Patent Application
20230248294
The present invention is in a field of a computer-implemented method and system for automatically measuring a level of anxiety, a level of a modified state of consciousness, and/or a level of pain in a subject.
Anxiety and, for example, the impact of anxiety on patient comfort and the effectiveness of medical treatments, is a well-known and universal problem. Anxiety management is thus an important branch of medicine. However prior art methods for assessment of the level of anxiety a subject is experiencing have important drawbacks and are not able to provide for an efficient, reliable, robust, objective and reproducible indication of the level of anxiety as experienced by a subject. This problem is immediately apparent when the subject is not capable of providing for a reliable or clear description of the level of anxiety experienced, such as for example in the case of non-verbal children, persons with a disability, . . . . Further, similarly, there is a need for an improved measurement of the level of pain as perceived by a subject. Still further, similarly there is specifically a need for a reliable measurement of the level of anxiety or the level of pain, while also being able to reliably quantify any modified state of consciousness that the subject might be experiencing. Such an improved measurement of the level of anxiety, level of pain and/or modified state of consciousness is important to robustly and reliably assess the impact of each of these parameters and/or any interactions between them on the subject. These measurements will provide a more reliable insight into the condition in which the subject is. Such insights might then be used to optimize a treatment plan and/or to reduce risks associated with treatments aimed at modifying the level of anxiety, the level of pain and/or modifying the state of consciousness of a subject.
Currently, in order to assess the level of anxiety as experienced by the patient or the level of pain as perceived by the subject, use is made of self-reporting tools. However, it is clear that such manual tools that rely on self-reported assessment of the patient are prone to undesired subjective bias and lack efficiency, reliability, precision and reproducibility. Further such self-reporting tools lack the ability to efficiently take into account the multi-dimensional aspect of anxiety, the level of pain as perceived by a subject, and are difficult to apply in a context of a modified state of consciousness, such as for example in the case of pharmacological or non-pharmacological sedation. Typically, such self-reporting tools are extensive and burdensome to administer and complex and intensive to process because of a large number of questions.
Accurately and reliably measuring anxiety, pain and/or a modified state of consciousness is important in a medical setting as it for example helps to determine an accurate diagnosis, a treatment plan, and evaluate the effectiveness of treatment. Additionally, there is a growing problem of treatment overdosing, especially in the context of pharmacological anxiety and pain treatments, such as for example anxiolytic and/or analgesic overdosing. There is also a need, when for example modifying a level of consciousness pharmacologically, for example by means of a sedative, to avoid any overdosing and/or underdosing in order to achieve the desired level of modified state of consciousness while minimizing any adverse events related to overdosing and/or underdosing. Similarly, also in non-pharmacological treatments, care workers are in need of more reliable tools in order to provide for a safe and effective measurement of anxiety, pain and a level of modified state of consciousness. It is further clear that anxiety and pain and the treatment thereof have an impact on medical outcomes and patient recovery. Anxiety has an impact on health-related effects such as for example fatigue, nausea, insomnia, pain, for example as experienced by a subject before, during and/or after a treatment, such as for example a treatment including surgery and/or any other suitable medical and/or non-medical treatment. Pain measurement can be used to screen for potential diseases or medical problems, to perform a triage by determining the urgency of the needs of one patient over the other, can be used to determine whether it is safe to engage and/or continue with a medical treatment, etc.
There thus exists a need for an improved, robust, reliable and efficient measurement of the level of anxiety as experienced by a subject, the level of pain as perceived by a subject and/or a modified state of consciousness of a subject.
According to a first aspect, there is provided a computer-implemented method for measurement of a level of anxiety combined with and/or correlated with a level of a modified state of consciousness, and/or a level of pain, wherein the method comprises the steps of:
Measuring the LoA combined with DoS, the LoA combined with LoP or the LoA, LoP and DoS all three in combination, it for example becomes possible to identify how the LoA influences the LoP or vice versa, how the LoA is modulated by a modified state of consciousness, how the ability to reach a particular modified state of consciousness is influenced by the LoA and/or the LoP, etc. By measuring the LoA, the LoP, the DoS in any suitable combination of at least two of these parameters, in this improved way, this enables an automated, efficient, accurate, reproducible, and objectivized determination and/or monitoring of the level of anxiety as experienced by the subject, the level of pain as perceived by the subject and the level of modified state of consciousness. As will be explained in further detail below measuring the LoA, LoP and/or DoS in a combined way is specifically advantageous as for example, a part of the LoA could be triggered by the LoP. As will be explained in further detail below there could be measured and/or determined interactions and/or correlations between the LoA, LoP and/or DoS, which for example allow to reduce the LoA by reducing the LoP, or are the cause that an increase in the LoA leads to an increases in the LoP as perceived by a subject, or which for example enable by a modification of the state of consciousness to reduce both LoP and LoA, or lead to the fact that a high level of anxiety can have a negative impact on a treatment aiming at modifying the level of consciousness, . . . . It is further clear that in addition to the embodiments described, there are further alternative suitable embodiment for correlating a plurality of LoA, LoP and/or DoS measurements and/or determining a correlation between a plurality of LoA, LoP and/or DoS measurements. It is clear that the level of anxiety of a subject, could also be referred to as the level of anxiety in a subject.
As will be explained in further detail below, with respect to P-power(dt) for determining the LoA, there was only found a specific correlation for this specific combination of brain wave frequencies of data that was collected at this specific location with an EEG electrode. Further, for both power(ta) for determining the LoP and P-power(dt) for determining the LoA, calculating the power from this data, which can be collected from a single EEG electrode, can be accomplished in a simple and efficient manner.
In the context of the present description, the MSPA (based on EEG or EMG) is defined in a given time window that may be time-locked to an external pain or other stimulus or that may be a rolling time window not linked or triggered by an external pain or other stimulus, wherein:
The signal peak amplitude is the maximum excursion of the signal wave from the zero point. The signal peak-to-peak amplitude is the distance from a negative peak to a positive peak. The time window for measurement could for example be in the range of 0.01 s to 10 s, such as for example in the range of 0.1-s to 5 s. The time window could for example be adapted based on the detection of an internal or external pain stimulus, type of stimulus, duration of stimulus, . . . . It is clear that still further embodiments are possible in which for example the stimulus is any suitable stimulus, such as for example a non-painful stimulus.
This improved, more robust and reliable measurement of LoA, LoP and DoS helps in determining a more accurate diagnosis, an improved and safer treatment plan, and an improved evaluation of the effectiveness of treatment. As a clear allocation can be made to the impact of anxiety, pain, and a modified state of consciousness, there the risk of administering a pain treatment when an anxiety treatment is needed or vice versa is reduced. Also the risk for overdosing and/or underdosing is reduced, for example as this measurement allows to make a clear decision on whether to use anxiolytics to treat anxiety and/or to use analgesics to treat pain and/or to use sedatives to modify the state of consciousness, and to optimize their dosing in function of the measured combination of LoA, LoP and/or DoS. It is however clear that such a measurement is not limited to optimization of pharmacological treatments, but is also useful when optimizing non-pharmacological treatments, and/or any combination of pharmacological and/or non-pharmacological treatments directed at treating anxiety, pain, and/or modifying a state of consciousness, or any other symptom related to anxiety, pain, and/or a specific state of consciousness, or any other suitable treatment.
It is thus clear that such improved measurement of a combination of at least two of LoA, LoP and DoS of a subject is beneficial when under any non-pharmacological and/or pharmacological treatment and/or mixed treatment, such as for example anxiety treatments, pain treatments, treatments leading to a modified state of consciousness, . . . , and/or even when not under any treatment, in order to measure the state of a subject. It is clear that treatments modifying the state of consciousness of the subject, for example pharmacologically by means of sedatives, or non-pharmacologically by treatments adjusting the level of dissociation, the level of absorption, etc. of a subject, impact the level of anxiety as experienced by the subject and/or the level of pain as perceived by the subject. It is further clear that pain triggers anxiety and that higher levels of anxiety lead to higher levels of pain as perceived by a subject, and measurement of each of these parameters in combination thus allows to measure and display these interactions. In this way measurement of at least two of LoA, DoS and LoP, allow to objectively measure and display such interactions, and for example allows for such measurements to be used for the creation of and/or to be based on individual and/or population-based benchmarks. This will allow to make more reliable objective decisions, especially in the context of anxiety and pain management, particularly when there are involved pharmacological and/or non-pharmacological treatments that modify the state of consciousness managing pain and/or anxiety indirectly, and/or in combination with pharmacological pain and/or anxiety treatments.
It should be clear that according to some embodiments, this method is limited to merely obtaining information, such as data and physical quantities from the living human body and is not directed to finding any significant deviation, i.e. a symptom during a comparison of the collected data with standard values and is not directed to the attribution of such a deviation to a particular clinical picture, i.e. the deductive medical decision phase. Preferably, according to some embodiments, the method is performed on measured data, received, after it has been collected, or in other words, the method excludes a step of collection of data practiced on the human body. According to some embodiments the computer-implemented method only concerns obtaining information, for measurement of the level of anxiety as experienced by a subject, which is a psychophysiological quality of the subject, for the measurement of the level of pain as perceived by the subject and/or for the measurement of a level of modified state of consciousness. According to some embodiments, the computer-implemented method excludes any steps for curing of a disease or malfunction of the body, nor any step relating to a therapeutic effect on the body of the subject.
It is clear that the level of anxiety as measured comprises at least a level of anxiety experienced by a subject as measured at the level of the brain of the subject or in other words comprising a cognitive dimension. Anxiety, being a response involving a psychophysiological and emotional aspect, clearly involves such a cognitive dimension. It has been shown based on the experiments above that anxiety as measured above is able to capture this cognitive dimension and is not limited to measurement of only non-cognitive parameters. Anxiety is for example associated with increased activity in the amygdala, and the activity of the amygdala can be influenced by activity in the higher brain structure, for example including the anterior cingulate cortex and the pre-frontal cortex responsible for focused attention. It is thus clear that anxiety as experienced by a subject comprises a cognitive dimension, optionally in addition to any other suitable dimensions.
It is clear that the level of pain relates to the perceived level of pain, or in other words the consciously perceived level of pain by a subject as measured at the level of the cortex of the brain of the subject. The level of pain thus corresponds to the consciously perceived level of pain perception of the subject. The level of pain as perceived by the subject is thus not directly correlated to the intensity of the external pain stimulus itself, but relates to the level of pain perception. In other words, the perception of the level of pain as it appears in the consciousness of the subject, typically associated with the cortex, after potential modulation and/or suppression by for example the thalamus and/or other downstream and/or upstream neural pathways.
This for example allows to dose local and/or IV medication to improve and optimize an anxiety, pain or sedative treatment. If a patient is doing fine during a treatment, and at one point there is measured an increase or a peak in the level of anxiety, level of pain or an undesired change to a modified state of consciousness, a local anesthetic, and/or IV analgesics dosages could be increased based on a combination of an objectivized DoS, a LoP as perceived by the subject, a LoA as experienced by the subject and not on a subjective estimation of patient's state of consciousness, pain and anxiety, for example by an anesthesiologist before, during and after a surgical treatment. Measurement of any combination of DoS, LoP and/or LoA also allows for an anxiety and/or a pain diagnostic for non-verbal patients (children, adults who are disabled, patients with dementia, . . . ). The measured combination of any of DoS, LoP and/or LoA is for example also a good indicator of the need or not for more sedation and/or analgesics and/or anxiolytics. In this way, a safe and reliable dose or titration of sedatives and/or analgesics and/or anxiolytics can be realized, with a reduced risk of overdosing and/or negative collateral effects of the analgesic or sedative or anxiolytic treatment.
Such an improved measurement of the LoA combined with DoS and/or LoP is for example advantageous in the following specific clinical cases:
According to an embodiment the method comprises the steps of:
In this way the modulation of the LoA by DoS can be determined. This is useful as, as will be described in further detail anxiety is inversely correlated with a modified state of consciousness or in other words a depth of state, such as for example corresponding to a depth of dissociation of the subject, a level of absorption of the subject, etc. This for example means that the LoA could be decreased by modifying the level of consciousness. It is further beneficial as, as a higher level of anxiety experienced before a treatment session can be associated with a lower level of dissociation during a treatment session. In this way for patients which experience a high level of anxiety, for example prior to a treatment involving a modified state of consciousness, there could now be determined more objectively if they could benefit from an anxiety treatment before initiation of the treatment involving a modified state of consciousness. It is clear that alternative embodiments are possible in which a particular treatment is first replaced and/or supplemented by another treatment based on the modulation of the LoA by DoS and/or vice versa.
A modified level of consciousness associated with a deeper depth of state, such as for example a deeper depth of dissociation, a higher level of absorption, etc. as further detailed seems to decrease the level of anxiety experienced by a subject. In this way, measurement of the LoA combined with DoS might enable to determine which part of anxiety could be treated by modifying the state of consciousness of the subject, for example modifying the DoS, such as for example modifying the level of absorption, depth of dissociation, . . . and additionally it might allow to differentiate between immediate and long-term effect of such changes to the depth of state to reduce anxiety, such as for example when used non-pharmacological treatments such as for example in psychotherapies, . . . .
According to an embodiment the method comprises the steps of:
In this way, it might be possible to determine how LoP is modulated by DoS and/or it may be possible to determine how LoP is modulated by LoA and/or vice versa. This is useful as an increased level of anxiety before, during and/or after a treatment session might increase the level of pain as perceived by a subject and can even trigger pain perception. This is important as for example anxiety plays a role in chronic pain. Based on the embodiment above, it would become for example possible to determine patients with a high LoA that may benefit from an anxiety reducing treatment to reduce LoP. Further anxiety is a risk factor for developing persistent/chronic pain following acute pain, and the embodiment above could thus for example be useful for determining a high risk group with respect to development of chronic pain and/or to reduce the risk of developing chronic pain. Further, also the LoP has an impact on the LoA as pain is an important anxiety inducing event.
According to an embodiment the method comprises the further step of:
In this way the value for NLoA would provide for a value of LoA at a predetermined reference DoS and/or LoP of interest, independently of the current DoS/LoP and/or any changes to the current DoS/LoP, thereby for example providing an indicator for the equivalent amount of anxiety that would be experienced when the subject would be at, or return to a normal awake state of consciousness and/or a painless state, when this reference DoS is the normal awake state and/or the reference LoP corresponds to a painless state.
According to an embodiment the method comprises the further step of:
In this way the value for NLoP would provide for a value of LoP at a predetermined reference DoS and/or LoA of interest, independently of the current DoS/LoA and/or any changes to the current DoS/LoA, thereby for example providing an indicator for the equivalent amount of pain that would be consciously perceived when the subject would be, or return to a normal awake state of consciousness and/or in a state without anxiety, when this reference DoS is the normal awake state and/or the reference LoA is a state without anxiety.
According to an embodiment the method comprises the further step of:
In this way, it is possible to determine, when for example the LoA and/or the LoP are too high to reach a desired modified state of consciousness, for example by means of a non-pharmacological method involving for example a suitable depth of dissociation, level of absorption, etc.
According to an embodiment the method comprises the further step of:
This is advantageous as when for example LoP is too high, anxiety becomes difficult to manage, and when LoA is too high pain becomes difficult to manage and might peak naturally. In such cases anxiety and/or pain treatments might experience difficulty in managing the LoA and/or LoP to desired levels. According to a further example when LoA and/or LoP are too high, it might be difficult to reach a desired modified level of consciousness, and for example no, insufficient, or too limited depth of state might be reached.
According to a second aspect there is provided a computer-implemented method for measuring and/or monitoring and/or predicting and/or aggregating a level of anxiety combined with and/or correlated with a level of a modified state of consciousness and/or a level of pain in a subject, preferably before, during and/or after a treatment, wherein the method comprises the steps of:
It is clear that the LoA, DoS and/or LoP only need to be measured respectively at at least two different points in time, and thus the LoA/DoS/LoP must not necessarily be measured concurrently.
In this way a measurement of an evolution of LoA combined with DoS and/or LoP is realized.
According to an embodiment, the method comprises the step of:
In this way the measurement of a treatment-induced evolution becomes possible. Similarly, as mentioned above, although concurrent measurements of LoA, DoS and/or LoP are possible according to some embodiments, it is clear that alternative embodiments are possible in which LoA, DoS and/or LoP are not necessarily measured concurrently.
According to an embodiment:
It is clear that the predetermined range could be defined by one or more suitable limit values, and/or one or more desired ranges, thresholds, limits, . . . which define the predetermined range for the LoP and/or LoA and/or DoS, as the range in which an anxiety management treatment, a pain management treatment and/or treatment modifying the state of consciousness still remains effective. The range could be defined in such a way that outside this range an anxiety management treatment, a pain-reducing treatment and/or treatment modifying the state of consciousness is no longer effective or is too difficult to manage. It is clear that the predetermined range could, according to some embodiments, be automated, dynamic, adaptive, etc. for example according to some embodiments be referred to as a form of auto-ranging, which means that the predetermined range is adapted based on for example earlier measured values of a subject (such as for example a reference range measured during a calibration phase, etc.) or population (such as for example predetermined ranges based on population characteristics, etc.).
According to an embodiment, the treatment is an anxiety-reducing treatment and the method comprises the step of:
According to an embodiment the anxiety treatment could for example be an anxiety-reducing treatment, or alternatively an anxiety-controlling or anxiety-preventing treatment that controls or prevents any undesired levels of anxiety, or any other suitable anxiety treatment.
According to an embodiment the pain treatment could for example be a pain-reducing treatment, or alternatively a pain-controlling or pain-preventing treatment that controls or prevents any undesired levels of pain, or any other suitable pain treatment.
According to an embodiment the treatment is a treatment modifying the state of consciousness for reducing anxiety and the method comprises the steps of:
According to a third aspect there is provided a computer-implemented method for determining a treatment and/or determining an adjustment to a treatment and/or determining an intensity of a treatment and/or determining the efficacy of a treatment and/or determining the choice of a treatment, wherein the method comprises the steps of:
According to an embodiment the method comprises the steps of:
According to an embodiment the method comprises the step of:
It is clear that further alternative embodiments are possible in which in addition to the EEG electrodes, there is also present a ground electrode and/or a reference electrode. Preferably the data from the EEG electrodes can be processed independently, which means that there is no need to provide for calculations on the interaction and/or interrelation of the signals of two or more EEG electrode.
According to an embodiment the method comprises the steps of:
A scaled and/or indexed LoA may for example be referred to as a level of anxiety index or LoAI.
A scaled and/or indexed LoP may for example be referred to as a level of pain index or LoPI.
A scaled and/or indexed DoS may for example be referred to as a Depth of State index or DoSI.
According to a fourth aspect of the invention, there is provided a computer-implemented method for measuring and/or monitoring and/or predicting an evolution and/or aggregating a level of anxiety combined with and/or correlated with a level of pain, and/or a level of modified state of consciousness of a subject, comprising the method for measurement of a level of anxiety combined with and/or correlated with a level of modified state of consciousness and a level of pain according to the first aspect of the invention applied on a subject by receiving the measured data of a subject.
The measured data of the subject could for example be real-time data as being received from suitable sensors, however, alternative embodiments are possible in which historic data, previously stored data, . . . and/or any combination thereof is used for measurement of a level of anxiety, a level of pain and/or a level of modified state of consciousness.
It is clear that according to particular embodiments, the treatment could for example comprise an anxiety treatment or a pain treatment, such as for example an anxiety-reducing treatment or a pain-reducing treatment. However it is clear that alternative embodiments of treatments are possible, such as for example a surgical treatment or any other medical intervention during which one or more anxiety or pain inducing acts are performed, such as for example a needle puncture, placement of a port of a catheter, an incision, introduction of a wire, etc. During some of these treatments the desired treatment-induced evolution will comprise a reduction of the LoA or LoP, however in alternative treatments, it might be more important to monitor the LoA or LoP for any undesired changes during the treatment, such that for example the need for extra anxiety or pain management measures could be reliably assessed. Similarly, a desired treatment induced evolution of DoS might comprise a desired change to the DoS by the treatment, or the prevention of an undesired change to the DoS by the treatment.
According to an embodiment the theta-alpha frequency band, ta, comprises one or more of the following:
It is clear that still further embodiments are possible, for example in which the theta-alpha frequency band consists of a frequency band:
It is clear that still further embodiments are possible, for example in which the delta-theta frequency band consists of a frequency band:
It is clear, that according to advantageous embodiments, the delta-theta frequency band for example comprise a combination of at least two, or preferably exactly two types of brainwaves.
According to an advantageous embodiment the delta-theta frequency band consists of a combination of:
According to an advantageous embodiment the delta-theta frequency band consists of a combination of at least part of a delta frequency band and at least part of a theta frequency band.
In other words, the delta-theta (dt) frequency band comprises, and preferably consists of a combination of at least part of the delta frequency band and at least part of the theta frequency band.
It is clear that such a delta-theta frequency band comprising and/or consisting of a combination of two brain wave frequencies, or at least a part thereof, is different from a frequency band only comprising a single brain wave frequency band and different from a frequency band comprising more than two brain wave frequency bands.
It has been found that such a combined frequency band, consisting of at least a part of two specific brain frequency bands, surprisingly provides for a better correlation with the level of anxiety, than each of the individual brain frequency bands, for data collected from the specific location of a P-EEG electrode.
It is clear, that according to advantageous embodiments, the theta-alpha frequency band for example comprises a combination of at least two, or preferably exactly two types of brainwaves or part thereof.
According to an advantageous embodiment the theta-alpha frequency band consists of a combination of:
According to an advantageous embodiment the theta-alpha frequency band consists of a combination of at least part of a theta frequency band and at least part of an alpha frequency band.
In other words, the theta-alpha (ta) frequency band comprises, and preferably consists of a combination of at least part of the theta frequency band and at least part of the alpha frequency band.
It is clear that such a theta-alpha frequency band comprising and/or consisting of a combination of two brain wave frequencies, or at least a part thereof, is different from a frequency band only comprising a single brain wave frequency band and different from a frequency band comprising more than two brain wave frequency bands.
