WO2017099749A1

WO2017099749A1 - Method and system of measurement, correlation, and analysis of simultaneous and independent parasympathetic and sympathetic autonomic nervous system activity

Info

Publication number: WO2017099749A1
Application number: PCT/US2015/064695
Authority: WO
Inventors: Joseph COLOMB
Original assignee: Ansar Group, Inc.
Priority date: 2015-12-09
Filing date: 2015-12-09
Publication date: 2017-06-15
Also published as: PH12018501232A1; CN108882883A; AU2015416686A1

Abstract

A system or method for measuring, correlating, and analyzing simultaneous and independent parasympathetic and sympathetic autonomic nervous system activity includes a first sensor for acquiring a first independent measurement of physiological activity from a subject and a second sensor for acquiring a second independent measurement of physiological activity from the subject. Further, the system includes a computer that receives the first independent measurement of physiological activity and the second independent measurement of physiological activity. Further still, the system includes a computer programmed to correlate the acquired time for the first independent measurement and the second independent measurement, compare the numerical value for sympathetic nervous system activity to the numerical value for parasympathetic nervous system activity to determine an instantaneous balanced measurement, compare the instantaneous balanced measurement to a subject balanced measurement.

Description

METHOD AND SYSTEM OF MEASUREMENT, CORRELATION, AND ANALYSIS OF SIMULTANEOUS AND INDEPENDENT PARASYMPATHETIC AND SYMPATHETIC AUTONOMIC NERVOUS SYSTEM ACTIVITY

FIELD

[0001] The present embodiments generally relate to a method of measuring, correlating, and analyzing of simultaneous and independent measurements of the parasympathetic nervous system and sympathetic nervous system, which together comprise the autonomic nervous system. BACKGROUND

[0002] The autonomic nervous system is responsible for the regulation of virtually every physiological process within the body. Typically, the autonomic nervous system is viewed as having two divisions, the sympathetic and parasympathetic nervous systems. These two systems often have opposing effects or responses to stimuli, although this is not a universal occurrence.

[0003] The sympathetic nervous system allows the body to physiologically respond in a stressful situation. Often called the "fight or flight" system, the sympathetic nervous system can increase heart rate and/or blood pressure and slow down digestion, etc. The sympathetic nervous system is generally slower to act than the parasympathetic nervous system, taking three to five heartbeats, or more, to respond.

[0004] The parasympathetic nervous system allows the body to homeostatically maintain itself. Often called the "rest and digest" system, the parasympathetic nervous system can lower heart rate, blood pressure, and/or speed digestion. The parasympathetic nervous system is generally faster to act than the sympathetic nervous system, taking one to two heart beats to respond.

[0005] The coordinated functioning of the sympathetic and parasympathetic systems is indicative of a physiologically healthy human being. Further, the analysis of sympathetic and parasympathetic system function can provide a great deal of information as to the physiological status of an individual.

[0006] However, disease, lifestyle, genetics, or environmental conditions can cause and imbalance in the autonomic nervous system, which causes the sympathetic and parasympathetic systems to be dominant too frequently, or not frequently enough. [0007] Imbalanced autonomic nervous system function can impair the functions of many organs. Due to the ambiguous use of medications affecting the autonomic nervous system, such as beta blockers, ACE inhibitors, sleep aids, antidepressants, etc., there can be resultant significant effect of the sympathetic nervous system and parasympathetic nervous system, causing further, or perpetuating, imbalance. [0008] Further, the concurrent usage of multiple medications that affect various autonomic nervous system functions makes assessment of total autonomic nervous system function, as well as the individual effects of any specific medication, very difficult to measure without specific, independent, yet simultaneous, measures of parasympathetic and sympathetic function. [0009] Due to the "background" nature of the functioning of the sympathetic nervous system and parasympathetic nervous system, activity is often very difficult to ascertain without assumption or approximation that is not generalizable to a clinical population, nor is it often specific for an individual patient. Further, accurate measurements of both systems, individually, are difficult to simultaneously accomplish. [0010] Often the activity of both systems is measured as total autonomic function, and the activity of the individual systems are estimated based on assumptions and approximations. This methodology is flawed, however, in that the underlying assumption is that both systems are functioning well and coordinating properly, or that there is a consistent relationship between the two (e.g., due to disease, one is functioning at a significantly higher level of activity than the other) regardless of environmental or clinical considerations. Further, the estimated value is based upon general principles and "rules of thumb," which can lead to gross inaccuracies. [0011] As autonomic nervous system function is crucial to the long-term well-being and health of an individual, and as many diseases and medications affect only one branch of the autonomic nervous system, there is a significant need for accurate, independent, simultaneous measurement of both the sympathetic nervous system and parasympathetic nervous system.

