Christian Cajochen, PhD
Centre for Chronobiology
Psychiatric Hospital of the University of Basel, Switzerland
Beyond our eyes: the non-visual impact of light
SLL-erate final event October 13, 2016, Brussels
Thomas Edison was maybe wrong !
Distribution of nighttime radiance calibrated lights
Artificial outdoor nighttime lights associate with altered sleep behavior in the American general population (n=19’136)
Ohayon and Miles, Sleep, 2016
Buttgereit, Smolen, Coogan, Cajochen, Nat Rev Rheumatol, 2015
Light is the most important Zeitgeber !
Induction of a Phase Delay in the Human Circadian Melatonin Rhythm by Light (10’000 lux for 6.5 h)
Khalsa et al., J Physiol (London) 2003
Time of Day
12 24 12 24 12 24 12 24 12
Pla
sma
Me
lato
nin
(p
Mo
l/L)
0
100
200
300
400 Light
Midpoint 4:45
Midpoint 8:21
Light and human circadian rhythms Melatonin as the best circadian marker in humans
Sleep period
Retina -4
-3
-2
-1
0
1
2
3
4
0 3 6 9 12 15 18 -3 -6 -9 -12 -15 -18
Initial Phase (time relative to DLMO=0)
Ph
ase
sh
ift
(h)
Khalsa, et al., J Physiol (London) 2003
6.7 hours 10’000 lux polychromatic white light
Phase-Response Curve
Light and circadian phase
«Light impacts on our circadian rhythms more powerfully than any drug»
Charles Czeisler «Casting light on sleep deficiency» Nature, 2013
Suppression of melatonin in a totally blind person with bright light
Sighted Person
Time of Day (h)
36.0
36.5
37.0
37.5
200
300
100 Plasma Melatonin
(pmol/liter)
Core Body Temperature (°C)
Blind Person
12 18 24 6 12 18 24 6 12
36.0
36.5
37.0
37.5
200
300
100
Core Body Temperature (°C)
Plasma Melatonin (pmol/liter)
12 18 24 6 12 18 24 6 12
Czeisler et al., New Engl Med 1995
Time of Day (h)
Light is more than vision non-visual / non-image forming light effects
Light can be «seen» without conscious vision
*
«Forced choice» test in a totally blind person
100
80
60
40
20
0 420 460 481 500 506 515 540 560 580
Wavelength (nm)
Co
rre
ct A
nsw
er
(%)
Nach Zaidi et al., Curr Biol, 2007
SCN (circadian Pacemaker)
Retina Cones
Eye A dual sensory organ
Rods
Non-classical Photoreceptor intrinsic photosensitive retinal ganglion
cells (iPRGs, Melanopsin)
Hattar et al. Science, 2002 Berson et al. Science, 2002
Retina -4
-3
-2
-1
0
1
2
3
4
0 3 6 9 12 15 18 -3 -6 -9 -12 -15 -18
Initial Phase (time relative to DLMO=0)
Ph
ase
sh
ift
(h)
Khalsa, et al., J Physiol (London) 2003
6.7 hours 10’000 lux polychromatic white light
Rüger, et al., J Physiol (London) 2013
75 % of the resetting response
6.5 hours blue light (480 nm) 11.8 μWcm−2, 11.2 lux)
Phase-Response Curve
Light and circadian phase
* p<0.04; Duncans‘ multiple range test
Salivary Melatonin
0
2
4
6
8
10
Time of Day (h)
Non-LED Screen
LED Screen
Dar
k A
dap
tati
on
Bas
elin
e
~ 60 min
* * * *
pg/
ml
18:15 19:15 20:15 21:15 22:15 23:15 00:15
Cajochen et al., J Appl Physiol. 2011
Effects of LED-backlit computer screens on salivary melatonin, alertness and cognitive performance in the evening
Cold Cathode Fluorescent Lamp
(CCFL)
Light Emitting Diode (LED )
Ja
nicht beantwortet
Use of smartphones 1 hour prior bedtime
99% yes
irgendwo in derWohnung
irgendwo im Zimmer
auf dem Nachttisch
im Bett
nicht beantwortet
Where do you keep your smartphone during night?
