Although schizophrenia is defined by waking phenomena, a growing literature documents a deficit in sleep spindles, a defining oscillation of stage 2 non-rapid eye movement sleep. Compelling evidence supports an important role for spindles in cognition, and particularly memory. In schizophrenia, although the spindle deficit correlates with impaired sleep-dependent memory consolidation, recent clinical trials find that increasing spindles does not improve memory. This may reflect that sleep-dependent memory consolidation relies not on spindles alone, but also on their precise temporal coordination with cortical slow oscillations and hippocampal sharp-wave ripples. Consequently, interventions to improve memory in schizophrenia must not only increase spindles, but also preserve or enhance slow oscillations, hippocampal ripples and their temporal relations. Because hippocampal ripples and the activity of the thalamic spindle generator are difficult to measure noninvasively, screening potential interventions requires complementary animal and human studies. In this review we (i) propose that sleep oscillations are novel pathophysiological targets for therapy to improve cognition in schizophrenia; (ii) summarize our understanding of how these oscillations interact to consolidate memory; (iii) suggest that a systems neuroscience strategy is essential to selecting and evaluating effective treatments, and illustrate this with findings from clinical trials; and (iv) selectively review the interventional literature relevant to sleep and cognition, covering both pharmacological and noninvasive brain stimulation approaches. We conclude that coordinated sleep oscillations are promising targets for improving cognition in schizophrenia and that effective therapies will need to preserve or enhance sleep oscillatory dynamics and restore function at the network level.

中文翻译：

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针对睡眠波动来改善精神分裂症患者的记忆力


尽管精神分裂症是通过清醒现象来定义的，但越来越多的文献记录了睡眠纺锤波的缺陷，这是第二阶段非快速动眼睡眠的典型振荡。令人信服的证据支持纺锤体在认知，特别是记忆中的重要作用。在精神分裂症中，尽管纺锤体缺陷与睡眠依赖性记忆巩固受损相关，但最近的临床试验发现，增加纺锤体并不能改善记忆。这可能反映出，睡眠依赖性记忆巩固不仅仅依赖于纺锤体，还依赖于它们与皮质慢振荡和海马尖波波纹的精确时间协调。因此，改善精神分裂症记忆力的干预措施不仅必须增加纺锤波，还必须保持或增强慢振荡、海马波纹及其时间关系。由于海马波纹和丘脑纺锤体发生器的活动难以无创测量，因此筛选潜在的干预措施需要补充动物和人体研究。在这篇综述中，我们 (i) 提出睡眠振荡是改善精神分裂症认知治疗的新病理生理学目标； (ii) 总结我们对这些振荡如何相互作用以巩固记忆的理解； (iii) 表明系统神经科学策略对于选择和评估有效治疗至关重要，并用临床试验的结果说明这一点； (iv) 有选择地回顾与睡眠和认知相关的介入文献，涵盖药理学和非侵入性脑刺激方法。 我们的结论是，协调的睡眠振荡是改善精神分裂症认知的有希望的目标，有效的治疗需要保持或增强睡眠振荡动力学并恢复网络水平的功能。