[0012] Further, there is a need for simultaneous measurement and analysis of the sympathetic nervous system and the parasympathetic nervous system in an accurate fashion to ascertain the function of the entire autonomic nervous system, both to provide an instantaneous picture of individual health, as well as to analyze long-term physiological well- being.

BRIEF DESCRIPTION OF THE DRAWINGS [0013] The detailed description may be better understood in conjunction with the accompanying drawings as follows:

[0014] FIG. 1 is a diagram of an embodiment of a system for measuring autonomic nervous system activity.

[0015] FIG. 2 is a flowchart for an embodiment of a method used to measure the activity of the autonomic nervous system of a subject.

[0016] FIG. 3 is an example of a spectral waveform of an electrocardiogram signal.

[0017] FIG. 4 is an example of a spectral waveform of an electrocardiogram signal.

[0018] The present embodiments are detailed below with reference to the listed FIGS.

DESCRIPTION OF THE EMBODIMENTS [0019] Before further explaining the present method and system, it is to be understood that the disclosed methods and systems are not limited to the particular embodiments; instead, the disclosed systems may be practiced or carried out in various ways.

[0020] Specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis of the claims and as a representative basis for teaching persons having ordinary skill in the art to variously employ the present invention. While reference may be made to the method or the system, it is to be understood that the system is for implementing the method, and the description herein is applicable to both.

[0021] The present disclosure relates to a method of measuring, correlating, and analyzing of simultaneous and independent measurements of the parasympathetic nervous system (PNS) and sympathetic nervous system (SNS), which together comprise the autonomic nervous system (ANS). The measurements can be made simultaneously or later correlated to provide a snapshot of PNS and SNS activity at a given instant of time.

[0022] The system for measuring and evaluating a subject's ANS activity may include the embodiment illustrated in FIG. 1. The system 10, as illustrated, includes a subject 12 that is being monitored while performing a particular activity. As explained in detail below, the subject 12 is monitored by sensors connected to a computer which may be transferable between multiple subjects 12. Additionally, multiple subjects 12 (i.e., second subject, third subject, etc.) may be simultaneously monitored by employing additional computers connected to additional sets of sensors connected to those additional subjects. The activity may include relatively sedentary activity, in which case the system 10 may focus on acquiring and comparing a first set of physiological measurements. Likewise, the system 10 may monitor the subject 12 during relatively stressful or dynamic situations, in which case other physiological measurements may be emphasized. The measurements and/or signals collected from the subject may be conveyed to a centralized computing facility 14 (e.g., "cloud") that analyzes and stores the data. The centralized computing facility 14 may evaluate signals from multiple subjects 12 to monitor each subject 12 for changes in ANS activity. The centralized computing facility 14 may notify the subject 12 of any changes and/or may send alarm or aggregated data (i.e., feedback) to a managing entity 16, as explained in detail below. [0023] The subject 12 wears an ANS monitoring system 18 that may include sensors 20 and a computer 22. The sensors 20 may include electrocardiogram sensors 24 temporarily stuck to the subject's 12 body to receive an electrocardiogram (EKG) signal continuously during a specified activity. In another embodiment (not shown), these same electrocardiogram sensors may also capture respiratory activity, e.g., from an impedance plethysmography circuit. The sensors 20 also may include other sensors 20 for tracking heart activity and rhythms. Alternatively or in addition to the EKG or heart tracking sensors 24, the ANS monitoring system 18 may include respiratory sensors. For example, the sensors 20 may include a chest strap sensor 26 or a respiratory mask 28 to monitor the breathing patterns of the subject 12. The sensors 20 may also include additional sensors 30 that track other information about the subject 12 or the subject's 12 surroundings. For example, the additional sensors 30 may include global positioning signal (GPS) trackers, barometric pressure sensors, temperature sensors (which may or may not detect the temperature of the subject 12), accelerometers, perspiration or sweat detectors, cardiac output sensors, beat-to- beat blood pressure sensors, blood glucose sensors, pulse oximetry (Sp0₂) sensors pulse wave velocity sensors, or other sensors. Additionally, the computer 22 may include memory 32 for storing instructions and the data provided by the sensors 20, a processor 34 (i.e., non- transitory data storage medium) for executing instructions, and a network device 36 for communicating with other computer devices. The network device 36 (e.g., receiver, transmitter, transceiver, etc.) may include wireless communication equipment so that the subject 12 may be monitored in a wide variety of activities. [0024] For example, the subject 12 may be a long haul truck driver that is engaged in relatively sedentary activity for long stretches of time. Under such conditions, the subject 12 may wear the sensors 20, the other sensors 30, and the computer 22 all together in the form of an undergarment. The sensors 20, 30, send the signals to the computer 22 where the signals may be stored, analyzed, processed, to determine, compute, and store PNS and SNS responses. Furthermore, the value representing sympathetic nervous system activity can be compared to the value representing parasympathetic nervous system activity. For example, a quotient resulting from dividing the value representing sympathetic nervous system activity by the value representing parasympathetic nervous system activity is called the sympathovagal balance (SB). This measure can be an individualized measure used to determine a subject's autonomic nervous system function.

