Patent Application
20180160944
The present disclosure pertains to a system and method for estimating the circadian phase of a subject, and, in particular, to using activity level measurements to estimate the circadian phase.
The medical importance of an individual person's circadian rhythm is well-documented, and includes, among other purposes, diagnostic purposes. Light deficiency disorders may include, but are not limited to, Seasonal Affective Disorder (SAD), circadian sleep disorders, and circadian disruptions associated with, e.g., jet-lag, shift-work, and/or other occupational conditions that may cause circadian disruptions.
Various models and methods may be used to determine and/or estimate a subject's circadian phase. Typically, determinations and/or estimations are made based on light exposure and/or other measurements during a preceding period, e.g. of one or more days. Once the circadian phase of a particular subject has been determined and/or estimated, the circadian phase may be adjusted as desired and/or recommended by, e.g., light therapy and/or exogenous melatonin intake.
Accordingly, it is an object of one or more embodiments of the present invention to provide a system to estimate circadian phase of a subject. The system comprises a sensor and one or more physical processors. The sensor is configured to generate output signals conveying information related to an activity level of the subject. The one or more physical processors are configured to determine a set of activity parameters related to the activity level of the subject, wherein the set of activity parameters is based on the generated output signals. The one or more physical processors are further configured to generate a set of estimated light exposure parameters based on the set of activity parameters and estimate the circadian phase of the subject based on the set of estimated light exposure parameters.
It is yet another aspect of one or more embodiments of the present invention to provide a method to estimate circadian phase of a subject. The method comprises generating output signals conveying information related to an activity level of the subject; determining a set of activity parameters related to the activity level of the subject, wherein the set of activity parameters is based on the generated output signals; generating a set of estimated light exposure parameters based on the set of activity parameters; and estimating the circadian phase of the subject based on the set of estimated light exposure parameters.
It is yet another aspect of one or more embodiments to provide a system configured to estimate circadian phase of a subject. The system comprises means for generating output signals conveying information related to an activity level of the subject; means for determining a set of activity parameters related to the activity level of the subject, wherein the set of activity parameters is based on the generated output signals; means generating a set of estimated light exposure parameters based on the set of activity parameters; and means for estimating the circadian phase of the subject based on the set of estimated light exposure parameters.
These and other objects, features, and characteristics of the present invention, as well as the methods of operation and functions of the related elements of structure and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of which form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures. It is to be expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the invention.
As used herein, the singular form of “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise. As used herein, the statement that two or more parts or components are “coupled” shall mean that the parts are joined or operate together either directly or indirectly, i.e., through one or more intermediate parts or components, so long as a link occurs. As used herein, “directly coupled” means that two elements are directly in contact with each other. As used herein, “fixedly coupled” or “fixed” means that two components are coupled so as to move as one while maintaining a constant orientation relative to each other. As used herein, the word “unitary” means a component is created as a single piece or unit. That is, a component that includes pieces that are created separately and then coupled together as a unit is not a “unitary” component or body. As employed herein, the statement that two or more parts or components “engage” one another shall mean that the parts exert a force against one another either directly or through one or more intermediate parts or components. As employed herein, the term “number” shall mean one or an integer greater than one (i.e., a plurality). As used herein, the term “include” shall be used inclusively to mean any item of a list, by example and without limitation, and/or any combination of items in that list, to the extent possible. Directional phrases used herein, such as, for example and without limitation, top, bottom, left, right, upper, lower, front, back, and derivatives thereof, relate to the orientation of the elements shown in the drawings and are not limiting upon the claims unless expressly recited therein.
Mammalian circadian systems coordinate the timing of an animal's physiological and behavioral functions with local position on the planet. The circadian system depends primarily upon the 24-hour light-dark pattern incident on the retinae. The phototransduction mechanisms responsible for human circadian phototransduction are understood well enough that devices may take advantage of this understanding and adjust circadian timing as desired and/or use it for diagnostic purposes.
