Effects of light on human circadian rhythms, sleep and cognition Christian Cajochen Centre for Chronobiology Psychiatric Hospital of the University of Basel Basel, Switzerland 17.12.214, Tel Aviv, Israel
«Light impacts on our circadian rhythms more powerfully than any drug» Charles Czeisler «Casting light on sleep deficiency» Nature, 213
Light effects on human circadian rhythms Phase & Tau Light on circadian rhythms Amplitude Width
Plasma Melatonin (pmol/l) Light and circadian phase Induction of a Phase Delay (3.6 h) in the Human Circadian Melatonin Rhythm by Light (1 lux for 6.5 h) Midpoint 4:45 Midpoint 8:21 4 Light 3 2 1 12 24 12 24 12 24 12 24 12 Time of Day Khalsa et al., J Physiol (London) 23
Plasma Melatonin (pmol/l) Light and circadian amplitude Progressive Amplitude Attenuation and Loss of Melatonin Rhythm in Response to a three-cycle Light Stimulus (95 lux) 3 Subject #1238 2 ~ 32 h 1 : : : : : : : : Time of Day (h) Shanahan et al., J Biol Rhythms, 1999 25 Subject #1757 2 15 1 ~ 55 h 5 : : : : : : : : Time of Day (h) Khalsa et al., unpublished
Plasma Melatonin (pg/ml) Plasma Cortisol (µg/dl) Light and circadian width Hormone Secretion during Continuous Wakefulness after Chronic Exposure to Short and Long Photoperiods 6 5 4 3 2 1 16 12 8 4 Short Photoperiod 8 light/14 h dark (Winter) 18 8 18 8 18 8 18 8 6 5 4 3 2 1 24 8 24 8 Time of Day (h) 16 12 8 4 24 8 24 8 Time of Day (h) Long Photoperiod 8 light/14 h dark (Summer) According to Wehr, Horm Res., 1998
Light has also «non-circadian» acute effects Light suppresses the soporific hormone melatonin within minutes (Lewy et al., 1985) Light inhibits sleep-promoting GABA neurons in the ventrolateral preoptic area in the hypothalamus (VLPO, Tsai et al., 29) Light activates wake-promoting orexin neurons in the lateral hypothalamus (McGregor et al., 211)
New Photoreceptor (Melanopsin) SCN (circadian Pacemaker) Eye Rods Retina Cones Provencio et al., 2, Hattar et al., 22, Hannibal et al., 24 Only ca. 1% of the ganglion cells express melanopsin and are photosensitive
Sleep Response (min) Acute sleep induction by light in nocturnal mice Lights ON Lights OFF 6 Wildtype Melanopsin adta 3 1 2 3 Time elapsed from light onset (h) According to Muindi et al., Front Syst Neurosci, 214
more alert Dose response relationship of the alerting action of light Subjective Alertness 5 1 15 2 12 lux! 25 1 1 1 1 Illuminance (lux) Cajochen et al., Beh Brain Res. 2
Xenon Lamp 3 W Non-Visual Color Vision Filters: 46 nm (1 nm half bandwith) 55 nm (1 nm half bandwith) 12.1 mw/cm 2 for 46 nm 1.5 mw/cm 2 for 55 nm
Superiority of Short-wavelength Light on Human Physiology pg/ml Karolinska Sleepiness Scale (KSS) DD Ct % of Total Sleep Time Melatonin PER2 Expression 16 No-Light ( lux) 55 nm 46 nm.8.4 12. 8 -.4 Subjective Sleepiness Slow Wave Sleep (Stage4) 8 1 7 8 6 6 Cajochen et al., J End Clin Metab. 25, Eur J Neurosci. 26, Münch et al., Am J Physiol. 26
Karolinska Sleepiness Scale (KSS) % Sleepiness Change = pre-light Karolinska Sleepiness Scale (KSS) The alerting response to light is blue-shifted Monochromatic light Energy Saving Lamps Computer Screens 8 5 6 4 7 3 2 5 6 1 4 Cajochen et al., Sleepiness and human impact assessment Book chapter, Springer, 214
EEG Slow-Wave Activity Evening Light Exposure and EEG Slow-Wave Activity Dynamics across Sleep Cycles 3 2 1 Bright Light 25 lux vs. 6 lux 2 15 1 5 Monochromatic Light at 46 nm vs. dark 1 2 3 6 1 2 3 6 1 2 3 6 Time of Day (h) 25 2 15 1 5 Blue-enriched (65K, 4 lux) vs. 3 K, 4 lux Cajochen et al., Sleep 1992 Münch et al., Am J Physiol. 26 Chellappa et al., J. Sleep Res. 213.