It has been found that such a combined frequency band, consisting of two specific brain frequency bands, surprisingly provides for a better correlation with the level of pain, than each of the individual brain frequency bands, for EEG data collected from a suitable electrode, such as for example for data collected from the specific locations of a P-EEG electrode, a F-EEG electrode and/or a C-EEG electrode, or any other EEG data collected from any suitable location.
According to an embodiment, the method comprises steps of:
According to such embodiments in which the level of anxiety is measured by means of a combination of a specific signal extracted from EEG data, which is more directly linked to the cognitive dimension of anxiety, and one or more specific signals like heart rate, heart rate variability, breathing frequency, breathing variability, oxygen saturation, . . . and/or other suitable specific embodiments of physiological parameters as mentioned below, which are more directly linked to the autonomic-emotional dimension provides for a specifically advantageous multidimensional measurement of the level of anxiety as experienced by a subject. Based on the specific signals extracted from both specific EEG data and at least one specific other signal from a specific physiological parameter thus allows for a measurement that takes into account the multi-dimensionality of anxiety, in which however the cognitive dimension as linked to the specific EEG data is essential in order to provide for a measurement that relates to the level of anxiety as experienced by the subject.
As will be explained in further detail below, a specific combination of heart rate and heart rate variability data, provides for a particularly advantageous and simple measurement with an improved correlation with the level of anxiety as experienced by a subject. However, it is clear that alternative embodiments are possible in which any other suitable cardiovascular data and/or combination thereof is used, such as for example cardiac activity data, hemodynamic activity data, . . . .
According to an embodiment, the method comprises steps of:
According to an embodiment, the method comprises steps of:
According to an embodiment:
According to an embodiment, the method comprises steps of:
According to an embodiment, the method comprises steps of:
According to a preferred embodiment the EMG data is captured at two or more electrode locations such that global muscle tension can be determined and locally isolated artefacts can be detected and removed.
According to an embodiment, the method comprises steps of:
According to such embodiments, the LoA is measured taken into account the multidimensional aspect of anxiety.
According to an embodiment, there is provided a method, wherein the treatment is an anxiety treatment and the method comprises the step of:
The anxiety treatment could for example be an anxiety-reducing treatment, or alternatively an anxiety-controlling or anxiety-preventing treatment that controls or prevents any undesired levels of anxiety, or any other suitable anxiety treatment.
According to an embodiment, there is provided a method, wherein the treatment is an anxiety treatment and the method comprises the step of:
As already mentioned above the anxiety treatment could for example be an anxiety-reducing treatment, or alternatively an anxiety-controlling or anxiety-preventing treatment that controls or prevents any undesired levels of anxiety, or any other suitable anxiety treatment.
According to a fifth aspect of the invention, there is provided a computer-implemented method for determining a treatment and/or determining an adjustment to a treatment and/or determining an intensity of a treatment and/or determining the efficacy of a treatment and/or determining the choice of a treatment, wherein the method comprises the steps of:
According to a sixth aspect of the invention, there is provided a system configured to measure a LoA combined with and/or correlated with a DoS and/or a LoP according to the method according to any previous aspect and/or embodiments, the system comprising:
According to an embodiment, wherein the monitoring apparatus comprises, for obtaining measured data, one or more of:
It is clear that still further alternative embodiments are possible comprising for example one or more sensors and/or capturing units for one or more other physiological measurements.
According to an embodiment, there is provided a system, further comprising a graphical user interface, GUI, configured to indicate numerically and/or graphically one or more of:
It is clear that in the context of this description measured at different points in time, could also refer to measured over a period of time.
It is clear that still further alternative embodiments are possible comprising for example one or more sensors and/or capturing units for one or more other electrophysiological and/or physiological measurements.
It is clear that alternative embodiments of the GUI are possible in which further data is displayed, such as for example ECG data, cardiovascular data, respiratory data, ocular movement data, EOG data, muscular activity data, EMG data, body temperature data, . . . .
It is clear that in the abovementioned embodiments of the method and/or systems any embodiments defined with reference to LoA, LoP and/or DoS, also refer to similar embodiments based on parameters derived from LoA, LoP and/or DoS, such as for example LoAI, LoPI, DoSI, LoA(I)S, LoP(I)S, etc.
In order to generate experimental data, according to this particular embodiment, an experiment including a hypnotic treatment session was set up. However, it is clear that alternative embodiments are possible in which any other suitable treatment session is used and/or in which no use is made of a treatment session. This experiment resulted in a study with 12 healthy subjects, of which 10 were included in the subsequent analysis. The experiment comprised measurement of a level of anxiety, a level of pain, and a modified state of consciousness, by self-reporting of the subject using a validated questionnaire.
The setup of the embodiment of the experiment will be clarified by means of
During an initial calibration phase 510, at a first step 512 the subjects were asked to provide self-reported values for rating parameters as explained in further detail below. Subsequently at step 514, by using a stair-case method, the subjects received a sequence of transcutaneous electrical stimulus, or in other words a pain stimulus, of increasing intensity, so that in step 516 the subject could indicate when the perceived level of pain corresponded to a level of pain with a value of 8 on a VAS pain scale. In other words, the intensity of the pain stimulus is calibrated for each subject individually using the stair-case method, by asking the subjects to indicate when they judged the perceived level of pain to corresponding to a value 8 on the pain scale, which corresponds to a level of pain qualified as “significantly painful and demanding some effort to tolerate”. Such a pain scale for self-reporting of pain according to the embodiment of the experiment was determined by means of a Visual Analogue Scale or VAS, which is a measurement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. According to this embodiment a VAS scale ranging from a value of 0 for “no pain” up to and including 10 for “severe or extreme amount of pain”. Such instruments are often used in clinical research to measure the intensity of symptoms, such as for example, the level of pain as perceived by a patient. It is clear that alternative embodiments for self-reporting values are possible, such as for example the Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain, which ranges from a value of 0 for “no pain” up to and including a value of 10 for “severe pain”.
Similar as for the self-reported level of pain, at step 512, and 516 of the calibration phase 510, and as will be described in further detail below at further steps during the experiment, such as for example step 534 of the normal awake state 530 and step 544 of the hypnotic treatment session 540, patients were also asked to provide self-reported values for rating their experienced level of anxiety. According to this embodiment a VAS scale ranging from a value of 0 for “no anxiety” up to and including 10 for “severe or extreme amount of anxiety”. It is clear that alternative embodiments for self-reporting values are possible.
As further schematically shown in
Subsequent to the time period 536 during which the measurements of the physiological signals were made, the subject was asked to provide self-reported values for the level of anxiety, the level of pain, modified level of consciousness, etc. for example by means a suitable VAS patient questionnaire during step 534.
According to the embodiment of the experiment shown in
During the experiment, for the EEG measurements, EEG electrodes were used that were placed so as to cover the scalp and so as to detect local voltage fluctuations resulting from localized regions of the brain. According to this embodiment, a high density EEG was employed with 256 sensors or channels, however it is clear that alternative embodiments with a different number of sensors are possible. According to the embodiment of the experiment, electrodes were placed according to the predefined layout for a 256-channel Hydrocel Geodesic Sensor Network. It is further known to a person skilled in the art that EEG electrodes mainly measure neural activity that occurs at the upper layers of the brain, or in other words the neural activity of the cortex of the brain. During the experiment, for the EMG measurements sensor, a pair of surface EMG sensors were placed on a leg of each patient to as to detect the electric potential generated by muscle cells when the muscles become activated. However it is clear that alternative embodiments are possible in which EMG sensors are provided at any other suitable location, such as for example the face, arm, . . . . It is however clear that according to alternative embodiments use can be made of other types of suitable EEG electrodes or sensors, EMG electrodes or sensors and/or any other suitable type of electrode or sensor for measuring EEG and/or EMG signals.
Below are the results of the above-mentioned experiment, according to the embodiment of
Table 1 below, shows a Wilcoxon signed-rank test of the self-reported data for subjects during the experiment of
It should first be noted that, in reaction to the application of the pain stimuli during the normal awake state 530, the self-reported level of anxiety has increased with respect to the level of anxiety as reported before the application of the pain stimuli. It is thus clear that the pain stimuli thus also function as an anxiety inducing stimulus or an anxiety inducing event. This is confirmed by the measurement of a self-reported level of anxiety before the normal awake state 530, which had as mean+/−SD: 2.65 (2.06) and as Median [IQR]: 2.15 [3.55], with a p-value=0.002 and adjusted p-value=0.008. In between the Normal awake state 530 and the Hypnotic treatment session 540, there was a pause or a break, and before the Hypnotic treatment session 540, also there was performed a measurement of the self-reported level of anxiety, which had as mean+/−SD: 2.79 (2.21) and as Median [IQR]: 2.65 [1.25], with a p-value=0.53 and adjusted p-value=1.
It is thus clear that, according to the embodiment described above, in which during both the normal awake state 530 and the hypnotic treatment session 540, pain stimuli of an identical intensity were applied, or in other words, identical pain conditions were experienced by the subjects during application of the pain stimuli of identical intensity, or in other words an identical anxiety inducing events and/or stimuli, the self-reported levels of anxiety are significantly different in both sessions 530, 540. As for example shown, the mean of the value for self-reported anxiety in the normal awake state 530 is 4.92, while in the hypnotic treatment session 540 it was reported to be 3.16. In other words, a reduction of more than 30% with respect to the normal awake state. It is thus clear that the self-reported level of anxiety corresponds to a level of anxiety as experienced by the subject, as clearly, the self-reported values for the level of anxiety triggered by an identical external pain stimulus are modulated by the modified state of consciousness caused by the hypnotic treatment session. In other words, the self-reported data for the level of anxiety are an indicator for the level of anxiety as experienced by the subject, or in other words the level of experienced anxiety. As the self-reported data relating to anxiety are triggered by the painful stimuli, it is clear that these painful stimuli can be considered as an anxiety inducing event, or in other words an adverse situation at a specific moment in time, and thus the self-reported data relates to the level of anxiety of the subject as experienced with respect to the painful, anxiety inducing stimuli. Further it should be noted that the experiment was set up with a first phase in the normal awake state 530 with increased levels of anxiety as compared to prior to the experiment, and still during the subsequent second phase in during the hypnotic treatment session 540, again reduced levels of anxiety are reported. A predetermined rest time between the normal awake state 530 and the hypnotic treatment session 540 was included.
It is further clear that, according to the embodiment described above, in which during both the normal awake state 530 and the hypnotic treatment session 540, pain stimuli of an identical intensity were applied, or in other words, identical pain conditions were experienced by the subjects during application of the pain stimuli of identical intensity, the self-reported levels of pain are significantly different in both sessions 530, 540. As for example shown, the mean of the value for self-reported pain in the normal awake state 530 is 4.21, while in the hypnotic treatment session 540 it was reported to be 1.39. In other words, a reduction of more than 50% with respect to the normal awake state. It is thus clear that the self-reported level of pain corresponds to a level of pain as perceived by the subject, as clearly the self-reported values for the level of pain correlated to an identical external pain stimulus are modulated by the modified state of consciousness caused by the hypnotic treatment session. In other words, the self-reported data for the level of pain are an indicator for the level of pain as consciously perceived by the subject, or in other words the level of perceived pain. It is further clear that this level of perceived pain is such that it is subject to modulation by means of a modification or change of the level of consciousness of a subject, such as for example by means of a change to the level of dissociation of the subject.
The change to the level of dissociation of the subject by means of the hypnotic treatment session versus the normal awake state is confirmed by means of the self-reported data in Table 1, which shows a mean self-reported value for the level of dissociation of 7.52 during the hypnotic treatment session 540 versus a value of 4.11 during the normal awake state 530. In other words, during the hypnotic treatment session 540, there is an increase in the level of dissociation of more than 80% with respect to the normal awake state 530.
Moreover, as shown in further detail with respect to table 2, a statistically relevant correlation within the self-reported data for both the hypnotic treatment session 540 and the normal awake state 530 was found, in that the value for the self-reported level of pain was found to be inversely correlated with the self-reported value for the level of dissociation. This thus means that, when the subject is in a state of consciousness associated with a higher value for the self-reported level of dissociation, this will lead to a lower value for the self-reported level of pain under identical pain conditions.
Additionally, as shown in further detail in table 2 below, there was found to be no statistically significant correlation between the self-reported level of anxiety and the stimulation intensity of the pain stimulus, or in other words the intensity of the applied transcutaneous electrical stimulus. As already mentioned above, the self-reported level of anxiety thus corresponds to the level of anxiety as experienced by the subject, and is thus not directly correlated to the intensity of the external pain stimulus, or in other words the intensity of the anxiety inducing event itself, but relates to the level of anxiety as cognitively experienced by the subject. In other words, the self-reported level of anxiety clearly relates to the experience of anxiety as it appears in the cognitive experience and optionally the autonomic physiological experience of the subject.
Additionally, as shown in further detail in table 2 below, there was found to be no statistically significant correlation between the self-reported level of pain and the stimulation intensity of the pain stimulus, or in other words the intensity of the applied transcutaneous electrical stimulus. As already mentioned above, the self-reported level of pain thus corresponds to the consciously perceived level of pain perception of the subject, and is thus not directly correlated to the intensity of the external pain stimulus itself, but relates to the conscious level of pain perception. In other words the perception of pain as it appears in the conscious perception consciousness of the subject, typically associated with the cortex, after potential modulation and/or suppression by for example the thalamus and/or other downstream and/or upstream neural pathways.
Additionally, there is a certain level of statistically relevant correlation between the stimulation intensity of the pain stimulus and the self-reported level of dissociation. This means that subjects that reported a higher value for the level of dissociation during the experiment, correlated a higher intensity of the applied electrical stimulus to the value of 8 on the pain scale during the calibration step.
Table 2 below shows the Spearman correlation for both hypnotic treatment session 540 and normal awake state 530:
In Table 2 rs refers to the spearman correlation coefficient. It can take a range of values from +1 to −1. A value of 0 indicates that there is no association between the two variables. A value greater than 0 indicates a positive association; that is, as the value of one variable increases, so does the value of the other variable. A value less than 0 indicates a negative association; that is, as the value of one variable increases, the value of the other variable decreases. The p is the p-value associated with the statistical test to evaluate whether the correlation is statistically significant and not just a coincidence. Generally, a p-value smaller than 0.05 is considered as statistically significant. When a p-value is closer to zero, this shows a higher statistical relevance, or in other words a better correlation.
Results from the analysis of the EEG measurement data generated during experiment 500 in combination with the self-reported data allowed associations to be made between localized brain structures/networks and the experience of anxiety, the perception of pain and/or a modified state of consciousness, such as for example dissociation. Identification of those localized structures/networks associated with the experience of anxiety, perception of pain and modified state of consciousness allows for an objective combined measurement of the level of anxiety, the level of pain as perceived by the subject, or in other words the level of pain perception of the subject and/or of the modifications to the state of consciousness of the subject, for example during a hypnotic treatment session or any other suitable treatment session. It also allows to determine a link between a level of anxiety experienced by a subject, a level of pain as perceived by the subject, when undergoing a calibrated external pain stimulus; which also serves as a calibrated anxiety inducing stimulus, and optionally the modification, suppression and/or modulation thereof by a modified state of consciousness of the subject, such as for example characterized by means of a level of dissociation has now been determined by means of the experiment 500.
In the brain, several types of brain activity occur at the same time, which is also referred to as parallel processing. Specific types of brain activity can be correlated to a specific frequency band in the measured EEG data during the experiment. In order to explore the different types of brain activity, use can be made of a suitable processing of the EEG measurement data generated during the experiment 500, by transforming the time domain signals into the frequency domain, for example by means of a fast Fourier transform or FFT operation. From such frequency domain signals, then for example the power of a specific signal frequency band can be determined, where power for example refers to a square of the amplitude of the frequency domain signals within a specified frequency range associated with one or more particular brain waves, such as described in further detail below. Such frequency bands could for example comprise a combination of at least two, or exactly two types of brainwaves, such as for example a delta-theta frequency band, or a theta-alpha frequency band. This means that such theta-alpha frequency band for example consists of a combination of at least part of a theta frequency band and at least part of an alpha frequency band. This means that such a theta-alpha frequency band for example consists of a combination of at least part of a theta frequency band and at least part of an alpha frequency band. This means that such delta-theta frequency band for example consists of a combination of at least part of a delta frequency band and at least part of a theta frequency band. This means that such a delta-theta frequency band for example consists of a combination of at least part of a delta frequency band and at least part of a theta frequency band. According to the embodiments described below, the frequency bands could for example comprise a combination of at least two, or exactly two types of brainwaves, such as for example the delta-theta frequency band comprising a combination of the two brainwaves delta and theta and the theta-alpha frequency band comprising a combination of the two brainwaves theta and alpha.
In the EEG data of the measured data during the experiment 500, there were found significant power differences in a specific delta-theta (dt) frequency band, comprising a combination of two different types of brain waves, when comparing the measured data of the subject during the hypnotic treatment session 540, which is an embodiment of a non-pharmacologically induced modified state of consciousness, as compared to a normal awake state 530, and which relates to two different self-reported levels of anxiety as experienced by the subject and two different self-reported levels of pain as perceived by the subject:
It is clear from the above-mentioned description that any suitable combination of at least two of the self-reported levels of anxiety, the self-reported levels of dissociation and/or the self-reported levels of pain are significantly different during the hypnosis treatment session 540 with respect to the normal awake state 530.
The early component refers to the power(dt) decrease that was measured in a time period from 0.1 to 0.5 sec after the pain stimulus onset and/or the onset of any other suitable anxiety inducing event. The late component refers to the power(ta) increase that was measured in a time period from 0.38 to 0.78 sec after the pain stimulus onset. According to this specific embodiment, in which there is an external pain stimulus, the power was calculated from −0.5 s to 1.5 s with reference to the stimulus onset, or in other words the power was calculated in a time window of 2 s including the stimulus onset. It is however clear that alternative embodiments are possible, in which for example a time window of at least 0.1 s, for example a time window in the range of 0.5 s up to and including 60 s, or any other suitable time window is used, at any other suitable point in time with respect to the stimulus onset, as long as the time window includes at least a portion at a point in time after the stimulus onset. According to still further embodiments, such as for example during continuous power measurements, not related to a specific external stimulus, the power can be continuously calculated based on overlapping time windows of for example 2s, or of any other suitable time period, such as for example at least 0.1 s, or in the range of 0.5 s up to and including 60 s, . . . .
The abovementioned results are the first identifying location-specific brain frequency band differences between an automated hypnosis treatment session and a normal awake state, especially for a brain frequency band comprising and/or consisting of a combination of at least part of two brain waves such as for example theta and alpha brainwaves, or delta and theta brain waves. It is clear, that these results are also the first at identifying this for any other suitable treatment sessions, for example pharmacological and/or non-pharmacological treatment sessions, and/or in which no use is made of a treatment session. It is clear that this is also the first identification of brain frequency band differences, especially a brain frequency band comprising a combination of two brain waves, with respect to different levels of anxiety as experienced by the subject and/or with respect to different levels of pain as perceived by the subject and/or with respect to different levels of dissociation. As already mentioned above, it is clear that such a frequency band comprising and/or consisting of a combination of two brain wave frequencies, or at least a part thereof, is different from a frequency band only comprising a single brain wave frequency band and different from a frequency band comprising more than two brain wave frequency bands.
From the measured EEG data during the experiment 500, there was extracted power(dt)) and/or power(ta) at EEG electrodes F, C and/or P, and the following results were obtained:
An embodiment of this experimental data is for example shown in
It should be clear that the P-power (dt) calculated from the combined brainwave frequency band delta-theta, surprisingly provides for a substantially higher correlation to the self-reported level of anxiety of the each of its composing individual brainwave frequency bands, i.e. delta and theta. The self-reported level of anxiety was correlated (spearman) with P-power (delta), i.e. the same power calculation for the individual delta brain wave frequency band, at the same EEG electrode P, with an rs=0.09 and a p-value=0.80. The self-reported level of anxiety was correlated (spearman) with P-power (theta), i.e. the same power calculation for the individual theta brain wave frequency band, at the same EEG electrode P, with an rs=0.24 and a p-value=0.4. It is thus clear that the P-power of the specific delta-theta combined frequency band provides for a surprising and unexpectedly high level of correlation, which could not have been foreseen based on either of the individual frequency band components delta and theta.
It is to be noted that the power (ta) calculated from the combined brainwave frequency band theta-alpha, surprisingly provides for a substantially higher correlation to the self-reported level of pain of each of its composing individual brainwave frequency bands, i.e. theta and alpha. The self-reported level of pain was correlated (spearman) with power (theta), i.e. the same power calculation for the individual theta brain wave frequency band, at the same EEG electrodes F, P and C, with the following correlation values
Likewise, the self-reported level of pain was correlated (spearman) with power (alpha), i.e. the same power calculation for the individual alpha brain wave frequency band, at the same EEG electrodes F, P and C, with the following correlation values:
It is thus clear that the power of the specific theta-alpha combined frequency band provides for a surprising and unexpectedly high level of correlation, which could not have been foreseen based on either of the individual frequency band components theta and alpha.
It is furthermore to be noted that the power (dt) calculated from the combined brainwave frequency band delta-theta, surprisingly provides for a substantially higher correlation to the self-reported level of dissociation of each of its composing individual brainwave frequency bands, i.e. delta and theta. The self-reported level of dissociation was correlated (spearman) with power (delta), i.e. the same power calculation for the individual delta brain wave frequency band, at the same EEG electrodes F and P, with the following correlation values:
Likewise, the self-reported level of dissociation was correlated (spearman) with power (theta), i.e. the same power calculation for the individual theta brain wave frequency band, at the same EEG electrodes F and P, with the following correlation values:
It is thus clear that the power of the specific delta-theta combined frequency band provides for a surprising and unexpectedly high level of correlation, which could not have been foreseen based on either of the individual frequency band components delta and theta.
The above experimental data generated during the experiment 500, which comprises both measurement data, such as EEG data, as well as self-reported data, and which could also be referred to as response data, confirms the existence of a correlation between self-reported level of anxiety and a power of a specific combined brain wave frequency band at a specific location, P-power (dt), associated with a delta-theta frequency band, dt, which according to this embodiment extends from 1 Hz up to and including 6 Hz, also referred to as a group 8 indicator. However, as already mentioned above, it is clear that alternative embodiments are possible in which the frequency band comprises a combination of both delta brainwaves and theta brainwaves.
