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  <article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML"
    article-type="review-article">
    <?properties open_access?>
    <front>
      <journal-meta>
        <journal-id journal-id-type="nlm-ta">J Circadian Rhythms</journal-id>
        <journal-title-group>
          <journal-title>Journal of Circadian Rhythms</journal-title>
        </journal-title-group>
        <issn pub-type="epub">1740-3391</issn>
        <publisher>
          <publisher-name>BioMed Central</publisher-name>
        </publisher>
      </journal-meta>
      <article-meta>
        <article-id pub-id-type="pmid">20377841</article-id>
        <article-id pub-id-type="pmc">2851666</article-id>
        <article-id pub-id-type="publisher-id">1740-3391-8-2</article-id>
        <article-id pub-id-type="doi">10.1186/1740-3391-8-2</article-id>
        <article-categories>
          <subj-group subj-group-type="heading">
            <subject>Review</subject>
          </subj-group>
        </article-categories>
        <title-group>
          <article-title>Circadian light</article-title>
        </title-group>
        <contrib-group>
          <contrib contrib-type="author" corresp="yes" id="A1">
            <name>
              <surname>Rea</surname>
              <given-names>Mark S</given-names>
            </name>
            <xref ref-type="aff" rid="I1">1</xref>
            <email>ream@rpi.edu</email>
          </contrib>
          <contrib contrib-type="author" id="A2">
            <name>
              <surname>Figueiro</surname>
              <given-names>Mariana G</given-names>
            </name>
            <xref ref-type="aff" rid="I1">1</xref>
            <email>figuem@rpi.edu</email>
          </contrib>
          <contrib contrib-type="author" id="A3">
            <name>
              <surname>Bierman</surname>
              <given-names>Andrew</given-names>
            </name>
            <xref ref-type="aff" rid="I1">1</xref>
            <email>bierma2@rpi.edu</email>
          </contrib>
          <contrib contrib-type="author" id="A4">
            <name>
              <surname>Bullough</surname>
              <given-names>John D</given-names>
            </name>
            <xref ref-type="aff" rid="I1">1</xref>
            <email>bulloj@rpi.edu</email>
          </contrib>
        </contrib-group>
        <aff id="I1">Lighting Research Center, Rensselaer Polytechnic Institute, 21 Union Street,
          Troy, NY 12180, USA</aff>
        <pub-date pub-type="collection">
          <year>2010</year>
        </pub-date>
        <pub-date pub-type="epub">
          <day>13</day>
          <month>2</month>
          <year>2010</year>
        </pub-date>
        <volume>8</volume>
        <fpage>2</fpage>
        <lpage>2</lpage>
        <history>
          <date date-type="received">
            <day>11</day>
            <month>12</month>
            <year>2009</year>
          </date>
          <date date-type="accepted">
            <day>13</day>
            <month>2</month>
            <year>2010</year>
          </date>
        </history>
        <permissions>
          <copyright-statement>Copyright &#xA9;2010 Rea et al; licensee BioMed Central
            Ltd.</copyright-statement>
          <copyright-year>2010</copyright-year>
          <copyright-holder>Rea et al; licensee BioMed Central Ltd.</copyright-holder>
          <license license-type="open-access"
            xlink:href="http://creativecommons.org/licenses/by/2.0">
            <license-p>This is an Open Access article distributed under the terms of the Creative
              Commons Attribution License (<ext-link ext-link-type="uri"
                xlink:href="http://creativecommons.org/licenses/by/2.0"
                >http://creativecommons.org/licenses/by/2.0</ext-link>), which permits unrestricted
              use, distribution, and reproduction in any medium, provided the original work is
              properly cited.</license-p>
          </license>
        </permissions>
        <self-uri xlink:href="http://www.jcircadianrhythms.com/content/8/1/2"/>
        <abstract>
          <p>The present paper reflects a work in progress toward a definition of circadian light,
            one that should be informed by the thoughtful, century-old evolution of our present
            definition of light as a stimulus for the human visual system. This work in progress is
            based upon the functional relationship between optical radiation and its effects on
            nocturnal melatonin suppression, in large part because the basic data are available in
            the literature. Discussed here are the fundamental differences between responses by the
            visual and circadian systems to optical radiation. Brief reviews of photometry,
            colorimetry, and brightness perception are presented as a foundation for the discussion
            of circadian light. Finally, circadian light (CL<sub>A</sub>) and circadian stimulus
            (CS) calculation procedures based on a published mathematical model of human circadian
            phototransduction are presented with an example.</p>
        </abstract>
      </article-meta>
    </front>
    <body>
      <sec>
        <title>Introduction</title>
        <p>The suprachiasmatic nuclei (SCN) in the hypothalamus host the master circadian clock that
          organizes and orchestrates the timing of all daily biological functions, from complicated
          physiological systems to single cells. The SCN in humans have, on average, an intrinsic
          period slightly greater than 24 hours [<xref ref-type="bibr" rid="B1">1</xref>] that is
          modulated by the temporal pattern of light and dark on the retina. As a result of the
          earth's rotation on its axis, the temporal pattern of light and dark on the retina
          synchronizes the SCN to a matching 24-h period. Recent research has demonstrated that
          disruption of the natural, 24-h pattern of light and dark from rapid flight across time
          zones or from rotating shift work can lead to a wide variety of maladies, from poor
          performance to sleep loss, weight gain, and even breast cancer [<xref ref-type="bibr"
            rid="B2">2</xref>-<xref ref-type="bibr" rid="B9">9</xref>]. Because it is increasingly
          evident that retinal light and dark exposures can profoundly affect human health and
          well-being, it is increasingly important to be able to quantify both light and dark as
          stimuli to the human circadian system.</p>
        <p>The present paper deals with the evolving definition of circadian light. Technically, the
          adjective <italic>circadian </italic>must be used to modify the noun <italic>light
          </italic>because light is defined specifically in terms of optical radiation capable of
          producing a visual sensation in humans [<xref ref-type="bibr" rid="B10">10</xref>,<xref
            ref-type="bibr" rid="B11">11</xref>]. Strictly speaking then, light cannot be used
          synonymously with optical radiation capable of producing a non-visual, circadian response
          in humans or with optical radiation producing a visual response in another species.