Various biomarkers may serve to establish a particular moment in the circadian process, which may be referred to as circadian phase. For example, the time at which the core body temperature attains a minimum value may be a biomarker. This time or moment may be referred to as core body temperature minimum or CBTmin. As used herein, the term CBTmin may be used to indicate the value of the minimum core body temperature or the moment of its attainment, depending on the context of the reference. In some embodiments, CBTmin is used as the zero phase (of the circadian rhythm), the zero-point of the circadian phase, or a circadian phase having value zero. Also the moment at which melatonin production starts, under dim-light conditions—is a so-called biomarker. This moment may be referred to as dim-light melatonin onset or DLMO. In some embodiments, DLMO is used to denote circadian phase. For example, under certain light conditions, DLMO occurs at around 22:30 h. The circadian phase is generally and/or grossly cyclical, repeating itself about every 24 hours.
In some embodiments, models that may be used to determine and/or estimate a subject's circadian phase may use one or more of the following information as input: light exposure during a preceding period, CBTmin, DLMO, subject-specific parameters, sleep-wake information, and/or other types of information. Note that light exposure may shift the circadian phase of a subject, depending on, at least, the intensity of the light and the relative timing of light exposure with respect to the current circadian phase. In some models, multiple types of information may be used in combination. For example, light administered after the CBTmin (typically early in the morning for a properly aligned circadian rhythm) may advance the circadian phase, whereas light administered before the CBTmin (typically in the evening or early in the night for a properly aligned circadian rhythm) may delay the circadian phase. Examples of such models include, but are not limited to, the human circadian pacemaker (HCP) model and its derivatives.
As used herein, the term “determine” (and derivatives thereof) may include measure, calculate, compute, estimate, approximate, generate, and/or otherwise derive, and/or any combination thereof. As used herein, the term “obtain” (and derivatives thereof) may include active and/or passive retrieval, determination, derivation, transfer, upload, download, submission, and/or exchange of information, and/or any combination thereof.
In some embodiments, a model that may be used to determine and/or estimate a subject's circadian phase may be described by a second-order differential equation, where the dependent variable x(t) is assumed to vary analogously with a subject's core body temperature (CBT):
This model may be referred to as the pacemaker oscillator model. In this equation, μ (a stiffness factor, e.g., between 0 and 1) and τ (the intrinsic period) are given model parameters. B(t) and N(t) are the photic driving term B and the non-photic driving term N. B(t) is traditionally obtained through light exposure measurements. N(t) is traditionally obtained through measurements of external stimuli other than light exposure, e.g. measurements of an activity level of the subject. Together, B(t) and N(t) form the ‘Zeitgeber’ term Z(t). The photic term B(t) may be obtained through a light pre-processor that comprises 3 main steps, namely, (1) a non-linear compression of one or more light exposure parameters, (2) a dynamic modeling of retinal saturation over time, (3) a light-sensitivity modulation depending on the circadian phase at which the subject is exposed to light. By way of non-limiting example, see the following references: Kronauer R. E., Forger D. B. and Jewett M. E., “Quantifying Human Circadian Pacemaker Response to brief, extended and repeated light stimuli over the photopic range” in J.Biological Rhythms, Vol. 14(6), pp. 501-516, 1999, (see also the Errata published in 2000), and M. A. St-Hilaire, E. B. Klerman, Sat Bir Khalsa, K. P. Wright Jr., C. A. Czeisler and R. E Kronauer, “Addition of a non-photic component to a light-based mathematical model of the Human Circadian Pacemaker”, Journal of Theoretical Biology, Vol. 247, pp. 583-599, 2007.
In some scenarios, subject-specific light exposure information may not be available, not reliable, and/or otherwise not suitable for determining and/or estimating a subject's circadian rhythm. By virtue of the features described in this disclosure, subject-specific information regarding the activity level of a subject may be used to determine and/or estimate a subject's circadian rhythm/phase, in particular in the absence of subject-specific light exposure information.
One or more sensors 142 of system 10 in
In some embodiments, one or more sensors 142 may generate output signals conveying information related to a location of subject 106, e.g. through a gyroscopic sensor in addition to an accelerometer, or GPS technology. The location may be a three-dimensional location of subject 106, a two-dimensional location of subject 106, a location of a specific body part of subject 106 (e.g., eyes, arms, legs, a face, a head, a forehead, and/or other anatomical parts of subject 106), the posture of subject 106, the orientation of subject 106 or one or more anatomical parts of subject 106, and/or other locations.
Sensors 142 may include one or more of a motion sensor, an accelerometer, a gyroscopic sensor, a light sensor, an optical sensor, a temperature sensor, a pressure sensor, a weight sensor, an electromagnetic (EM) sensor, an infra-red (IR) sensor, a microphone, a transducer, a heart-rate sensor, a still-image camera, a video camera, and/or other sensors and combinations thereof.
