Circadian phase estimation, modeling and control

• US 10,529,440 B2
• Filed: 06/04/2013
• Issued: 01/07/2020
• Est. Priority Date: 06/05/2012
• Status: Active Grant

• Current Assignee: Rensselaer Polytechnic Institute
• Original Assignee: Rensselaer Polytechnic Institute
• Inventors: Zhang, Jiaxiang, Wen, John T., Julius, Agung
• Primary Examiner(s): Wathen, Brian W
• Assistant Examiner(s): Seye, Abdu K
• Application Number:
  US14/405,973
• Publication Number:
  US 20150186594A1
• Time in Patent Office: 2,408 Days
• Field of Search: None
• CPC Class Codes: A61B 5/4857 Indicating the phase of biorhythm clocks or watches with indicators for biological cycles G04B19/264
• CPC Class Codes: A61N 2005/0626 Monitoring, verifying, controlling systems and methods
• CPC Class Codes: A61N 5/0618 Psychological treatment
• CPC Class Codes: G06N 7/02 using fuzzy logic computing arrangements based on biological models G06N3/00; computing arrangements using knowledge-based models G06N5/00
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Method, system and computer program product are provided for estimating a circadian phase of a subject by: obtaining a sensed biological signal for the subject; and using, by one or more processors, adaptive frequency tracking to adaptively estimate the circadian phase of the subject from the sensed biological signal. Circadian phase estimation may be accelerated by providing a feedback loop for the adaptive frequency tracking, which utilizes, in part, a circadian phase model in automatically ascertaining a phase correction for the adaptive frequency tracking. The circadian phase estimation may be used in automatically constructing a light-based circadian rhythm model for the subject using a linear parameter-varying (LPV) formulation, and once constructed, the circadian rhythm model for the subject may be used to provide light-based circadian rhythm regulation.

Claims

1. A method comprising:

estimating a circadian phase of the subject using a circadian rhythm control system to facilitate regulating a subject'"'"'s circadian rhythm, the estimating comprising;

obtaining a sensed biological signal for the subject;

using, by one or more processors, adaptive frequency tracking to adaptively estimate the circadian phase of the subject from the sensed biological signal;

sensing circadian light intensity exposure of the subject commensurate with a sensing of the sensed biological signal of the subject;

constructing a light-based circadian rhythm model for the subject using a linear parameter-varying system formulation with the sensed circadian light intensity as input and a model-based circadian phase of the subject as output;

using the light-based circadian rhythm model to ascertain and apply a phase correction to the adaptive frequency tracking providing the estimated circadian phase of the subject; and

the circadian rhythm control system initiating control of circadian light input to the subject based on the estimated circadian phase of the subject to regulate the subject'"'"'s circadian rhythm; and

wherein the adaptive frequency tracking utilizes an adaptive notch filter, and the measured biological signal obtained from the subject can be represented as a linear combination of N harmonics and a component;

n=d*+A*₁ sin(*t+₁)+A*₂ sin(2*t+₂)++A*_N sin(N*t+_N),

wherein internal variables of the adaptive frequency tracking converge to;

2. The method of claim 1, wherein the adaptive frequency tracking utilizes single-harmonic or multi-harmonic filtering, the single-harmonic or multi-harmonic filtering being a model-less process for adaptively estimating the circadian phase of the subject from the sensed biological signal for the subject.

3. The method of claim 2, wherein using adaptive frequency tracking comprises ascertaining, by the one or more processors, the circadian phase of the subject by determining a fundamental harmonic phase of the sensed biological signal from a set of internal variables provided by the single-harmonic or multi-harmonic filtering, the set of internal variables comprising state variables for a first or higher order oscillator.

4. The method of claim 3, further comprising adapting internal parameters used by the single-harmonic or multi-harmonic filtering, the adapting utilizing a tracking error ascertained by comparing the sensed biological signal to filtered biological data determined by the single-harmonic or multi-harmonic filtering, the internal parameters comprising at least one of a constant bias of the sensed biological signal or an angular frequency of circadian rhythm.

5. The method of claim 4, wherein adaptively estimating the circadian phase of the subject from the sensed biological signal occurs in real time, and adapting the internal parameters used by the single-harmonic or multi-harmonic filtering occurs automatically.

6. The method of claim 1, wherein the using by the one or more processors adaptive frequency tracking comprises using, by the one or more processors, a set of recursive, non-linear filters computed in real time to adaptively estimate the circadian phase of the subject from the sensed biological signal from the subject.

7. The method of claim 1, further comprising accelerating estimating of the circadian phase from the sensed biological signal by providing a feedback loop for the adaptive frequency tracking, the feedback loop utilizing, in part, the light-based circadian rhythm model, in ascertaining the phase correction for the adaptive frequency tracking.

8. The method of claim 7, wherein the feedback loop determines a phase estimate discrepancy between a phase estimate of the adaptive frequency tracking and a phase estimate of the circadian phase model, and utilizes the phase estimate discrepancy to, in part, determine the phase correction for the adaptive frequency tracking.

9. The method of claim 8, wherein the feedback loop utilizes the sensed circadian light exposure as input to the circadian rhythm model and as input to a tunable gain element, the tunable gain element outputting a first phase correction signal as the phase correction for the adaptive frequency tracking, the first phase correction signal being determined, in part, using the determined phase estimate discrepancy.

10. The method of claim 9, wherein the tunable gain element further outputs a second phase correction signal for the circadian phase model, the second phase correction signal being determined, in part, using the phase estimate of the adaptive frequency tracking and the phase estimate of the circadian phase model.