[0025] Additionally or alternatively, the signals may be captured and transmitted, in realtime, to the centralized computing facility 14 that stores, analyzes, processes, or determines PNS, SNS, and SB responses. The centralized computing facility 14 may include a server 40 (e.g., one or more servers 40 working together to retrieve and store data) that networks with one or more of the computers 22 that are hooked up to the subjects 12. The server 40 may include a processor 42, memory/storage 44, and instructions stored on the memory/storage 44 for receiving, analyzing, and storing the responses detected and sent from one or more ANS monitoring systems 18 that may be deployed on one or more subjects 12. Additionally, the server 40 includes a receiver 46 that receives signals, either through wired connections or through wireless signals, so that the server 40 may receive signals from a remotely located computer 30. In certain embodiments, the receiver 46 may include a transmitter and/or a transceiver so that signals may be received and transmitted by the server 40.

[0026] The detected responses may then be compared with previously determined thresholds that are stored, for instance, on the computer 22, the server 40, or elsewhere that is accessible by local or remote electronic communication. The comparisons may indicate a state of the nervous system for the subject 12. In the above example of a driver, the responses determined and compared may indicate how alert or awake the driver is. If the server 40 determines that the subject's 12 state falls into a range that indicates the subject 12 may be sleepy or otherwise at risk, giving rise to what may be a "compromised state," then the central computing facility 14 sends a warning signal to the subject 12, the managing entity 16, or some combination thereof. The warning signal may include an audio, visual, or haptic warning alarm to the subject, and may warn the subject 12 about the compromised state and advise the subject 12 to pull over, to rest, wait a fixed period of time to resume activity, etc. Furthermore, the computer 22, the server 40, or combination of both, may determine that emergency conditions, such as syncope or heart attack, have occurred in connection with the subject 12, in which case the warning signal may advise the subject 12 to seek medical attention immediately. In cases where the compromised state involves health issues or conditions where the driver may be intoxicated with alcohol or chemical or other substances, the warning signal may include a notification to emergency response crews or other authorities. If this first warning signal is ignored and the driver's PNS, SNS, or SB responses fall into a range that indicate that the subject 12 is sleeping or otherwise compromised, then an additional warning signal may be sent to the subject 12 (and, optionally, the managing entity 16, or combinations thereof) to attempt to arouse them 12, and/or a second alarm may be sent to local authorities to enable them to assist the driver, e.g., the subject 12.