The illustration of sensor 142 including one member in
One or more sensors 142 may be configured to generate output signals in an ongoing manner, e.g. throughout the day, week, month, and/or years. This may include generating signals intermittently, periodically (e.g. at a sampling rate), continuously, continually, at varying intervals, and/or in other ways that are ongoing during at least a portion of period of a day, week, month, or other duration. The sampling rate may be about 0.001 second, 0.01 second, 0.1 second, 1 second, about 10 seconds, about 1 minute, about 2 minutes, about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 30 minutes, and/or other sampling rates. In some embodiments, the sampling rate may be any sampling rate between 0.01 and 100 Hz. It is noted that multiple individual sensors may operate using different sampling rates, as appropriate for the particular output signals and/or (frequencies related to particular) parameters derived therefrom. For example, in some embodiments, the generated output signals may be considered as a set of output signals, an ordered set of output signals, a sequence of output signals, and/or a vector of output signals, such that multiple measurements and/or samples of information are conveyed. A particular parameter determined in an ongoing manner from multiple output signals may be considered as a vector of that particular parameter. In some embodiments, system 10 may include two or more sensors 142, e.g. two or more accelerometers.
Physical processor 110 (interchangeably referred to herein as processor 110) is configured to provide information processing and/or system control capabilities in system 10. As such, processor 110 may include one or more of a digital processor, an analog processor, a digital circuit designed to process information, an analog circuit designed to process information, and/or other mechanisms for electronically processing information. In order to provide the functionality attributed to processor 110 herein, processor 110 may execute one or more components. The one or more components may be implemented in software; hardware; firmware; some combination of software, hardware, and/or firmware; and/or otherwise implemented. Although processor 110 is shown in
As is shown in
It should be appreciated that although components 111-114 are illustrated in
Parameter determination component 111 of system 10, depicted in
One or more physiological parameters may be related to and/or derived from electro-encephalogram (EEG) measurements, electromyogram (EMG) measurements, respiration measurements, cardiovascular measurements, heart-rate-variability (HRV) measurements, autonomic nervous system (ANS) measurements, and/or other measurements. Some or all of this functionality may be incorporated or integrated into other computer program components of processor 110.
In some embodiments, parameter determination component 111 may be configured to determine, track, and/or monitor one or more parameters during a period spanning minutes, hours, days, and/or weeks. For example, in some embodiments, parameter determination component 111 may be configured to determine a light exposure parameter, based on output signals generated by one or more sensors 142, during a period spanning at least 24 hours, and/or intermittently, periodically (e.g. at a sampling rate), continuously, continually, at varying intervals, and/or in other ways that are ongoing during at least a day, at least 24 hours, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least a week, about 2 weeks, about 3 weeks, about 4 weeks, about a month, about two months, or other duration. For example, parameter determination component 111 may be configured to determine a vector of light exposure parameters.
Exposure component 112 may be configured to generate one or more light exposure parameters, including but not limited to estimated light exposure parameters. A light exposure parameter may be the amount of light that a person and/or one or more sensors have been exposed to (and/or would have been exposed to) in a predetermined period of time. For example, a light exposure parameter may represent the amount of light that has been received by (and/or that would have been received by) a light sensor and/or light meter.
In some embodiments, exposure component 112 may be configured to generate a set of estimated light exposure parameters based on one or more activity parameters and/or other parameters (e.g. as determined by parameter determination component 111). In some embodiments, individual estimated light exposure parameters may be based on individual activity parameters. In some embodiments, individual estimated light exposure parameters may be based on multiple activity parameters, e.g. by aggregating multiple activity parameters. In some embodiments, exposure component 112 may be configured to process and/or pre-process parameters that are used to generate a light exposure parameter. For example, activity parameters may be averaged, smoothed, clipped at a low or minimum threshold, clipped at a high or maximum threshold, and/or otherwise processed.
In some embodiments, an estimated light exposure parameter LE may be described by the following equation, where K, c0, and γ are constants, and activity(t) is an activity parameter that represents an activity level of a subject. For example, these constants may depend on characteristics of sensor 142 (e.g. an accelerometer).