It was determined from the experimental data above that, surprisingly, only measured data received from the P EEG electrodes show a certain level of correlation of power (dt) with the self-reported level of anxiety. In the current experiment there was found no correlation at different electrode locations such as for example the C and F electrode location. The experimental data for the C-EEG electrode, provided a C-power(dt) with an rs=−0.09 with a p-value=0.69 for the correlation with the self-reported level of anxiety. Similarly, the experimental data for the F-EEG electrode, provided for a F-power(dt) with an rs=0.18 with a p-value=0.44 for the correlation with the self-reported level of anxiety. It is thus clear, that only the EEG measurement data resulting from electrodes at a parietal location provided for a sufficiently high level of correlation with the level of anxiety, while the EEG measurement data from electrodes at other locations, such as the central and frontal location, did not provide for such a sufficiently high level of correlation, or in other words, there was no or a level of correlation that was very low. According to the embodiment described here the absolute value of the rs value at the parietal location was greater than or equal to 0.45 and the absolute value of the rs value at other locations was lower than or equal to 0.20.
It is clear that according to alternative embodiments, an alternative external pain and/or anxiety stimulus could be provided. It is clear that instead of and/or in addition to measurement of the level of anxiety in reaction to an external pain and/or anxiety stimulus, the experimental data can also be used for measurement of a level of anxiety caused by internal events or states of the subject, which for example could relate to anxiety experienced, which is not caused by an external event, such as an external pain and/or anxiety stimulus, being applied. It is clear that alternative embodiments of the experiment are possible, in which the P-power(dt) is determined for any other suitable frequency band comprising and/or consisting of a combination of both delta brain waves and theta brainwaves, or at least part thereof, such as for example any suitable frequency band extending in the frequency range of 0 Hz up to and including 8 Hz.
The above experimental data generated during the experiment 500, which comprises both measurement data, such as EEG data, as well as self-reported data, and which could be referred to as response data, confirms the existence of a correlation between self-reported pain and a power, power (ta) associated with a theta-alpha frequency band, ta, which according to this embodiment extends from 6 Hz up to and including 12 Hz, also referred to as a group 4 indicator. However it is clear that alternative embodiments are possible in which the frequency band comprises a combination of both theta brainwaves and alpha brainwaves. It is clear from the experimental data above that measured data received from the C, P and F EEG electrodes all show a certain level of correlation of power (ta) with the self-reported measure of pain. Although, in the current experiment the correlation is highest at the C EEG electrode, it is clear that according to alternative embodiments, the distribution of the level of the correlations amongst different EEG electrodes might be different. However, it is clear that according to alternative embodiments an alternative external pain stimulus could be provided. It is clear that instead of and/or in addition to measurement of the level of pain in reaction to an external pain stimulus, the experimental data can also be used for measurement of a level of pain caused by internal events or states of the subject, which for example could relate to pain experienced, which is not caused by an external event, such as an external pain stimulus, being applied. It is clear that alternative embodiments of the experiment are possible, in which the power(ta) is determined for any other suitable frequency band comprising a combination of both theta brain waves and alpha brainwaves, such as for example any suitable band extending in the frequency range of 4 Hz up to and including 12 Hz.
Furthermore, as described in further detail below, the above experimental data generated during the experiment 500, which comprises both measurement data, such as EEG data, as well as self-reported data, and which could be referred to as response data, confirms the existence of a correlation between self-reported level of dissociation and a power, power (dt) associated with a delta-theta frequency band, dt, which according to this embodiment extends from 1 Hz up to and including 6 Hz, also referred to as a group 1 indicator. However it is clear that alternative embodiments are possible in which the frequency band comprises and/or consists of a combination of both delta brainwaves and theta brainwaves.
These findings have been advantageously applied in a computer-implemented method for measurement of a level of anxiety, a level of modified consciousness and/or a level of pain. Based on the insight that there exists a correlation between P-power(dt) and self-reported measurements of the level of anxiety, and that there exists a correlation between power(ta) and self-reported measurements of the level of pain, it now becomes possible to more objectively measure a level of anxiety and/or a level of pain, even in cases where self-reported anxiety and/or pain measures are not possible or available, such as for example when the subjects are in a state in which they are unable or experience difficulties to communicate, when the subjects are young children, . . . . It is clear that the Level of Anxiety, or LoA is an indicator of the strength of the psychophysiological response to an anxiety inducing event or situation. It is clear that such a level of anxiety as experienced by the subject can be modulated by for example its emotional, psychological, cognitive state, such as for example the state of consciousness of the subject. The LoA is thus an indicator for the level of anxiety as it is experienced of the subject and can thus be used as an indicator of the degree to which the subject experiences anxiety, for example on a cognitive, emotional and/or physical level.
It is clear that the Level of Pain, or LoP is an indicator of the level or degree to which a subject is aware and receptive to pain. In other words, it refers to the level of pain as consciously perceived by the subject. It is clear that such a level of pain perception by the subject can be modulated by for example its emotional, psychological, cognitive state, such as for example the state of consciousness of the subject. The LoP is thus an indicator for the subjective pain perception of the subject and can thus be used as an indicator of the degree to which the subject experiences pain, for example on an emotional, cognitive and/or physical level.
It is thus clear that anxiety, and more specifically anxiety as defined above, includes a cognitive experience and optionally also a physiological experience by the subject. In other words, the level of anxiety as experienced by the subject is a subjective, psychophysiological experience that is influenced to varying degrees by for example biological, psychological, cognitive, physiological, neurophysiological and social factors. The experience that something causes anxiety includes for example cognitive features, such as for example intensity, quality, . . . of an anxiety stimulus and/or affective emotional aspects. It should further be noted that in this way anxiety as experienced and purely autonomic physiological stress responses are different, and can for example occur independently of each other.
As explained in further detail below, in the context of this application a Level of Anxiety Index, or LoAI, or Anxiety index, refers to a standardized index indicating the level of anxiety of which the subject is at least cognitively experiencing and optionally physiologically experiencing. In other words, the degree to which the subject experiences anxiety at a cognitive dimension, optionally supplemented by for example an autonomic sensory and/or an emotional level as described in further detail below. This LoAI for example varies systematically with the intensity of anxiety as experienced by the subject, independently of factors not affecting the experience of anxiety. A first limit of the LoAI, for example a lower limit of the LoAI, may for example indicate that the subject experiences no anxiety. A second limit of the LoAI, for example an upper limit of the LoAI, may for example indicate that the subject experiences the strongest/worst possible experience of anxiety.
It is thus clear that pain in the context of this description, as for example defined by the International Association for the Study of Pain or IASP is an aversive sensory and emotional experience typically caused by, or resembling that caused by, actual or potential tissue injury. It is thus clear that pain is experienced as a conscious perception by the subject. In other words, the level of pain as experienced by the subject is a subjective experience that is influenced to varying degrees by for example biological, psychological and social factors. The conscious perception that something causes pain includes for example sensory-discriminative features, such as for example intensity, quality and location, . . . and/or affective emotional aspects. It should further be noted that in this way pain as consciously perceived and nociception are different phenomena, which can occur independently of each other. The conscious experience or perception of pain cannot always be reduced to activity in sensory pathways. Nociception as defined by IASP is the neural process of encoding noxious and/or painful stimuli. The consequences of such encoding may be automatic such as for example an increased blood pressure, or behavioral, such as for example a motor reflex. However, it is clear that a conscious pain experience is not necessarily implied. As explained in further detail below, in the context of this application a Level of Pain Index, or LoPI, or Pain index, refers to a standardized index indicating the level pain of which the subject is consciously aware. In other words, the degree to which the subject consciously perceives pain at for example a sensory and/or an emotional level. This LoPI for example varies systematically with pain intensity as perceived by the subject, independently of factors not affecting pain perception. A first limit of the LoPI, for example a lower limit of the LoPI, may for example indicate that the subject experiences no conscious perception of pain. A second limit of the LoPI, for example an upper limit of the LoPI, may for example indicate that the subject experiences the strongest possible conscious perception of pain.
According to the embodiment shown in
According to the embodiment shown in
According to the embodiment of the experimental data generated above, it was found that for a population with a mean self-reported anxiety value of 4.92, there was measured a mean P-power(dt) of 0.84 mV2, when a calibrated pain stimulus of value 8 on the pain scale was applied in normal awake state 530. For a population with a mean self-reported anxiety value of 3.16, there was measured a mean P-power (dt) of 0.44 mV2, when a calibrated pain stimulus of value 8 on the pain scale was applied during the hypnotic treatment session 540. As already mentioned above, from the experimental data above, the LoA is correlated to the group 8 indicator, P-power(dt), or in other words an increase in P-power(dt) corresponds to an increase in the LoA, and a decrease in P-power(dt) corresponds to an decrease in the LoA as experienced by the subject. As already mentioned above, it is clear that the P-power(dt) values mentioned above, were calculated from −0.5 s to 1.5 s from with reference to the stimulus onset, or in other words the power was calculated in a time window of 2 s including the stimulus onset, according to an embodiment where there was an external pain and/or anxiety stimulus. As further mentioned above, it is however clear that alternative embodiments are possible, in which alternative suitable time windows are being used, and/or in which the time window is not related to a specific external stimulus, such that for example the power can be continuously calculated based on overlapping time windows.
Further, according to the embodiment of the method shown in
Optionally and preferably according to the embodiment of
According to the embodiment of the experimental data generated above, it was found that for a population with a mean self-reported pain value of 4.2, there was measured a mean power(ta) of 0.16 mV2, when a calibrated pain stimulus of value 8 on the pain scale was applied in normal awake state 530. For a population with a mean self-reported pain value of 1.4, there was measured a mean power (ta) of 0.29 mV2, when a calibrated pain stimulus of value 8 on the pain scale was applied during the hypnotic treatment session 540. As already mentioned above, from the experimental data above, the LoP is inversely correlated to the group 4 indicator, power(ta), or in other words an increase in power(ta) corresponds to a decrease in the LoP, and a decrease in power(ta) corresponds to an increase in the LoP as consciously perceived by the subject.
It is further clear, that the response data, for example representing a subject's response to the treatment session can also be used to determine the state of consciousness of the subject, in particular a level of a modified state of consciousness.
According to a further aspect, as schematically shown in
It is clear that according to such an embodiment, similar as explained above, there is received measured data at step 302 comprising EEG data comprising data collected from at least one frontal (F) EEG electrode located on the scalp anatomical region corresponding to a frontal lobe of the subject. This then allows the extraction of a group 1 indicator at step 308 based on, a power, F-power(dt), associated with a delta-theta frequency band, dt, within a delta-theta frequency range extracted from the at least one F-EEG electrode data. Based on this group 1 indicator, there can then be determined a DoS. Based on the group 1 indicator, there can then be determined a depth of state, DoS, which is a value indicative of the level of a modified state of consciousness.
According to a preferred embodiment, there are determined a plurality of LoA and/or LoP at different DoS; and/or a plurality of LoP at different LoA; and/or a plurality of LoA at different LoP; etc. from measurement data and/or measurement data comprising simultaneous measurement of LoA and/or LoP and DoS obtained, preferably, but not necessarily under identical pain conditions and/or under identical anxiety inducing events. It should be clear that identical pain conditions, do not necessarily mean constant pain conditions, it only means that at the time of measurement of the LoA and/or LoP and DoS are measured, the anxiety and/or pain conditions are identical, substantially identical and/or similar to. It is clear that alternative embodiments are possible in which the measurement of LoA, LoP and/or DoS is not performed simultaneous. Based on such measurements there can then for example be determined the modulation of LoA and/or LoP by DoS, by evaluating the evolution of the LoA and/or LoP at different DoS and/or the evolution of the LoA and/or LoP with respect to the evolution of DoS from the measurement data obtained, preferably, but not necessarily under identical pain and/or anxiety conditions. According to an alternative embodiment the LoP can be adjusted based on said DoS and/or said LoA to a level of normalized pain, NLoP, which is a value indicative of the level of pain in the subject at a predetermined reference DoS and/or a predetermined reference LoA. According to an alternative embodiment the LoA can be adjusted based on said DoS and/or said LoP to a level of normalized anxiety, NLoA, which is a value indicative of the level of anxiety of the subject at a predetermined reference DoS and/or at a predetermined reference LoP. The reference DoS could for example be that of a normal awake state, the reference LoP could for example be a level of pain where no or a minimal amount of pain is perceived and/or the reference LoA could for example be a level of anxiety where no or a minimal level of anxiety is experienced, such as for example shown in
However it should be clear that in the context of this description, with respect to calculation, displaying, etc. of values related to DoS, LoA, NLoA, LoP, NLoP, and any other parameters, where examples are given with respect to the indexed and/or scaled parameters such as DoSI, LoAI, NLoAI, LoPI, NLoPI, etc. according to alternative embodiments these can be replaced by the non-indexed and/or scaled values such as DoS, LoA, NLoA, LoP, NLoP, etc. or vice versa. In this way the value for NLoP would provide for a value of LoP at a predetermined reference DoS of interest, independently of the current DoS and/or any changes to the current DoS, thereby for example providing an indicator for the equivalent amount of pain that would be consciously perceived when the subject would be, or return to a normal awake state of consciousness, when this reference DoS is the normal awake state such as for example shown in
According to still further alternative embodiments, based on the insight that the LoP may be modulated by the LoA and the DoS as shown in further detail below, according to still further embodiments it might be useful to determine a plurality of LoP at different DoS and/or LoA from measurement data and/or measurement data comprising simultaneous measurement of LoA and DoS. According to a specific embodiment, this will for example help to determine the modulation of LoP by DoS and/or LoA, by evaluating the evolution of the LoP at different DoS and/or LoA and/or the evolution of the LoP with respect to the evolution of DoS and/or LoA from the measurement data.
It is thus clear from the above that pain can be a causes of anxiety and vice versa, and that the combined measurement of LoA and LoP and optionally the calculation of any correlations therebetween make it possible to determine the root cause, modulator, aggravating factor, etc. of anxiety and/or pain and to treat it effectively by means of a suitable treatment, for example an anxiety management treatment when the LoA is the main contributing component, or a pain management treatment when the LoP is the main contributing component, and/or a suitable weighted mix of an anxiety and pain management treatment, depending on the respective weights in the contribution of the LoA and/or the LoP and their respective correlation. It is clear that such correlations can most easily be determined between simultaneous measurements of LoA and LoP, however it is clear that alternative embodiments are possible in which the LoA and LoP that are correlated are not measured simultaneously, but during similar time periods and/or events, such as for example before, during and/or after a treatment. According to still further embodiments, when subject-based and/or population-based correlations are available, for example based on prior measurements of LoA, LoP and/or DOS, then these correlations could be stored and retrieved from for example a suitable database, for use during measurement of LoA, LoP and/or DoS and/or when making use of any correlations therebetween.
According to a particular advantageous use, based on the fact that anxiety plays an important role in chronic pain, such combined measurement of LoA and LoP and/or any associated correlation, it may be possible to for example determine patients with a high LoA, that may benefit from an anxiety management treatment in order to reduce the LoP associated with their chronic pain.
As further, schematically shown in the embodiment of the correlation of
It is clear that alternative embodiments, are possible in which for example there is calculated, based on the LoA and/or the LoP, at least one limit and/or range for the DoS, DoSLimit, which is indicative of the at least one limit and/or range of the modification of the level of consciousness attainable when the subject experiences the LoA and/or the LoP. According to still further alternative embodiments, there can be calculated, based on the LoA, at least one limit and/or range for said LoP, LoPLimit, which is indicative of the at least one limit and/or range of the level of pain attainable when the subject experiences said LoA. Similarly as explained above when for example a LoA is measured associated with a LoPLimit that is higher than a desired LoP, then before for example engaging in a pain management treatment, it will be required to adjust the LoA by means of a suitable treatment such that a LoPLimit is reached for which the desired LoP does fall within its range and/or limits. According to still a further embodiment, there can for example be calculated, based on said LoP, and for example a suitable correlation with LoA, at least one limit and/or range for said LoA, LoALimit, which is indicative of the at least one limit and/or range of the level of pain attainable when the subject experiences said LoP. Similarly, as explained above if a desired LoA falls outside the range and/or limits of the LoALimit associated with a measured LoP, then first a treatment adjusting the LoP will need to be adjusted, such as for example a suitable pain management treatment, such that a suitable associated LoALimit can be attained, of which the desired LoA falls inside its range and/or limits.
This is for example illustrated by means of
Specifically with respect to NLoA(I), alternative embodiments are possible with respect to the one shown in
According to still a further embodiment, schematically illustrated by means of
It is further clear from the embodiment shown in
According to
The treatment, and its associated chronology, has been schematically illustrated by means of arrow 408 in the embodiment of
As shown at step 402 the LoA, DoS and/or LoP is measured, for example with the embodiment of the method for measurement of DoS and LoP 300 according to the embodiment shown in
Based on a respective comparison of at least two LoA, at least two LoP and/or at least two DoS measured at at least two different points in time, there can then be measured and/or monitored a treatment-induced evolution of the LoA, the LoP and/or the DoS. According to a particularly simple embodiment the treatment-induced evolution of the LoA, the LoP and DoS is determined based on a respective comparison of the LoA, the LoP and DoS measured for example during and/or after the treatment with the LoA, the LoP and DoS respectively measured before the treatment. However, it is clear that such comparisons could be performed to determine any suitable evolution of the LoA, the LoP and DoS during any suitable time period.
Additionally, and/or alternatively according to some embodiments the LoA, the LoP and/or the DoS could also be predicted. As for example described in further detail below with respect to
According to still further embodiments, additionally and/or alternatively there may be aggregated a level of anxiety score or LoAS, a level of pain score or LoPS and/or a Depth of State Score or DoSS based on an aggregation of respectively at least two LoA, at least two LoP and/or at least two DoS measured at at least two different points in time. It is thus clear that according to such embodiments the aggregation of respectively at least two LoA, at least two LoP and/or at least two DoS measured could be performed over a predetermined period of time. Such aggregated parameters such as LoAS related to anxiety measurement could be useful in determining the impact of a chronic state of anxiety, which might be related to a personality trait and/or an anxiety disorder. An aggregated parameter such as a LoPS related to pain measurement could be useful in determining the impact of chronic pain, in which for example during a longer period, of for example several hours and/or days the level of pain is continuously measured, and the aggregated LoPS is able to provide for an indicator of the impact of a constant, chronic level of pain as perceived by a subject as opposed to an instantaneous peak of pain. This is useful as even moderate or low levels of anxiety and/or pain, when experienced chronically, may have a high impact on the quality of life of subjects, while for example short, infrequent bursts of anxiety and/or pain, even when they are intense can be tolerated more easily. Similarly, an aggregated DoSS may be useful in identifying the level of safety and stability associated with a modified level of consciousness during a particular time period. For example, during surgery, it is valuable to ascertain whether the modified level of consciousness has been established in a sufficiently stable way, and is not the result of a temporary, short term, evolution of the level of consciousness. It is clear that such aggregated forms could also be useful for any other parameters related to the level of pain and the state of consciousness as detailed in this description, and/or their scaled and/or indexed versions, such as for example LoA(I), LoP(I), DoS(I), NLoP(I), DoD(I), DoH(I), etc. thereby allowing for similar scores of these parameters that correspond to the aggregation of at least two values of these parameters. According to particular embodiments the LoA(I)S, LoP(I)S, DoS(I), NLoP(I)S, DoD(I)S, DoH(I)S, etc. could for example comprise any suitable embodiment of aggregation of the respective LoA(l), LoP(l), DoS(I), NLoP(I), DoD(I), DoH(I), etc. values over a predetermined time period, such as for example a sum, mean, average, etc. and the value could for example be presented in a GUI of a system similarly as described below, for example presenting the aggregated value, optionally in relation to the time period during which the LoA(I), LoP(I), DoS(I), NLoP(I), DoD(I), DoH(I), etc. was aggregated.
It is clear that still further alternative embodiments are possible of such methods for measuring and/or monitoring and/or predicting and/or aggregating a level of anxiety combined with and/or correlated with a level of a modified state of consciousness and/or a level of pain in a subject, preferably before, during and/or after a treatment, wherein the method comprises the steps of:
According to a specific embodiment the treatment-induced evolution of the LoA combined with DoS and/or LoP can be determined based on a respective comparison of the LoA combined with DoS and/or LoP determined during and/or after a treatment, with the LoA combined with DoS and/or LoP determined before a treatment. This means that the treatment induced evolution of the LoA is determined by a comparison of the LoA determined during and after the treatment according to this embodiment, and/or that the treatment induced evolution of the DoS, similarly is determined by a comparison of DoS determined during and after the treatment, and/or that the treatment induced evolution of the LoP is determined by a comparison of the LoP determined during and after the treatment.
According to a particular embodiment, similar as explained above with respect to the DoSLimit, LoALimit, and/or LoPLimit, when the treatment is a pain management treatment, the pain management treatment could be replaced and/or combined with an anxiety management treatment; and/or when the treatment is an anxiety management treatment, the anxiety management treatment could be replaced and/or combined with a pain management treatment, when the LoP and/or the LoA is outside the predetermined range and/or until the LoP and/or the LoA is inside the predetermined range. According to such an embodiment, when the LoA is too high, this might limit the effect of a pain management treatment, so when for example the LoA is outside a predetermined range, for example by exceeding one or more predetermined limits associated with the inability to further efficiently manage the LoP by means of a pain management treatment. In such a case, it is beneficial to replace and or combine the pain management treatment with an anxiety management treatment, at least until the anxiety management treatment was able to provide for a treatment induced evolution of the LoA, for example by suitably reducing the LoA to within predetermined limits, such that the LoA is again in the predetermined range in which a pain management treatment is known to be effective for managing the LoP upon which the pain management treatment can be continued and/or resumed and optionally the anxiety management treatment can be stabilized, reduced and/or ended. Similarly, as described above, according to an embodiment when the treatment is an anxiety management treatment, the anxiety management treatment can be replaced with a pain management treatment when the LoP and/or the LoA is outside a predetermined range and/or until the LoP and/or the LoA is inside the predetermined range. This will ensure that, when for example the LoP is exceeds a predetermined limit and/or threshold for any anxiety management treatment to be effective, for example first the LoP is reduced till the predetermined limit is no longer exceeded, or until it is within any suitable predetermined range for the anxiety management treatment to be effective in managing the LoA again. It is clear that still further embodiments are possible in which any suitable combination of an anxiety management treatment and/or a pain management treatment and/or a treatment involving a modification of the state of consciousness are used in order to ensure that LoP and/or LoA and/or DoS are respectively managed such that they become and/or remain within a respective predetermined range for enabling any further treatment to be efficient. According to still a further embodiment, when the treatment is a treatment modifying the state of consciousness it might for example be beneficial to replace and/or combine the treatment modifying the state of consciousness with an anxiety and/or pain reducing treatment when the LoP and/or LoA is outside a predetermined range and/or until the LoP and/or the LoA is inside the predetermined range.