[0027] As another example of how the system 10 may be employed, consider a subject 12 working as an emergency responder who is called to an emergency (whether land-based or ship-board, this also works for a soldier called into battle). Again, the subject 12 is wearing a sensored undergarment that collects data including positions, temperature, perspiration level, air quality, pulse wave velocity, Sp0₂, as well as EKG and respiratory activity. These signals may be captured and transmitted, in real-time, to a centralized computing facility 14 where the signals are stored, analyzed, processed, and PNS, SNS, and SB responses are computed and stored. These responses are then compared with previously determined thresholds that indicate the subject's 12 state. These indications may then be transmitted to the managing entity 16 that includes personnel overseeing the emergency (or to ranking officers engaged in the battle). These indications may be used by the managing entity 16 to help maintain a level of safety for the subject 12, or to determine when to extract the subject 12, or send in more assistance, or to send in emergency medical assistance (in which case the indications are used to remotely triage the subject 12).

[0028] The computer 22, the server 40, or combination thereof, may be programmed with computer instructions to use a method 60 illustrated in FIG. 2 to measure, correlate, and analyze simultaneous and independent PNS, SNS, and ANS activity. Because the parasympathetic nervous system and the sympathetic nervous system work in concert in the human body, it is useful to have an independent measure of each because, even when one system or the other is operating abnormally, the two systems still operate in a coordinated fashion. Furthermore, using a single physiological measurement to approximate both sympathetic nervous system and parasympathetic nervous system function can mask abnormal operation within one system or the other. Much in the same way that two independent equations must be provided to solve an algebra problem with two independent variables, two independent physical measurements are required to independently characterize the parasympathetic nervous system and sympathetic nervous system.

[0029] The method 60 can include acquiring a first independent measure of physiological activity (block 62). The first independent measurement of physiological activity can be indicative of PNS or SNS or total ANS activity. For example, in embodiments where the first independent measurement includes SNS activity, an EKG signal obtained from the EKG sensors 24 or otherwise can be used to evaluate the SNS. The SNS activity can be evaluated by other parameters including but not limited to: blood pressure, pulse wave velocity, beat- to-beat variation in the heart rate, microneurography, measurement of regional plasma noradrenaline, or other measurements. [0030] The method 60 can also include acquiring a second independent measure of physical activity (block 64). The second independent measure of physical activity can also be indicative of SNS or PNS or total ANS activity. For example, in embodiments where the first independent measure includes SNS activity, the second independent measure will likely include PNS activity. As one possible example, a respiratory activity signal can be used to evaluate the PNS. The PNS activity can be evaluated by other parameters including but not limited to: gastrointestinal activity, heart rate variation at rest and in response to deep respiration, Valsalva maneuver, postural changes, and apneic facial immersion, and other measurements.

[0031] The signals acquired for the first independent measure of physiological activity and the second independent measure of physiological activity can then be analyzed to determine sympathetic and parasympathetic nervous system activity. For each independent measurement, a numeric value may be determined as the ANS monitoring system 18 or the server 40 manipulates the measurement (block 66, block 68). For example, the two signals may be manipulated to compute two separate frequency spectra. An exemplary embodiment of a frequency spectrum 80 from the first independent measure of physiological activity (e.g., EKG frequency spectra, heart rate frequency spectra, SNS frequency spectra, etc.) is illustrated in FIG. 3. The frequency spectrum 80 illustrates the frequencies 82 detected by the ANS monitoring system 18 (and associated sensors 20) in relation to the number of occurrences 84 over a given time period. A similar frequency spectrum is computed for the second independent measure of physiological activity (e.g., PNS frequency spectra, breathing rate frequency spectra, etc.). The ANS monitoring system 18 and/or the server 40 correlates an acquired time for the first and second measurements (block 70 of the method 60 of FIG. 2). By correlating the acquired time, the frequency spectrum 80 of the first independent measure of physiological activity may be used to calculate useful information about the ANS and the relative activity of the subject 12.