          Nevertheless, in the vernacular, light is used as a term to describe optical radiation
          with a spectral power distribution anywhere within the "visible region" of the
          electromagnetic spectrum (approximately 380 nm to 730 nm), irrespective of its biological
          consequences. Moreover, the term light is always used, with or without strict regard for
          its ability to stimulate human vision, as a noun to describe <italic>the stimulus to
          </italic>rather than <italic>the response from </italic>a biological system. This is an
          important point because light is circularly defined; light as a stimulus to the human
          visual system was derived from responses by the human visual system. Thus, any formal
          definition of circadian light as a stimulus to the circadian system must also be dependent
          on the measured response from the circadian system. Fundamentally then, it is necessary to
          be able to measure a reliable response of the human circadian system to optical radiation
          incident on the retina to define the stimulus to the human circadian system. This
          inherent, and potentially confusing, circularity always must be considered as a formal
          definition of circadian light develops.</p>
        <p>Notwithstanding this potentially confusing circularity, it will be difficult to develop a
          definition of light for the circadian system that is strictly homologous with the formal
          definition of light for the visual system because, for reasons discussed in this paper,
          the responses by these two systems to optical radiation on the retina are fundamentally
          different. The biophysical mechanisms underlying phototransduction for the two systems are
          similar but different enough to require thoughtful deliberation as a definition of
          circadian light evolves. Without a clear understanding of these differences, experimental
          results from studies of the impact of optical radiation on circadian physiology can be
          easily misinterpreted. Since, however, so much history and thought underlie our concept of
          light based upon the human visual system, these insights make the discussion of circadian
          light more readily explained and more easily understood. For this reason brief reviews of
          photometry, colorimetry and brightness perception are presented as a foundation for the
          discussion of circadian light.</p>
      </sec>
      <sec>
        <title>The photopic luminous efficiency function</title>
        <p>Psychophysical experiments were conducted by several laboratories nearly a century ago to
          develop "the spectral sensitivity of human vision." Following a consensus process, the
          data from these experiments were combined to form V<sub>&#x3BB;</sub>, the photopic
          luminous efficiency function formally defining <italic>light </italic>[<xref
            ref-type="bibr" rid="B12">12</xref>], shown in Figure <xref ref-type="fig" rid="F1"
            >1</xref>. V<sub>&#x3BB; </sub>then is the bridge between radiometry, the measurement of
          radiant energy, and photometry, the measurement of light. Depending upon the geometric
          properties of interest, radiant flux (radiant energy per unit time) is weighted by
            V<sub>&#x3BB; </sub>in the fundamental definitions of <italic>luminous intensity
            </italic>(V<sub>&#x3BB;</sub>-weighted radiant intensity, or radiant flux within a solid
          angle), <italic>illuminance </italic>(V<sub>&#x3BB;</sub>-weighted irradiance, or radiant
          flux incident on a surface area), and <italic>luminance
          </italic>(V<sub>&#x3BB;</sub>-weighted radiance, or luminous intensity per unit area of a
          surface) [<xref ref-type="bibr" rid="B11">11</xref>]. Circadian light could then similarly
          bridge radiometry to circadian photometry and would have parallel definitions with those
          used for light based upon geometrical considerations.</p>
        <fig id="F1" position="float">
          <label>Figure 1</label>
          <caption>
            <p><bold>Photopic and scotopic luminous efficiency functions </bold>[<xref
                ref-type="bibr" rid="B10">10</xref>]<bold> and other spectral sensitivity functions
                measured with humans (mesopic: Rea et al</bold>. [<xref ref-type="bibr" rid="B13"
                >13</xref>], <bold>glare: Bullough </bold>[<xref ref-type="bibr" rid="B14"
              >14</xref>], <bold>brightness, central: CIE </bold>[<xref ref-type="bibr" rid="B10"
                >10</xref>], <bold>brightness, peripheral: Weale </bold>[<xref ref-type="bibr"
                rid="B15">15</xref>]<bold>)</bold>. Peak wavelengths for each function are noted in
              the legend.</p>
          </caption>
          <graphic xlink:href="1740-3391-8-2-1.jpg"/>
        </fig>
        <p>The photopic luminous efficiency function is actually only one of a wide variety of
          functions that can be used to characterize the spectral sensitivity of the human visual
          system. Figure <xref ref-type="fig" rid="F1">1</xref> also shows a small sample of human
          spectral sensitivity functions published in the literature [<xref ref-type="bibr"
            rid="B12">12</xref>-<xref ref-type="bibr" rid="B15">15</xref>]. In fact, depending upon
          the experimental conditions, <italic>many </italic>spectral response functions can be
          obtained from the human visual system. V<sub>&#x3BB; </sub>is quite special, however,
          because, in addition to its metrological seniority, it has the important practical feature
          of exhibiting additivity. Additivity means that when two lights (A and B) of different
          spectral power distributions but of equal luminance (A = B) are combined by unit
          fractional amounts, they will continue to have the same luminance [<xref ref-type="bibr"
            rid="B13">13</xref>]. That is,<disp-formula id="bmcM1"><label>1</label><graphic
              xlink:href="1740-3391-8-2-i1.gif"/></disp-formula></p>
        <p>where p and q are unit fractional amounts, such that p + q = 1</p>
        <p>Additivity as defined by Equation 1 significantly restricts the relevance of
            V<sub>&#x3BB; </sub>for representing the spectral sensitivity of the human visual system
          to a small handful of visual task conditions [<xref ref-type="bibr" rid="B16">16</xref>].