According to a further particular embodiment, when the treatment is a pain management treatment, the pain management treatment can be replaced and/or combined with a treatment modifying the state of consciousness when the DoS is outside a predetermined range and/or until the DoS is inside the predetermined range.
Similarly, the treatment modifying the state of consciousness can be replaced and/or combined with a pain management treatment when the LoP is outside a predetermined range and/or until the LoP is inside the predetermined range. According to an alternative embodiment, the efficacy of a pain management treatment, such as for example a pain-reducing, pain-controlling, pain-preventing, or any other suitable pain management treatment can be determined and/or monitored based on the treatment-induced evolution of the NLoP. Similarly the efficacy of an anxiety-reducing treatment can be determined and/or monitored based on the treatment-induced evolution of the NLoA.
When the treatment is a treatment modifying the state of consciousness for reducing anxiety, such as for example a non-pharmacological treatment such as a hypnosis treatment session, a mind-body treatment, cognitive behavioral therapy, etc., or a pharmacological treatment, for example a sedative treatment, by measuring the DoS at at least two different points in time, for example before, during and/or after the treatment modifying the state of consciousness; there can be determined a treatment-induced evolution of the DoS and/or the LoA, based on a comparison of for example the DoS and/or the LoA measured during and/or after the treatment modifying the state of consciousness with the DoS and/or the LoA measured before the treatment modifying the state of consciousness.
When the treatment is a treatment modifying the state of consciousness for reducing pain, such as for example a non-pharmacological treatment such as a hypnosis treatment session, or a pharmacological treatment, for example a sedation treatment, by measuring, the DoS at at least two different points in time, before, during and/or after the treatment modifying the state of consciousness; there can be determined the treatment-induced evolution of the DoS and/or the LoP, based on a comparison of the DoS and/or the LoP measured during and/or after the treatment modifying the state of consciousness with the DoS and/or the LoP measured before the treatment modifying the state of consciousness.
Alternatively, in order to determine the efficacy of treatment, independent of any changes to the level of consciousness, for example to allow for a comparison between subjects and/or populations, for example to determine/adjust titration or dosage regimen, or to determine/adjust the required depth of state during a hypnosis treatment session, there can be determined a treatment and/or determined an adjustment to a treatment and/or determined an intensity of a treatment based on the determined and/or monitored NLoA and/or NLoP and/or DoSLimit and/or LoPLimit and/or LoALimit respectively. This then allows for example for a determination of for example the efficacy of the treatment with respect to the level of anxiety and/or the level of pain respectively, independently of any changes to the state of consciousness of the subject. It for example allows an anesthetist to assess the LoA independent of any changes to the DoS for example prior to and/or during the initial phases of a sedative treatment, and/or to assess the LoP a sedated patient will experience when brought back to a normal awake state, prior to bringing this sedated patient back to the normal awake state. This then allows to provide for a suitable anxiolytic, analgesic and/or sedative treatment plan to be set up and implemented prior to the sedative treatment and/or prior to awakening of the patient from the sedated state. It is clear that still further alternative embodiments of the use of the NLoA and/or the NLoP are possible. According to further embodiments this for example allows to determine a treatment and/or an adjustment to a treatment and/or an intensity of a treatment and/or the efficacy of a treatment and/or the choice of a treatment based on the measured and/or monitored and/or predicted and/or aggregated NLoA and/or NLoP and/or DoSLimit and/or LoPLimit and/or LoALimit.
If the treatment, for example is an anxiety management treatment, then a treatment-induced evolution of the LoA, which for example corresponds to a reduction of the second LoA measured at step 304 as compared to the first LoA measured at step 302 and treatment-induced evolution of the DoS that for example corresponds to a decrease of the second DoS measured at step 304 as compared to the first DoS measured at step 302, is able to confirm the effectiveness of the treatment. According to some embodiments the value of the treatment-induced evolution of the DoS and LoA also provides for an indication of the intensity of the treatment. For example, according to an embodiment, an anxiety management treatment reduces a first LoA measurement with a first value at step 402 to second value, that corresponds to a 50% reduction of the first value, at a second measurement at step 404, which thus corresponds to a treatment-induced evolution of the LoA of −50% or in other words a change in the LoA corresponding to a reduction of 50% with respect to the measurement at step 302 before the treatment. When this treatment is adapted or another treatment is applied, which only causes a treatment induced evolution of the LoA of −25%, it is clear that this latter treatment has an intensity that is lower than the former. When no change is detected with respect to the first LoA measurement, it can be concluded that the treatment-induced evolution of the LoA corresponds to no change to the LoA, or in other words, that the treatment at that point in time is for example not effective in reducing the LoA and might need adaptation or change to another type of treatment. Similarly, a treatment induced evolution of the DoS could also be quantified to indicate the intensity of the treatment, preferably in combination with the LoA. However, according to alternative embodiments, in which for example the treatment comprises the application of anxiety inducing stimuli, such as for example during a medical treatment involving an injection, administration of local sedation, etc. when the LoA as measured before the treatment, and/or the DoS attained during a particular phase of the treatment, does not change, does not increase and/or does not increase outside a predetermined desired range, during the treatment, especially during and/or after the application of the anxiety inducing stimuli, it is clear that the anxiety management treatment, for example in the form of pharmacological and/or non-pharmacological anxiety management treatment is performing effectively.
If the treatment, for example is a pain reducing treatment, then a treatment-induced evolution of the LoP that for example corresponds to a reduction and/or the absence of an undesired increase of the second LoP measured at step 304 as compared to the first LoP measured at step 302 and treatment-induced evolution of the DoS that for example corresponds to an decrease of the second DoS measured at step 304 as compared to the first DoS measured at step 302, is able to confirm the effectiveness of the treatment. According to some embodiments the value of the treatment-induced evolution of the DoS and LoP also provides for an indication of the intensity of the treatment. For example, according to an embodiment, a pain reducing treatment reduces a first LoP measurement with a first value at step 402 to second value, that corresponds to a 50% reduction of the first value, at a second measurement at step 404, which thus corresponds to a treatment-induced evolution of the LoP of −50% or in other words a change in the LoP corresponding to a reduction of 50% with respect to the measurement at step 302 before the treatment. When this treatment is adapted or another treatment is applied, which only causes a treatment induced evolution of the LoP of −25%, it is clear that this latter treatment has an intensity that is lower than the former. When no change is detected with respect to the first LoP measurement, it can be concluded that the treatment-induced evolution of the LoP corresponds to no change to the LoP, or in other words, that the treatment at that point in time is for example not effective in reducing the LoP and might need adaptation or change to another type of treatment. Similarly, a treatment induced evolution of the DoS could also be quantified to indicate the intensity of the treatment, preferably in combination with the LoP. However, according to alternative embodiments, in which for example the treatment comprises the application of painful stimuli, such as for example during a surgical treatment, when the LoP as measured before the treatment, and/or the DoS attained during a particular phase of the treatment, does not change, does not increase and/or does not increase outside a predetermined desired range, during the treatment, especially during and/or after the application of the painful stimuli, it is clear that the pain treatment, for example in the form of pharmacological and/or non-pharmacological sedation is performing effectively.
As schematically shown by means of striped line 410, according to an optional embodiment, the measurement of a further LoA combined with and/or correlated with a DoS and/or LoP at step 404, at a later point in time than at step 402, could be repeated or could be performed continuously, which allows for a repeated and/or continuous monitoring of the treatment-induced evolution of the LoA, DoS and/or LoP, or in other words the comparison of two LoA, DoS and/or LoP respectively measured at two different points in time. It is clear that alternative embodiments are possible in which any suitable plurality of LoA, DoS and/or LoP measurements at different points in time, before, during and/or after the treatment, are used in order to determine and/or monitor a treatment-induced evolution of the LoA, DoS and/or LoP, based on a comparison of these at least two LoA, DoS and/or LoP measured at at least two different points in time. It is thus clear that such a treatment induced evolution of the LoA, DoS and/or LoP is indicative of a treatment induced change, if any, to the LoA, DoS and/or LoP.
In addition to the group 4 indicator mentioned above with respect to the experiment 500 as shown in
According to such an embodiment, during the embodiment of the experiment as shown in
Such a time-domain EEG analysis showed an overall decrease in the ERP components during the hypnotic treatment session 540 as compare to the normal awake state 530. Based on the measured EEG data, there was found a difference in overall mean signal peak-to-peak amplitude, or MSPA, time-locked to the painful stimulus onset. According to a particular embodiment, as shown, in
The study based on this experiment is thus showing statistically significant MSPA changes at those specific locations of the EEG measurement data, when comparing a modified state of consciousness for example during a non-pharmacologically, e.g. hypnotically induced treatment session, with a normal awake state 530, and which correlate to the different level of pain perceived in reaction to a calibrated painful stimulus.
The extraction of the mean signal peak-to-peak amplitude, or MSPA, for electrodes F, C and/or P, from the EEG data of the measurement data of the experiment 500, which can also be referred to as group 3 indicators, provided the following results:
As already mentioned above in relation to the signals shown in
The study of the experiment 500 mentioned above, thus shows significant MSPA changes in the measured EEG data at those specific EEG sensor locations when comparing a modified state of consciousness during a hypnotic treatment session 540, or any other suitable non-pharmacological or pharmacological treatment inducing a modified state of consciousness, with a normal awake state 530, or in other words when comparing different levels or depths of dissociation or DoD, which is an embodiment of different depth of states or DoS. It is clear that this also means that significant MSPA changes in the measured EEG data have been observed when comparing different levels of pain as perceived by the subject, as the level of pain perceived by the subject during the normal awake state 530 differed from the level of pain perceived by the subject during the hypnotic treatment session 540.
Similar as described above, the insights of the experiment 500 above allow for an alternative embodiment of a computer-implemented method 300 for measurement of a level of pain comprising the further step of extracting from the EEG data, a group 3 indicator corresponding to a mean signal peak-to-peak amplitude, MSPA. Then at a subsequent step the LoP is determined based on the group 4 indicator and at least the group 3 indicator. It is clear that similarly an alternative embodiment of the computer-implemented method 400 for determining and/or monitoring a level of anxiety, a level of modified consciousness and/or a level of pain of a subject, comprising this alternative method for measurement of a level of anxiety, a level of modified consciousness and/or a level of pain is possible.
According to still a further embodiment there is provided a computer-implemented method 300 for measurement of a level of pain comprising the further step of receiving measured data comprising muscular activity data, such as for example electromyography, EMG, data, for example collected from one or more EMG electrodes or any other suitable electrode. These EMG electrodes could for example be positioned at one or more of the following positions: a leg, face, arm, or any other suitable position, . . . . According to still further embodiments it is possible to derive EMG signals and/or EMG data from signals and/or data received from any other suitable electrodes, such as for example EEG electrodes, etc. During a subsequent step extracting from the EMG data, a group 5 indicator corresponding to a mean signal peak-to-peak amplitude, EMG-MSPA. Subsequently then determining the LoP based on the group 4 indicator and at least the group 5 indicator.
Such an embodiment is made possible by means of the following insights resulting from the embodiment of the experiment 500 mentioned above, in which EMG measurement data resulted from suitable measurement of EMG signals during the test phase 520. There was found a decreased MSPA of the ERP-EMG triggered by the pain stimulus during the hypnotic treatment session 540 as compared to the normal awake state 530. There was also found a correlation between the ERP-EMG triggered by the pain stimuli between the EMG-MSPA and the self-reported level of pain perception (r=0.387, p-value=0.09). It was further found that a wider ERP-EMG was associated with an increased self-reported level of pain perception.
According to a preferred embodiment of the method 300 the LoP is determined based on the group 4 indicator, the group 3 indicator, and the group 5 indicator.
Similar as described above, according to a preferred embodiment, the method for measuring the LoA, DoS and/or LoP 300 comprises the step of receiving the measured data of the subject comprising the electroencephalogram, EEG, data collected from one or more of the following EEG electrodes:
Such EEG data is related to brain waves generated by parts of the brain close to the scalp, including the cortex, and therefor are related to the conscious perception of the level of pain by the subject.
Electroencephalography (EEG) is a technique well known in the art for recording electrical activity of the brain. EEG Electrodes placed along the scalp at certain locations measure voltage fluctuations resulting from electrical impulses within the neurons of the brain, mainly in the region of the brain close to the scalp, including the cortex. EEG measurement data reflects how different neurons/populations of neurons in the brain networks communicate with each other by means of electrical impulses. Electroencephalography produces an electroencephalogram. The electroencephalogram, which thus forms the EEG data, may be refined to a particular electrode location, such as the frontal, parietal or central electrodes mentioned above. From the EEG data there may for example be extracted a frequency-based parameter and/or a phase-based parameter, and/or amplitude-based parameter. Frequency-based parameters may for example be obtained by a frequency-based analysis of EEG measurement data. Such a frequency based analysis of EEG measurement data may for example be used to measure the power contained in a specific signal frequency band, where power refers to a square of amplitude of the frequency domain signals typically within a specified band in a frequency band or range, such as for example a frequency band spanning or within a delta-theta frequency range, or a frequency band spanning or within a theta-alpha frequency range. The “delta-theta” (dt) frequency band refers for example to a band of frequencies in a range encompassing both delta and theta brain waves. The delta-theta (dt) frequency band is typically greater than 0 Hz and equal to or less than 8 Hz. The theta brain waves are preferably slow theta brain waves, for example greater than 3 Hz and equal to or less than 6 Hz. The width of the delta-theta (dt) frequency band may be at least 2 Hz. Most preferably the delta-theta (dt) frequency band is greater than or equal to 1 Hz and less than or equal to 6 Hz. In other words, the delta-theta (dt) frequency band comprises and preferably consists of a combination of at least part of the delta frequency band and at least part of the theta frequency band.
The “theta-alpha” (ta) frequency band refers to a band of frequencies in a frequency range encompassing both theta and alpha brain waves. The theta-alpha (ta) frequency range is typically greater than or equal to 4 Hz and equal to or less than 12 Hz. The theta brain waves are preferably fast theta brain waves, for example greater than 6 Hz and equal to or less than 8 Hz. The width of the theta-alpha (ta) frequency band may be at least 2 Hz. Most preferably the theta-alpha (ta) frequency band is greater than 6 Hz and less than or equal to 12 Hz. In other words, the theta-alpha (ta) frequency band comprises and preferably consists of a combination of at least part of the theta frequency band and at least part of the alpha frequency band.
A phase-based parameter may be obtained by phase-based analysis of EEG measurement data. An amplitude-based parameter may be obtained by amplitude-based analysis of EEG measurement data, such as for example a mean signal peak-to-peak amplitude or MSPA in a time domain. The signal peak amplitude is the maximum excursion of the signal wave from the zero point. The signal peak-to-peak amplitude is the distance from a negative peak to a positive peak.
During the experiment 500 a subject may experience during the hypnotic treatment session 540 an increased activity in the frontal cortex and/or in the frequency range of delta waves and a decreased activity in the frontal and/or occipital network and/or in the frequency range of alpha waves, as compared to the activity during the normal awake state 530.
The EEG data may be acquired with one or more EEG electrodes placed on the scalp in the anatomical regions corresponding to the position of the frontal lobe, the parietal lobe and/or both precentral and postcentral gyrus.
A frontal EEG electrode or F-EEG electrode is located on the scalp anatomical region corresponding to the frontal lobe. It is configured for attachment to or contact with the scalp anatomical region corresponding to the frontal lobe. It records F-EEG electrode data. The frontal lobe refers to the anatomical part of the brain.
The region of the frontal lobe may be along the sagittal plane, more preferably in the middle of the scalp anatomical region corresponding to the frontal lobe, along the midsagittal plane.
A parietal EEG electrode or P-EEG electrode is located on the scalp anatomical region corresponding to the parietal lobe. It is configured for attachment to or contact with the scalp anatomical region corresponding to the parietal lobe. It records P-EEG electrode data. The parietal lobe refers to the anatomical part of the brain. The region of the parietal lobe may be along the sagittal plane, more preferably in the middle of the scalp anatomical region corresponding to the parietal lobe, along the midsagittal plane.
A central EEG electrode or C-EEG electrode is located on the scalp anatomical region corresponding to the precentral and postcentral gyrus. It is configured for attachment to or contact with the scalp anatomical region corresponding to the precentral and postcentral gyrus. It records C-EEG electrode data. The precentral and postcentral gyrus refers to the anatomical part of the brain. The region of the precentral and postcentral gyrus may be along the sagittal plane, more preferably in the middle of the scalp anatomical region corresponding to the precentral and postcentral gyrus, along the midsagittal plane.
It is clear that alternative embodiments are possible in which in one or more EEG electrodes are arranged at the above positions, and or additional suitable scalp anatomical regions. As a minimum one localized EEG electrode may be used, such as for example positioned at the scalp anatomical region of the frontal lobe. However, it is understood that a second electrode, or ground electrode may be employed for common mode rejection, i.e. to dissociate relevant information from noise; this can be placed anywhere on the scalp, for instance in another region of the scalp, in a bilateral position. A third electrode, or reference electrode, may be employed to compute voltage differences. This third electrode can be placed anywhere on the scalp, for instance at an electrically neutral location.
It is thus clear that the measured data may comprise one or more measured data components, such as for example EEG data, which is a measured data component, such as for example also EMG data, ECG data, EOG data, . . . .
In addition to the measured data, the embodiments of the experiment 500, method for measurement of the LoA combined with DoS and LoP 300, etc. may in addition to measured data optionally also take into account observational data and/or self-reported data. In other words, these methods may make use of response data that may comprise measured data and optionally observational data and/or self-reported data. The response data may comprise measured data and/or observational data and/or self-reported data. The response data contains one or more data components, each component being derived from a single measurement (e.g. EEG, EMG, EDA, ECG, EOG), single observation (e.g. movement, skin color), or single self-reported event such as for example a self-reported level of anxiety, a self-reported level of pain or a self-reported level of dissociation as mentioned above.
It is clear that the measured data is data obtained from the subject using one or more devices such as an electrode and/or sensor, such as for example a transducer, camera, motion sensor, . . . disposed in relation to the subject. Observational data is then data obtained from a non-self, or hetero, observation of the subject. Self-reported data is data or information reported by the subject, for example before, during or after the measurement of the LoA, LoP, DoS and/or the treatment.
According to particular embodiments the response data may comprise electrical activity data. Electrical activity data is measured data. Electrical activity data is any data derived from a measurement obtained by an electrical electrode. The electrode is typically placed on the skin. Usually the data is captured by at least 2 electrodes (e.g. 2, 3, 4, 5 or more). Examples of electrode-captured data include electroencephalogram (EEG) data, electromyography (EMG) data, electrodermal activity (EDA) data, galvanic skin response (GSR), electrocardiogram (ECG) data, electrooculogram (EOG) data. It is preferred that the response data comprises at least EEG data. Any electrical data component (e.g. EEG data) may or may not be processed prior to being used as measured data and/or response data.
According to particular embodiments the response data may comprise physiological data. Physiological data is measured data. Physiological data is data derived from a measurement on the subject obtained by a device usually containing a transducer, camera, motion sensor. Physiological data excludes the above-mentioned electrical activity data. Examples of physiological data include pulse rate data, cardiovascular data (e.g. heart rate, heart rate variability data), blood pressure data, respiratory (rate) data (e.g. respiratory rate, respiratory rate variability data), brain oxygenation data, blood O2 saturation data, regional and/or central blood O2 saturation data, body temperature data, photoplethysmogram (PPG) data. Blood oxygen saturation may be, for instance SpO2, SvO2, and the like. Any physiological data component (e.g. pulse rate data) may or may not be processed prior to being used as response data. It is clear that, according to some embodiments, physiological data could be derived from electrical activity data, such as for example cardiovascular data could for example be derived from ECG data, etc.
According to exemplary embodiments in which the response data further comprises cardiovascular data such as for example ECG, heart rate, heart rate variability, etc. and/or respiratory data, such as for example breathing rate, breathing rate variability, etc., the LoP can further be determined in function of such response data, as during the experiment it was detected that:
According to particular embodiments, the response data may comprise motion-tracking data. Motion-tracking data is measured data. The motion tracking data is data derived from a movement of the body or of a part of the body. Typically, motion tracking data is measured by one or more motion sensors (e.g. a 2- or 3-axis accelerometer, gyroscope, one or more cameras). The motion-tracking data may comprise one or more of body tracking data (e.g. head, limb (arms legs hands), bodily shaking) and/or eye tracking data. The motion may be spontaneous and/or as a result of a stimulation.
According to particular embodiments, the response data may comprise facial expression data. Facial-expression data is measured data. The facial expression data is data relating an emotion and/or pain perception. Typically, facial expression data is measured by one or more cameras directed at the face (or EMG sensors).
According to particular embodiments the response data may comprise observational data. The observational data is data observed about the subject by another person. The observational data is data observed by the user (e.g. care provider such as a physician, or medical assistant, or non-medical assistant (e.g. friend, relative, helper)), or by a stakeholder associated with the user (e.g. hospital), or obtained from a database (e.g. medical records). The observed data may comprise one or more observed data components (e.g. a subject's movements is an observed data component). Observational data may include one or more of subject's movements/lack of movement; procedural events; clinical observation (skin color, groaning or verbalization of discomfort . . . ); age, type of surgery, ethnic origin, language; dosages of sedation drugs.