Does light also affect higher cognitive functions? Does light make you bright?
Background We spent more and more time in front of computer and/or multimedia screens Displays are becoming larger in size Many displays are equipped with LED background light The light of the diplay is rather close and directed towards the eyes
Effects of LED-backlit computer screens on salivary melatonin, alertness and cognitive performance in the evening Displays: 24 inch 192x12 pixel Cold Cathode Fluorescent Lamp (CCFL) Light Emitting Diode (LED )
pg/ml Baseline Dark Adaptation Salivary Melatonin 1 8 Non-LED Screen 6 ~ 6 min 4 2 LED Screen 18:15 19:15 2:15 21:15 22:15 23:15 :15 Time of Day (h) p<.4; Duncans multiple range test Cajochen et al., J Appl Physiol. 211
# Per Hour Baseline Dark Adaptation EEG Power Density [μv 2 /Hz] Baseline Dark Adaptation Electrophysiological Correlates of Subjective Sleepiness Slow Rolling Eye Movements Non-LED Screen 1.5 Frontal EEG Activity (1-7 Hz) Non-LED Screen 3 2 1.4 1 1.3 LED Screen LED Screen 18:15 19:15 2:15 21:15 22:15 23:15 :15 18:15 19:15 2:15 21:15 22:15 23:15 :15 Time of Day (h) Time of Day (h) Monitor: F 1,11 =26.2; p<.4 Time of day: F 11,44 =7.8; p<.1 Monitor x Time: n.s. Cajochen et al., J Appl Physiol. 211
slower Relative Reaction Time (%) faster Baseline Dark Adaptation Sustained Attention and Response Control (Go/noGo Task) Letter W : go Letter M : no-go 9 95 LED Screen 1 15 Non-LED Screen Monitor: F 1,11 =12.2; p<.4 Time of day: F 11,44 =7.8; p<.2 Monitor x Time: F 12,132 =3.; p=.41 11 18:15 19:15 2:15 21:15 22:15 23:15 :15 Time of Day (h) P <.5 Cajochen et al., J Appl Physiol. 211
% Declarative Learning (Word pairs) Correctly identified word pairs Correctly identified new word pairs 7 65 7 65 6 6 55 55 5 5 45 45 LED Screen Non-LED P <.5 Cajochen et al., J Appl Physiol. 211
Light is not just for vision Cortex Thalamus Hypothalamus Brainstem - Locus coeruleus Limbic system - Amygdala - Hippocampus Modified from Vandewalle et al. Trends Cogn Sci, 29
Increase in media use in adolescents Multiscreen Society: 53 hours per week in 8-18 year old kids/adolescents, particularly in the evening in front of LED sources Generation M 2 : Media in the lives of 8- to 18-years old. Kaiser Foundation 21
Relative Amplitude Ipad versus Blue-blockers Absorption Spectrum 1..8.6.4.2 4 45 5 55 6 65 7 Wavelength ipad Orange-tinted glasses (blue blockers)
pg/ml Sleep Evening melatonin secretion in adolescents Dim Dark LED/glasses Dim 16 14 12 1 Blue Blockers for one week Clear Lenses for one week 8 6 4 2 Time of day van der Lely et al., J Adolesc Health, 214
Subjective Sleepiness (KSS) Sleep Sleep more sleepy Subjective Sleepiness in Adolescents Dim Dark LED/glasses Dim 8 7 Blue Blockers Clear Lenses for one week for one week 6 5 4 3 2 Time of day van der Lely et al., J Adolesc Health, 214
Reaction time (ms) Sleep PVT Performance in Adolescents (1% fastest RTs) 27 265 Dim Dark Dark LED/glasses Dim 26 255 Blue Blockers Clear Lenses for one week for one week 25 245 24 235 23 225 19.22h 21.22h 22.22h 8.52h Time of day van der Lely et al. 214, in press
Interindividual Differences Age Effects of light on human alertness Gender Clock-Gene polymorphism (PER3)