          Because of additivity, however, V<sub>&#x3BB; </sub>has become the universal "visual
          response function" for commerce and for government regulations [<xref ref-type="bibr"
            rid="B11">11</xref>].</p>
        <p>Despite its assumed universality, the psychophysical techniques used to develop
            V<sub>&#x3BB; </sub>only functionally characterize the spectral sensitivity of the
          achromatic (luminance) channel for the human fovea which is dominated by input from only
          two of the three cone types. The fovea constitutes only about 2% of the retina and
          provides humans with high spatial resolution. Only densely packed long-wavelength (L) and
          middle-wavelength (M) sensitive cones are found in the center of the fovea; although all
          three cone types are found throughout the remainder of the retina, the short-wavelength
          (S) sensitive cones are much rarer and, like the rods, absent from the center of the
          fovea. The S cone is also slower to respond to rapid modulations of light level than the L
          and M cones [<xref ref-type="bibr" rid="B17">17</xref>]. V<sub>&#x3BB; </sub>is largely
          (but not exclusively) based upon a psychophysical technique known as flicker photometry. A
          small disc presented to an observer at the center of the fovea oscillates in time
          (flickers) between two lights of different spectral power distributions (perceived
          colors). By gradually adjusting the radiance of one light and the flicker rate, the two
          lights eventually appear as a steady light of a single hue. At this point where the two
          oscillating lights just fuse into what appears to be a fixed luminous disc, the two lights
          are defined as having the same luminance. V<sub>&#x3BB; </sub>is determined by taking the
          reciprocal of the radiance at each wavelength needed to reach this constant-luminance
          flicker criterion and normalizing these values to the reciprocal of the radiance
          associated with the wavelength requiring the least amount of optical radiation needed to
          elicit the criterion response (&#x3BB;<sub>max </sub>= 555 nm). By utilizing rapidly
          oscillating lights in the fovea, the S cone is functionally excluded from the definition
          of light even though this photoreceptor plays an extremely important role in our
          perception of brightness [<xref ref-type="bibr" rid="B15">15</xref>]. Nevertheless,
            V<sub>&#x3BB; </sub>has gained ubiquity in metrology because additivity is essential for
          any system of photometry supporting commerce and government.</p>
        <p>To be useful, a system of photometry first must, more or less, describe the relative
          brightness of a light source. The current system of photometry based on V<sub>&#x3BB;
          </sub>does so, more or less. As a "white" light source (e.g., daylight, incandescent,
          fluorescent) generates greater radiance, the light source should appear brighter and the
          photometric quantity should increase. Further, as the spectral power distribution of the
          light emitted by a source shifts to the middle of the "visible spectrum" (i.e., near 555
          nm) the source should also appear brighter and the photometric quantity should also
          increase. In general, photometry based upon V<sub>&#x3BB; </sub>provides quantities
          consistent with these expectations. Ironically perhaps, a photometric system based on
          apparent brightness will not conform to these <italic>prima facie </italic>expectations.
          As will be discussed in more detail in the next section, it is possible to show that when
          two lights of equal brightness are added together their sum can actually appear
            <italic>less </italic>bright than <italic>either </italic>light alone. Commerce and
          government simply could not employ a non-additive system of photometry where summing more
          optical radiation produced less light.</p>
        <p>The significance of additivity in the definition, and thereby, the sale and regulation of
          light should not be underestimated. Not only does additivity ensure that the combination
          of optical radiation always increases the amount of measured light, additivity also
          provides for inexpensive and practical means of measuring that light. Additivity ensures
          that, at any level of optical radiation, a linear detector-filter combination matching the
          spectral response of V<sub>&#x3BB; </sub>will provide photometric quantities identical to
          the sum of the spectral power obtained at each wavelength by a much more expensive and
          complicated spectroradiometer. Additivity is the dominant and perhaps only reason
            V<sub>&#x3BB; </sub>has not been displaced by commerce and government after nearly a
          century of research showing the inherent limitations of V<sub>&#x3BB; </sub>for
          characterizing the visual stimulus [<xref ref-type="bibr" rid="B16">16</xref>,<xref
            ref-type="bibr" rid="B18">18</xref>].</p>
      </sec>
      <sec>
        <title>Spectral sensitivity of brightness perception</title>
        <p>In addition to the visual system's achromatic luminance channel, the spectral sensitivity
          of which is well characterized by V<sub>&#x3BB;</sub>, two spectrally opponent color
          channels simultaneously contribute to our perceptions of brightness. The three visual
          channels leading to brightness perceptions are formed in the retina from the three cone
          photoreceptor types (L, M, and S cones) but, depending upon the subsequent neural
          connections, they are combined in different ways to provide brightness information to the
          visual cortex. As previously discussed, the spectral sensitivity of the luminance channel
          is dominated by the summed input from the L and M cones. The two color channels, red
          versus green (r-g) and blue versus yellow (b-y) are termed spectrally opponent channels
          because each provides opposing color information to the brain [<xref ref-type="bibr"
            rid="B19">19</xref>].</p>
        <p>For one type of r-g channel, excitatory input is provided by the L cones and inhibitory
          input is provided by the M cones. For example, when the L cone provides relatively more
          input to the r-g channel than the M cone, the r-g channel signals "red" to the brain.