According to particular embodiments the response data may comprise self-reported data. The self-reported data is data reported by the subject. The self-reported data may for example be provided during a treatment session. Preferably, the self-reported data is provided before, during and/or after the treatment session. The self-reported data may comprise one or more self-reported data components (e.g. level of pain during measurement, or during treatment is a self-reported data component). Self-reported data may include one or more of a self-reported level of pain, for example before, during and/or after treatment, a self-reported level of dissociation before, during and/or after treatment, estimated duration of the procedure, recall of the events during the session, . . . .
According to embodiments the muscular activity data comprises EMG measured data, EMG data may be acquired using one, two or more EMG electrodes placed on the skin, preferably on limbs or face; or derived from another sensor like EEG. It represents electrical activity data from the subject muscle tissue. It may comprise a frequency-based parameter and/or a phase-based parameter and/or an amplitude-based parameter. However, it is clear that according to alternative embodiments EMG measured data, might for example be extracted from any suitable electrodes, such as for example from signals measured by EEG electrodes.
According to further embodiments the following measured data my optionally and/or additionally be captured and processed during alternative embodiments of the methods described above and/or below.
Cardiovascular measurement data may be acquired using two or more electrocardiogram (ECG) electrodes placed on the skin using peripheral or precordial placement, or using any other placement where ECG data can be derived. ECG detects electrical activity of the heart. Alternatively or in addition, cardiovascular data may be acquired using a photoplethysmogram (PPG) sensor placed on the skin. PPG detects blood volume changes vasculature below the skin. cardiovascular data may comprise heart rate, heart rate variability, derived metrics, phase-based parameters, frequency-based parameters. However, it is clear that according to alternative embodiments ECG measured data, might for example be extracted from any suitable electrodes, such as for example from signals measured by EEG electrodes.
Respiratory measurement data may be acquired using one or more force/movement transducer (e.g. chest band) or air pressure sensors, or derived from a PPG sensor or from ECG electrodes placed at a location where respiratory rate is detectable. The respiratory data may comprise one or more of respiration rate, respiration rate variability (also known as respiration variability), inhalation pressure, exhalation pressure, respiratory rhythm, respiratory depth, respiratory pattern and derived indexes. Changes of respiration patterns may for example also indicate changes to the LoP and/or LoA. Respiratory data may be known herein as respiratory rate data. However, it is clear that according to alternative embodiments, respiratory measurement data might for example be extracted from any suitable sensors, such as for example from signals measured by a 2- or 3-axis accelerometer or a gyroscope[CT2][DR3].
The eye movement measurement data or eye tracking measurement data may include one or more of pupil dilation, eye fixation, blink rate or frequency, eye-EOG, eye movement, blink closing duration, blink flurries, eye closure rate, eyelid distance change (with respect to the normal eyelid distance). Pupil dilation can give information about the activity in the coeruleus, the main site of norepinephrine (stress hormones) synthesis in the brain, as well as the state of sleepiness/alertness.
Eye movement data, such as for example electrooculogram (EOG) measurement data may be acquired using two or more EOG electrodes placed on the skin around the eye (e.g. above and below, or to the left and right of the eye). EOG records eye movements based on the corneo-retinal standing potential that exists between the front and the back of the human eye. EOG data may comprise eye movements/fixation, eye blinks, synchronization of both eye's movements.
Skin galvanic measurement data may be acquired using two or more conductance-measuring electrodes placed on the skin. The data represents skin conductivity and is linked to changes in sweat glands activity that are reflective of sympathetic activity. Skin galvanic data may comprise conductivity variability, peak amplitude/latency, trends.
SpO2 measurement data is a measure of blood oxygen saturation. It may be measured using a number of techniques such as pulse oximetry. SpO2 data may comprise timeline values. It is a key parameter for anesthesiologists since it is linked to respiratory function and it reflects tissue oxygenation.
The body motion tracking measurement data (e.g. head, limb (arms legs hands)) may include an indication of increased or reduced body movement. A change in motion of the head may be a sign of lack of concentration in the tasks/low immersiveness/distraction during passive “deepening” phase of the treatment session. It is clear that alternative embodiments are possible, for example when instructions and/or a treatment session request for interaction resulting in body motion, then the lack of detection of such body motion could be an indicator of the lack of absorption in this task.
The response data according to a particular embodiment may comprise measured data that comprises EEG data, and optionally muscular activity data, such as for example EMG data, and cardiovascular data, such as for example ECG data, and eye movement data, such as for example EOG or eye tracking data, observational data that comprises patient's observed movement or lack of movement and dosages of received medication and/or self-reported data that comprises self-reported consciously perceived level of pain ratings, level of dissociation ratings, optionally amnesia ratings, . . . . Preferably the response data comprises EEG data. Preferably the self-reported data (if any) comprises ratings for a level of anxiety, a level of pain and optionally a depth of state, such as for example a level of dissociation., a level of absorption, etc.
According to some embodiments cardiovascular data and/or respiratory data could also be derived from motion tracking data and/or data generated by one or more cameras directed at the face.
According to exemplary embodiments in the response data further comprises ECG and/or cardiovascular data and/or respiratory data and/or muscular activity data and/or EOG data and/or body temperature data, from which the LoA can be determined.
Preferably the measured data comprises EEG data that comprises data collected from the F-EEG electrode and/or P-EEG electrode and/or C-EEG electrode, and the group 4 indicator is determined by:
The embodiments of the Group 4 indicators:
Preferably the EEG data comprises data collected from the C-EEG electrode and optionally from the P-EEG electrode and optionally from the F-EEG electrode, and the determining comprises:
Preferably the EEG data comprises data collected from the C-EEG electrode and from the P-EEG electrode and optionally from the F-EEG electrode, and the determining comprises:
The EEG data may comprise data collected from the C-EEG electrode and the P-EEG electrode and the F-EEG electrode, and the determining comprises:
It is clear that alternative embodiments of the EEG data collected from any suitable combination of one or more of the above-mentioned EEG electrodes, and/or at least one other EEG electrode are possible. It is thus clear that still further embodiments of the group 4 indicator are possible in which EEG electrode data from one or more electrodes at any suitable scalp location is used to extract a power (ta) or in other words a power associated with a theta-alpha frequency band that is indicative of the LoP consciously experienced by the subject.
According to a particular embodiment a value of power (ta) compared with a reference value is further indicative of the LoP experienced by a subject. For example, a value of said F-power (ta) compared with a reference value is further indicative of the LoP experienced by a subject, a value of said P-power (ta) compared with a reference value is further indicative of the LoP experienced by a subject, and/or a value of said C-power (ta) compared with a reference value is further indicative of the LoP experienced by a subject.
According to such an embodiment an increase of power(ta), for example of F-power (ta) and/or P-power (ta) and/or C-power (ta) compared with a respective reference value(s) is indicative of a reduced LoP and vice versa.
According to such embodiments an increase of power(ta), for example F-power (ta), P-power (ta), and/or C-power (ta), compared with a reference value is further also indicative of a lower state of consciousness, for example associated with a higher level of dissociation, of a subject and/or vice versa.
As will be explained in further detail below such reference values, or reference data can be used to scale and/or index the measured data, such as for example power(ta) or any other measured data and/or the parameters determined from it, such as for example the LoP. According to such embodiments reference data comprising measured data of a subject and/or a population correlated to at least one predetermined reference LoP is received. This could for example be reference data generated by the subject itself, such as a process similar as the calibration phase or the normal awake state of the experiment, for example prior to a treatment session. According to alternative embodiments the reference data and the correlations could result from separate and distinct subject or population-based reference measurements. There can then be determined at least one correlation of at least one predetermined reference LoP and at least one group indicator extracted from the reference data. In this way, similar as described above, for example one or more particular values of the group 4 indicator power(ta) can be correlated with one or more corresponding particular reference values for LoP. These correlations then allow to scale and/or index any subsequent measurements of such a group indicator, such as for example the group 4 indicator power(ta). It is clear that similarly for other group indicators there can be scaled and/or indexed a subsequently measured LoP with respect to the at least one predetermined reference LoP by means of said at least one correlation.
According to a particular embodiment, similar as already mentioned above, the LoP is also based on a group 3 indicator. According to such an embodiment, preferably the EEG data comprises data collected from the C-EEG electrode, and/or P-EEG electrode and/or F-EEG electrode, and the determining comprises:
Similar as explained above, pain perception, for example under identical pain conditions, can also be an indicator of the state of consciousness of a subject.
The embodiments of Group 3 indicators:
Similar as explained above with reference to the group 4 indicator, also for the group 3 indicator there can be made use of reference data to scale and/or index the measured data for determining the LoP. For example, a change of said C-MSPA and/or P-MSPA and/or F-MSPA compared with a respective reference value(s) is indicative of a change to the LoP of the subject. In particular a reduction of said C-MSPA and/or of said P-MSPA and/or of said F-MSPA is indicative of a decrease in the LoP of the subject and an increase with respect to the reference value is thus indicative of an increase in the LoP. Similar as explained above with respect to the group 4 indicator, for example under identical pain conditions, a change to the LoP can also be indicative of a corresponding change to the state of consciousness of the subject. It is clear that similar as described above with respect to group 4 indicators, also for group 3 indicators, and/or any suitable combination of group indicators and/or other group indicators, there can be scaled and/or indexed a subsequently measured LoP with respect to the at least one predetermined reference LoP by means of said at least one correlation, which could be subject-based or population-based.
According to a preferred embodiment the EEG data comprises data collected from the C-EEG electrode and optionally from the P-EEG electrode and optionally from the F-EEG electrode, and the determining comprises:
According a further embodiment the EEG data may comprise data collected from the C-EEG electrode and from the P-EEG electrode and optionally from the F-EEG electrode, and the determining comprises:
According to a further embodiment the EEG data may comprise data collected from the C-EEG electrode and the P-EEG electrode and the F-EEG electrode, and the determining comprises:
According to a particular embodiment, similar as already mentioned above, the LoP is also based on a group 5 indicator. According to such an embodiment, preferably the measured data may further comprise electromyography, EMG, data, for example collected from one or more EMG electrodes, or derived from any other suitable electrode, such as for example EEG electrodes. There can be extracted from the EMG data, a group 5 indicator, which is for example a mean signal peak-to-peak amplitude, or EMG-MSPA, wherein the EMG-MSPA, or Group 5 indicator, is indicative of the level of pain the subject consciously perceives. Similar as explained above, pain perception, for example under identical pain conditions, can also be an indicator of the state of consciousness of a subject.
The Group 5 indicator:
Similar as explained above with reference to the group 4 indicator, also for the group 5 indicator there can be made use of reference data to scale and/or index the measured data for determining the LoP. For example, a change of said EMG-MSPA compared with a reference value is further indicative of a change to the LoP of the subject. A reduction of said EMG-MSPA compared with a reference value is further indicative of a reduced LoP of the subject. It is clear that an increase compared to a reference value, is thus indicative of an increase of the LoP. Similar as explained above with respect to the group 4 indicator, for example under identical pain conditions, a change to the LoP can also be indicative of a corresponding change to the state of consciousness of the subject. It is clear that similar as described above with respect to group 4 indicator, also for a group 5 indicator, and/or any suitable combination of group indicators and/or other group indicators, there can be scaled and/or indexed a subsequently measured LoP with respect to the at least one predetermined reference LoP by means of said at least one correlation, which could be subject-based or population based.
As already mentioned above, a level of pain or LoP of the subject may be determined from a Group 4 indicator and optionally, a Group 3 indicator and/or a Group 5 indicator.
In particular, the level of pain, LoP may be determined from:
In particular, the level of pain LoP may be determined from:
In particular, the level of pain (LoP) may be determined from:
In addition to the group 8 indicator mentioned above with respect to the experiment 500 as shown in
According to such embodiments, during the embodiment of the experiment as shown in
As will be described in further detail below, and already mentioned above, the group 8 indicator is based on measured data comprising EEG data, which can be referred to as a cognitive, electrophysiological signal, and is related to corticoidal signals, and is related to the cognitive dimension of the level of anxiety as experienced by the subject. The group 6, 7, 9, 10 and/or 11 indicators are all related to non-cognitive physiological and/or non-cognitive electrophysiological signals for generating measured data, such as for example cardiovascular data, ECG data, respiratory data, ocular movement data, EOG data, muscular activity data, EMG data, body temperature data, etc. It is thus clear that, a combination of the group 8 indicator for measuring the cognitive dimension of the level of anxiety and optionally, additionally and/or preferably at least one non-cognitive physiological group indicator such as for example group 6, 7, 9, 10 and/or 11 as described in further detail below provides for measuring a combination of this cognitive dimension of anxiety with the autonomic dimension, thereby allowing for measurement of the multi-dimensional aspect of the level of anxiety as experienced by a subject.
According to an exemplary embodiment the measured data may comprise cardiovascular data. Such cardiovascular data may for example be acquired using two or more electrocardiogram (ECG) electrodes placed on the skin using peripheral or precordial placement, or using any other placement where ECG data can be derived. ECG detects electrical activity of the heart. Alternatively, or in addition, cardiovascular data may be acquired using a photoplethysmogram (PPG) sensor placed on the skin. PPG detects blood volume changes vasculature below the skin, from which for example heart rate, heart rate variability, etc. can be derived. Cardiovascular data may alternatively, or in addition be acquired from at least one other suitable electrode, such as for example one or more EEG electrodes, etc., configured to detect a signal from which cardiovascular data, such as heart rate, heart rate variability, . . . can be detected and/or extracted. Cardiovascular data may comprise heart rate, heart rate variability, derived metrics, phase-based parameters, frequency-based parameters. However, it is clear that, according to alternative embodiments, ECG measured data, might for example be extracted from any suitable electrodes, such as for example from signals measured by EEG electrodes. In general, and as described in further detail below such cardiovascular data may be received from any suitable cardiovascular data capturing unit.
According to such an embodiment, based on the received measured data further comprising the cardiovascular data in addition to the P-EEG data, there can be extracted from the cardiovascular data a group 7 indicator based on a heart rate and/or heart rate variability. Preferably, as will be described in further detail with respect to the embodiments shown in
The correlation between a specific combination of heart rate or HR and heart rate variability HRV providing for a group 7 indicator is shown in
One subject of the embodiment of the experiment above, for example provided a self-reported level of anxiety of 4.1 during the normal awake phase 530, during which a corresponding HR=58 bpm, which was for example the mean, average, weighted mean, . . . of the HR during the normal awake phase. Additionally a HRV=53 ms was measured, as the standard deviation of the normal R-R interval during the normal awake phase 530. Subsequently during the second phase 540 with the hypnotic treatment session a lower self-reported level of anxiety of 1.1 was provided by the subject and this corresponded to a measured HR=51 bpm and a HRV=169 ms.
In order to further visualize the effect on the HRV
According to a particular advantageous embodiment, in which a combination of the group 8 indicator and the group 7 indicator is used for determining the LoA, there is made use of the following specific formula for computing the LoA:
LoAs,t˜ƒ4(group 8 indicators,t,α1ƒi(HRs,[t′,t])+α2ƒ2(HRVs,[t′,t])+α3ƒ3(HRs,[t′,t],HRVs,[t′,t]))
This specific embodiment of the group 7 indicator is particularly advantageous, as it not only combines the HR and HRV, but also comprises what can be referred to as a combined HR-HRV factor: α3 ƒ3 (HRs,[t′,t], HRVs,[t′,t]). To demonstrate the surprising, advantageous effect of this combined HR-HRV,
Optionally a time-frequency analysis of the HRV could be performed in order to extract from the HRV signal a signal correlated to the breathing rate, which could also be used for determining a group indicator, as will be described in further detail below. It is however clear that alternative embodiments are possible in which the HR and HRV can be extracted from the measured data. As shown in
According to still a further embodiment there is provided a computer-implemented method 300 for measurement of a level of anxiety comprising the further step of receiving measured data further comprising respiratory data. From this respiratory data there can then be extracted a group 6 indicator based on respiration rate and/or a respiration variability and/or a predetermined respiration pattern and/or oxygen saturation. This then allows to determine the LoA based on the group 8 indicator and at least the group 6 indicator, which similar as described above provides for a multi-dimensional measurement of the LoA.
From the measured data from the experiment of
Further there was also found a correlation between the respiration rate variability, such as for example the standard deviation of the Inter-cycles interval or ICI, was found to be significantly higher during a period with a higher LoA. There was thus found to be a correlation with the self-reported level of anxiety, with an rs=0.434, and p-value=0.005, i.e. an increased level of anxiety leads to a less regular respiration pattern.
Further
According to a particular advantageous embodiment, the LoA is calculated based on the group 8 indicator, in combination with an embodiment the group 6 indicator and the group 7 indicator, or in other words:
LoA˜ƒ(group 8 indicator,group 7 indicator,group 6 indicator)
According to a particular advantageous embodiment, similar as explained above, with respect to the combined HR-HRV factor, preferable there is additionally made use of a combined factor taking into account the influence of the respiration rate or BR on the heart rate and/or the heart rate variability, so similar as explained above such a combined HR-BR factor, such as for example could be included in the formula for calculation of the LoA, such as for example αiƒi (HRs,[t′,t], BRs,[t′,t]) and/or αiƒi (HRVs,[t′,t], BRs,[t′,t]), for example as part of the group 7 indicator and/or the group 6 indicator.
It is clear that still further alternative embodiments for determining a group 6 indicator from the respiratory data, for example it is possible to take into account data with respect to the volume and/or depth of breathing, which could for example be directly measured, and/or indirectly derived from data relating to oxygen saturation, such as for example by means an SpO2 sensor, or from the amount of belly and/or chest movement during breathing. A person with a higher level of anxiety has been detected to have a shallower breath, with a reduced volume of breathing, then when a subject is experiencing a lower level of anxiety. This is for example also illustrated in the embodiment of
According to still a further embodiments there is provided a computer-implemented method 300 for measurement of a level of anxiety comprising the further step of receiving measured data relating to a autonomic physiological parameter for providing a multi-dimensional measurement of the LoA similar as described above and as will be explained in more detail below. According to these embodiments the LoA can be determined based on the group 8 indicator and at least one or more of a group 6, 7, 9, 10 and/or 11 indicator. Such as for example
According to such an embodiment the received measured data further comprises ocular movement data, and there can be extracted a group 9 indicator based on an ocular movement rate and/or ocular movement amplitude and/or predetermined ocular movement patterns from the ocular movement data. This then allows to determine the LoA based on the group 8 indicator and at least the group 9 indicator, and optionally any other suitable autonomic physiological group indicator.
According to a particular embodiment the ocular movement data was captured as EOG data and the group 9 indicator is based on the detection of saccadic eye movements from the ocular movement data.
The EOG data could be captured by a suitable sensor for electrooculography, which is a technique for measuring the corneo-retinal standing potential that exists between the front and the back of the human eye. The resulting signal is called the electrooculogram or EOG. An EOG allows to record eye movements.
There are four basic types of eye movements: saccadic eye movements, smooth pursuit eye movements, vergence eye movements, and vestibulo-ocular eye movements. Saccadic eye movements are rapid, ballistic movements of the eyes that abruptly change the point of fixation. It has been found that the frequency and/or number in predetermined time frame of saccadic eye movements increases when a higher level of anxiety is experienced by a subject.
According to such a further embodiment the received measured data further comprises muscular activity data, such as for example electromyography, EMG, data from which a group 10 indicator based on muscular activity, such as for example electromyographic, EMG, activity can be extracted, which allows to determine the LoA based on said group 8 indicator and at least the group 10 indicator, and optionally any other suitable group indicator.
According to such a further embodiment the received measured data further comprises body temperature data from which a group 11 indicator based on body temperature can be extracted so that the LoA based on said group 8 indicator and at least the group 11 indicator or any other suitable indicator.
Similar as described above, according to a preferred embodiment, the method for measuring the LoA 300 comprises the step of receiving the measured data of the subject comprising the electroencephalogram, EEG, data collected from one or more of the following EEG electrodes:
Such EEG data is related to brain waves generated by parts of the brain close to the scalp, including the cortex, and therefor are related to the level of anxiety as cognitively experienced and optionally physiologically experienced by the subject.
According to a particular embodiment a value of P-power (dt) compared with a reference value is further indicative of the LoA experienced by a subject. For example, a value of said P-power (dt) compared with a reference value is further indicative of the LoA experienced by a subject. According to such an embodiment an increase of P-power (dt) compared with a respective reference value(s) is indicative of an increased LoA and vice versa.
As will be explained in further detail below such reference values, or reference data can be used to scale and/or index the measured data, such as for example P-power(dt) or any other measured data and/or the parameters determined from it, such as for example the LoA. According to such embodiments reference data comprising measured data of a subject and/or a population correlated to at least one predetermined reference LoA is received. This could for example be reference data generated by the subject itself, such as a process similar as the calibration phase or the normal awake state of the experiment, for example prior to a treatment session. According to alternative embodiments the reference data and the correlations could result from separate and distinct subject or population-based reference measurements. There can then be determined at least one correlation of at least one predetermined reference LoA and at least one group indicator extracted from the reference data. In this way, similar as described above, for example one or more particular values of the group 8 indicator P-power(dt) can be correlated with one or more corresponding particular reference values for LoA. These correlations then allow to scale and/or index any subsequent measurements of such a group indicator, such as for example the group 8 indicator P-power(dt). It is clear that similarly for other group indicators there can be scaled and/or indexed a subsequently measured LoA with respect to the at least one predetermined reference LoA by means of said at least one correlation.
Similar as explained above with reference to the group 8 indicator, also for any of the other group indicators, such as the group 6, 7, 9, 10, and/or 11 indicator there can be made use of reference data to scale and/or index the measured data for determining the LoA. It is clear that similar as described above with respect to group 8 indicator, also for any the group 6, 7, 9, 10, and/or 11 indicators, and/or any suitable combination of group indicators and/or other group indicators, there can be scaled and/or indexed a subsequently measured LoA with respect to the at least one predetermined reference LoA by means of said at least one correlation, which could be subject-based or population-based.