[0032] As illustrated in FIG. 4, a specific peak mode frequency 86 of the second independent measure of physiological activity frequency spectrum may be determined, stored, and mapped to the frequency spectrum 80 of the first independent measure of physiological activity. After the first and second independent measurements of physiological activity have been correlated, the ANS monitoring system 18 or the server 40 compares the numeric values (block 72). Comparing the numeric values may include calculating the area of the frequency spectrum 80 with regard to the relationship between the first and second independent measurements of physiological activity. For example, as illustrated in FIG. 5, the area under the frequency spectrum 80 over a specified range 88 may be used to calculate the PNS response. The specified range may include 0.03 Hz, 0.04 Hz, 0.05 Hz, 0.06 Hz, 0.07 Hz, 0.08 Hz, or other frequency ranges measured above and below the peak mode frequency 86. In one embodiment, the peak mode frequency 86 may be measured as 0.19 Hz. The specified range may be 0.06 Hz above and below the peak mode frequency 86. Thus, the area under the frequency spectrum 80 between 0.13 Hz and 0.25 Hz would equate to the PNS response. The specified range 88 may change depending on the predetermined characteristics of the subject 12, or may be consistent for all subjects 12. [0033] The SNS Response may also be calculated from the frequency spectrum 80. As illustrated in FIG. 6, the ANS monitoring system 18 may be programmed to include a SNS default range 90. In one specific embodiment, for example, the default range 90 may include the frequencies 0.04 Hz to 0.15 Hz. To calculate the SNS response, however, the frequencies 92 that are overlapped by the frequencies of the PNS response must be removed. The area under the frequency spectrum 80 over the remaining range 94 equates to the PNS response. A ratio of the sympathetic response to parasympathetic response is computed as sympathovagal balance (SB = S/P), which is used to determine instantaneous function of an autonomic nervous system of the subject 12 (block 74). The sympathovagal balance is highly dependent upon an individual, as well as the activity the individual is undertaking at the time. A static sympathovagal balance, applicable when the subject is at rest or engaged in more sedentary activities, will be considerably distinguished from a dynamic sympathovagal balance, applicable when the subject is engaged in more strenuous activities.

[0034] Depending on the activity of the subject 12 at the time the monitoring sensors 20 are connected, the subject 12 is either at rest or engaged in activities. If the subject 12 is at rest, then SB is a measure of resting balance. If the subject is engaged in activities, then SB is a measure of dynamic balance. These balance responses from the subject may then be compared with previously determined thresholds or ranges ("predetermined ranges") that define a plethora of operational, health, or wellness states for the subject being monitored. Where the subject's response(s) fall within these predetermined ranges may be used to evaluate the fitness of the individual, whether regarding her/his health or wellness or her/his fitness to operate or function efficiently in his/her environment. [0035] Prior methods have made use of standards and approximations that are inaccurately applied to many individuals. Further, application of standards approximated to individuals with improperly functioning autonomic nervous system results in information that is even more inaccurate.

[0036] The two separate physiological measurements are converted to an instantaneous value to determine parasympathetic nervous system and sympathetic nervous system function at a specific moment. The values are then time correlated to ensure a viable comparison. The signals can be manipulated in multiple ways. The signals can be filtered to remove noise and smooth the acquired data. The acquired data can then be converted into a quantified numerical value to allow for objective comparison. [0037] The sympathetic nervous system and parasympathetic nervous system can then be independently and simultaneously measured. The functions can be correlated and analyzed to provide a total picture of the autonomic nervous system. A numerical value for instantaneous heart rate can be calculated as an indication of sympathetic nervous system. A numerical value for respiratory rate can be calculated as an indication of parasympathetic nervous system. Upon computing a sympathovagal balance, it can be compared to previously determined or stored data specific to the individual to indicate the subject's condition. In this manner, the present invention offers a highly specific, accurate, and individualized assessment of a subject's complete autonomic nervous system.

[0038] While these embodiments have been described with emphasis on the embodiments, it should be understood that within the scope of the appended claims, the embodiments might be practiced other than as specifically described herein.

Claims

What is claimed is:

1. A method for measuring, correlating, and analyzing simultaneous and independent parasympathetic and sympathetic autonomic nervous system activity comprising: acquiring a first independent measurement of physiological activity from a subject, wherein the first independent measurement is indicative of sympathetic nervous system activity or total autonomic nervous system activity; acquiring a second independent measurement of physiological activity from a subject, wherein the second independent measurement is indicative of parasympathetic nervous system activity; determining a numeric value for parasympathetic nervous system activity from the second independent measurement; determining a numeric value for sympathetic nervous system activity from the first independent measurement or a combination of the first independent measurement and the second independent measurements; correlating an acquired time for the first independent measurement and the second independent measurement; comparing, subsequent to the correlating, the numerical value for sympathetic nervous system activity to the numerical value for parasympathetic nervous system activity for the acquired time; and determining instantaneous function of an autonomic nervous system (ANS) of the subject.