          Similarly, for one type of b-y channel, excitatory input is provided by the S cones and
          inhibitory input is provided by both the L cones and the M cones. When a light stimulates
          the S cones more than the combined input from the L and M cones, the b-y channel signals
          "blue" to the brain.</p>
        <p>As spectrally opponent systems, these channels can signal <italic>either </italic>"red"
          or "green" and <italic>either </italic>"blue" or "yellow" to the brain. Moreover, a
          spectrally opponent system is inherently a subadditive system because the addition of,
          say, a "green" light to a "red" light can <italic>decrease </italic>the response of the
          r-g system cell. Since the two spectral opponent channels contribute to brightness
          perception, two lights added together can actually appear <italic>less </italic>bright
          than either light alone.</p>
        <p>Much of the research attempting to understand human brightness perception has utilized
          both photometry and colorimetry as indirect methods of measuring the apparent brightness
          of lights of different spectral compositions. Colorimetry originated from controlled
          observations in the 19<sup>th </sup>century showing that with three, and only three, so
          called <italic>primary </italic>lights humans can match the appearance of any other test
          light [<xref ref-type="bibr" rid="B20">20</xref>]. In other words, by adjusting the
          radiances of the three primary lights, it was possible to create an additive mixture of
          these primary lights that was completely indistinguishable from the test light. (Some very
          saturated color stimuli cannot be matched using a set of three physical primaries without
          slightly changing the color of the test light by adding one of the physical primaries to
          it. Mathematically, this is equivalent to using a negative amount of primary to make the
          match. To avoid the use of negative amounts of primaries, the CIE color system [<xref
            ref-type="bibr" rid="B21">21</xref>] makes use of imaginary primaries that are
          mathematically defined, but not physically realizable.) As shown in subsequent research,
          the mixture matches the test light because the photon absorptions by the three cone
          photoreceptors are exactly the same for the mixture of primaries and for the test. Thus,
          the color of any test light can be quantified in terms of the relative amounts of the
          primary lights needed to match its appearance. The radiant powers in the three primaries
          are typically normalized with a linear transformation so that their sum is unity. By
          knowing two of the normalized values, the third value is also known. In this way the
          color, or more precisely the chromaticity, of the test light can be illustrated
          graphically in two dimensions. Figure <xref ref-type="fig" rid="F2">2</xref> illustrates
          the results of colorimetric calculations based on the spectral power distribution of the
          light source and the three color matching functions in the (x', y') color system. (This
          color system is nearly identical to the Commission Internationale de l'Eclairage (x, y)
          1931 color system presently in common use [<xref ref-type="bibr" rid="B21">21</xref>], but
          with small differences for short [&lt;460 nm] wavelengths [<xref ref-type="bibr" rid="B22"
            >22</xref>].) The physical specification of the chromaticity of any light, natural or
          fabricated, can be defined as a single point within the area enclosed by the outermost
          contour.</p>
        <fig id="F2" position="float">
          <label>Figure 2</label>
          <caption>
            <p><bold>Chromaticity diagram based on the Judd correction </bold>[<xref ref-type="bibr"
                rid="B22">22</xref>], <bold>showing contours of equal B/L value </bold>[<xref
                ref-type="bibr" rid="B23">23</xref>]. Also shown are the chromaticity coordinates
              for a red light (RED) and for a green light (GRN) that, when added, produce a yellow
              light (YEL) with the illustrated chromaticity coordinates as described in the
              text.</p>
          </caption>
          <graphic xlink:href="1740-3391-8-2-2.jpg"/>
        </fig>
        <p>Of course, quantifying the relative amounts of three primaries needed to match the test
          light does not fully characterize its color appearance. A stimulus that is recognized as
          orange and another that is recognized as brown can have the same chromaticities, but
          factors such as the objects' relative luminances against their surrounding luminances will
          influence their perceived colors. Unlike photometry, where V<sub>&#x3BB; </sub>closely
          characterizes the spectral sensitivity of the human fovea for some types of visual tasks
            [<xref ref-type="bibr" rid="B16">16</xref>], colorimetric specification of a test light
          does not represent the response of a single visual channel or even the combination of
          multiple visual channels. Since brightness is influenced by both chromatic as well as
          achromatic visual channels, additional techniques must be used to characterize and measure
          apparent brightness.</p>
        <p>One common method of quantifying the brightness of lights is combining photometry and
          colorimetry by utilizing the ratio of the luminance needed by a test light of a given
          chromaticity to match the brightness of a reference light of another chromaticity and of a
          known luminance. The luminance of the reference light is designated B and the luminance of
          the test light that matches its brightness is designated L. Therefore, the brightness of
          any light in chromaticity space relative to a given reference light source can be
          described in terms of a unitless ratio, its B/L value. Figure <xref ref-type="fig"
            rid="F2">2</xref> also shows constant B/L contours in the (x', y') color space [<xref
            ref-type="bibr" rid="B23">23</xref>] and, as described next, illustrates the subadditive
          nature of brightness perception.</p>
        <p>Consider a red light (a 630-nm spectral light) and a green light (a 520-nm spectral
          light), with (x', y') chromaticity coordinates of (0.70, 0.30) and (0.07, 0.83),
          respectively, as shown in Figure <xref ref-type="fig" rid="F2">2</xref>. Suppose the
          luminance of the red light is 10 cd/m<sup>2 </sup>and that of the green light is 15
            cd/m<sup>2</sup>. Using the B/L values from Guth et al. [<xref ref-type="bibr" rid="B23"
            >23</xref>] shown in Figure <xref ref-type="fig" rid="F2">2</xref> (2.93 for red and
          2.15 for green), their apparent brightnesses can be calculated from the product of their
          luminance (L, in cd/m<sup>2</sup>) and their B/L value:</p>
        <p>&#x2022; red: 10 cd/m<sup>2 </sup>&#xD7; 2.93 = 29.3</p>
        <p>&#x2022; green: 15 cd/m<sup>2 </sup>&#xD7; 2.15 = 32.3</p>
        <p>If the red and the green lights are superimposed onto each other, the luminance of the
          resulting yellow light would, of course, be 25 cd/m<sup>2 </sup>(10 + 15
          cd/m<sup>2</sup>). The (x', y') chromaticity coordinates of this yellow light are (0.48,
          0.49), corresponding to a B/L value of 1.07 using the B/L contours from Guth et al. [<xref
            ref-type="bibr" rid="B23">23</xref>] in Figure <xref ref-type="fig" rid="F2">2</xref>.