According to a preferred embodiment the reference data is received comprising measured data of a subject and/or a population correlated to at least one predetermined reference LoA, combined with DoS and/or LoP respectively. From the reference data there is determined at least one correlation of at least one predetermined reference LoA, combined with DoS and/or LoP respectively and at least one respective group indicator extracted. A subsequently measured LoA can then be scaled and/or indexed combined with DoS and/or LoP with respect to the at least one predetermined reference LoA, combined with DoS and/or LoP respectively by means of said at least one respective correlation, and optionally determining a level of anxiety index or LoAI, and a Depth of State index or DoSI and/or a level of pain index or LoPI therefrom.
Described herein are one or more indexes, which are standardized indexes indicating the level of anxiety as experienced by the subject. Typically, an index is standardized or normalized as compared to a reference. As mentioned above such a reference could for example be subject-based or population-based.
Indexes described herein include a level of anxiety index (LoAI).
A level of anxiety index (LoAI) is a standardized index of the level of anxiety (LoA) indicating the level of anxiety as experienced by the subject. Such an index also allows to determine how much the LoA has been modified, for example by a treatment session, in particular by a pharmacological, and/or non-pharmacological treatment session as compared to a reference state.
An index, for example one or more of LoAI, may have a scale with a first and a second limit. The first limit may represent a lowest level of anxiety, or alternatively a lowest level of anxiety associated with no anxiety and the second limit may represent the highest level of anxiety when compared to a reference state. The first limit may represent an initial state or a reference state of the subject and/or population. The first limit may represent a normal level of anxiety and the second limit may represent a highest level of anxiety. The first limit may represent a normal level of anxiety, and the second limit may represent a significantly increased level of anxiety. The first and second limits may be numerically represented e.g. 0 to 20, 20 to 0, 0 to 60, 60 to 0, 0 to 100, 100 to 0, 0 to 1, 1 to 0 respectively. The second limit may be higher than the first limit, or the first limit may be higher than the second limit. The choice of a higher number for the second limit may depend on the subject or user perspective. An anesthetist may have a preference that the first limit is higher (e.g. 1, 60, 100, 100%) than the second limit (e.g. 0, 0%).
A subject with an index, for example a LoAI which remains close to the first limit, for instance, can be safely approached for further treatments, for example as long as the level of anxiety remains sufficiently low.
The index may have a scale between the first and second limits; the scale may be linear, logarithmic, or other. The scale may be continuous, categorical, discrete, percentage, ratio.
The index, e.g. LoAI, may be indicative of a number of different levels of anxiety or different LoA, for the subject. The number of levels may be any, for instance 3 to 10, preferably 4 to 8 levels. There may be 4, 6, or 8 levels. The levels may be divided within the first and second limits. The division may be even (linear), logarithmic, or according to another scheme. The lowest level (e.g. 1st level) may correlate with or contain the first limit, the highest level (e.g. 4th level) may correlate with or contain the second limit. When an index is a value between 100 (first limit) and 0 (second limit) and the number of levels is 4, the 4 levels may be 100-76 (1st level), 75 to 51 (2nd level), 50 to 26 (3rd level), 25 to 0 (4th level). It is appreciated that the end points of the levels may allow a continuous numerical scale (not interrupted) into the next level. When the index is a value between 100 (first limit) and 0 (second limit) and the number of levels is 8, the 8 levels may be 100-87.5 (1st level), 87.5 to 75 (2nd level), 75 to 62.5 (3rd level), 62.5 to 50 (4th level), 50 to 37.5 (5th level), 37.5 to 25 (6th level), 25 to 12.5 (7th level), 12.5 to 0 to (8th level). The skilled person would be able to determine the extent of the scale (e.g. 100 to 0, or 60 to 0), the number of levels within the scale (e.g. 4, 6 or 8), the type of scale (e.g. linear, logarithmic) and the boundaries between the levels according to the situation.
The index may be a subject-based index in which the state of each subject is compared to a reference state of the subject itself or of a group of subjects, or one or more particular populations. The index may be a population-based index in which the state of each subject is compared to a population-based reference. It is clear that alternatively, the index may also be scaled according to an absolute scale. It is clear that any suitable combination of relative, absolute, individual and/or population-based could be used to scale the index.
With respect to the subject-based index, a reference state e.g. a reference value for LoA, is for example measured for the subject before the treatment session. During or after the treatment session, based on response data comprising measured data, real-time values for one or more of LoA are measured for the subject. During the treatment session, based on a comparison between the reference value and the real-time LoA values, real-time values for one or more of LoAI are calculated.
With respect to the population-based index, a reference state e.g. a reference value for one or more of LoA is for example drawn from a database. The database for example comprises reference values that are based on population studies. The reference value may vary according to certain factors include age, gender, ethnicity, intervention characteristics hence, the reference value may be adapted according to the subject and/or the user. During, or after the treatment session, based on response data comprising measured data, real-time values for one or more of LoA is measured for the subject. During, or after the treatment session, based on a comparison between the database comprising the population-based reference value and the real-time LoA values, real time values for one or more of LoAI is calculated.
It is clear that, alternatively, for example the LoA could be scaled according to a subject-based or population-based absolute scale, such that no further reference measurement is required, and that for example measurement of LoA to determine real-time values could be performed without the need for any treatment session. In other words, with a subject-based or population-based absolute scale it is possible to measure LoA and/or LoAI in any suitable context.
The response data may be transformed into an index e.g. into a LoAI using an evaluation protocol. The evaluation protocol may comprise use of one or more of a mathematical (e.g. statistical) model, trained machine-leaning model, mathematical index, reference data. The evaluation protocol takes as input the response data, and outputs the index.
The evaluation protocol may include a step of extracting from the response data of the group 8 indicator and optionally one or more of the group 6, 7, 9, 10 and/or 11 indicators.
The measured data may comprise one or more data components. A data component is attributed to a single measurement data, for example EEG data, ECG data, . . . , a single observation data, for example movement, skin color, . . . , or a single self-reported event data, for example a self-reported level of anxiety, . . . .
The evaluation protocol may weight the data components of the response data equally or differently. The weighting given to a data component depends, amongst other things, on relevance and precision of the component. For instance, the evaluation protocol may give EEG data a higher rating, reflecting its high relevance and precision. The evaluation protocol may use data components which have less relevance and precision, that are still indicative enough for the situation. In some situations, the response data may comprise a smaller number of data components that have high relevance and precision that are indicative enough for the situation. In some situations, the response data may comprise a larger number of data components that have lower relevance and precision that are indicative enough for the situation. It is clear that various embodiments are possible in which for example according to some embodiments the weighting given to the different group indicators mentioned throughout this description for calculation of the LoA could be adapted in order to adjust and/or fine-tune the calculation of the LoA depending on for example the desired weight and/or effect of the different dimensions of the LoA. According to some embodiments the weighting could be configured to provide a greater weight to the group 8 indicator, when the LoA is measured in a context where the cognitive dimension of LoA outweighs that of the other dimensions of LoA. However it is clear that according to alternative embodiments the group 8 indicator could be provided with a lower weight, and/or be outweighed by other group indicators in a context in which the combination of the cognitive dimension of the LoA with other dimensions of the LoA is more important.
The evaluation protocol may be refined as more subjects are evaluated using the method. A method of refining the evaluation protocol may comprise:
A method of refining the evaluation protocol may comprise:
The evaluation protocol may additionally or alternatively be refined using analytics. The data collected before, during and/or after one or more previous measurements, and/or one or more previous treatment sessions may contribute to a refinement of the evaluation protocol.
It is clear that such methods for creation and/or refinement of such an evaluation protocol, refer to computer-implemented methods, which according to some embodiments could make use of suitable artificial intelligence and/or data mining methods as will be described in further detail below.
As the evaluation protocol is created and/or refined, it may be apparent that one or more data components of the response data become redundant in measuring, or in other words determining, and/or monitoring the level of Anxiety, or for example the modification of the Level of Anxiety by means of a pharmacological and/or non-pharmacological treatment, for example involving an anxiety treatment, a treatment involving the modification of the state of consciousness of a subject, etc. According to a preferred embodiment at least one, preferably all, of the measured data, observation data and response data are used to create and/or refine the evaluation protocol. According to a preferred embodiment only measured data is used in the method for measuring the LoA.
An embodiment of an evaluation protocol for determining a LoAI is set out below. Generally speaking, it may for example comprise 5 principal steps:
Step 1: receive and digitize response data comprising EEG data, for example during a treatment session. The EEG data could for example be provided from a P-EEG electrode, and optionally one or more of C-EEG and F-EEG electrodes or any other suitable EEG electrodes and optionally from one or more ECG electrodes. According to still further embodiments, optionally there could be provided suitable capturing units, where applicable comprising suitable sensors and/or electrodes to capture one or more of the following: cardiovascular data, respiratory data, ocular movement data, muscular activity data, body temperature data, etc.
Step 2: generate:
Group 8 indicators P-power(dt) from the digitized response data, and optionally Group 6, 7, 9, 10 and/or 11 indicators.
Step 3: generate one or more indicator values, which means values for any of the group indicators, such as for example group 8 indicator, group 6, 7, 9, 10, 11 indicator, or any other suitable group indicators, from step 2), using for instance, integrative analysis.
Step 4: comparing the value of Step 3) with reference values, for example a population-based index or subject-based index such as mentioned above.
Step 5: obtain from Step 4) a LoAI index e.g. a number of a scale 0 to 20, or a word, or category. It is clear, as explained in further detail in this description that such a LoAI index according to some embodiments could be provided by means of a suitable graphical visualization.
In step 2, the digitized response data may undergo a pre-processing protocol including one or more of re-referencing to average reference, bandpass and/or notch filtering to exclude low and high frequency artifacts, signal segmentation into so called epochs (=sets of x seconds time windows), artifact rejection (ocular, muscular, . . . ), and baseline adjustment. For time domain analysis of EEG, ECG, EMG, EOG, body temperature, . . . signals, there is typically peak detection to for example determine the time period between peaks, peak amplitude, latency (in form of a time series if multiple epochs), and mathematical transformations performed (e.g.: mean or change variable if multiple epochs. The time window for measurement could for example be in the range of 0.01 s to 10 s, such as for example in the range of 0.1 s to 5 s.
For a frequency domain analysis of for example EEG signals: there is typically a time to frequency transform (e.g. Fourier transform), relevant frequency bands (e.g. delta-theta (dt)) are extracted, amplitude/power and phase for each frequency band (and each epoch) are determined, and mathematical transformations performed (e.g.: mean if multiple epochs).
For signals analyzed in the time domain, peaks can be detected, time interval between peaks, mathematical transformations performed (e.g.: mean if multiple epochs).
From this, one obtains at least one of the following features for at least one electrode: delta-theta frequency band related amplitude/power, delta-theta frequency band related phase, ECG R-R peak interval, . . . . There may be a normalization step for instance to correct for the time of intervention to ensure that every subject contributes similarly.
In step 3, one or more group indicator values is generated using integrative analysis, for instance, using the equation:
Where αi is an optional parameter that evolves with the population size and characteristics, and may be determined using learning processes based on response data and/or independently measured data of the LoA, ƒi is a function determined using learning processes based on response data and/or independently measured data of the LoA, Fi,s,[t′,t] is the value(s) of the feature obtained from point 2 from time t′ to time t (t′<t) and for the subjects. The above-mentioned [t′−t] interval means that the value of LoA at time t may be computed based on features extracted from several Fi,s,t values. For example, taking the mean and the standard deviation from the past x milli-seconds leads to a more sensitive and more robust determination of LoA. It is clear that the [t′−t] interval thus refers to the time window mentioned above.
In step 4, there is a comparison of values with reference values If the index is a subject-based index (each subject is its own control),
ΔrLoAs,t=S(β(LoA*p−LoAs,[t′,t])+K)
If the index is population-based (absolute) and that subject s is part of population p,
ΔaLoAs,t=S(β(LoA*p−LoAs,[t′,t])+K)
Where S is a scale-up parameter, β is a parameter accounting for the population characteristics (age, sex, ethnicity, . . . ) determined using learning processes based on response data and/or independently measured data of the LoA, LoA*s,p is the individual/subject-based reference state, LoA*p is the absolute/population-based reference state using learning processes based on response data and/or independently measured data of the LoA, and K is a “translation” parameter allowing to adjust thresholds based on user preference.
An example of steps 1 to 4 based on an experiment, similar as described above with reference to
Step 1: According to this embodiment, there is received and digitized EEG data and EMG data
Step 2: According to this embodiment there are:
Step 3: An example of an embodiment of the equation mentioned above, which represents an embodiment of a model or evaluation model or evaluation protocol will now be described. This evaluation protocol was for example built, using a computing system configured with an artificial intelligence module, such as for example a machine learning module that for example receives the digitized EEG data and cardiovascular data such as HR and HRV data of a population on which the study is performed, for example by means of an experiment such as for example described in
LoA=1.31*P−Power(dt)+0.15*HR−0.006 HRV−0.00008*HR*HRV=3.72.
Or in other words, according to this particular embodiment LoA=group 8 indicator+group 7 indicators, in which:
It is however clear that alternative embodiments are possible. It is further clear that according to this embodiment the LoA value is calculated on a scale of 0-10, in order to correlate to the scale of the reported VAS pain scale values by the subject during the experiment.
Step 4: According to a particular embodiment, a subject-based index can be calculated, which is presented on a 0-100 scale by means of the formula mentioned above. It is clear that alternative embodiments are possible, in which other suitable scales are used. According to such an embodiment:
In order to demonstrate the accuracy of the evaluation model of this embodiment, there is shown in the box plot graph in
As shown, the differences are all within a narrow range of about −1 to about +1.
As shown in
According to alternative embodiments, such AI CII methods could also be used to select, calculate and/or optimize factors, based on the data from the database, in order to determine the most relevant cohorts.
As shown in
In step 5 the LoAI index is generated. The value obtained in step 4 is compared to a predefined scale depending on subject/intervention characteristics determined following a process described above in the section relating to the refinement of the evaluation protocol, for example using trained machine-learning models and/or artificial intelligence, based on response data and/or independently measured data and/or reference data. It is clear, that such refining, or in other words optimizing, of an evaluation protocol refers to the computer-implemented methods, making use of artificial intelligence and/or data mining similar as described above with respect to
Preferably there is provided a GUI configured to display such predetermined ranges and/or thresholds.
These predetermined ranges and/or thresholds could be related to the level of safety of a subject. For example, a level of safety for starting, continuing, stopping a treatment, a medical intervention, a sports performance, a training program or any other suitable action that could impact the safety of the subject.
In LoAI, the index may be a population-based index, or in other words an absolute scale, in which a subject is compared with a population and/or any other suitable absolute reference. The first limit may indicate that the level of anxiety corresponds to no anxiety being experienced or being free from any anxiety as determined by the population. The second limit may indicate that the level of anxiety corresponds to experiencing the highest possible level of anxiety as determined by the population. Intermediate values represent intermediate levels of anxiety.
In LoAI, the index may be a subject-based index, or in other words a relative scale, in which each subject is compared with itself. The first limit may indicate that the level of anxiety, corresponds to no anxiety being experienced or being free from any anxiety as determined by the subject itself. The second limit may indicate that the level of anxiety corresponds to experiencing the highest possible level of anxiety as determined by the subject itself.
The method and system may determine an expected LoAI and/or ratio, for example for a point in time before, during and/or after the treatment session, for example based on the particular phase, acts of treatment already performed, etc. before, during and/or after the treatment session. For instance, if the treatment comprises a hypnotic session, an expected LoAI may be determined from the phase, for example one of phases (i) to (iv), as will be described in further detail below, of the hypnotic session, and for example from the position within such a phase. For instance, if the treatment comprises a pharmacological treatment session, an expected LoAI may be determined from the dose, titration, and/or timing of the administration of anxiolytic. The expected LoAI may for example be determined from population data or subject data, namely from historical and/or precedence data.
Because an administered treatment does not always lead to the expected LoA a difference between the measured LoA and the expected LoA provides the user with guidance for corrective measures with respect to the treatment.
It is clear that still further alternative embodiments are possible, in which there is provided a computer-implemented method for measuring, or in other words determining, and/or monitoring a level of anxiety of a subject, which comprises the method for measurement of a level of anxiety, according to one or more of the embodiments as described above, applied on a subject by receiving the measured data of a subject.
According to a further aspect, similar as described above, there is thus also provided a method for determining and/or monitoring a level of anxiety of a subject at at least two different points in time, for example before, during and/or after a treatment. According to such a method, there is measured a LoA at at least two different points in time, for example before, during and/or after the treatment. Based on a comparison of at least two LoA measured at at least two different points in time, there is then determined and/or monitored an evolution, for example a treatment-induced evolution of the LoA. However it is clear that such comparisons could be performed to determine any suitable evolution of the LoA during any suitable time period. Additionally and/or alternatively according to some embodiments the LoA could also be predicted. As for example described in further detail below with respect to
According to some treatments, such as for example anxiety treatments, in which for example a pharmacological and/or non-pharmacological treatment is used to reduce a particular level of anxiety the subject is experiencing for example by means of an anxiolytic, it is clear that the goal of the treatment is to reduce the LoA, and that such a reduction in the LoA, for example during and/or after the treatment, corresponds to a desired treatment-induced evolution of the LoA. However according to certain other treatments, for example in a context of a sedative treatment, for example prior to a chirurgical treatment, a dental treatment, etc., it could be desired to retain the LoA as experienced in the normal awake state in which the subject does not undergo the treatment, also during the treatment. In this way, it is clear that the desired treatment induced evolution of the LoA is the prevention of an increase of the LoA, or the prevention of an increase of the LoA beyond an undesirable threshold. It is clear that according to such embodiments, the treatment-induced evolution of the LoA can for example be based on a comparison of the LoA measured before and during the treatment, or measured before and after the treatment, etc. It is thus clear that, according to an embodiment in which the treatment is an anxiety reducing treatment, then the efficacy of such an anxiety treatment, such as for example an anxiety-reducing, anxiety-controlling, anxiety-preventing, or any other suitable anxiety treatment, can be determined and/or monitored based on the treatment-induced evolution of the LoA. In other words, when the LoA is sufficiently reduced, for example to below a desired threshold, or when the LoA does not undesirably increase, for example to above an undesired threshold. Preferably, this treatment-induced evolution of the LoA allows to optimizing and/or adapting an anxiety treatment, such as for example an anxiety-reducing, anxiety-controlling, anxiety-preventing, or any other suitable anxiety treatment.
It is further also clear that based on the measured LoA, there could be determined a treatment and/or determined an adjustment to a treatment and/or determined an intensity of a treatment. For example, a higher value for the LoA could lead to a higher dosage of a sedative or anxiolytics. According to another example, if a particular anxiety treatment doesn't result in a decrease of the LoA, doesn't prevent an increase of the LoA, then an alternative treatment could be initiated. The desired level of titration of a pharmacological anxiety treatment, or the desired intensity of a non-pharmacological treatment, such as for example the depth of hypnosis, the intensity of a non-pharmacological anxiety management treatment, could for example be increased or decreased based on a desired LoA or treatment induced change thereto. According to still further embodiments, there based on a measured and/or desired LoA, there could be made a decision to choose and/or adapt and/or replace specific anxiety management treatment and/or any combination and/or mix of anxiety management treatments, such as for example one or more pharmacological and/or non-pharmacological anxiety management treatments.
Described herein are one or more indexes, which are standardized indexes indicating the level or degree to which subject's level of pain or state of consciousness has been modified by the treatment session.
Typically an index is standardized or normalized as compared to a reference. As mentioned above such a reference could for example be subject-based or population-based.
Indexes described herein include depth of hypnosis index (DoHI), depth of state index (DoSI), depth of dissociation index (DoDI), level of pain index (LoPI), a level of anxiety index (LoAI) A level of anxiety index (LoAI) is a standardized index of the level of anxiety (LoA) indicating the level of anxiety as experienced by the subject. Such an index also allows to determine how much the LoA has been modified, for example by a treatment session, in particular by a pharmacological, and/or non-pharmacological treatment session as compared to a reference state.
A level of pain index (LoPI) is a standardized index of the level of pain (LoP) indicating the level of pain as consciously perceived by the subject. Such an index also allows to determine how much the LoP has been modified, for example by a treatment session, in particular by a pharmacological, and/or non-pharmacological treatment session as compared to a reference state.
A depth of state index (DoSI) is a standardized index of the depth of state (DoS) indicating the level or degree to which the state of consciousness of the subject has been modified, for example by means of a treatment session that is non-pharmacological (e.g. hypnotic) treatment session and/or by a pharmacological treatment session, as compared to a reference state.
A depth of hypnosis index (DoHI) is a standardized index of the depth of hypnosis (DoH) indicating the level or degree to which the state of consciousness of the subject has been modified by a treatment session that is non-pharmacological (e.g. hypnotic), as compared to a reference state.
A depth of dissociation index (DoDI) is a standardized index of the depth of dissociation (DoD) indicating the level or degree to which dissociation of the subject has been modified by the treatment session, in particular by a non-pharmacological treatment session as compared to a reference state.
An index, for example one or more of DoHI, DoSI, DoDI, LoPI, LoAI may have a scale with a first and a second limit. The first limit may represent a lowest level of pain, or alternatively a lowest level of pain associated with no pain, or a normal awake state of consciousness and the second limit may represent the highest level of pain, or the deepest modified state of consciousness when compared to a reference state.
The first limit may represent an initial state or a reference state of the subject and/or population. The first limit may represent a normal level of pain or a normal awake state or only a lightly modified state of consciousness and the second limit may represent a highest level of pain or a fully or deeply modified state of consciousness. The first limit may represent a normal level of pain, and the second limit may represent a significantly increased level of pain. The first limit may represent a light level of trance and the second limit may represent a deep level of trance or vice versa. The first and second limits may be numerically represented e.g. 0 to 20, 20 to 0, 0 to 60, 60 to 0, 0 to 100, 100 to 0, 0 to 1, 1 to 0 respectively. The second limit may be higher than the first limit, or the first limit may be higher than the second limit. The choice of a higher number for the second limit may depend on the subject or user perspective. An anesthetist may have a preference that the first limit is higher (e.g. 1, 60, 100, 100%) than the second limit (e.g. 0, 0%). The latter is for example illustrated in some of the embodiments in this description with respect to DoS, in which a normal awake state or a state with a high/increased/maximum level of consciousness, corresponds to a DoS of for example 100%, which is then an embodiment of the first limit and in which a deeply dissociated state/immersive state or a state with a low/decreased/minimum level of consciousness corresponds to a DoS of for example 0%, which is then an embodiment of the second limit.
