Self-Organized Criticality as a new paradigm of sleep regulation

In addition to the regular circadian sleep-wake pattern, humans and animals often exhibit brief awakenings from sleep (arousals), lasting from seconds to minutes, which appear random in time and occur throughout the entire sleep period. Arousals are traditionally viewed as random disruptions of sleep caused by external stimuli or as involved in the pathophysiology of sleep disorders. According to the American Sleep Disorders Association criteria, arousals are a marker of sleep disruption representing a detrimental feature for sleep (Atlas Task Force 1992).

We have recently discovered that brief arousals exhibit temporal organization characterized by a power-law probability distribution for their durations, while sleep-stage durations exhibit exponential behavior. Such complex scale-invariant organization of the arousals makes it unlikely that they are merely a linear response to random external stimuli or that they are primarily associated with sleep pathology, as we observe this behavior under healthy conditions and across various mammalian species.

This unique coexistence of both scale-invariant (no characteristic time scale) and exponential (with a characteristic time scale) processes as an output of a single sleep regulatory mechanism has not been observed in other integrated physiological systems under neural regulation prior to our discovery. This coexistence resembles the dynamical features of certain physical systems out of equilibrium exhibiting self-organized criticality (SOC), where “quiet” periods following an exponential law are interrupted by recurring “active” periods having scale invariant power-law characteristics for their size and duration; and where triggering of frequent active periods over a broad range of time scales is an essential component in the self-organization of the system, needed to maintain its critical state. The current conceptual framework for sleep regulation, which is based on homeostasis and oscillatory rhythms at and above ultradian time scales, cannot account for the scale-invariant temporal structure of arousals and cannot explain the SOC-type fine architecture of sleep dynamics that occurs at time scales much shorter than the ultradian and circadian time scales.

We propose a new framework, based on the concept of SOC, to investigate non-equilibrium features in sleep dynamics, where specific neuronal groups and signaling pathways, nonlinear neuronal feedback interactions and network topologies lead to emergent scale-invariant organization at the system level. Novel markers of sleep dynamics derived from this new framework will capture very different aspects of sleep regulation as compared to traditional measures, and thus, have the potential to improve current diagnosis and treatment of sleep disorders. We propose an innovative approach that combines sleep physiology and biochemical/genetic experiments with modern concepts from statistical physics and recent advances in the theory of complex networks, to address our specific aim: (i) to elucidate the basic mechanisms leading to scale-invariant organization of arousals during healthy sleep in coexistence with a scale-specific (exponential) structure of the sleep-stage durations; (ii) to uncover how pathologic conditions affect this complex SOC-type organization of arousals and sleep-stage transitions at short, sub-ultradian scales; (iii) to derive novel diagnostic markers of sleep disorders, which could be utilized to quantitatively assess effects of pharmacological treatments.

We analyze large pre-existing databases of polysomnographic recordings from (i) healthy human subjects; (ii) human subjects with sleep disorders; (iii) data from wild type mice and rats; and (iv) data from mouse and rat models, where certain wake- and sleep-promoting neuronal pathways are blocked or specific neuronal groups are lesioned, in order to discern which key elements of the biochemical circuitry of neuronal interactions may be responsible for the emergence of SOC-type complexity in sleep dynamics at the system level.

Provided our analyses and modeling of these data in relation to the micro-architecture of arousals and sleep-stage transitions confirm the presence of SOC, this will challenge the current dominant paradigm of sleep regulation as a system in equilibrium. Indeed, our preliminary analyses suggest that local neuronal interactions in the sleep regulatory network may exhibit fluctuating patterns of excitations and avalanches which are simultaneously and heterogeneously distributed throughout the network, preserving an out-of-equilibrium “critical” state, which enables the system to flexibly respond to stimuli and to facilitate rapid arousal and sleep-stage transitions.

Related Publications:

Book Chapters:

Parmeggiani PL, Bartsch RP, and Ivanov PCh.

Physiologic Regulation in Sleep. [ PDF ]

In "Atlas of Clinical Sleep Medicine", edited by Kryger M. Elsevier Inc. Publisher; 2013; p.36-40.

Ivanov PCh, Lo C-C.

Stochastic Approaches to Modeling of Physiological Rhythms. [ PDF ]

In "Modelling Biomedical Signals", edited by Nardulli G, Stramaglia S. Singapore: World Scienti.c; 2002; pp. 28-50.

Peer-Reviewed Articles and Conference Proceedings:

Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper, C.B., Scammell, T.E. and Ivanov, P.C.

Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. [PDF]

Journal of Neuroscience, 2020, 40(1), pp.171-190.

Jilin W. J. L. Wang,Fabrizio Lombardi,Xiyun Zhang ,Christelle Anaclet, Plamen Ch. Ivanov

Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. [PDF]

(Supporting Information [PDF])

PLOS Computational Biology 15(11): e1007268.

Hila Dvir, Idan Elbaz, Shlomo Havlin, Lior Appelbaum, Plamen Ch. Ivanov, and Ronny P. Bartsch

Neuronal noise as an origin of sleep arousals and its role in sudden infant death syndrome. [PDF]

Science Advances, 2018:Vol. 4, no. 4, eaar6277

Lo C-C, Bartsch RP, Ivanov PCh.

Asymmetry and basic pathways in sleep-stage transitions. [ PDF ]

Europhysics Letters (EPL) 2013; 102(1): 10008

Ivanov PCh, Lo C-C, and Bartsch RP.

Scale-invariant pattern in arousals during sleep.

Proceedings of Biosignal: Advanced Technologies in Intensive Care and

Sleep Medicine, Berlin, Germany, 2010; p.17-20.

Ivanov PCh, Lo C-C.

Quantification of sleep fragmentation through the analysis of sleep-stage transitions.

Sleep 2007; 30:A212-A212 629 Suppl. S.

Penzel T, Lo C-C, Ivanov PCh, Kesper K, Becker HF, Vogelmeier C.

Analysis of sleep fragmentation and sleep structure in patients with sleep apnea and normal volunteers. [ PDF ]

2005 27TH Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2005; 1-7:2591-2594

Lo C-C, Chou T, Penzel T, Scammell T, Strecker RE, Stanley HE, and Ivanov PCh.

Common scale-invariant patterns of sleep-wake transitions across mammalian species. [ PDF ]

Proc. Natl. Acad. Sci. 2004;101(52):17545-17548.

Lo C-C, Amaral LAN, Havlin S, Ivanov PCh, Penzel T Peter J-H, Stanley HE.

Dynamics of sleep-wake transitions during sleep. [ PDF ]

Europhysics Letters 2002;57(5):625-631.