          Therefore, the apparent brightness of this yellow light can be calculated as it was for
          the red and green lights:</p>
        <p>&#x2022; yellow: 25 cd/m<sup>2 </sup>&#xD7; 1.07 = 26.8</p>
        <p>Remarkably, the brightness of the yellow light created by combining the original red and
          green lights appears <italic>less </italic>bright than either the red or the green light
          alone, despite the yellow light being created from the superimposition of the red and
          green lights.</p>
      </sec>
      <sec>
        <title>A "photodian" luminous efficiency function</title>
        <p>It seems natural that as more research is conducted on the impact of optical radiation on
          the circadian system, particularly as it might affect human health, attempts would be made
          to develop a spectral sensitivity function for the circadian system. It also seems natural
          that attempts would be made to develop an additive sprectral efficiency function
          comparable to V<sub>&#x3BB; </sub>for the circadian system, a C<sub>&#x3BB; </sub>[<xref
            ref-type="bibr" rid="B24">24</xref>,<xref ref-type="bibr" rid="B25">25</xref>].
          Certainly it is possible to develop such a function from the available data (e.g., [<xref
            ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B27">27</xref>]) through
          international consensus to support commerce and government, but it is important to point
          out why an additive function like C<sub>&#x3BB; </sub>could probably never be exactly
          comparable to V<sub>&#x3BB;</sub>.</p>
        <p>Intrinsically photosensitive retinal ganglion cells (ipRGCs) have been shown to provide
          direct input to the SCN [<xref ref-type="bibr" rid="B28">28</xref>,<xref ref-type="bibr"
            rid="B29">29</xref>]. Figueiro et al. [<xref ref-type="bibr" rid="B30">30</xref>] were
          the first to suggest that multiple photoreceptors contributed to human circadian
          phototransduction via color opponent processes distal to the ipRGCs in the retina.
          Spectral opponency is an inherent attribute of the human retina, initiated distal to the
          ipRGCs in the outer plexiform layer of the retina, and underlies both color perception and
          the subadditive nature of apparent brightness perception previously described.
          Demonstrations of subadditivity in human circadian phototransduction have been performed
          by Figueiro et al. [<xref ref-type="bibr" rid="B31">31</xref>] specifically designed to
          test the conclusions by Figueiro et al. [<xref ref-type="bibr" rid="B30">30</xref>]. More
          recently, Figueiro and colleagues demonstrated, as predicted, that the subadditive
          response to light by the circadian system is formed from spectral opponent mechanisms in
          the retina [<xref ref-type="bibr" rid="B32">32</xref>]. It is interesting in this regard
          that additivity has been demonstrated in mouse circadian phototransduction [<xref
            ref-type="bibr" rid="B33">33</xref>,<xref ref-type="bibr" rid="B34">34</xref>]. This
          species does not exhibit subadditivity presumably because, quite unlike humans, mice have
          very little neural apparatus to support color vision [<xref ref-type="bibr" rid="B35"
            >35</xref>].</p>
        <p>V<sub>&#x3BB;</sub>, as previously discussed, is based upon a specific experimental
          paradigm isolating the achromatic visual channel in the fovea. This channel has been shown
          to be additive in response to optical radiation for a given criterion response (i.e., a
          constant-luminance flicker criterion). Our current understanding of the circadian system
          indicates that there is only one functional channel leading to the SCN from the retina,
          and that in humans, this channel exhibits subadditivity to certain combinations of
          wavelengths [<xref ref-type="bibr" rid="B36">36</xref>]. Clearly, a more detailed
          understanding of input to the SCN may emerge following additional research. For example,
          Aggelopolous and Meissl [<xref ref-type="bibr" rid="B37">37</xref>] suggest that there are
          multiple neural pathways providing input to the SCN in rats. Whether these different
          neuron pathways exist in humans or constitute different functional channels for the SCN
          has yet to be determined. Since there is no evidence to date that the human circadian
          system exhibits additivity, an additive "photodian" luminous efficiency function for
          measuring circadian light (i.e., a C<sub>&#x3BB;</sub>) would only serve as a convenience
          to commerce and government. In other words, unlike V<sub>&#x3BB;</sub>, there would be no
          physiological foundation for a system of metrology based upon C<sub>&#x3BB;</sub>. This
          lack of homology between physiology and metrology may or may not be an important aspect in
          the deliberations for developing a system of circadian photometry, but it is certainly
          important to draw attention to this difference for scientific purposes, much as it is
          important to draw attention to the difference between luminance and brightness.</p>
      </sec>
      <sec>
        <title>Spectral sensitivity of the circadian system</title>
        <p>The retino-hypothalamic tract (RHT) is comprised of ipRGC axons and carries photic
          information from the retina to the SCN. In addition to the direct conversion of optical
          radiation to neural signal input to the master clock, the ipRGCs also carry
          spectrally-opponent information originating from the classical photoreceptors and
          processed by vertical (bipolar cells) and lateral (horizontal and amacrine cells) neurons,
          to the SCN. Of particular interest with regard to developing a definition of circadian
          light are the spectrally-opponent (color) mechanisms in the distal retina that provide
          synaptic connections to the ipRGCs [<xref ref-type="bibr" rid="B32">32</xref>]. In
          addition, amacrine cells that control the transition from scotopic (rod) to photopic
          (cone) responses in retinal ganglion cells also appear to provide synaptic threshold
          control of the ipRGC responses. These complicated neural connections have been
          mathematically modeled to develop a definition of the circadian (light) stimulus [<xref
            ref-type="bibr" rid="B36">36</xref>]. The mathematical model of human circadian
          phototransduction developed by Rea et al. [<xref ref-type="bibr" rid="B36">36</xref>] is
          based on the neuroanatomy and neurophysiology of the retina and on published
          psychophysical studies of nocturnal melatonin suppression using lights of different
          spectral power distributions. The model generates values of circadian light (CL) for any
          spectral power distribution (i.e., for any light source, real or imagined, at any