A subject with an index, for example DoSI, DoHI, DoDI towards the second limit and a LoPI and/or LoAI which remains closer to the first limit, for instance, can be safely operated on by surgery when the perception of the level of pain, the level anxiety and/or the state of consciousness has been sufficiently modified in order to attain the desired analgesic, anxiolytic and/or anesthetic effect.
The index may have a scale between the first and second limits; the scale may be linear, logarithmic, or other. The scale may be continuous, categorical, discrete, percentage, ratio.
The index, e.g. one or more of DoHI, DoSI, DoDI, LoPI, LoAI may be indicative of a number of different levels of consciousness, such as for example a depth of state (DoSI), a depth of dissociation (DoDI), or may be indicative of a number of different levels of pain (LoPI), or may be indicative of a number of different levels of anxiety (LoAI) for the subject. The number of levels may be any, for instance 3 to 10, preferably 4 to 8 levels. There may be 4, 6, or 8 levels. The levels may divided be within the first and second limits. The division may be even (linear), logarithmic, or according to another scheme. The lowest level (e.g. 1st level) may correlate with or contain the first limit, the highest level (e.g. 4th level) may correlate with or contain the second limit. When an index is a value between 100 (first limit) and 0 (second limit) and the number of levels is 4, the 4 levels may be 100-76 (1st level), 75 to 51 (2nd level), 50 to 26 (3rd level), 25 to 0 (4th level). It is appreciated that the end points of the levels may allow a continuous numerical scale (not interrupted) into the next level. When the index is a value between 100 (first limit) and 0 (second limit) and the number of levels is 8, the 8 levels may be 100-87.5 (1st level), 87.5 to 75 (2nd level), 75 to 62.5 (3rd level), 62.5 to 50 (4th level), 50 to 37.5 (5th level), 37.5 to 25 (6th level), 25 to 12.5 (7th level), 12.5 to 0 to (8th level). The skilled person would be able to determine the extent of the scale (e.g. 100 to 0, or 60 to 0), the number of levels within the scale (e.g. 4, 6 or 8), the type of scale (e.g. linear, logarithmic) and the boundaries between the levels according to the situation.
The index may be a subject-based index in which the state of each subject is compared to a reference state of the subject itself, or of a group of subjects, or one or more particular populations. The index may be a population-based index in which the state of each subject is compared to a population-based reference. It is clear that alternatively, the index may also be scaled according to an absolute scale. It is clear that any suitable combination of relative, absolute, individual and/or population-based could be used to scale the index.
With respect to the subject-based index, a reference state e.g. a reference value for one or more of LoA, LoP, DoS, DoD, DoH is for example measured for the subject before the treatment session. During or after the treatment session, based on response data comprising measured data, real-time values for one or more of LoA, LoP, DoS, DoD, DoH is measured for the subject. During the treatment session, based on a comparison between the reference value and the real-time LoA, LoP, DoS, DoD, DoH values, real-time values for one or more of LoAI, LoPI, DoSI, DoDI, DoHI is calculated.
With respect to the population-based index, a reference state e.g. a reference value for one or more of LoA, LoP, DoS, DoD, DoH is for example drawn from a database. The database for example comprises reference values that are based on population studies. The reference value may vary according to certain factors include age, gender, ethnicity, intervention characteristics hence, the reference value may be adapted according to the subject and/or the user. During, or after the treatment session, based on response data comprising measured data, real-time values for one or more of LoA, LoP, DoS, DoD, DoH is measured for the subject. During, or after the treatment session, based on a comparison between the database comprising the population-based reference value and the real-time LoA, LoP, DoS, DoD, DoH values, real time values for one or more of LoAI, LoPI, DoSI, DoDI, DoHI is calculated.
It is clear that, alternatively, for example the LoP and/or the LoA could be scaled according to a subject-based or population-based absolute scale, such that no further reference measurement is required, and that for example measurement of LoP and/or LoA to determine real-time values could be performed without the need for any treatment session. In other words, with a subject-based or absolute and/or population-based scale it is possible to measure LoP and/or LoA in any suitable context.
The response data may be transformed into an index e.g. into a LoAI, LoPI, DoDI, DoHI, DoSI using an evaluation protocol. The evaluation protocol may comprise use of one or more of a mathematical (e.g. statistical) model, trained machine-leaning model, mathematical index, reference data. The evaluation protocol takes as input the response data, and outputs the index.
The evaluation protocol may include a step of extracting from the response data one or more of:
The measured data may comprise one or more data components. A data component is attributed to a single measurement data, for example EEG data, EMG data, muscular activity data, EDA data, ECG data, cardiovascular data, respiratory data, ocular movement data, EOG data, body temperature data . . . , a single observation data, for example movement, skin color, . . . , or a single self-reported event data, for example a self-reported level of anxiety, a self-reported level of pain perception, a self-reported level of dissociation, . . . .
The evaluation protocol may weight the data components of the response data equally or differently. The weighting given to a data component depends, amongst other things, on relevance and precision of the component. For instance, the evaluation protocol may give EEG data a higher rating, reflecting its high relevance and precision. The evaluation protocol may use data components which have less relevance and precision, that are still indicative enough for the situation. In some situations, the response data may comprise a smaller number of data components that have high relevance and precision that are indicative enough for the situation. In some situations, the response data may comprise a larger number of data components that have lower relevance and precision that are indicative enough for the situation.
The evaluation protocol may be refined as more subjects are evaluated using the method. A method of refining the evaluation protocol may comprise:
A method of refining the evaluation protocol may comprise:
The evaluation protocol may additionally or alternatively be refined using analytics. The data collected before, during and/or after one or more previous measurements, and/or one or more previous treatment sessions may contribute a refinement of the evaluation protocol.
As the evaluation protocol is created and/or refined, it may be apparent that one or more data components of the response data become redundant in determining and/or monitoring the level of Pain, or for example the modification of the Level of Pain by means of a pharmacological and/or non-pharmacological treatment, for example involving a modification of the state of consciousness of a subject. According to a preferred embodiment at least one, preferably all of the measured data, observation data and response data are used to create and/or refine the evaluation protocol. According to a preferred embodiment only measured data is used in the method for measuring the LoP.
An embodiment of an evaluation protocol for determining a LoPI is set out below. Generally speaking, it may for example comprise 5 principal steps:
Step 1: receive and digitize response data comprising EEG data, for example during a treatment session. The EEG data could for example be provided from one or more of C-EEG, P-EEG and F-EEG electrodes, or any other suitable EEG electrodes and optionally from one or more EMG electrodes.
Step 2: generate:
Step 3: generate one or more indicator values, which means values for any of the group indicators, such as for example group 4 indicator, group 3 indicator, group 5 indicator, or any other suitable group indicators, from step 2), using for instance, integrative analysis.
Step 4: comparing the value of Step 3) with reference values, for example a population-based index or subject-based index such as mentioned above.
Step 5: obtain from Step 4) a LoPI index e.g. a number of a scale 0 to 20, or a word, or category.
In step 2, the digitized response data may undergo a pre-processing protocol including one or more of re-referencing to average reference, bandpass and/or notch filtering to exclude low and high frequency artifacts, signal segmentation into so called epochs (=sets of x seconds time windows), artifact rejection (ocular, muscular, . . . ), and baseline adjustment. For time domain analysis of EEG signals, there is typically peak detection to determine peak amplitude and latency (in form of a time series if multiple epochs), and mathematical transformations performed (e.g.: mean or change variable if multiple epochs). For a frequency domain analysis of EEG signals: there is typically a time to frequency transform (e.g. Fourier transform), relevant frequency bands (e.g. theta-alpha (ta)) are extracted, amplitude/power and phase for each frequency band (and each epoch) are determined, and mathematical transformations performed (e.g.: mean if multiple epochs). According to an embodiment, for example in case there is only a single peak in the time window for measurement of the MSPA, the MSPA is equal to the peak-to-peak amplitude of the signal.
According to such an embodiment, for example in case there are multiple peaks in the signal in the time window for measurement of the MSPA, the MSPA will be calculated in function of the mean, average, weighted mean, etc. of the individual peak-to-peak amplitudes of the plurality of these peaks of the signals.
According to such embodiments, the time window for measurement could for example be in the range of 0.01 s to 10 s, such as for example in the range of 0.1 s to 5 s.
For each pair of EMG electrode, or each EMG electrode if there is only one, (and each epoch) signals are analyzed in the time domain, peaks are detected, mean signal peak-to-peak amplitude (MSPA) and MSPA latency are determined, mathematical transformations performed (e.g.: mean if multiple epochs).
From this, one obtains at least one of the following features for at least one electrode: MSPA amplitude, MSPA power, MSPA latency, theta-alpha (ta) frequency band related amplitude/power, theta-alpha (ta)frequency band related phase, EMG MSPA, EMG MSPA latency. There may be a normalization step for instance to correct for the time of intervention to ensure that every subject contributes similarly.
In step 3, one or more group indicator values is generated using integrative analysis, for instance, using the equation:
Where αi is an optional parameter that evolves with the population size and characteristics, and may be determined using learning processes based on response data and/or independently measured data of the LoP, ƒi is a function determined using learning processes based on response data and/or independently measured data of the LoP, Fi,s,[t′,t] is the value(s) of the feature obtained from point 2 from time t′ to time t (t′<t) and for the subjects. The above-mentioned [t′−t] interval means that the value of LoP at time t may be computed based on features extracted from several Fi,s,t values. For example, taking the mean and the standard deviation from the past x milli-seconds leads to a more sensitive and more robust determination of LoP. It is clear that the [t′−t] interval thus refers to the time-window mentioned above.
In step 4, there is a comparison of values with reference values
If the index is a subject-based index (each subject is its own control),
ΔrLoPs,t=S(β(LoP*s,p−LoPs,[t′,t])+K)
If the index is absolute and/or population-based and that subject s is part of population p,
ΔaLoPs,t=S(β(LoP*p−LoPs,[t′,t])+K)
Where S is a scale-up parameter, β is a parameter accounting for the population characteristics (age, sex, ethnicity, . . . ) determined using learning processes based on response data and/or independently measured data of the LoP, LoP*s,p is the individual/subject-based reference state, LoP*p is the absolute/population-based reference state using learning processes based on response data and/or independently measured data of the LoP, and K is a “translation” parameter allowing to adjust thresholds based on user preference.
An example of steps 1 to 4 based on an experiment, similar as described above with reference to
The experiment was performed on one particular subject during the second session 540 of the test phase 520, which comprises an automated hypnotic treatment session 548 that was delivered using a system that comprises a virtual reality headset as described in further detail above. In this embodiment of the experiment, the subject was a woman, age 25, the applied time windows were 2 seconds, from −0.5 s to 1.5 s with reference to the stimulus onset.
Step 1: According to this embodiment, there is received and digitized EEG data and EMG data.
Step 2 According to this embodiment there are:
Step 3: An example of an embodiment of the equation mentioned above, which represents an embodiment of a model or evaluation model or evaluation protocol will now be described. This evaluation protocol was for example built using a computing system configured with an artificial intelligence module, such as for example a machine learning module that for example receives the digitized EEG data and EMG data of a population on which the study is performed, for example by means of an experiment such as for example described in
An example of such an embodiment of the equation is the following:
LoP=0.07*F-MSPA+0.24*C-MSPA+0.024*P-MSPA−10.38*F-Power(ta)−2.64*C-Power(ta)−0.07*P-Power(ta)+0.2*EMG-MSPA=1.92. Or in other words, according to this particular embodiment LoP=group 3 indicators+group 4 indicators+group 5 indicator, in which:
It is however clear that alternative embodiments are possible. It is further clear that according to this 20 embodiment the LoP value is calculated on a scale of 0-10, in order to correlate to the scale of the reported VAS pain scale values by the subject during the experiment.
Step 4: According to a particular embodiment, a subject based index can be calculated, which is presented on a 0-100 scale by means of the formula mentioned above. It is clear that alternative embodiments are possible, in which other suitable scales are used. According to such an embodiment:
In order to demonstrate the accuracy of the evaluation model of this embodiment, there is shown in the box plot graph in
As shown in
As shown in
In step 5 the LoPI index is generated. The value obtained in step 4 is compared to a predefined scale depending on subject/intervention characteristics determined following a process described above below in the section relating to the refinement of the evaluation protocol, for example using trained machine-learning models and/or artificial intelligence, based on response data and/or independently measured data and/or reference data. It is clear that such refining, or in other words optimizing, of an evaluation protocol refers to the computer-implemented methods, making use of artificial intelligence and/or data mining similar as described above with respect to
Preferably there is provided a GUI configured to display such predetermined ranges and/or thresholds.
These predetermined ranges and/or thresholds could be related to the level of safety of a subject. For example, a level of safety for starting, continuing, stopping a treatment, a medical intervention, a sports performance, a training program or any other suitable action that could impact the safety of the subject.
In LoPI, the index may be a population-based index, or in other words an absolute scale, in which a subject is compared with a population and/or any other suitable absolute reference. The first limit may indicate that the level of pain corresponds to no pain being perceived or being free from any pain as determined by the population. The second limit may indicate that the level of pain corresponds to perceiving the highest possible level of pain as determined by the population. Intermediate values represent intermediate levels of pain.
In LoPI, the index may be a subject-based index, or in other words a relative scale, in which each subject is compared with itself. The first limit may indicate that the level of pain, corresponds to no pain being perceived or being free from any pain as determined by the subject itself. The second limit may indicate that the level of pain corresponds to perceiving the highest possible level of pain as determined by the subject itself.
The evaluation protocol may include a step of extracting from the response data one or more of the Group 1 indicator, Group 2 indicator for determining embodiments of DoS(I), DoD(I), and/or DoH(I).
An example of an evaluation protocol for determining a DoDI is set out below. Generally speaking, it may comprise 5 principal steps:
Step 1: receive and digitise response data during a treatment session from F-EEG-electrode and optionally P-EEG electrode.
Step 2: generate:
Step 3: generate one or more indicator value from step 2), using for instance, integrative analysis. As explained above with respect to the group 1 indicator, when P-Power(dt) is used in step 2, then it is always in combination with F-power(dt) and with a lower weight than F-power(dt).
Step 4: comparing the value of Step 3) with reference values (population-based index or subject-based index)
Step 5: obtain from Step 4) a DoDI index e.g. a number of a scale 0 to 20, or a word, or category.
In step 2, the digitised response data may undergo a pre-processing protocol including one or more of re-referencing to average reference, bandpass and/or notch filtering to exclude low and high frequency artifacts, signal segmentation into so called epochs, artifact rejection (ocular, muscular, . . . ), and baseline adjustment. Segmentation into epochs refers to a procedure in which specific time-windows are extracted from the continuous EEG signal. These time windows are called “epochs”, and usually are time-locked with respect an event, e.g. electrical stimulus. ERP or MSPA are measured based on epochs. For time domain analysis of EEG signals, there is typically peak detection to determine peak amplitude and latency (in form of a time series if multiple epochs), and mathematical transformations performed (e.g.: mean or change variable if multiple epochs). For a frequency domain analysis of EEG signals: there is typically a time to frequency transform (e.g. Fourier transform), relevant frequency bands (e.g. delta-theta (td)) are extracted, amplitude/power and phase for each frequency band (and each epoch) are determined, and mathematical transformations performed (e.g: mean if multiple epochs). From this, one obtain at least one of the following features for at least one electrode: delta-theta (td) frequency band related amplitude/power, delta-theta (td) frequency band related phase, EEG mean signal peak-to-peak amplitude (MSPA), EEG MSPA latency.
There may be a normalization step for instance to correct for the time of intervention to ensure that every subject contributes similarly.
In step 3, one or more indicator values are generated using integrative analysis, for instance, using the equation:
Where αt is an optional parameter that evolves with the population size and characteristics, and may be determined using learning processes based on response data and/or independently measured data of the DoD, ƒi is a function determined using learning processes based on response data and/or independently measured data of the DoD, Fi,s,[t′,t] is the value(s) of the feature obtained from point 2 from time t′ to time t (t′<t) and for the subjects. The upper [t′−t] interval means that the value of dissociation at time t may be computed based on features extracted from several Fi,s,t values. For example, taking the mean and the standard deviation from the past x milli-seconds leave to a more sensitive and more robust determination of DoDI. It is clear that the [t′−t] interval thus refers to the time window mentioned above.
In step 4, there is a comparison of values with reference values If the index is a subject-based index (each subject is its own control),
ΔrDoDs,t=S(β(DoD*s,p−DoDs,[t′,t])+K)
If the index is population-based (absolute) and that subject s is part of population p,
ΔaDoDs,t=S(β(DoD*p−DoDs,[t′,t])+K)
Where S is a scale-up parameter, β is a parameter accounting for the population characteristics (age, sex, ethnicity, . . . ) determined using learning processes based on response data and/or independently measured data of the DoD, DoD*s,p is the individual/subject-based reference state, DoD*p is the absolute/population-based reference state determined using learning processes based on response data and/or independently measured data of the DoD, and K is a “translation” parameter allowing to adjust thresholds based on user preference.
In step 5 the DoDI index is generated. The value obtained in step 4 is compared with a predefined scale depending on subject/intervention characteristics determined following process described in the refine protocol below (Using trained machine-learning models and/or artificial intelligence, based on collected measured, observed and self-reported data/reference data).
In DoDI, the index may be a population-based index_(absolute scale, a subject is compared with a population). The first limit may represent “no dissociation”, or full attention regarding stimulus coming from the actual environment and/or regarding internal event. The second limit may represent “the most complete dissociation”, or complete inattention regarding stimulus coming from the actual environment and/or regarding internal event; the subject has fully a feeling of being present in an alternative reality. Intermediate values represent intermediate levels of dissociation which are intermediate levels of inattention regarding stimulus coming from the actual environment and/or regarding internal event.
In DoDI, the index may be a subject-based index (relative scale, each subject compared with itself). The first limit may indicate that the subject is dissociated as initially (reference state). The subject's degree of inattention regarding stimulus coming from the actual environment and/or regarding internal event is the same as before the treatment session. The second limit may indicate that the subject is fully dissociated. The subject's degree of inattention regarding stimulus coming from the actual environment and/or regarding internal event is maximal (for itself); the subject has fully a feeling of being present in an alternative reality. Intermediate values represent intermediate levels of dissociation which are intermediate levels of inattention regarding stimulus coming from the actual environment and/or regarding internal event.
An example of an evaluation protocol for determining a DoHI is set out below. In this protocol, steps 1 and 2 generate one or more groups indicators 1 to 2 from the response data. Generally speaking, it may comprise 5 principal steps:
Step 1: receive and digitise response data during a treatment session from F-EEG-electrode and optionally P-EEG electrode;
Step 2: generate one or more of Group indicators 1 to 2; As explained above with respect to the group 1 indicator, when P-Power(dt) is used in step 2, then it is always in combination with F-power(dt) and with a lower weight than F-power(dt).
Step 3: generate one or more indicator values from step 2), using for instance, integrative analysis;
Step 4: comparing the value of Step 3) with reference values (population-based index or subject-based index);
Step 5: obtain from Step 4) a DoHI index e.g. a number of a scale 0 to 20, or a word, or category.
Alternatively, the evaluation protocol for determining a DoHI may be based on one or more of DoDI already generated. Steps 1 and 2 may be replaced with steps of obtaining one or more of DoDI, and normalising them.
Step 1: Obtain DoDI;
Step 2: Normalise one or more of DoDI;
Step 3: generate one or more indicator values from step 2), using for instance, integrative analysis;
Step 4: comparing the value of Step 3) with reference values (population-based index or subject-based index);
Step 5: obtain from Step 4) a DoHI index e.g. a number of a scale 0 to 20, or a word, or category.
In step 2, the normalise step is a transformation to bring one or more of DoDI to a comparable scale.
In step 3, one or more indicator values is generated using integrative analysis, for instance, using the equation:
Where αt is an optional parameter that evolves with the population size and characteristics, and may be determined using learning processes based on response data and/or computed DoD, DoH and/or independently measured data of the DoD, DoH, ƒi is a function determined using learning processes based on response data and/or computed DoD, DoH and/or independently measured data of the DoD, DoH, Fi,s,[t′,t] is the value(s) of the feature obtained from point 2 from time t′ to time t (t′<t) and for the subjects. It is clear that the [t′−t] interval thus refers to the time window mentioned above.
In step 4, there is a comparison of values with reference values.
If the index is a subject-based index (each subject is its own control),
ΔrDoHs,t=S(β(DoH*s,p−DoHs,t)+K)
If the index is population-based (absolute) and that subject s is part of population p,
ΔaDoHs,t=S(β(DoH*p−DoHs,t)+K)
Where S is a scale-up parameter, β is a parameter accounting for the population characteristics (age, sex, ethnicity, . . . ) determined using learning processes based on response data and/or computed DoD, DoH and/or independently measured data of the DoD, DoH, DoH*s,p is the individual/subject-based reference state, DoH*p is the absolute/population-based reference state determined using learning processes based on response data and/or computed DoD, DoH and/or independently measured data of the DoD, DoH, and K is a “translation” parameter allowing to adjust thresholds based on user preference.
In step 5 the DoHI index is generated. The value obtained in step 4 is compared with a predefined scale depending on subject/intervention characteristics determined following process described below in the section “refinement of the evaluation protocol”, (Using trained machine-learning models and/or artificial intelligence, based on collected measured, observed and self-reported data/reference data).
In DoHI, the index may be a population-based index_(absolute scale, a subject is compared with a population). The first limit may indicate that the subject level of consciousness is similar to the level of consciousness generally observed for normal awake subjects. The second limit may represent the deepest modified state of consciousness, or completely reduced perception of peripheral stimuli and a subject's modified perception of the self and the self in the environment. Intermediate values represent intermediate levels of modified state of consciousness.
