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

睡眠不足和睡眠恢复对人类奖励系统的神经影响

• 批准号: 8458528
• 负责人: Matthew P Walker
• 金额: $ 19.88万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8458528
• 关键词: Acute; Adult; Attention; Behavior; Behavioral; Binding; Brain; Cell Nucleus; Clinical; Comorbidity; Control Groups; Corpus striatum structure; Crossover Design; Cues; Disease; Dopamine; Dopamine Receptor; Drug Addiction; Electroencephalography; Episodic memory; Evaluation; Functional Magnetic Resonance Imaging; Functional disorder; Habits; High Prevalence; Hippocampus (Brain); Human; Incentives; Lead; Learning; Life; MRI Scans; Maintenance; Measures; Memory; Neurophysiology - biologic function; Nucleus Accumbens; Participant; Pharmaceutical Preparations; Physiological; Population; Process; Public Health; REM Sleep; Recovery; Relative (related person); Research; Rest; Rewards; Risk Factors; Risk-Taking; Rodent; Role; Scanning; Sleep; Sleep Deprivation; Societies; Stimulus; System; Testing; Time; Withdrawal; addiction; brain pathway; density; deprivation; emotional stimulus; experience; high reward; indexing; innovation; memory encoding; mesolimbic system; pleasure; radioligand; receptor sensitivity; relating to nervous system; response; reward processing; therapeutic target

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.

描述（由申请人提供）：对愉快、有益的经历的最佳解释有利于提高生存率的决定。然而，寻求快乐也可能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冒险行为。这些奖励机制部分受到大脑多巴胺通路活动的支持，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越来越相关的一种情况是睡眠剥夺状态。睡眠不足会引发多巴胺能网络的放大反应 对愉悦体验的反应，提高这些回路内的多巴胺水平，并进一步增强整个这些网络中的多巴胺受体敏感性。尽管有这些新的证据，但睡眠不足对人类大脑奖励处理和相关行为的影响在很大程度上仍然未知。此外，剥夺后通过恢复性睡眠可以在多大程度上恢复这些神经和行为过程，同样也是未知的。考虑到已知的许多与奖赏性大脑活动改变相关的成瘾性疾病中的睡眠中断，描述这种潜在因果相互作用的必要性值得关注。确定这种相互作用将表明睡眠不足是反应性增强的诱发风险因素，因此可能对奖励刺激药物成瘾。这进一步表明睡眠中断在维持成瘾习惯中的作用，特别是在尝试戒断期间。使用功能性 MRI 扫描与已建立的奖励范式和睡眠生理记录相结合，我们建议测试以下中心假设：（i）睡眠剥夺会增强人类多巴胺能系统对奖励激励的敏感性，此外（ii）使大脑偏向于不成比例的海马奖励驱动学习，以及（iii）剥夺后一晚的恢复性睡眠 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 提案代表了对睡眠不足和睡眠恢复如何因果增强人类大脑奖励敏感性、改变相关行为以及恢复睡眠是否可以逆转这种功能障碍的系统评估。考虑到成瘾障碍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，并具有合理的下一步转化目标。