Assessment and modification of a subject's endogenous circadian cycle

• US 5,163,426 A
• Filed: 06/26/1987
• Issued: 11/17/1992
• Est. Priority Date: 06/26/1987
• Status: Expired due to Term

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Czeisler, Charles A., Kronauer, Richard E., Allan, James S.
• Primary Examiner(s): Smith, Ruth S.
• Application Number:
  US07/066,677
• Time in Patent Office: 1,971 Days
• Field of Search: 364/413, 364/414, 128/395-398
• US Class Current: 607/88
• CPC Class Codes: A61M 2021/0044 by the sight sense
• CPC Class Codes: A61M 21/00 Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis
• CPC Class Codes: A61N 2005/0648 the light being directed to the eyes
• CPC Class Codes: A61N 5/0618 Psychological treatment

Abstract

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.

Claims

1. A method of modifying a subject'"'"'s endogenous circadian cycle to a desired state, comprising the steps of:

assessing predefined specific characteristics of a present endogenous circadian cycle of the subject;

selecting one or more appropriate times in the present endogenous circadian cycle, based on the assessed characteristics, at which to apply a stimulus to effect a desired modification of said cycle;

applying said stimulus, comprised of a pulse of bright light, at each of said selected appropriate times in said present endogenous circadian cycle, to effect the desired modification of said cycle;

whereby the characteristics of the present endogenous circadian cycle of the subject are rapidly modified to substantially reduce the amplitude of the subject'"'"'s endogenous circadian cycle and

applying a single pulse of bright light, after said applying step has modified the amplitude so that the amplitude is substantially reduced with respect to the present circadian cycle, to set the endogenous circadian cycle to a desired phase.

2. The method of claim 1, wherein said first applying step further comprises:

applying, at preselected times in said assessed present endogenous circadian cycle, episodes of imposed strict darkness of preselected duration.

3. The method of claim 2, wherein said assessing step comprises:

assessing the phase of the present endogenous circadian cycle of the subject.

4. The method of claim 2, wherein said assessing step comprises:

assessing the amplitude of the present endogenous circadian cycle if the subject.

5. The method of claim 2, wherein said assessing step comprises:

assessing the phase and the amplitude of the present endogenous circadian cycle of the subject.

6. The method of claim 2, wherein said first applying step comprises:

applying pulses of light in the range of 7,000-12,000 lux.

7. The method of claim 6, wherein said first applying step comprises:

applying pulses of light of approximately 9,500 lux.

8. The method of claim 2, wherein said assessing step comprises:

placing the subject in a semi-recumbent position;

minimizing the subject'"'"'s physical activity;

feeding the subject small amounts of food at regular, closely-timed intervals;

keeping the subject awake;

measuring the characteristics of the present endogenous circadian cycle by measuring physiological parameters of the subject; and

forming a representation of the physiological parameters as a function of time.

9. The method of claim 8, wherein said measuring step comprises:

measuring one or more of core body temperature, cortisol secretion, and other endocrine functions.

10. The method of claim 2, wherein said assessing step comprises:

using normative data to estimate the characteristics of the present endogenous circadian cycle of the subject.

11. A method of modifying a subject'"'"'s endogenous circadian cycle to a desired state, comprising the steps of:

assessing predefined specific characteristics of a present endogenous circadian cycle of the subject;

selecting one or more appropriate times in the present endogenous circadian cycle, based on the assessed characteristics, at which to apply a stimulus to effect a desired modification of said cycle; and

applying said stimulus, at certain ones of said selected appropriate times in said assessed present endogenous circadian cycle, to effect the desired modification of said cycle, said stimulus comprised of a pulse of bright light, and, optionally, an episode of imposed strict darkness, so as to modify the amplitude of the endogenous circadian cycle to be substantially reduced with respect to the present circadian cycle; and

applying a subsequent stimulus comprised of a pulse bright light or an episode of imposed strict darkness at another one of said selected appropriate times to set the endogenous circadian cycle of the subject to the desired state.

12. The method of claim 11, wherein said selecting step further comprises the step of:

selecting a duration of said stimulus based on the assessed characteristics.

13. The method of claim 11, wherein the steps of applying comprises applying said stimulus to the subject'"'"'s retinas.

14. A method of assessing modification capacity of a stimulus on a subject'"'"'s endogenous circadian cycles, comprising the steps of:

assessing predefined specific characteristics of a pre-stimulus endogenous circadian cycle of the subject;

selecting one or more appropriate times in the pre-stimulus endogenous circadian cycle, based on the assessed characteristics, at which to apply a stimulus;

applying pulses of bright light and optionally episodes of imposed strict darkness to the subject at the selected appropriate times so as to modify the amplitude of the prestimulus endogenous circadian cycle of the subject to a desired state; and

assessing predefined specific characteristics of a post-stimulus endogenous circadian cycle of the subject;

wherein said assessing steps comprise;

placing the subject in a semi-recumbent position;

minimizing the subject'"'"'s physical activity;

feeding the subject small amounts of food at regular, closely-timed intervals;

keeping the subject awake; and

measuring the characteristics of the endogenous circadian cycles by measuring physiological parameters of the subject.

15. The method of claim 14, wherein said measuring step comprises:

measuring one or both of core body temperature and cortisol secretion.

16. The method of claim 14, wherein said assessing steps comprise:

measuring the phase of the endogenous circadian cycles of the subject.

17. The method of claim 14, wherein said assessing steps comprise:

measuring the amplitude of the endogenous circadian cycles of the subject.

18. The method of claim 14, wherein said assessing steps comprise:

measuring the phase and the amplitude of the endogenous circadian cycles of the subject.

19. The method of claim 14, wherein said applying step further comprises:

applying pulses of light in the range of 7,000-12,000 lux.

20. The method of claim 14, wherein said applying step further comprises:

applying pulses of light of approximately 9,500 lux.

21. The method of claim 14, further comprising the steps of:

compensating for an endogenous circadian cycle having a period not equal to 24 hours.

22. A method of shifting the phase of a subject'"'"'s endogenous circadian cycle to a desired phase comprising the steps of:

(a) determining a subject'"'"'s endogenous circadian cycle;

(b) modifying the amplitude of the subject'"'"'s endogenous circadian cycle;

(c) selecting a time at which to apply a stimulus in order to effect the desired shift in the phase of said cycle;

(d) applying said stimulus, comprised of bright light, at the time selected to shift the phase of the subject'"'"'s endogenous circadian cycle.

23. The method of claim 22, further comprising:

(e) repeating steps (c) and (d) one or more times according to the subject'"'"'s determined endogenous circadian cycle until the desired phase shift is achieved.

24. The method of claim 22, wherein step (b) further comprises:

reducing the amplitude of the subject'"'"'endogenous circadian cycle.

25. A method of changing the amplitude of a subject'"'"'s endogenous circadian cycle comprising the steps of:

(a) determining a subject'"'"'endogenous circadian cycle;

(b) selecting, based on said determining step, a time at which to apply a stimulus in order to effect a desired change in the amplitude of said cycle;

(c) applying said stimulus, comprised of bright light, at the time selected, to change the amplitude of the subject'"'"'s endogenous circadian cycle.

26. The method of claim 25, further comprising:

(d) repeating steps (b) and (c) one or more times according to the subject'"'"'s determined endogenous circadian cycle until the desired amplitude change is achieved.