          irradiance). CL is characterized by a high absolute threshold to optical radiation with a
          peak spectral response at short wavelengths. The model accounts for participation of
          ipRCGs as well as rods and cones in circadian phototransduction via neural connections,
          including spectral opponency, in the outer plexiform layer of the retina. Additional file
            <xref ref-type="supplementary-material" rid="S1">1</xref> describes the computation
          procedure for calculating CL. It should be noted that the term CL is used in this paper to
          replace the term <italic>circadian stimulus </italic>(CS), used in the paper that
          describes the model of circadian phototransduction [<xref ref-type="bibr" rid="B36"
            >36</xref>]. Notwithstanding the nonlinearities inherent in the circadian
          phototransduction model, CL is spectrally weighted irradiance for the human circadian
          system, a term more comparable to illuminance, which is spectrally weighted irradiance for
          the human visual system. As described in more detail below, the term CS will be henceforth
          used to describe the <italic>effective </italic>photic stimulus for the circadian system
          as measured by acute nocturnal melatonin suppression.</p>
        <p>Figure <xref ref-type="fig" rid="F3">3</xref> shows the modeled spectral sensitivity of
          the circadian system for both narrowband and polychromatic light stimuli [<xref
            ref-type="bibr" rid="B36">36</xref>]. Because the model includes spectral opponency,
          responses from light stimuli created by a combination of narrowband sources cannot be
          predicted from the spectral sensitivity derived from narrowband light stimuli alone. In
          fact, for light stimuli with a particular balance of short-wavelength (e.g., around 450
          nm) and long-wavelength (e.g., longer than about 510 nm) components, the response of the
          human circadian system to light is less than what would be predicted by an additive
          spectral efficiency function derived from responses to narrowband stimuli [<xref
            ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr" rid="B31">31</xref>]. Emphasis
          for modeling was placed upon studies measuring nocturnal melatonin suppression because, in
          fact, there are presently no comparable spectral sensitivity functions for the circadian
          system using any other outcome measure (e.g., phase shifting). The values of the
          coefficients in Additional file <xref ref-type="supplementary-material" rid="S1">1</xref>
          relating the opponent channels were optimized to align with published nocturnal human
          melatonin suppression data using narrowband spectra [<xref ref-type="bibr" rid="B26"
            >26</xref>,<xref ref-type="bibr" rid="B27">27</xref>]. This resulted in a good fit
            (r<sup>2 </sup>= 0.82) between all comparable suppression data using both narrowband and
          broadband spectra [<xref ref-type="bibr" rid="B24">24</xref>,<xref ref-type="bibr"
            rid="B26">26</xref>,<xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr"
            rid="B30">30</xref>,<xref ref-type="bibr" rid="B38">38</xref>,<xref ref-type="bibr"
            rid="B39">39</xref>] and a four-parameter logistic function [<xref ref-type="bibr"
            rid="B40">40</xref>] characterizing the melatonin suppression response as the light
          stimulus increases from threshold to saturation (Figure <xref ref-type="fig" rid="F4"
            >4</xref>). CL is defined in terms of irradiance, not radiance as with brightness
          because image formation on the retina is not believed to be important to the circadian
          system. Rather, CL is geometrically described in terms of radiant flux density on the
          cornea and therefore is geometrically comparable to illuminance at the eye.</p>
        <fig id="F3" position="float">
          <label>Figure 3</label>
          <caption>
            <p><bold>Nocturnal human melatonin suppression data from Brainard et al</bold>. [<xref
                ref-type="bibr" rid="B26">26</xref>]<bold> and Thapan et al</bold>. [<xref
                ref-type="bibr" rid="B27">27</xref>]<bold> for narrowband spectra (symbols), and a
                spectral sensitivity function resulting from exposure to narrowband illumination
                (solid curve).</bold> Also shown is the spectral sensitivity for broadband
              illumination when spectral opponency is exhibited [<xref ref-type="bibr" rid="B36"
                >36</xref>].</p>
          </caption>
          <graphic xlink:href="1740-3391-8-2-3.jpg"/>
        </fig>
        <fig id="F4" position="float">
          <label>Figure 4</label>
          <caption>
            <p><bold>Nocturnal human melatonin suppression data </bold>[<xref ref-type="bibr"
                rid="B24">24</xref>,<xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr"
                rid="B27">27</xref>,<xref ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr"
                rid="B38">38</xref>,<xref ref-type="bibr" rid="B39">39</xref>]<bold> (left
                ordinate), plotted as a function of CL quantities (abscissa) predicted by the model
                of Rea et al</bold>. [<xref ref-type="bibr" rid="B36">36</xref>]. Also shown is the
              best-fitting four-parameter logistic function [<xref ref-type="bibr" rid="B40"
                >40</xref>] to all of the data from threshold to saturation. The circadian light
              quantity CL was formerly named circadian stimulus (CS) [<xref ref-type="bibr"
                rid="B36">36</xref>]; CS (right ordinate) now refers to the effective stimulus based
              on nocturnal melatonin suppression.</p>
          </caption>
          <graphic xlink:href="1740-3391-8-2-4.jpg"/>
        </fig>
        <p>Previously published studies have been conducted to test the utility of the model of
          human circadian phototransduction [<xref ref-type="bibr" rid="B32">32</xref>,<xref
            ref-type="bibr" rid="B41">41</xref>]. Nocturnal melatonin suppression by light was
          assessed by Figueiro et al. [<xref ref-type="bibr" rid="B41">41</xref>] for two light
          source spectra and four light levels. <italic>A priori </italic>predictions of melatonin
          suppression were made based on calculations of CL given by each light level and spectra.
          Results demonstrated that the model predictions were consistent with melatonin suppression
          obtained at all four light levels, although uncertainty was greater at the lowest light
          level, which was close to threshold response. Also, Figueiro et al. [<xref ref-type="bibr"
            rid="B32">32</xref>] measured nocturnal melatonin suppression following exposure to
          lights presented monocularly and binocularly to demonstrate that the subadditive response
          to light by the circadian system originated in the retina as predicted by Rea et al.