In some embodiments, the resulting set of estimated light exposure parameters LE(t) may be constrained to positive values. In some embodiments, a derived set of estimated light exposure parameters Le′(t) may be derived from LE(t). For example, LE′(t) may be averaged, smoothed, clipped at a low or minimum threshold, clipped at a high or maximum threshold, and/or otherwise processed. For example, a maximum threshold for a value of estimated light exposure may be a value that corresponds to direct sunlight, e.g. 50.000 lux. In some embodiments, individual values of LE′(t) may be based on measurements and/or generated output signals spanning at least a minute of a subject's activity level, at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 20 minutes, at least 30 minutes, and/or another suitable period and/or duration. For example, in some embodiments, smoothing of LE(t) values to produce LE′(t) values may be accomplished through a moving average filter, and/or other filters.
Circadian phase component 113 may be configured to determine and/or estimate circadian phases of subjects, e.g. subject 106. In some embodiments, operation of circadian phase component 113 may be based on a model for circadian phase, including, but not limited to the models described herein that involve core body temperature (e.g. CBTmin), dim-light melatonin onset (DLMO), and/or other biomarkers, physiological parameters, and/or environmental parameters. p In some embodiments, operation of circadian phase component 113 may be based on a pacemaker oscillator model. In some embodiments, one or both of the photic driving term B and the non-photic driving term N may be based on estimated light exposure parameters, including but not limited to LE(t) and LE′(t) as described elsewhere in this disclosure. In some embodiments, values of estimated light exposure parameters LE′(t) may substitute and/or replace values of photic driving term B(t). Alternatively, and/or simultaneously, values of non-photic driving term N(t) may be discarded, removed, ignored, and/or otherwise rendered ineffectual for the operation of circadian phase component 113. In some embodiments, the second-order differential equation may be integrated numerically step by step over time, from an initial time t0 (corresponding to an initial activity parameter x0) and a discrete time step. The circadian phase may be estimated as the time of the minimum core body temperature. In some embodiments, the circadian phase may be estimated as being offset by a predetermined duration from the time of the minimum core body temperature. In some embodiments, the predetermined duration of this offset may be subject-specific, e.g. based on a subject's chronotype and/or based on prior measurements. For example, the predetermined duration of this offset may be about 30 minutes, about 45 minutes, about 1 hour, about 75 minutes, about 90 minutes, and/or another suitable duration for the offset used to determine the circadian phase from the time of the minimum core body temperature based on a pacemaker oscillator model in which photic driving term B(t) has been replaced and/or substituted by estimated light exposure parameters. Operation of phase component 112 may be based on one or more parameters, including but not limited to parameters determined and/or generated by computer program components described herein
In some embodiments, operation of one or more computer program components may be based on seasonal information, dusk and dawn information, geographical information, global positioning information, weather information, forecasts and/or predictions, subject-specific travel plans, subject-specific calendar information, and/or other information.
Aggregation component 114 may be configured to aggregate and/or otherwise process multiple activity parameters into fewer values. For example, aggregation component 114 may be configured such that individual values of an estimated light exposure parameter are based on an aggregation of multiple activity parameters, e.g. from a set of activity parameters. In some embodiments, aggregation component 114 may be configured to aggregate and/or otherwise process multiple parameters and/or output signals into fewer parameters and/or output signals.
Power source 72 provides the power to operate one or more components of system 10. Power source 72 may include a portable source of power (e.g., a battery, a fuel cell, etc.), and/or a non-portable source of power (e.g., a wall socket, a large generator, etc.). In one embodiment, power source 72 includes a portable power source that is rechargeable. In one embodiment, power source 72 includes both a portable and non-portable source of power, and the subject may be able to select which source of power should be used to provide power to system 10.
Electronic storage 74 includes electronic storage media that electronically store information. The electronic storage media of electronic storage 74 may include one or both of system storage that is provided integrally (i.e., substantially non-removable) with system 10 and/or removable storage that is removably connectable to system 10 via, for example, a port (e.g., a USB port, a FireWire port, etc.) or a drive (e.g., a disk drive, etc.). Electronic storage 74 may include one or more of optically readable storage media (e.g., optical disks, etc.), magnetically readable storage media (e.g., magnetic tape, magnetic hard drive, floppy drive, etc.), electrical charge-based storage media (e.g., EPROM, EEPROM, RAM, etc.), solid-state storage media (e.g., flash drive, etc.), and/or other electronically readable storage media. Electronic storage 74 may store software algorithms, information determined by processor 110, information received via user interface 76, and/or other information that enables system 10 to function properly. For example, electronic storage 74 may record or store one or more activity parameters (as discussed elsewhere herein), one or more models, representations and/or implementations of one or more models, and/or other information. Electronic storage 74 may be a separate component within system 10, or electronic storage 74 may be provided integrally with one or more other components of system 10 (e.g., processor 110).
