circuits, and further enhance dopamine receptor sensitivity throughout these networks. Despite such emerging evidence, the impact of sleep loss on human brain reward processing and associated behaviors remains largely uncharacterized. Furthermore, the degree to which these neural and behavioral processes can be restored by recovery sleep, following deprivation, is similarly unknown. The need to characterize this potentially causal interaction is worthy of attention considering the known disruption of sleep in numerous addiction disorders associated with altered reward brain activity. Identifying such an interaction would implicate sleep loss as a predisposing risk factor in heightened responsivity and hence addiction potential to reward-stimulating drugs. It would further indicate a role for sleep disruption in the maintenance of addiction habits, especially during attempted withdrawal. Using functional MRI scanning in combination with established reward paradigms and sleep physiological recordings, here we propose to test the central hypothesis that (i) sleep deprivation amplifies sensitivity of the huma dopaminergic system in response to reward incentives, which additionally (ii) biases the brain towards disproportionate hippocampal reward-driven learning, and (iii) one night of recovery sleep, following deprivation, is sufficient to restore optimal functioning of these neural and behavioral reward processes. Therefore, this R21 proposal represents a systematic evaluation of how sleep loss and sleep recovery causally amplify human brain reward sensitivity, altering associated behaviors, and whether such dysfunction is reversed by recovery sleep. Considering the high prevalence and comorbidity of sleep disruption in addiction disorders, the proposed research holds substantive and direct clinical as well as broad public-health ramifications, with logical next-step translational targets. PUBLIC HEALTH RELEVANCE: This proposal represents a systematic evaluation of how sleep loss may causally amplify human brain reward sensitivity; maladaptively altering associated behaviors, and whether such dysfunction is reversed by recovery sleep. Considering the high prevalence and comorbidity of sleep disruption in addiction disorders, the proposed research holds substantive and direct clinical as well as broad public- health ramifications, with logical next-step translational targets. Moreover, considering the continued erosion of sleep time across society, particularly in young populations additionally susceptible to reward and addiction difficulties, the applicability of these studies further increases in relevance.