The Brigham and Women's Hospital, Inc.

Light Sciences Corporation

Charles A Czeisler

Richard E Kronauer

James S Allan

Christopher J Kyricos

Heinz Martens

Theresa L Shanahan

The present invention is a method for modifying the circadian cycle of a human subject to a desired state including the steps of determining the characteristics of the desired circadian cycle, selecting an appropriate time during which to apply a light stimulus to effect a desired modification of the present circadian cycle, and applying the stimulus at the selected time to achieve the desired circadian cycle for the subject. The light stimulus of the present invention includes an episode of intermittent light consisting of at least two pulses of enhanced light separated by at least one pulse of reduced light.

Intermittent use of bright light to modify the circadian phase

The present invention is an apparatus for producing and delivering high-intensity light to the eyes of a subject to modify the subject's circadian phase. The apparatus includes a support for positioning the apparatus above the eyes of the subject, a light generator for producing a cool, high-intensity light which is radiated to the eyes of the subject, and a power source coupled to the apparatus for supplying power to the light generator. The support of the invention is preferably a visor which does not obstruct the subject's vision when positioned on the head.

Apparatus for producing and delivering high-intensity light to a subject

Assessment and modification of a human subject's circadian cycle

A method for accurately assessing and rapidly modifying the phase and amplitude of the endogenous circadian pacemaker is disclosed. A circadian cycle modification capacity assessment method comprises (before and after a stimulus) eliminating activity-related confounding factors associated with the sleep-rest cycle which otherwise mask the state of the endogenous circadian pacemaker. Based on either individual or normative assessment data, the circadian phase and amplitude modification method involves the application of bright (about 9,500 lux) light and, advantageously, episodes of imposed darkness, at critically chosen phases to achieve rapid and stable changes in phase and amplitude. The timing of the episodes of bright light may be chosen either by reference to empirically-derived phase response data, or by using a mathematical model in which the endogenous circadian pacemaker is a van der Pol oscillator. A forcing function in the model is substantially proportional to changes in the cube root of the surrounding illuminance, in lux. The amplitude of the endogenous circadian pacemaker may actually be reduced to substantially zero, so as to bring about dramatic phase modifications in diminishingly small periods of time. The methods find special utility in treating 'jet lag' sufferers, shift workers, advanced circadian phase experienced by many elderly subjects, and those afflicted with delayed sleep phase insomnia.

Assessment and modification of circadian phase and amplitude

A method for accurately assessing and rapidly modifying the phase and amplitude of the endogenous circadian pacemaker is disclosed. A circadian cycle modification capacity assessment method comprises (before and after a stimulus) eliminating activity-related confounding factors associated with the sleep-rest cycle which otherwise mask the state of the endogenous circadian pacemaker. Based on either individual or normative assessment data, the circadian phase and amplitude modification method involves the application of bright (about 9,500 lux) light and, advantageously, episodes of imposed darkness, at critically chosen phases to achieve rapid and stable changes in phase and amplitude. The timing of the episodes of bright light may be chosen either by reference to empirically-derived phase response data, or by using a mathematical model in which the endogenous circadian pacemaker is a second order differential equation of the van der Pol type, transformed into two complementary first order equations. A forcing function in the model is substantially proportional to changes in the cube root of the surrounding illuminance, in lux. The amplitude of the endogenous circadian pacemaker may actually be reduced to substantially zero, so as to bring about dramatic phase modifications in diminishingly small periods of time. The methods find special utility in treating 'jet lag' sufferers, shift workers, advanced circadian phase experienced by many elderly subjects, and those afflicted with delayed sleep phase insomnia.

Assessment and modification of endogenous circadian phase and amplitude

Assessment and modification of a subject's endogenous circadian cycle

A method of determining the functional integrity of the visual system (including the photoreceptive elements, the retino-hypothalamic tracts and their connections to the suprachiasmatic nuclei of the hypothalamus) of visually imparied human beings. The method includes measuring the melatonin content in blood samples taken before, during and after application of a stimulus (e.g. light) to the subject's retinas, and comparing the measured melatonin content to determine if the melatonin content was suppressed during application of the stimulus.

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Cambridge, MA, United States of America

Charles A Czeisler