User interface 76 is configured to provide an interface between system 10 and a user (or medical professional, or other device, or other system) through which the user can provide and/or receive information. This enables data, results, and/or instructions and any other communicable items, collectively referred to as “information,” to be communicated between the user and system 10. An example of information that may be conveyed to a subject is the current time, a current activity level, an estimated circadian phase, a scheduled wake-up time, or a scheduled light therapy/treatment. Other examples of information that may be conveyed are: circadian rhythm related information like phase and/or intensity, or user performance related information like activity level, scheduled physical events, and/or mental performance events. Examples of interface devices suitable for inclusion in user interface 76 include a keypad, buttons, switches, a keyboard, knobs, levers, a display screen, a touch screen, speakers, a microphone, an indicator light, an audible alarm, and a printer. Information may be provided to the subject by user interface 76 in the form of auditory signals, visual signals, tactile signals, and/or other sensory signals.
By way of non-limiting example, user interface 76 may include a light source capable of emitting light. The light source may include, for example, one or more of at least one LED, at least one light bulb, a display screen, and/or other sources. User interface 76 may control the light source to emit light in a manner that conveys to the subject information related to operation of system 10. Note that subject 106 and the user of system 10 may be one and the same person.
It is to be understood that other communication techniques, either hard-wired or wireless, are also contemplated herein as user interface 76. For example, in one embodiment, user interface 76 may be integrated with a removable storage interface provided by electronic storage 74. In this example, information is loaded into system 10 from removable storage (e.g., a smart card, a flash drive, a removable disk, etc.) that enables the user(s) to customize the implementation of system 10. Other exemplary input devices and techniques adapted for use with system 10 as user interface 76 include, but are not limited to, an RS-232 port, RF link, an IR link, modem (telephone, cable, Ethernet, internet or other). In short, any technique for communicating information with system 10 is contemplated as user interface 76
In some embodiments, method 200 may be implemented in one or more processing devices (e.g., a digital processor, an analog processor, a digital circuit designed to process information, an analog circuit designed to process information, and/or other mechanisms for electronically processing information). The one or more processing devices may include one or more devices executing some or all of the operations of method 200 in response to instructions stored electronically on an electronic storage medium. The one or more processing devices may include one or more devices configured through hardware, firmware, and/or software to be specifically designed for execution of one or more of the operations of method 200.
At an operation 202, output signals are generated that convey information related to an activity level of the subject. In some embodiments, operation 202 is performed by a sensor the same as or similar to sensor 142 (shown in
At an operation 204, a set of activity parameters related to the activity level of the subject is determined. The set of activity parameters is based on the generated output signals. In some embodiments, operation 204 is performed by a parameter determination component the same as or similar to parameter determination component 111 (shown in
At an operation 206, a set of estimated light exposure parameters is generated based on the set of activity parameters. In some embodiments, operation 206 is performed by an exposure component the same as or similar to exposure component 112 (shown in
At an operation 208, the circadian phase of the subject is estimated based on the set of estimated light exposure parameters. In some embodiments, operation 208 is performed by a circadian phase component the same as or similar to circadian phase component 113 (shown in
In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim. The word “comprising” or “including” does not exclude the presence of elements or steps other than those listed in a claim. In a device claim enumerating several means, several of these means may be embodied by one and the same item of hardware. The word “a” or “an” preceding an element does not exclude the presence of a plurality of such elements. In any device claim enumerating several means, several of these means may be embodied by one and the same item of hardware. The mere fact that certain elements are recited in mutually different dependent claims does not indicate that these elements cannot be used in combination.
Although the embodiments have been described in detail for the purpose of illustration based on what is currently considered to be most practical and preferred, it is to be understood that such detail is solely for that purpose and that the disclosure is not limited to the disclosed embodiments, but, on the contrary, is intended to cover modifications and equivalent arrangements that are within the spirit and scope of the appended claims. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment can be combined with one or more features of any other embodiment.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2016/053106 | 5/27/2016 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62174162 | Jun 2015 | US |
