This paper studies mechanisms of synchronisation and loss of synchrony among the three key oscillatory processes controlling sleep–wake cycles in the human brain: the 24-h circadian oscillator, the homeostatic sleep drive, and the environmental light–dark cycle. Synchronisation of these three rhythms promotes sleep and brain clearance and is critical for human health. Their desynchrony, on the other hand, is associated with impaired performance and disease development, including cancer, cardiovascular disease, and mental disorders. A biophysical model of arousal dynamics simulating sleep–wake cycles and circadian rhythms is used as the study system. It is based on established neurobiological mechanisms controlling sleep–wake transitions and incorporates the three oscillatory processes. Nonlinear dynamics methods and synchronisation theory are used to numerically investigate model dynamics under conditions that are not easily achievable in experiments. The role of homeostatic brain clearance rate in synchronisation is investigated, and selective turning on and off of coupling strengths between the oscillators allows us to determine their role in oscillators’ dynamics. We find that, in the absence of coupling between the circadian and homeostatic oscillators, the default state of the model corresponds to the endogenous homeostatic period that is far from \(\sim \)24-h rhythm of the circadian and light–dark cycles. Combined action of light and circadian oscillator on the homeostatic rhythm is required to achieve the typical sleep–wake pattern that is observed in young healthy people. Under 12-/12-h light–dark conditions with light at 80 lux, change of homeostatic clearance rate is found to induce two types of desynchronisation: (i) fast clearance rates \(\tau _H<58.1\) h desynchronise the homeostatic oscillator from the circadian, while the circadian rhythm remains entrained to the light–dark cycle, and (ii) slow clearance rates \(\tau _H>69\) h maintain synchronisation between the homeostatic and circadian oscillators, but the period of both is different from that of the light–dark cycle. Between these regimes, all three rhythms are synchronised under the studied conditions. The model predicts that the system is highly sensitive to external inputs to the neuronal populations of the sleep–wake switch, which affect the endogenous period of the homeostatic oscillator and can lead to complete loss of sleep. Model dynamics show that loss of synchronisation, which is traditionally ascribed solely to impairment of the circadian oscillator, can be caused by changes in the homeostatic clearance rate of the brain or external input to the neuronal populations of the sleep–wake switch. Thus, changes in circadian, homeostatic, and external factors (combined or specific) may be responsible for conditions of desynchronisation. This has significant implications for understanding individual variability in sleep–wake patterns and in mechanisms of sleep and circadian disorders, indicating that both the homeostatic and circadian mechanisms can be responsible for the same clinical or behavioural presentation of a disease.

本文研究了控制人脑睡眠－觉醒周期的三个关键振荡过程之间的同步和失步机制：24小时昼夜节律振荡器，体内稳态睡眠驱动和环境明暗周期。这三个节律的同步促进睡眠和大脑清除，对人类健康至关重要。另一方面，它们的失步与性能下降和疾病发展相关，包括癌症，心血管疾病和精神疾病。模拟睡眠-觉醒周期和昼夜节律的觉醒动力学的生物物理模型被用作研究系统。它基于控制睡眠-觉醒过渡的既定神经生物学机制，并结合了三个振荡过程。非线性动力学方法和同步理论用于对在实验中不易实现的条件下的模型动力学进行数值研究。研究了稳态脑清除率在同步中的作用，并且有选择地打开和关闭振荡器之间的耦合强度使我们能够确定它们在振荡器动力学中的作用。我们发现，在昼夜节律振荡器和稳态振荡器之间没有耦合的情况下，模型的默认状态对应于远离 选择性地打开和关闭振荡器之间的耦合强度使我们能够确定它们在振荡器动力学中的作用。我们发现，在昼夜节律振荡器和稳态振荡器之间没有耦合的情况下，模型的默认状态对应于远离 选择性打开和关闭振荡器之间的耦合强度使我们能够确定它们在振荡器动力学中的作用。我们发现，在昼夜节律振荡器和稳态振荡器之间没有耦合的情况下，模型的默认状态对应于远离\（\ sim \）昼夜节律和明暗周期的24小时节奏。需要光和昼夜节律振荡器共同作用于稳态节律，以实现在年轻健康人中观察到的典型的睡眠-觉醒模式。在光通量为80 lux的明暗条件下的12 // 12h下，发现稳态清除率的变化会引起两种类型的失步：（i）快速清除率\（tau _H <58.1 \） h使稳态失谐昼夜节律产生的振荡，而昼夜节律仍被带入明暗循环，（ii）清除速率慢（\ tau _H> 69 \）h保持稳态和昼夜节律振荡器之间的同步，但是两者的周期与明暗周期的周期不同。在这些模式之间，所有三个节奏在研究的条件下都是同步的。该模型预测，该系统对睡眠-觉醒开关的神经元群体的外部输入非常敏感，这会影响稳态振荡器的内源性周期，并可能导致睡眠完全丧失。模型动力学表明，同步性的丢失（传统上仅归因于昼夜节律振荡器的损害）可能是由于大脑的稳态平衡清除率或睡眠-觉醒开关的神经元群体的外部输入的变化而引起的。因此，昼夜节律，体内平衡，外部因素（综合因素或特定因素）可能是造成失步状况的原因。这对于理解个体在睡眠-苏醒模式以及睡眠和昼夜节律紊乱的机制中的可变性具有重要意义，表明稳态和昼夜节律机制均可以负责疾病的相同临床或行为表现。