11. The method of claim 1, wherein the constructing comprises:

ascertaining multiple linear time-invariant models using multiple light profiles;

transforming the multiple linear time-invariant models into observable canonical form; and

combining the multiple linear time-invariant models into the light-based circadian rhythm model for the subject using the linear parameter-varying system formulation.

12. The method of claim 1, wherein the linear parameter-varying system formulation comprises:

13. A method comprising:

utilizing a circadian rhythm control system to facilitate regulating a subject'"'"'s circadian rhythm, the circadian rhythm control system;

ascertaining a light-based circadian rhythm model for a subject, the ascertaining comprising;

obtaining biological data from a subject and estimating therefrom circadian phase of the subject;

sensing circadian light intensity exposure of the subject commensurate with obtaining the biological data;

using, by one or more processors, a linear parameter-varying system formulation with the sensed circadian light as input and the estimated circadian phase of the subject as output to ascertain the light-based circadian rhythm model; and

initiating, via the circadian rhythm control system, control of circadian light input to the subject based on the ascertained light-based circadian rhythm model for the subject to regulate the subject'"'"'s circadian rhythm;

wherein estimating circadian phase of the subject comprises using, by the one or more processors, adaptive frequency tracking to adaptively estimate the circadian phase of the subject from the obtained biological data; and

wherein the adaptive frequency tracking utilizes an adaptive notch filter, and measured biological signal obtained from the subject can be represented as a linear combination of N harmonics and a component;

n=d*+A*₁ sin(*t+₁)+A*₂ sin(2*t+₂)++A*_N sin(N*t+_N)

wherein internal variables of the adaptive frequency tracking converge to;

14. The method of claim 13, wherein the adaptive frequency tracking utilizes single-harmonic or multi-harmonic filtering, the single-harmonic or multi-harmonic filtering being a model-less process for adaptively estimating the circadian phase of the subject from the sensed biological signal for the subject.

15. The method of claim 14, wherein using adaptive frequency tracking comprises ascertaining, by the one or more processors, the circadian phase of the subject by determining a fundamental harmonic phase of the sensed biological signal from a set of internal variables provided by the single-harmonic or multi-harmonic filtering, the set of internal variables comprising state variables for a first or higher order oscillator.

16. The method of claim 13, further comprising accelerating estimating of the circadian phase from the obtained biological data by providing a feedback loop for the adaptive frequency tracking, the feedback loop utilizing, in part, the light-based circadian rhythm model in ascertaining the phase correction for the adaptive frequency tracking.

17. The method of claim 16, wherein the feedback loop determines a phase estimate discrepancy between a phase estimate of the adaptive frequency tracking and a phase estimate of the circadian rhythm model, and utilizes the phase estimate discrepancy to, in part, determine the phase correction for the adaptive frequency tracking.

18. The method of claim 17, wherein the feedback loop utilizes the sensed circadian light exposure as input to the circadian rhythm model, and as input to a tunable gain element, the tunable gain element outputting a first phase correction signal as the phase correction for the adaptive frequency tracking, the first phase correction being determined, in part, using the determined phase estimate discrepancy.

19. The method of claim 18, wherein the tunable gain element further outputs a second phase correction signal for the circadian phase model, the second phase correction signal being determined, in part, using the phase estimate of the adaptive frequency tracking and the phase estimate of the circadian phase model.

20. A system comprising:

a circadian rhythm control system to facilitate regulating a subject'"'"'s circadian rhythm, the circadian rhythm control system comprising one or more processors, which facilitate;

obtaining a sensed biological signal for the subject;

using, by the one or more processors, adaptive frequency tracking to adaptively estimate the circadian phase of the subject from the sensed biological signal;

sensing circadian light intensity exposure of the subject commensurate with a sensing of the sensed biological signal of the subject;

constructing a light-based circadian rhythm model for the subject using a linear parameter-varying system formulation with the sensed circadian light intensity as input and a model-based circadian phase of the subject as output;

using the light-based circadian rhythm model to ascertain and apply a phase correction to the adaptive frequency tracking providing the estimated circadian phase of the subject; and

the circadian rhythm control system initiating control of circadian light input to the subject based on the estimated circadian phase of the subject to regulate the subject'"'"'s circadian rhythm; and

wherein the adaptive frequency tracking utilizes an adaptive notch filter, and measured biological signal obtained from the subject can be represented as a linear combination of N harmonics and a component;

n=d*+A*₁ sin(*t+₁)+A*₂ sin(2*t+₂)++A*_N sin(N*t+_N)

wherein internal variables of the adaptive frequency tracking converge to;

21. A computer program product for adaptively estimating circadian phase of a subject, the computer program product comprising:

a non-transitory computer-readable storage medium readable by one or more processors and storing instructions for execution by the one or more processors for performing a method comprising;

obtaining a sensed biological signal for the subject;

using adaptive frequency tracking to adaptively estimate the circadian phase of the subject from the sensed biological signal;

sensing circadian light intensity exposure of the subject commensurate with a sensing of the sensed biological signal of the subject;

constructing a light-based circadian rhythm model for the subject using a linear parameter-varying system formulation with the sensed circadian light intensity as input and a model-based circadian phase of the subject as output;

using the light-based circadian rhythm model to ascertain and apply a phase correction to the adaptive frequency tracking providing the estimated circadian phase of the subject; and

initiating control of circadian light input to the subject based on the estimated circadian phase of the subject to regulate the subject'"'"'s circadian rhythm; and

wherein the adaptive frequency tracking utilizes an adaptive notch filter, and measured biological signal obtained from the subject can be represented as a linear combination of N harmonics and a component;

n=d*+A*₁ sin(*t+₁)+A*₂ sin(2*t+₂)++A*_N sin(N*t+_N)

wherein internal variables of the adaptive frequency tracking converge to;