2. The method of claim 1, wherein the numeric value for sympathetic nervous system activity and the numeric value for parasympathetic nervous system activity comprise values obtained from frequency spectra. 3. The method of claim 1, wherein the first independent measurement of physiological activity comprises a measurement of respiratory activity of the subject, and the second independent measurement of physiological activity comprises a measurement of heart rate of the subject.

The method of claim 1, wherein acquiring the second independent measurement of physiological activity comprises measuring the heart rate using an electro-cardiogram monitor.

The method of claim 1, comprising comparing the instantaneous function of the ANS of the subject with predetermined ranges.

The method of claim 1, further comprising sending an electronic signal to an administrator that indicates the instantaneous function of the ANS of the subject.

The method of claim 1, further comprising providing feedback based upon the instantaneous function of the autonomic nervous system.

The method of claim 1, wherein the acquiring the first independent measurement of physiological activity comprises measuring the heart rate using an electro-cardiogram monitor.

A system for measuring, correlating, and analyzing simultaneous and independent parasympathetic and sympathetic autonomic nervous system activity in a subject, comprising: a first sensor for acquiring a first independent measurement of physiological activity from the subject; a second sensor for acquiring a second independent measurement of physiological activity from the subject; a computer, wherein the computer comprises: a computer processor; a receiver for receiving the first independent measurement of physiological activity and the second independent measurement of physiological activity; and a non-transitory data storage medium comprising computer instructions instructing the computer processor to: correlate acquired time for the first independent measurement and the second independent measurement; compare a numerical value for sympathetic nervous system activity to a numerical value for parasympathetic nervous system activity; determine instantaneous function of an autonomic nervous system of the subject.

The system of claim 9, wherein the first sensor comprises an electrocardiogram sensor and the second sensor comprises a sensor to monitor breathing patterns of the subject.

The system of claim 9, further comprising one or more servers in local or remote network communication with the computer, wherein the one or more servers comprise the computer instructions.

The system of claim 9, wherein the one or more servers are configured to receive a second instance of the first independent measurement of physiological activity and a second instance of the second independent measurement of physiological activity from a second computer monitoring a second subject.

The system of claim 9, wherein the one or more servers are configured to notify a managing entity about the instantaneous function of the autonomic nervous system of the subject, the second subject, or both.

A system for measuring, correlating, and analyzing simultaneous and independent parasympathetic and sympathetic autonomic nervous system activity comprising: a first sensor for acquiring a first independent measurement of physiological activity from a subject; a second sensor for acquiring a second independent measurement of physiological activity from the subject; a computer, wherein the computer comprises: a computer processor; a receiver for receiving the first independent measurement of physiological activity and the second independent measurement of physiological activity; and a non-transitory data storage medium comprising computer instructions instructing the computer processor to: correlate acquired time for the first independent measurement and the second independent measurement; compare a numerical value for sympathetic nervous system activity to a numerical value for parasympathetic nervous system activity to determine an instantaneous balanced measurement; and compare instantaneous balanced measurement to a subject-referenced balanced measurement to determine an instantaneous function of the autonomic nervous system of the subject.

15. The system of claim 14, wherein the computer instructions are programmed to provide feedback based upon the determined instantaneous function of the autonomic nervous system.

16. The system of claim 15, wherein the feedback is provided as an audio, visual, or haptic warning alarm to the subject.

17. The system of claim 15, wherein the feedback is provided to a managing entity located locally or remotely from the subject.

18. The system of claim 14, further comprising a server in local or remote network communication with the computer.

19. The system of claim 18, wherein the one or more servers are configured to receive a second instance of the first independent measurement of physiological activity and a second instance of the second independent measurement of physiological activity from a second computer monitoring a second subject.

20. The system of claim 18, wherein the one or more servers are configured to notify a managing entity about the instantaneous function of the autonomic nervous system of the subject, the second subject, or both.