Nonlinear dynamical systems and

chronobiology
Mauro Forlino
 Contents
● Introduction
– Nonlinear dynamical systems
– Chronobiology
● Case Study
– Model
– Entrainment Features and Constrains
– Method
– Results
● Conclusions
 Nonlinear dynamical systems

Linear system: x̄ '=f ( x̄)= A . x̄ x1

.
x̄=( . )
Nonlinear system: f ( x̄) contains nonlinear terms .
such as: x1x2, (x1)2, cos(x2)
xn
 Nonlinear dynamical systems
● Most non-linear systems are impossible to
solve analytically. We can only solve them
numerically.

● Nature doesn’t always behave like a linear

system.
Phase space representation

Stable, periodic oscillation → closed orbit

 Chronobiology
● Chronobiology is a field of biology that
examines timing processes, including periodic
(cyclic) phenomena in living organisms, such as
their adaptation to solar- and lunar-related
rhythms
Patricia J. DeCoursey; Jay C. Dunlap; Jennifer J. Loros (2003). Chronobiology. Sinauer Associates Inc. ISBN 978-0-
87893-149-1.
 Cellular clocks: self-sustained
oscillators
The oscillation is:
● Self-sustained, endogenous.
● Period determined by internal parameters.
● Stable: perturbations – transient – restoration.
● Delayed or advanced by phase shifts time.
dependently
● Phase shifts are not transient.
 Limit cycles
● Self-sustained, endogenous.
● Period determined by internal parameters.
● Stable: perturbations – transient – restoration.

● Limit cycle: Isolated closed trajectory.

● Isolated: neighboring trajectories are not
closed.
 Why not using a linear system?
● Stable limit cycles model systems that exhibit
self-sustained oscillations.
● Limit cycles are inherently nonlinear
phenomena
● If x(t) is a solution of x’ = Ax
Then cx(t) is also a solution of x’ = Ax
Phase Response Curve (PRC)

● Delayed or
advanced by
phase shifts
time.
dependently
● Phase shifts are
not transient.
PRC representation in a limit cycle
Advance Limit cycle with fast
radial relaxation:
● Delayed or
advanced by
No phase shift phase shifts
time.
dependently
● Phase shifts are
not transient.
Delay
 Entrainment
● Entrainment occurs when a biological oscillator
matches their period to that of an environmental
oscillation (Zeitgeber).
● After entrainment the phase difference between
zeitgeber and oscillator remains constant (Phase of
entrainment ψe).
● Entrainment is due to the daily resetting of the
pacemaker by the Zeitgeber.
● The PRC determines the range of entrainment.
 Entrainment

τ=T
Zeitgeber period: T
Free runing period: τ
Phase of entrainment: ψe

ψe

τ>T
3 way of modeling
 Case Study
● Model oscillator with a nonlinear dynamical
sytem that fullfils certain constrains and
entrainment features.
Model: Poincaré Oscilator
Model: Poincaré Oscilator
Model in Cartesian coordinates
 Entrainment Features and Model
Constraints
● PRC with small phase shifts.
● Fast recovery from jet lag.
● Phase markers can lock to dusk or dawn for
varying day-lengths.
 PRC with small face shifts

● Max phase shift: 1 or 2 hr

Khalsa, S. B. S., Jewett, M. E., Cajochen, C., and Czeisler, C. A. (2003). A phase response curve to single bright light pulses in
human subjects.
 PRC with small face shifts
Numerically calculate the phase response curve PRC (φ )
of the free running oscillator to which a 6 hour long pulse is
added at φ

The maximum phase shift is: Δ φ max =maxφ |PRC (φ )|

 Fast recovery from jet lag

● Reduce the jet lag-induced phase

shift by 50 % within 2 days.

Reddy, A., Field, M., Maywood, E., and Hastings, M. (2002). Differential resynchronisation of circadian clock gene expression within
the suprachiasmatic nuclei of mice subjected to experimental jet lag
 Fast recovery from jet lag
Phase difference: ψ =Ψ−φ
Converges to the phase of entrainment: ψe
An increase in the Zeitgeber phase is added (jet lag): ΔΨ
New phase difference: ψ =ψ e +Δ Ψ
Half-time of re-entrainment: T e When: |ψ −ψ e|<0.5 Δ Ψ
Phase markers can lock to dusk or
dawn for varying day-lengths

● Phases change by 4h, if we switch

from 16:8 LD conditions to 8:16 LD
conditions

Rémi, J., Merrow, M., and Roenneberg, T. (2010). A circadian surface of entrainment:
varying T, τ , and photoperiod in Neurospora crassa.
Phase markers can lock to dusk or
dawn for varying day-lengths
Numerically solve the phase of entrainment ψ e for
various photoperiods x

Δ ψ =max x∈[1/3,2/3] ψ e −min x∈[1/3,2/3] ψ e

 Minimization of the cost function
2 2
(T e −48 h) (Δ φ max −1 h) 2
(Δ ψ −4 h)
E ( A , ω , λ )= 2
+ 2
+ 2
(24 h) (1 h) (4 h)

● Te: Half-time to re-entrainment.

● Δφmax: Maximum phase shift.
● Δψ: Seasonal phase variability.
 Method
● To find optimal parameter values, the cost function
was minimized by a particle swarm optimization
algorithm (Eberhart and Kennedy, 1995; Trelea, 2003).
● Search ranges of the parameter values were set to:
– A∈[0, 5]
– ω∈[2π/30 rad/h, 2π/18 rad/h]
– λ∈[0h−1, 0.5h−1]
Results
Phase response curve
Seasonal variability
Phase response curve
Parameter values in the optimized ensamble
Arnold Onions
 Conclusions
● Biological oscillators can be modeled by nonlinear dynamical systems.
● Many parameter sets where found that reproduced experimentally
observed features:
– A is adjusted to reproduce PRC
– Fast relaxation rates to support fast recovery from jet lag.
– Specific period selected that leads to a 4h phase variation between x=1/3 and
x=2/3
– Period mismatch (T-τ) and photoperiod have strong effects over entrainment
phase.
Thank you for your attention