Quantitative modelling of sleep-wake cycles and application to shiftwork Svetlana Postnova Alertness CRC Ltd & School of Physics, The University of Sydney, Australia Alumni of the Physics Faculty at the Saratov State University, year 2004

Why model sleep-wake cycles? We spend 1/3 of our lives asleep Still don’t know why we need to sleep Lack of sleep leads to fatigue, accidents, stress, and disease 20% of fatal road accidents happen due to driver’s fatigue. Picture from Picture from

Significant risk group - shiftworkers work irregular hours  sleep is disturbed every 5 th person works shifts, e.g. medical personnel, police force, pilots, … Poor quality of life have twice the number of accidents increased risk of disease, e.g., diabetes, obesity, heart disease, and cancer. Why model sleep-wake cycles? Modelling can help to understand the biological system predict dynamics develop interventions Photo from /

Biology of sleep-wake cycles Sleep-wake cycles result from interaction between circadian and homeostatic processes Homeostatic (H) –sleep need increases a function of time awake Circadian (C)– oscillator with a ~24h period whose phase depends on light input Borbely and Achermann, 1999, J Biol Rhythms These processes affect the dynamics of sleep- and wake-active neuronal populations Saper et al., 2005, Nature H C

Quantitative model of sleep-wake cycles Based on biology Simulates mean activity of neuronal populations involved in sleep-wake regulation (Neural Field Theory) Validated against experiments For full system of equations and detail see Postnova et al., 2013 PLoS one (open access) Postnova et al., 2012, 2014 J Biol Rhythms For sleep-wake part of the model see Phillips et al., 2007 J Biol Rhyths Fulcher et al., 2010 J Theor Biol Postnova et al., 2012, J Biol Rhythms

Quantitative model of sleep-wake cycles: how it works Sleep Drive, D (mV) V MA, (mV) Fulcher et al., 2010, J Theor Biol wake sleep Circadian phase is affected by light input: Light in the morning – advance Light in the evening – delay Light input depends on what you do, e.g. Go outside into sunlight Stay up late with lights on Circadian (C) Homeostatic (H) Sleep drive (D) Fulcher et al., 2010, J Theor Biol wake sleep wake sleep

Application to shiftwork: effects of shift light intensity Postnova et al., 2013, PLoS one Shift – awake Break – sleep Light intensity * Circadian phase marker room lightbright light Bright light improves adaptation to night shifts Amount of sleep increases in bright light case Sleep drive, D (mV) before after room lightbright light after before Sleepiness during shifts is significantly reduced in bright light case

Summary Quantitative biology-based modelling is a powerful tool that can improve understanding of the system and be applied to real-life problems The model of sleep-wake cycles was validated against experiments and also used to study - sleep of different animals, including dolphins and wales - effects of caffeine - effects of alarm clock set at different volume and time - effects of sleep deprivation - adaptation to jetlag - dynamics on different types of shift schedules For references see dynamics/index.shtmlhttp://sydney.edu.au/science/physics/research/complex-systems/brain- dynamics/index.shtml or google “brain dynamics complex systems USYD” Write to for

Acknowledgements Prof. Peter Robinson (University of Sydney, Australia) Dr Andrew Philips (Harvard University, USA) Dr Ben Fulcher (Monash University, Australia) Dmitry Postnov (University of Copenhagen, Denmark) Romesh Abeysuriya (University of Sydney, Australia) Andrew Layden (University of Sydney, Australia) And many other people who worked on the model Funded by Australian Research Council and National Health and Medical Research Council through the Centre for Integrated Research and Understanding of Sleep (CIRUS)