alert Sleepiness sleepy Melatonin (pg/ml) Age-related effects of moderate light (25 lux) on melatonin and alertness during 4-h of sleep loss 2 15 Young Dim Light (8 lux, 4h) Moderate Light (25 lux, 4h) Older 1 5 1 12 16 2 4 8 12 16 2 12 16 2 4 8 12 16 2 Young Time of day (h) Older 8 6 4 2 12 16 2 4 8 12 16 2 Time of day (h) 12 16 2 4 8 12 16 2 Ongoing study by V. Gabel and A. Viola
Number of Participants Light and gender Gender and preference of light temperature 14 25K 12 1 65K 8 6 4 2 Chi-square= 9.6; p =.2
alert Sleepiness sleepy ( KSS, difference to pre-light baseline) Light and gender Gender and alerting response to light 3 N=16 3 N=21 2 65K 25K 2 65K 25K 1 1-1 18 19 2 21 22 23 24 Time of day (h) -1 18 19 2 21 22 23 24 Time of day (h) Gender x Time x Light: p=.7
Median Reaction time Slower ms Faster Light and gender Gender and Psychomotor Vigilance Performance N=16 N=21 15 175 65K 25K 15 175 2 2 225 225 Dim light (8 lux) Dark ( lux) Light exposure (4 lux) Dim light (8 lux) Dark ( lux) Light exposure (4 lux) Gender x Time x Light: p<.4
Light and PER3 (i.e. clock gene) A PER3 VNTR polymorphism is implicated: Chronotype: PER3 5/5 earlier types than PER3 4/4 (Archer et al. 23; Pereira et al, 25; Jones et al. 27) Homeotype : PER3 5/5 more sleep pressure (EEG SWA) than PER3 4/4 (Viola et al. 27, 212; Goel et al. 29) Cognotype : PER3 5/5 more vulnerable to detrimental effects of sleep deprivation and adverse circadian phase than PER3 4/4 (Viola et al. 27; Groeger et al. 28; VandeWalle 29, 211)
Could some of these effects be explained by a differential response to light in PER3 5/5 and PER3 4/4 individuals?
KDT µv 2 /Hz less KSS more pg/ml 15 12 9 6 4 2 PER3 polymorphism and response to light PER3 4/4 Light exposure 65K 25K 15 12 9 6 4 2 PER3 5/5 Light exposure 6 6 3 3 Melatonin 9 9 4 4 7 2 7 2 5 5 Sleepiness 3 3.8.8.6.4.2. 15 1 5 18 19 2 21 22 23 24.6.4.2. 15-15 -3-45 Time of Day (h) 18 19 2 21 22 23 24 Frontal EEG power density during wakefulness (1-7 Hz) Chellappa et al., J Clin End Metab., 212
Summary Non-visual effects of light can be seen from genes up to complex neurobehavioral performance such as higher cognitive functions Evening light levels < 4 lux affect human circadian physiology, alertness and cognitive performance levels, if these light sources emit a strong blue portion of the visible spectrum Some of these effects are age and gender dependent Light sensitivity in humans may be modulated by a clock gene polymorphism implicated in sleep-wake regulation
Take home message The selection of commercially available lamps and computer screens may play an important role because they considerably impact on circadian physiology and cognitive performance at home and in the workplace
Acknowledgements Centre for Chronobiology (www.chronobiology.ch) Antoine Viola, PhD Christina Schmidt, PhD Virginie Gabel Mirjam Münch, PhD Sarah Chellappa, PhD Sylvia Frey, PhD Doreen Anders, PhD Micheline Maire Carolin Reichert Jakub Späti, PhD Fraunhofer Institute Oliver Stefani Swiss Federal Office for Public Health Daimler-Benz Foundation EU IP
Sleep Response (min) Acute sleep induction by light in nocturnal mice Lights ON Lights OFF 6 3 Wildtype Melanopsin knockout Rodless/coneless Melanopsin adta 1 2 3 Time elapsed from light onset (h) According to Muindi et al., Front Syst Neurosci, 214