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1 Quantifying non-image forming (NIF) responses of light Petteri Teikari, S Licentiate course in measurement science and technology CONTENTS: 1. Introduction 2. Physiology 3. Measuring NIF-responses 4. Hot topics

2 Introduction Eyerespondsto lightand convertsthe light stimulus into a visual perception of our surroundings. In addition to normal visual responses, light can also modulate several non-visual responses via eye. These are typically referred as Non-Image Forming (NIF) responses of light

3 Introduction: NIF-responses NIF-responses include Entrainmentof circadianrhythms(e.g. hormones) to environmentallight-darkcycle(circa=about, diesday). Pupillary light reflex(plr) Light-inducedalertness

4 Physiology: the Eye Three type of photoreceptors: Rods(scotopic, night vision) Cones(photopic, day vision) iprgcs ( intrinsically photosensitive retinal ganglion cells ), NIF-vision, discovered 2002 Two pure vision types Photopic(only cones active) Scotopic(only rods active) Two mixed vision types Mesopic(cones&rods active, night-time driving ) NIF (iprgcs, cones, rods active)

5 Physiology: Action spectra Sensitivity of NIF-responses are shifted towards blue end of spectrum compared to daytime(color) vision. E.g. lux as an unitis notsuitablefor NIF-responses.

6 Physiology: the Eye In early literature ( ) iprgcswere considered to drive NIF-responses solely. It seems likely that the involvement of iprgcs to NIF-responses depend on: Previous light history Light intensity Light exposure duration Light timing Cones and rods are too involved in NIFresponses

7 Physiology: Lightcharacteristics Timing of light exposure(phase-response Curve), example for phase shift with melatonin as a marker. Intensity of light exposure: light-induced melatonin suppression as a parameter

8 Physiology: Lightcharacteristics Duration of light exposure(does not follow Bunsen-Roscoe law) Previous light history Previous bright light exposure increases thresholds for NIF-responses. Spatial distribution of light Outer-upper visual field elicits strongest response

9 Measurement: Typicalparameters Melatonin suppression Phase shift(melatonin, CBT as markers) Temperature(rectal, proximal, distal) Pupil size and behavior Change in alertness Subjectivescales, EEG (cortical), fmri/pet (subcortical), HRV/PUI (autonomic activation) Change in psychomotor performance Visual search task, reaction time, memory, etc. Sleep quality/hygiene Light characteristics

10 Measurement: Melatonin Nocturnally secreted, sleep hormone Light suppresses melatonin production Canbeanalyzedfromplasma (the best), urine and saliva(the most common and easiest) Plasma sampling frequency can be as high as once per minute. Salivasamplingfrequencynotbelowonceper 15 minutes. This typically sufficient for light-related research.

11 Measurement: Phaseshift Phaseshiftin practiceis the temporalshiftof a physiological rhythm (e.g. melatoninpeak) in reaction to some zeitgeber(time-giver). Right melatonin peak (circle) has shifted over a month s recording.

12 Measurement: Temperatures(1) Staying awake/upright position/light exposure mask the dropof CBT. Correlateswithalertnessand cognitive performance. Causality of observed responses not fully known. Time course(from the bottom up) of distal and proximal skin temperatures, core body temperature(cbt) and the distal proximal temperature gradient(dpg) during an 8- nocturnal sleep episode

13 Measurement: Temperatures(2) Core Body Temperature measurement Rectal thermistor and wireless transmitter Distal/Proximal Skin temperature With Dallas/Maxim ibuttons

14 Measurement: Pupilsize& behavior Pupilconstrictsin response to light. Retinalirradiancevs. corneal irradiance Pupildilatesin excited state. Pupillary dynamics(plr) alsodependon the spectral content of light and circadian time. Pupillary fatiguewaves ( Hz) appear as sleepiness increases.