            [<xref ref-type="bibr" rid="B36">36</xref>].</p>
        <p>Figueiro et al. [<xref ref-type="bibr" rid="B42">42</xref>] measured nocturnal melatonin
          suppression from short-wavelength light stimuli; these data were consistent with
          predictions made using the model by Rea and colleagues [<xref ref-type="bibr" rid="B36"
            >36</xref>]. Similarly, noctural melatonin suppression measurements reported by Revell
          and Skene [<xref ref-type="bibr" rid="B43">43</xref>] in response to narrowband and
          broadband light stimuli varying in intensity were shown [<xref ref-type="bibr" rid="B44"
            >44</xref>] to be consistent with predictions using this model [<xref ref-type="bibr"
            rid="B36">36</xref>].</p>
      </sec>
      <sec>
        <title>Utilization of circadian light</title>
        <p>As previously described, Rea et al. [<xref ref-type="bibr" rid="B36">36</xref>] proposed
          a mathematical model for quantifying circadian light for any spectral irradiance
          distribution. Two changes in the circadian light nomenclature from that paper have been
          made for metrological clarity. First, because the units of CL (spectrally weighted
          irradiance in W/m<sup>2</sup>) are new and, therefore, are not particularly intuitive to a
          user, a normalized quantity, CL<sub>A</sub>, was derived to more easily compare CL values
          with values of photopic illuminance, in lux (lx). A value of CL can be determined,
          measured or calculated, for 1000 lx of CIE standard illuminant A [<xref ref-type="bibr"
            rid="B21">21</xref>], a blackbody radiator at a color temperature of 2856 K similar in
          relative spectral power distribution to an incandescent lamp, and a scalar multiplier
          determined to make the product of CL and the multiplier equal 1000. The product of CL and
          this multiplier defines the quantity CL<sub>A</sub>. Any value of CL can then be
          normalized in terms of a reference illuminance of 1000 lx from the standard illuminant A
          equaling 1000 CL<sub>A </sub>units. CL<sub>A </sub>is numerically identical to orthodox
          photopic illuminance when illuminant A produces 1000 lx, but can differ, sometimes
          significantly, for other spectral power distributions and illuminance levels due to
          nonlinear operations in the CL formulation (see Additional file <xref
            ref-type="supplementary-material" rid="S1">1</xref>). Nevertheless, for many common
          white light sources values of CL<sub>A </sub>are similar in magnitude to illuminance
          values (in lx) at any level.</p>
        <p>Second, <italic>circadian stimulus </italic>(CS; [<xref ref-type="bibr" rid="B3"
            >3</xref>,<xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B44"
            >44</xref>,<xref ref-type="bibr" rid="B45">45</xref>]) in the original formulation is
          now defined as CL and, after normalization, as CL<sub>A</sub>. To understand why, consider
          two light sources producing very different irradiance and spectral quantities, resulting
          in CL<sub>A </sub>values of 10,000 and of 20,000 units. Despite a large difference in the
          values of CL<sub>A</sub>, the two sources would not be expected to produce different
          outcomes from the circadian system, at least in terms of nocturnal melatonin suppression.
          Both would produce saturating levels of suppression of about 75% percent after an hour of
          exposure. Thus, while the two sources would be characterized as being very different in
          terms of CL<sub>A</sub>, their effectiveness as a circadian stimulus in terms of nocturnal
          melatonin suppression would be identical. The term CS for a given light source is
          therefore now defined in terms of the <italic>relative effectiveness </italic>of CL, or
            CL<sub>A</sub>, for producing a meaningful circadian response. The logistic function in
          Figure <xref ref-type="fig" rid="F4">4</xref> is used to relate a given CL, or
            CL<sub>A</sub>, value to its corresponding CS value, between 0 (or 0%) and 0.75 (or
          75%), characterizing the relative effectiveness of the source as a stimulus to the
          circadian system.</p>
        <p>The implications for establishing quantitative measures of CL, CL<sub>A </sub>and CS are
          key to developing an understanding of how temporal patterns of light and dark affect human
          health and well-being. Without a quantitative understanding of the circadian light
          stimulus it will be difficult or impossible to make significant progress in unraveling the
          role that circadian disruption has on diseases such as breast cancer [<xref
            ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>],
          cardiovascular disease [<xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr"
            rid="B6">6</xref>], diabetes [<xref ref-type="bibr" rid="B7">7</xref>,<xref
            ref-type="bibr" rid="B8">8</xref>] and sleep disorders [<xref ref-type="bibr" rid="B9"
            >9</xref>].</p>
        <p>Toward this end a circadian light dosimeter, the Daysimeter (Figure <xref ref-type="fig"
            rid="F5">5</xref>), was developed to quantify circadian light exposures in these
          vulnerable populations. The Daysimeter, previously described [<xref ref-type="bibr"
            rid="B46">46</xref>] and subsequently refined [<xref ref-type="bibr" rid="B47"
          >47</xref>], is a personal head-worn device that measures CL<sub>A </sub>and photopic
          illuminance near the plane of the wearer's cornea. The Daysimeter also includes calibrated
          accelerometers to measure rest and activity. Data from the Daysimeter are recorded for as
          long as one month of wear and retrieved for post-processing. Each Daysimeter has its own
          spectral, spatial, and absolute light calibration so, following post-processing, it is
          possible to quantify individual CL<sub>A </sub>exposures in real life over extended
          periods. These data have great potential for understanding the impact of circadian
          disruption on human health because, for the first time, researchers and clinicians can
          actually measure circadian disruption among individuals in these vulnerable populations.
