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