Steven W. Lockley, Ph.D.

Dr. Steven Lockley is currently an Associate Neuroscientist at Brigham and Women’s Hospital (BWH), Boston and an Instructor in Medicine at Harvard Medical School. He graduated with a degree in Biology from Manchester University in the UK in 1992 and completed a PhD at the University of Surrey, UK entitled “Sleep, melatonin and other circadian rhythms in the Blind” in 1997. After two years of post-doctoral studies, he was appointed to the faculty at Surrey in 1999. In September 2000, Dr. Lockley joined the BWH as a Research Fellow in Medicine and was appointed to the faculty there in January of this year.

Dr. Lockley's research, published in more than 20 original reports and book chapters, has primarily focused on the characterization of circadian rhythm disorders in relation to light loss and visual impairment in the blind. These studies led to the development of melatonin administration regimes that were the first to treat the resultant non-24-hour sleep-wake disorder by using melatonin to reset the free-running circadian system.

More recently, he has studied the properties of light that are important in understanding how light resets the human circadian pacemaker, including the timing, duration and intensity of light. He has also conducted some of the first studies to examine the spectral sensitivity of the circadian system, or how different wavelengths of light affect the internal 24-hour body clock, and discovered that short-wavelength light is more effective at resetting the internal biological clock. These findings, and others, suggest that a novel photoreception system exists in the human eye, with different spectral, temporal and electrophysiological properties than photoreception used for sight.

Effects of Light on Human Circadian Rhythms

Human physiology and behavior is dominated by near-24-hour rhythms that have a major impact on our health and well-being. For example, sleep-wake cycles, alertness and performance patterns, core body temperature rhythms and the production of hormones such as melatonin and cortisol are all regulated by an endogenous near-24-hour oscillator in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. In order for the circadian pacemaker to ensure that physiology and behavior are timed appropriately with the outside world, environmental time cues must be able to reset this internal clock. The major environmental time cue able to reset these rhythms is the 24-hour light-dark cycle. Light information is captured by specialized retinal photoreceptors and transduced directly to the SCN via a dedicated neural pathway, the retinohypothalamic tract (RHT). The daily light-dark cycle resets the internal clock on a daily basis which in turn resets the physiology and behavior controlled by the clock.

The vital importance of light input to the pacemaker is readily observed when the circadian rhythms of totally blind individuals, particularly those who are bilaterally enucleated, are examined. In such people, the sleep-wake cycle, alertness and performance patterns, and the rhythms of temperature and some hormones become desynchronized from the 24-hour day as a result of light information failing to reach the brain to synchronize the clock and its outputs. The resulting clinical condition – non-24-hour sleep-wake disorder – is observed in the majority of totally blind people and is characterized by a cyclic sleep disorder with episodes of good sleep followed by episodes of bad sleep and excessive day-time naps as the internal pacemaker runs in and out of synchrony with the 24-hour day. Properties of light that have been shown to relate to circadian resetting include the intensity, number, duration, pattern and timing of exposures, and more recently, the wavelength of light used. The human circadian pacemaker is extremely sensitive to dim light, with a light intensity equivalent to indoor room light able to significantly shift the timing of the circadian system. More recent work has shown that light as dim as candlelight can maintain synchronization to the 24-hour day. Another important aspect of light exposure is its timing which determines whether light shifts the clock to an earlier time (advance) or a later time (delay). Under normal conditions, light exposure in the late evening will delay the circadian system to a later phase and light in the early morning will advance the circadian system to an earlier phase. This property of photic resetting is the underlying cause of sleep and other rhythmic disorders associated with ‘jet-lag’ and shiftwork.

The impact of wavelength on light-induced resetting of circadian rhythms is only recently emerging in humans. We have recently shown that the circadian system is most sensitive to short wavelength light and has a spectral sensitivity different to that from conventional scotopic and photopic vision. These findings, and others in both animals and humans, suggest that a novel photoreception system exists in the eye that has evolved to detect light for the circadian system separate from that used for sight.

The longer term effects on health of inappropriate light exposure are under investigation. Misalignment between the internal circadian pacemaker and the external environment is thought to contribute to health problems such as cardiovascular disease, diabetes, sleep disorders, and gastro-intestinal disorders. As more is learned about the properties of light exposure that affect the circadian system, such information can be used to optimize light exposure regimes to ensure proper synchro-nization. These regimes can be used to reset the pacemaker after extreme desynchronization, for example following long-haul flights, space flight, and the transition from day shift to night shift, or to correct less obvious, but still possibly damaging misalignment, for example during ageing or in relation to diurnal preference (‘owls’ vs ‘larks’). In conjunction with parallel advances in understanding how light affects the pacemaker at a molecular level, physiological studies can be used to develop and optimize therapies to treat not only clinical disorders of the circadian system, but also to help maintain normal circadian synchronization in our 24/7 society.

Effects of Light on Human Circadian Rhythms (pdf) - Steven W. Lockley, Ph.D.
 

SPEAKERS

Bidwell, Tony
Buchanan, Bryant
Crawford, Dr. David L.
Dick, Robert Stephen
Dickinson, Terence
French, Randy P.
Hill, Tom
Hills, Reverend Johanne
Hollan, Jenik
Hummel, Monte
Lickers, F. Henry
Lockley, Steven W.
Mesure, Michael
Moore, Chad A.
Reid, Ron
Riley, John L.
Roberts, Dr. Joan
Rutenberg, Tony
Shaver, Dorothy
Welch, David
Whitehead, Brian
Wise, Sharon