          Although beyond the scope of this paper, the Daysimeter has, in fact, recently been used
          to quantify and compare circadian disruption in day-shift and rotating-shift nurses [<xref
            ref-type="bibr" rid="B47">47</xref>,<xref ref-type="bibr" rid="B48">48</xref>]. Future
          research will undoubtedly utilize instruments like the Daysimeter to develop, for example,
          new shift-work schedules, new architectural practices and new light sources, all of which
          will depend upon our collective ability to measure and calculate circadian light.</p>
        <fig id="F5" position="float">
          <label>Figure 5</label>
          <caption>
            <p><bold>Close-up photograph of the Daysimeter</bold>. Two light sensors are located
              near the plane of the cornea, calibrated in terms of their absolute, spatial and
              spectral response to provide both photopic and circadian light readings. The rear
              housing attached to the earpiece contains accelerometers for measuring activity as
              well as memory and control circuitry, all powered by a coin-cell battery.</p>
          </caption>
          <graphic xlink:href="1740-3391-8-2-5.jpg"/>
        </fig>
      </sec>
      <sec>
        <title>Circadian light as a work in progress</title>
        <p>The definition of circadian light proposed here is based on the current knowledge of the
          neuroanatomy and neurophysiology of the human retina and on published psychophysical
          studies of nocturnal melatonin suppression using lights of different spectral power
          distributions. CL<sub>A </sub>and CS are provisionally defined then in terms of what is
          known about nocturnal melatonin suppression in humans (for an hour-long exposure to light,
          near the midpoint of the melatonin production curve, and with naturally-constricted
          pupils). Of course, acute melatonin suppression is not the only non-visual response by the
          circadian system; other non-visual responses include phase shifting and alertness. For at
          least these two cases, however, light-induced phase-shifting and light-induced nocturnal
          alertness appear to have similar threshold-to-saturation response characteristics [<xref
            ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B44">44</xref>]. A very
          recent study, however, has shown that both red and blue lights can affect alertness [<xref
            ref-type="bibr" rid="B49">49</xref>] as well as cortisol and alpha amylase production
          (Figueiro and Rea., unpublished data) at night indicating that not all light-induced,
          non-visual responses have the same spectral sensitivity as nocturnal melatonin
          suppression. The development of new response characteristics for these non-visual systems,
          if they emerge, would be very reminiscent of those that were developed in visual science
          where multiple spectral sensitivity functions for different visual channels were
          established (cf. Figure <xref ref-type="fig" rid="F1">1</xref>). If it is shown that the
          relationships between CL<sub>A </sub>and other non-visual responses, such as phase
          shifting, are different than the one demonstrated for nocturnal melatonin suppression,
          another CS function could be developed and designated with an appropriate subscript (such
          as CS<sub>nmel </sub>for nocturnal melatonin suppression and CS<sub>pshift </sub>for phase
          shifting). Again, this development would be quite similar to the evolution of different
          visual spectral sensitivity functions.</p>
        <p>As a final note, even the model of human circadian phototransduction based upon nocturnal
          melatonin suppression and used to calculate CL<sub>A </sub>and CS is probably incomplete.
          It does not take into account possible participation of different types of ipRGCs [<xref
            ref-type="bibr" rid="B50">50</xref>] and recent evidence that the melanopsin
          photopigment in the ipRGCs follows a very different regenerative process than that
          employed by the classical photoreceptors [<xref ref-type="bibr" rid="B51">51</xref>].
          These phenomena may have heretofore unknown effects on the spectral and absolute
          sensitivities of the circadian system that would demand consideration in a revised model
          of phototransduction and therefore an evolving definition of circadian light. Hopefully,
          however, the information presented here is an important step toward the precise
          application of light stimuli for the human circadian system.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>Light is formally defined as optical radiation capable of providing visual sensation in
          humans. The current definition of light does not directly relate to its effects on the
          human circadian system. Since temporal patterns of retinal light (and dark) exposures
          regulate the human circadian system and since disruption of the circadian system has broad
          implications for health and well-being [<xref ref-type="bibr" rid="B2">2</xref>-<xref
            ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B52">52</xref>,<xref
            ref-type="bibr" rid="B53">53</xref>], it is becoming increasingly important to develop a
          new definition of circadian light.</p>
        <p>Toward that end, the present paper has placed the evolving development of a definition of
          circadian light into the historical context of light as it has been defined for metrology
          and as it affects human vision. As described here, an additive "photodian" luminous
          efficiency function for circadian light will probably never be exactly comparable to the
          photopic luminous efficiency function used in conventional photometry based upon the human
          visual system. Nevertheless, it is increasingly important that a measurement system, such
          as CL, CL<sub>A</sub>, and CS as presented here, be developed for quantifying the photic
          stimulus for the human circadian system.</p>
      </sec>
      <sec>
        <title>Competing interests</title>
        <p>The authors declare that they have no competing interests.</p>
      </sec>
      <sec>
        <title>Authors' contributions</title>
        <p>The outline of the article was developed by all co-authors. MSR led the effort and wrote
          a partial draft of the manuscript with MGF. AB and JDB wrote specific sections of the text
          and prepared the figures. All co-authors reviewed and approved the final manuscript.</p>
      </sec>
      <sec sec-type="supplementary-material">
        <title>Supplementary Material</title>
        <supplementary-material content-type="local-data" id="S1">
          <caption>
            <title>Additional file 1</title>
            <p><bold>Circadian light (CL, CL<sub>A</sub>) and circadian stimulus (CS) calculation
                procedure </bold>[<xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr"
                rid="B21">21</xref>,<xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr"
                rid="B54">54</xref>-<xref ref-type="bibr" rid="B56">56</xref>].</p>
          </caption>
          <media xlink:href="1740-3391-8-2-S1.PDF" mimetype="text" mime-subtype="plain">
            <caption>
              <p>Click here for file</p>
            </caption>
          </media>
        </supplementary-material>
      </sec>
    </body>
    <back>
      <sec>
        <title>Acknowledgements</title>
        <p>This research was supported in part by the Trans-NIH Genes, Environment and Health
          Initiative Grant U01 DA023822 to the first author and by CDC Grant R01 OH008171 to Dr. Eva
          Schernhammer at Harvard Public Health. The New York Energy Research and Development
          Authority through the National Science Foundation (NSF) Smart Lighting Engineering
          Research Center (EEC-0812056) provided support for improvements to the Daysimeter. The
          authors thank Dennis Guyon for manuscript editing and preparation of the final
          graphics.</p>
      </sec>
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