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

描述（由申请人提供）：愉快的最佳解释，奖励的经验有利于提高生存的决定。然而，寻求快乐也会导致有害和危及生命的行为，例如滥用药物成瘾，冲动寻求刺激和不良风险。这些奖赏机制部分地由大脑的多巴胺通路的活动支持，包括腹侧被盖核和纹状体。与多巴胺能大脑奖赏敏感性改变相关的一种情况是睡眠剥夺状态。睡眠不足可以触发多巴胺能网络的放大反应， 对愉快体验的反应，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。尽管有这些新的证据，睡眠不足对人类大脑奖励处理和相关行为的影响仍然很大程度上没有被描述。此外，这些神经和行为过程可以在多大程度上恢复恢复睡眠，剥夺后，同样是未知的。考虑到许多成瘾性疾病中已知的睡眠中断与奖励脑活动的改变有关，需要描述这种潜在的因果相互作用是值得关注的。识别这种相互作用将暗示睡眠不足是提高反应性的诱发风险因素，因此对奖励刺激药物成瘾的可能性。这将进一步表明睡眠中断在维持成瘾习惯中的作用，特别是在试图戒断期间。使用功能性MRI扫描结合已建立的奖励范例和睡眠生理记录，在这里，我们建议测试中心假设，即（i）睡眠剥夺放大了人类多巴胺能系统对奖励激励的敏感性，另外（ii）使大脑偏向不成比例的海马奖励驱动学习，以及（iii）一晚的恢复睡眠，剥夺后，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建议代表了对睡眠丧失和睡眠恢复如何因果地放大人类大脑奖励敏感性，改变相关行为，以及这种功能障碍是否被恢复性睡眠逆转的系统评估。考虑到成瘾性疾病中睡眠中断的高患病率和合并症，拟议的研究具有实质性和直接的临床以及广泛的公共卫生影响，具有合乎逻辑的下一步翻译目标。

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.