Human phase response curve to a single 6.5 h pulse of short-wavelength light

Authors

  • Melanie Rüger,

    1. Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Melissa A. St Hilaire,

    1. Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • George C. Brainard,

    1. Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA
    Search for more papers by this author
  • Sat-Bir S. Khalsa,

    1. Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Richard E. Kronauer,

    1. Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA
    3. School of Engineering and Applied Sciences, Harvard, University, Cambridge, MA, USA
    Search for more papers by this author
  • Charles A. Czeisler,

    1. Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Steven W. Lockley

    1. Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author

M. Rüger: Circadian Physiology Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.Email: mrueger@rics.bwh.harvard.edu

Key points

  • • The human ∼24 h circadian pacemaker ensures appropriate timing of physiological, behavioural and metabolic events and is synchronized to the 24 h day primarily by the 24 h light–dark cycle.
  • • The direction and magnitude of photic resetting depend on the timing of light exposure, and are described by a phase response curve (PRC).
  • • The human circadian photoreception system is functionally and anatomically distinct from the visual system and employs a novel photoreceptor, melanopsin, which is maximally sensitive to short-wavelength (blue) visible light.
  • • We constructed a PRC to 6.5 h of blue (480 nm) light and compared it with a prior 6.7 h white light PRC; the blue light PRC achieved ∼75% of the resetting response of the white light PRC.
  • • This study suggests that short-wavelength visible light exposures may be more efficient than traditional high-intensity white light exposures for treatment of circadian rhythm sleep disorders.

Abstract  The photic resetting response of the human circadian pacemaker depends on the timing of exposure, and the direction and magnitude of the resulting shift is described by a phase response curve (PRC). Previous PRCs in humans have utilized high-intensity polychromatic white light. Given that the circadian photoreception system is maximally sensitive to short-wavelength visible light, the aim of the current study was to construct a PRC to blue (480 nm) light and compare it to a 10,000 lux white light PRC constructed previously using a similar protocol. Eighteen young healthy participants (18–30 years) were studied for 9–10 days in a time-free environment. The protocol included three baseline days followed by a constant routine (CR) to assess initial circadian phase. Following this CR, participants were exposed to a 6.5 h 480 nm light exposure (11.8 μW cm−2, 11.2 lux) following mydriasis via a modified Ganzfeld dome. A second CR was conducted following the light exposure to re-assess circadian phase. Phase shifts were calculated from the difference in dim light melatonin onset (DLMO) between CRs. Exposure to 6.5 h of 480 nm light resets the circadian pacemaker according to a conventional type 1 PRC with fitted maximum delays and advances of −2.6 h and 1.3 h, respectively. The 480 nm PRC induced ∼75% of the response of the 10,000 lux white light PRC. These results may contribute to a re-evaluation of dosing guidelines for clinical light therapy and the use of light as a fatigue countermeasure.

Ancillary