60%
14% 23%
97% in bedroom
nie
selten
gelegentlich
häufig
nicht beantwortet
How often do you use your smartphone after «Lights off»
49%
25%
15%
10%
74% occasionally-often
Smartphone use in adolescents (14-20 years)
Strube et al. Somnologie, 2016
99 %
400 450 500 550 600 650 700
0
0.2
0.4
0.6
0.8
1.0 R
ela
tive
Am
plit
ud
e
Wavelength
“Ipad” versus “Blue-blockers” Transmission Spectra
iPad Orange-tinted glasses (blue blockers)
Time of day
pg/
ml
0
2
4
6
8
10
12
14
16
Dim Dim
Sle
ep
LED/glasses Dark
*
* *
* Blue Blockers for one week
Clear Lenses for one week
Evening Melatonin Levels in Adolescents
van der Lely et al., J Adolesc Health, 2014
Light has also «non-circadian» acute effects
• Light suppresses the soporific hormone melatonin within minutes (Gronfier et al., 2002)
• Light inhibits sleep-promoting GABA neurons in the ventrolateral preoptic area in the hypothalamus (VLPO, Tsai et al., 2009)
• Light activates wake-promoting orexin neurons in the lateral hypothalamus (McGregor et al., 2011)
0 1 2 3
Time elapsed from light onset (h)
Sle
ep
Re
spo
nse
(m
in)
0
30
60
Lights ON Lights OFF
Wildtype
Melanopsin knockout
According to Muindi et al., Front Syst Neurosci, 2014
Melanopsin aDTA
Acute sleep induction by light in nocturnal mice
Illuminance (lux)
10 100 1000 10000
Subjective Alertness
5
10
15
20
25
mo
re a
lert
Cajochen et al., Beh Brain Res. 2000
120 lux !
Acute alerting effects of light in diurnal humans
Kar
olin
ska
Sle
ep
ine
ss S
cale
(K
SS)
6
7
8
The human alerting response to light is blue-shifted
% S
leep
ines
s C
han
ge
0 =
pre
-lig
ht
0
10
20
30
40
50
4
5
6
Kar
olin
ska
Sle
ep
ine
ss S
cale
(K
SS)
Cajochen et al., Sleepiness and human impact assessment Book chapter, Springer, 2014
Monochromatic light Energy Saving Lamps Computer Screens
Sle
ep
Time of day
KSS
-sco
re
2
3
4
5
6
7
8
Blue Blockers for one week
Clear Lenses for one week
* *
Dim LED/glasses Dim
Sle
ep
*
Subjective Sleepiness in Adolescents
Blocking blue light in the evening
Dark
van der Lely et al., J Adolesc Health, 2014
Does light affect higher cognitive functions ?
Does light make you bright?
Sustained Attention and Response Control (Go/noGo Task)
LED Screen
Monitor: F1,11=12.2; p<0.04 Time of day: F11,44=7.8; p<0.02 Monitor x Time: F12,132=3.0; p=0.041
Letter „W“: go Letter „M“ : no-go
18:15
Time of Day (h)
Non-LED Screen
Dar
k A
dap
tati
on
Bas
elin
e
Re
lati
ve R
eac
tio
n T
ime
(%
)
19:15 20:15 21:15 22:15 23:15 00:15
90
95
100
105
110
fast
er
slo
we
r
* *
* P <0.05
Cajochen et al., J Appl Physiol. 2011
Declarative Learning (Word pairs)
Non-LED
LED Screen
Correctly identified word pairs
%
45
50
55
60
65
70
Cajochen et al., J Appl Physiol. 2011
Correctly identified new word pairs
45
50
55
60
65
70
*
* P <0.05
Modified from Vandewalle et al. Trends Cogn Sci, 2009
Light is not just for vision
Cortex
Thalamus
Hypothalamus
Brainstem - Locus coeruleus
Limbic system - Amygdala - Hippocampus
Light has many non-visual biological effects in humans (only peer reviewed data)
• Synchronization of circadian rhythms
• Suppression of the «darkness hormone» melatonin
• Alerting and enhancing of cognitive performance
• Regulation of pupil size
• Enhancing mood (antidepressant)
• Enhancing physical performance in top athletes
• Light color modulates mental effort
• Light rules our body via its non-visual effects
• Blue wavelengths -- which are beneficial during daylight hours because they boost attention, reaction times, mood, and physical performance -- are most disruptive at night
• The proliferation of electronics with screens, as well as energy-efficient lighting, is increasing our exposure to blue wavelengths, especially after sundown
Conclusion
Non-visual lighting solutions should be:
Dynamic • Intensity and duration • Spectral composition • According to time of day
Individual • Age • Gender • Chronotype (early vs.late people)
Intelligent human centric lighting to adapt our illuminated surroundings such that we do not jeopardize quality of life and health but positively influence our
sleep, circadian physiology, cognition and well-being
Wanted
Human Centric Lighting
enter
the room by
Human centric lighting supports your health
and promotes
Acknowledgements
Centre for Chronobiology www.chronobiology.ch
• Antoine Viola, PhD
• Christina Schmidt, PhD
• Mirjam Münch, PhD
• Sarah Chellappa, PhD
• Vivien Bromundt, PhD
• Jakub Späti, PhD
• Sylvia Frey, PhD
• Virginie Gabel
• Micheline Maire
• Carolin Reichert
• Stephanie van der Lely
Swiss Federal Office for Public Health Daimler-Benz Foundation EU IP