15 Measurement: Alertness(1) Light exposure can increase alertness Underlying physiological mechanisms not fully understood yet. Can be measured: Subjectively( how alert you feel? ) EEG Power Spectrum(alpha/beta bands) Cortical activation Eyemovement(SEM) and blinkrate(eog) Heart rate variability(hrv) / Pupillary behavior Autonomic Nervous System(ANS) activation Functional brain imaging(fmri, MEG, PET) Subcortical activation

16 Measurement: Alertness(2) Subjective measuring the easiest However hard to measure slight changes Optimalcase wouldbeto combine: Subjective(e.g. Karolinska Sleepiness Scale) ANS arousal(hrv, PUI) Cortical arousal(eeg) Subcortical arousal(fmri) And possibly cognitive performance(pvt) Reaction time testing

17 Measurement: Cognitiveperformance Diurnal variation (homeostatic and circadian influence) E.g. Psychomotor vigilance task (PVT) Recordsreactiontimesand errors.

18 Measurement: Sleepquality Actigraphy(wrist-worn accelerometer) Measures how stable sleep/wake pattern is EEG measurement needed to quantify different sleep stages properly and their ratio.

19 Measurement: NIF-Luminance Canon EOS 400D DSLR Custom filters To weight the RGB-response so that it would correspond some otheraction spectruminsteadof the V(λ) million effective pixels 22.2 x 14.8 mm CMOS sensor(1.6x crop) 12 bitadc per channel(rgb) Sigma 4.5mm EX DC Circular Fisheye HSM Angleof view: 180 (for 1.6 cropfactor) Aperture: F2.8 - F22 Non-photopic luminances

20 HOT: Acutealertnessresponse Immediatealertness/arousingresponseto light. Hard to quantify with traditional methods In Liège(CyclotronResearchCentre) functional imaging has been used. Seemsthatthereis an earlyresponsein subcorticalstructureswhichis thenrelayedto higher structures to cortex. Combined EEG and fmri would be valuable. Methodological problems(one MSc. Thesis from S-114)

21 HOT: Naturallightexposure Quantifying natural light exposures and their effect to circadian rhythms By EUCLOCK, EU fundedprojectfor the research of circadian clock 30 institutions participating 0 from Finland Similar project in USA by Lighting Research Center (LRC).

22 HOT: Polychromaticlightsources NIF action spectra have been estimated using monochromatic light sources Not very naturalistic as the interplay with different photoreceptors is not that strong then. PreviouslyipRGCaction spectrum= NIF action spectrum. Most probably not so and possibly different NIFresponses can have slightly different spectral behavior. Study design for this is rather heavy and requires quite a lot of resources.

23 HOT: Melanopsin bistability In addition to excitation spectra(right): Melanopsin (photopigment of iprgcs) probablyis regenerated faster with preceeding longwavelength light Twodifferentaction spectraareneededto quantify iprgc-responsivity

24 Conclusions Afterthe discoveryof iprgcsin 2002, nonvisual responses have become a hot topic. EUCLOCK labs producingthe majorityof scientific knowledge in Europe More and more institutions are doing their own research Lamp manufacturers are eager to exploit this fact and market their lamps with incorrect slogans Badmouthing the field(imho)

25 References Teikari P(2006) Biologicaleffectsof light. Master'sThesis. Helsinki Universityof Technology. Teikari P(2006) Circadianfieldphotometry, Project Workon MeasurementScience and Technology Teikari P(2007) Automatedpupillometry, Project Workon MeasurementScience and Technology REVIEWS & KEY PAPERS David M Berson, FeliceA Dunn, and MotoharuTakao 2002 Phototransductionby Retinal Ganglion Cells That Set the Circadian Clock, Science 295, no. 5557: , Lockley, SW & Gooley, JJ 2006, Circadian Photoreception: Spotlight on the Brain. Current Biology, vol. 16, no. 18, pp. R795-R797, Wirz-Justice, A 2007 Chronobiology and psychiatry. Sleep Medicine Reviews, vol. 11, no. 6, pp , Van Gelder, RN 2008, Non-Visual Photoreception: Sensing Light without Sight. Current Biology, vol. 18, no. 1, pp. R38- R39. KEY JOURNALS Chronobiology International (Impact Factor: 2.517) Journal of Biological Rhythms (Impact Factor 4.633) Journal of Pineal Research (Impact Factor: 4.228)

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