In DoHI, the index may be a subject-based index (relative scale, each subject compared with itself). The first limit may indicate that the subject's state of consciousness is not (or not significantly) modified as compared to the reference state; Both the subject perception of peripheral stimuli and perception of the self and the self in the environment are not modified as compared to the reference state. The second limit may indicate that the subject's state of consciousness is fully/deeply modified as compared to the reference state. Intermediate values represent intermediate levels of modified state of consciousness.
An example of an evaluation protocol for determining a DoSI is set out below. In this protocol, steps 1 and 2 generate one or more groups indicators 1 to 2 from the response data. Generally speaking, it may comprise 5 principal steps:
Step 1: receive and digitise response data during a treatment session from F-EEG-electrode and optionally P-EEG electrode.
Step 2: generate one or more of Group indicators 1 to 2; As explained above with respect to the group 1 indicator, when P-Power(dt) is used in step 2, then it is always in combination with F-power(dt) and with a lower weight than F-power(dt).
Step 3: generate one or more indicator values from step 2), using for instance, integrative analysis
Step 4: comparing the value of Step 3) with reference values (population-based index or subject-based index)
Step 5: obtain from Step 4) a DoSI index e.g. a number of a scale 0 to 20, or a word, or category.
Alternatively, the evaluation protocol for determining a DoSI may be based on one or more of DoDI already generated. Steps 1 and 2 may be replaced with steps of obtaining one or more of DoDI, and normalising them.
Step 1: Obtain DoDI.
Step 2: Normalise one or more of DoDI.
Step 3: generate one or more indicator values from step 2), using for instance, integrative analysis
Step 4: comparing the value of Step 4) with reference values (population-based index or subject-based index)
Step 5: obtain from Step 3) a DoSI index e.g. a number of a scale 0 to 20, or a word, or category.
Alternatively, the evaluation protocol for determining a DoSI may be based on one or more of DoDI already generated. Steps 1 and 2 may be replaced with steps of obtaining one or more of DoDI, and normalising them.
Step 1: Obtain one or more of DoDI, a measure of state consciousness induced pharmacologically, a measure of state of consciousness induced by other treatments;
Step 2: Normalise one or more of DoDI, measure of state of consciousness induced pharmacologically, measure of state of consciousness induced by other treatments;
Step 3: generate one or more indicator values from step 2), using for instance, integrative analysis
Step 4: comparing the value of Step 4) with reference values (population-based index or subject-based index)
Step 5: obtain from Step 3) a DoSI index e.g. a number of a scale 0 to 20, or a word, or category.
In step 2, the normalise step is a transformation to bring one or more of DoDI, measure of state of consciousness induced pharmacologically, measure of state of consciousness induced by other treatments to a comparable scale.
In step 3, one or more indicator values is generated using integrative analysis, for instance, using the equation:
Where αi is an optional parameter that evolves with the population size and characteristics, using learning processes based on response data and/or computed one or more of DoD, DoH, DoS, measure of state of consciousness induced pharmacologically, measure of state of consciousness induced by other treatments and/or independently measured data of the one or more of DoD, DoH, DoS, measure of state of consciousness induced pharmacologically, measure of state of consciousness induced by other treatments, ƒi is a function determined using learning processes based on response data and/or computed one or more of DoD, DoH, DoS, measure of state of consciousness induced pharmacologically, measure of state of consciousness induced by other treatments and/or independently measured data of the one or more of DoD, DoH, measure of state of consciousness induced pharmacologically, measure of state of consciousness induced by other treatments, Fi,s,[t′,t] is the value(s) of the feature obtained from point 2 from time t′ to time t (t′<t) and for the subjects. It is clear that the [t′−t] interval thus refers to the time window mentioned above.
In step 4, there is a comparison of values with reference values
If the index is a subject-based index (each subject is its own control),
ΔrDoSs,t=S(β(DoS*s,p−DoSs,t)+K)
If the index is population-based (absolute) and that subject s is part of population p,
ΔaDOSs,t=S(β(DoS*p−DoSs,t)+K)
Where S is a scale-up parameter, β is a parameter accounting for the population characteristics (age, sex, ethnicity, . . . ) using learning processes based on response data and/or computed DoD, DoH, DoS, measure of state of consciousness induced pharmacologically, measure of state of consciousness induced by other treatments and/or independently measured data of the DoD, DoH, measure of state of consciousness induced pharmacologically, measure of state of consciousness induced by other treatments, DoS*s,p is the individual subject-based reference state, DoS*p is the absolute/population-based reference state determined using learning processes based on response data and/or computed DoD, DoH, DoS and/or independently measured data of the DoD, DoH, Do, and K is a “translation” parameter allowing to adjust thresholds based on user preference.
Similar steps 1 to 5 as described above are applicable also—mutatis mutandis—to the determination of a level of dissociation, for example by means of a Depth of State or DoS, from obtained EEG data.
An example of steps 1 to 4 for determining DoS based on an experiment, similar as described above with reference to
Step 1: According to this embodiment, there is received and digitized EEG data.
Step 2 According to this embodiment there are:
Step 3: An example of an embodiment of the equation mentioned above, which shows an embodiment of a model or evaluation model or evaluation protocol will now be described. This evaluation protocol was for example built using a computing system configured with an artificial intelligence module, such as for example a machine learning module that for example receives the digitized EEG data of a population on which the study is performed for example by means of an experiment such as for example described in
DoS=0.1*F-MSPA−7.46*F-Power(dt)−2.46*P-Power(dt)=−4.09.
Or in other words, according to this particular embodiment DoS=group 2 indicator+group 1 indicators, in which:
It is however clear that alternative embodiments are possible. It is further clear that according to this embodiment the DoS value is calculated on a scale of 0-10, in order to correlate to the scale of the reported VAS scale values by the subject during the experiment.
As already mentioned above,
Step 4: According to a particular embodiment, a subject based index can be calculated, which is presented on a 0-100 scale by means of the formula mentioned above. It is clear that alternative embodiments are possible, in which other suitable scales are used. According to such an embodiment:
In order to demonstrate the accuracy of the evaluation model of this embodiment, there is shown in the box plot graph in
As shown, the differences have a narrow interquartile range from about −1 to about +1.
As already mentioned above,
As already mentioned above, as shown in
As already mentioned above, as shown in
In step 5 the DoSI index is generated. The value obtained in step 4 is compared with a predefined scale depending on subject/intervention characteristics determined following process described above in the section relating to the refinement of the evaluation protocol, for example using trained machine-learning models and/or artificial intelligence, based on response data, independently measured data, observed data, self-reported data and/or reference data. It is clear that such refining, or in other words optimizing, of an evaluation protocol refers to the computer-implemented methods, making use of artificial intelligence and/or data mining similar as described above with respect to
In DoSI, the index may be a population-based index, or in other words an absolute scale, in which a subject is compared with a population and/or any other suitable absolute reference. The first limit may indicate that the level of dissociation corresponds to a normal awake state or a state with a high/increased/maximum level of consciousness, as determined by the population. The first limit may represent “no modified state of consciousness”. The first limit may indicate that the subject level of consciousness is similar to the level of consciousness generally observed for normal awake subjects. The second limit may indicate that the level of dissociation corresponds to perceiving the highest possible level of dissociation or a deeply dissociated state/immersive state or a state with a low/decreased/minimum level of consciousness as determined by the population. Intermediate values represent intermediate levels of dissociation. The second limit may represent the deepest modified state of consciousness, or completely reduced perception of peripheral stimuli and a subject's modified perception of the self and the self in the environment. Intermediate values represent intermediate levels of modified state of consciousness. As mentioned elsewhere, DoSI can be a measure of DoHI optionally with measure of state of consciousness induced pharmacologically and optionally with a measure of state of consciousness induced by other treatments.
In DoSI, the index may be a subject-based index, or in other words a relative scale, in which each subject is compared with itself. The first limit may indicate that the subject's state of consciousness is not (or not significantly) modified as compared to the reference state. Both the subject perception of peripheral stimuli and perception of the self and the self in the environment are not modified as compared to the reference state. The first limit may indicate that the level of dissociation, corresponds a normal awake state or a state with a high/increased/maximum level of consciousness as determined by the subject itself. The second limit may indicate that the subject's state of consciousness is fully/deeply modified as compared to the reference state. Intermediate values represent intermediate levels of modified state of consciousness. As mentioned elsewhere, DoSI can be a measure of DoHI optionally with measure of state of consciousness induced pharmacologically and optionally with a measure of state of consciousness induced by other treatments. The second limit may indicate that the level of dissociation corresponds to perceiving the highest possible level of dissociation or a deeply dissociated state/immersive state or a state with a low/decreased/minimum level of consciousness as determined by the subject itself.
When more subjects have been evaluated, more data becomes available which can be used to refine the evaluations protocols for each of DoDI, DoHI and DoSI. Described herein are exemplary ways (a) to (c) in which the respective evaluation protocols can be refined, using at least one, preferably all of measured data, observational data and self-reported data.
(a) Model Parameter's Incrementation
Model parameters (αi,ƒi,β) are evaluated based on measured data, and self-reported or independently measured DoD(I), DoH(I) and/or DoSI, using mathematical and/or statistical and/or machine learning processes.
As the evaluation protocol is refined, it may be apparent that one or more data components of the response data become redundant in determining and/or monitoring the level of consciousness/dissociation of a subject. This data will automatically be weighted by a (close to) zero weights αi when using the upper described method.
(b) Identifying New Relevant Features for the Computation of DoS/DoD/DoH and Including them in the Evaluation Protocol
With new incoming data, it may be apparent that one or more data components of the response data appears as relevant in determining and/or monitoring the level of consciousness/dissociation of a subject and should be included it in the evaluation protocol. New model's parameters should be modified accordingly as described above.
(c) Building Population-Based Reference States/Thresholds
Population-based thresholds and/or reference state are computed based on measured data and/or observed data and/or self-reported and/or computed DoD(I), DoH(I), DoS(I) and/or independently measured DoD(I), DoH(I) and DoSI, using mathematical and/or statistical and/or machine learning processes. They should further be validated for convergence and stability.
The response data is transformed into the DoS(I) and/or DoH(I) using an evaluation protocol. The evaluation protocol may comprise use of one or more of a mathematical (e.g. statistical) model, trained machine-leaning model, mathematical index, reference data. The evaluation protocol takes as input the response data, and outputs the DoSI and/or DoHI.
The measured data may comprise one or more data components. A data component is attributed to a single measurement (e.g. EEG, EMG, EDA, or ECG), single observation (e.g. movement, skin colour), or single self-reported event. The evaluation protocol may weight the data components of the response data equally or differently. The weighting given to a data component depends, amongst other things, on relevance and precision of the component. In this way it is clear that as explained above with respect to the group 1 indicator, when P-Power(dt) is used in the evaluation protocol for determining DoS(I), DoD(I) and/or DoH(I), then it is always in combination with F-power(dt) and with a lower weight than F-power(dt).
The method and system may determine an expected LoAI, LoPI, DoSI, DoDI or DoHI and/or ratio, for example for a point in time before, during and/or after the treatment session, for example based on the particular phase, acts of treatment already performed, etc. before, during and/or after the treatment session. For instance, if the treatment comprises a hypnotic session or alternatively any other treatment modifying a level of consciousness of a subject, an expected LoAI, LoPI, DoSI, DoDI and/or DoHI may be determined from the phase, for example one of phases (i) to (iv), as will be described in further detail below, of the hypnotic session, and for example from the position within such a phase. For instance, if the treatment comprises a pharmacological sedation session, an expected LoAI, LoPI, DoSI, DoDI may be determined from the dose, titration, timing of the administration of the sedative, anxiolytic, analgesic, etc. The expected LoAI, LoPI, DoSI, DoDI and/or DoHI may for example be determined from population data or subject data, namely from historical and/or precedence data.
Because an administered treatment does not always lead to the expected LoA, LoP, DoS, DoD, DoH, a difference between the measured LoA, LoP, DoS, DoD, DoH and the expected LoA, LoP, DoS, DoD, DoH provides the user with guidance for corrective measures with respect to the treatment.
It is clear that still further alternative embodiments are possible, in which there is provided a computer-implemented method for determining and/or monitoring a level of anxiety and/or a level of pain of a subject, which comprises the method for measurement of a level of modified consciousness and a level of anxiety and a level of pain, according to one or more of the embodiments as described above, applied on a subject by receiving the measured data of a subject.
According to a further aspect, similar as described above, there is thus also provided a method for determining and/or monitoring a level of pain and/or a level of anxiety of a subject before, during and/or after a treatment. According to such a method, there is measured a LoP and/or LoA at at least two different points in time, before, during and/or after the treatment. Based on a comparison of at least two LoP and/or LoA measured at at least two different points in time, there is then determined and/or monitored a treatment-induced evolution of the LoP and/or LoA respectively.
According to some treatments, such as for example pain treatments, in which for example a pharmacological and/or non-pharmacological treatment is used to reduce a particular level of pain the subject is experiencing for example by means of a sedative, it is clear that the goal of the treatment is to reduce the LoP, and that such a reduction in the LoP, for example during and/or after the treatment, corresponds to a desired treatment-induced evolution of the LoP. However according to certain other treatments, for example in a context of an anesthetic treatment, for example prior to a chirurgical treatment, it could be desired to retain the LoP as experienced in the normal awake state, in which the subject does not undergo the chirurgical treatment, also during the chirurgical treatment. In this way, it is clear that the desired treatment induced evolution of the LoP is the prevention of an increase of the LoP, or the prevention of an increase of the LoP beyond an undesirable limit or outside a predetermined desired range. It is clear that according to such embodiments, the treatment-induced evolution of the LoP can for example be based on a comparison of the LoP measured before and during the treatment, or measured before and after the treatment, etc. It is thus clear that, according to an embodiment in which the treatment is a pain reducing treatment, then the efficacy of such a pain treatment, such as for example a pain-reducing, pain-controlling, pain-preventing, or any other suitable pain treatment, can be determined and/or monitored based on the treatment-induced evolution of the LoP. In other words, when the LoP is sufficiently reduced, for example to within a desired range, or when the LoP does not undesirably increase, for example to outside a desired range. Preferably, this treatment-induced evolution of the LoP allows to optimizing and/or adapting a pain treatment, such as for example a pain-reducing, pain-controlling, pain-preventing, or any other suitable pain treatment. Similarly, as for the LoP, also for anxiety management treatments, similar embodiments of a desired treatment-induced evolution of the LoA can for example be allow to optimize and/or adapt an anxiety management treatment, such as for example an anxiety-reducing, anxiety-controlling, anxiety-preventing, or any other suitable anxiety management treatment.
It is further also clear that based on the measured LoA, LoP and/or DoS, there could be determined a treatment and/or determined an adjustment to a treatment and/or determined an intensity of a treatment. For example, a higher value for the LoA and/or LoP could lead to a higher dosage of a sedative treatment, for example when such increases are noted during a surgical intervention on the subject. According to another example, if a particular anxiety and/or pain management treatment doesn't result in a decrease of the LoA and/or LoP, and/or doesn't prevent an increase of the LoA and/or LoP, then an alternative treatment could be initiated. The desired level of titration of a pharmacological pain and/or anxiety management treatment, or the desired intensity of a non-pharmacological treatment, such as for example the depth of hypnosis, the level of absorption, etc. could for example be increased or decreased based on a desired LoA, LoP or a treatment induced change thereto.
The method and system may provide an output to a graphical user interface (GUI). The system may comprise a GUI. As will be described in further detail below the system may comprise a graphical user interface, GUI, configured to indicate numerically and/or graphically one or more of:
It is clear that alternative embodiments of the GUI are possible in which further data is displayed.
The output to the GUI may additionally or alternatively show one or more current data components (e.g. one or more measured data components, one or more observed data components, and/or one or more self-reported data components). Examples of current data components include those listed elsewhere herein, preferably one or more of EEG data, cardiovascular data, respiratory data, muscular activity data, ocular movement data, body temperature data, . . . .
The output to the GUI may comprise a graphical indicator wherein a position and/or color on the screen provide the user (e.g. doctor) an indication of the state of the subject and if necessary steps to be taken. For example, a green color may indicate a positive status in terms of patient experience of signal for the user. For example, a red color may indicate a negative status in terms of patient experience of signal for the user. For example, a left position may indicate a positive status in terms of patient experience of signal for the user. For example, a right position may indicate a negative status in terms of patient experience of signal for the user. For example, an upper position may indicate a positive status in terms of patient experience of signal for the user. For example, a lower position may indicate a negative status in terms of patient experience of signal for the user.
The output to the GUI may additionally or alternatively show one or more derived indexes. A derived index is an index derived from one or more data components and/or from another index. A derived index might be based on a ratio of LoAI, LoPI and/or DoSI. These derived indexes may be based on collected data as observed for the subject, optionally refined using analytics (i.e. historical/population data).
A graphical output may comprise a timeline and a marker on the timeline indicating one or more of the LoAI, NLoAI, LoPI, NLoPI, DoSI, DoDI, DoHI, . . . and/or a ratio thereof. One or more of the LoAI, NLoAI, LoPI, NLoPI, DoSI, DoDI, DoHI, . . . and/or a ratio thereof may be on scale with a first and second limit e.g. 0 to 1, 0 to 100.
The GUI may show one or more of the current LoAI, NLoAI, LoPI, NLoPI, DoSI, DoDI, DoHI on one or more scales between the first and second limits; the scale may be linear, logarithmic, or other. The scale may be continuous, categorical, discreet, percentage, ratio.
Examples of GUIs (200, a to g) are given in
In
Historical or trending LoAI for the subject during the treatment session is shown as a dashed line (214). Current units (percent) are indicated (260); the box (260) may also serve as a button to cycle between different units (e.g. to unitless and/or other units). In
As already mentioned above, it is clear that alternative embodiments are possible for such derived indexes, which optionally could be aggregated indexes. Such derived and/or aggregated indexes may be computed based on one or more of LoA, LoP and DoS, and/or any correlations, aggregation, indexing, range detection, limit detection, etc. thereof, for example by means of a suitable evaluation protocol. According to embodiments the evaluation protocol may dynamically weight LoA, LoP and DoS with different weights depending on for example the relevant population, the treatment, the type of intervention, the individual current values of LoA, LoP and DoS and/or current evolution of LoA, LoP and DoS, etc. According to a particular example, if LoA suddenly increases by an amount that exceeds a certain limit or threshold, for example due to an anxiety triggering event, the evaluation function might give a higher weight to the LoA for the current computation of the derived and/or aggregated index.
According to such embodiments the derived and/or aggregated index at time t based on LoA, LoP and DoS might be calculated by an evaluation function based on the following formula:
derived indext=S*ƒ(ƒ1,t(LoAt),ƒ2,t(LoPt),ƒ3,t(DoSt))+K
Where S and K are scale up parameters and ƒ, ƒ1,t, ƒ2,t, ƒ3,t are any suitable functions, such as for example functions such as weighting, aggregating, limit monitoring, range monitoring, . . . , which for example vary depending on the population, the treatment, the intervention, the individual current values of LoA, LoP and DoS, and/or any correlations thereof, and/or current evolution of LoA, LoP and DoS, etc.
According to the embodiment shown in
A system may be provided for measuring and/or monitoring a level of anxiety combined with and/or correlated with a level of pain and/or a modified state of consciousness of a subject, the system comprising:
It is thus clear that, according to an embodiment, there is provided a system configured to measure a level of anxiety combined with and/or correlated with a level of pain and/or a modified state of consciousness according to the method for measuring the LoA, LoP and/or DoS as described above. Such a system comprises a monitoring apparatus configured to obtain measured data comprising electroencephalogram, EEG, data collected from one or more suitable electrodes. The EEG data comprises data, collected from at least one of: at least one parietal (P) electrode configured for collection of P-EEG data from the scalp anatomical region corresponding to a parietal lobe of a subject; and at least one frontal (F) electrode configured for collection of F-EEG data from the scalp anatomical region corresponding to a frontal lobe of a subject. It further comprises a controller module configured for receiving the measured data from the monitoring apparatus. The controller module is configured for extracting from the EEG data collected from the P-EEG data, a group 8 indicator based on a power, P-power (dt), associated with a delta-theta frequency band, dt, within a delta-theta frequency range. Optionally, the controller module is further configured for extracting from the EEG data, a group 1 indicator based on, a power, F-power(dt), associated with a delta-theta frequency band, dt, within a delta-theta frequency range extracted from the at least one F-EEG electrode data; and/or optionally for extracting from the EEG data, a group 4 indicator corresponding to a power, power (ta), associated with a theta-alpha frequency band, ta, within a theta-alpha frequency range. The controller module is configured for determining, based on said group 8 indicator, a level of anxiety, LoA, which is a value indicative of the level of anxiety of the subject. The controller module is further configured for determining, based on said group 1 indicator, a depth of state, DoS, which is a value indicative of the level of a modified state of consciousness; and/or determining, based on said group 4 indicator, a level of pain, LoP, which is a value indicative of the level of pain in the subject. Optionally, it is clear that according to similar embodiments as explained above, the LoP could be further determined by means of group 3 and/or group 5 indicators. Optionally, it is clear that according to similar embodiments as described above the LoA could be further determined by means of a group 6, 7, 9, 10, and/or 11 group indicator in combination with the group 8 indicator.
Preferably the monitoring apparatus comprises, for obtaining measured data, one or more parietal (P) electrodes configured for collection of P-EEG data from the scalp anatomical region corresponding to a parietal lobe of the subject, and one or more frontal (F) electrodes configured for collection of F-EEG data from the scalp anatomical region corresponding to a frontal lobe of the subject. Optionally, the monitoring apparatus comprises one or more central (C) electrodes configured for collection of C-EEG data from the scalp anatomical region corresponding to a precentral and postcentral gyrus of the subject, and optionally, one or more further electrodes configured for collection of electroencephalogram, EEG, data. Optionally the monitoring apparatus comprises one or more of the following: a respiratory data capturing unit; a cardiovascular data capturing unit; an ocular movement data capturing unit; a muscular activity data capturing unit; optionally a body temperature data capturing unit. It is clear, as will be explained in further detail below, that still further embodiments of the system are possible.
According to an embodiment the monitoring apparatus may be configured to capture response data of the subject, in particular measured data of the subject. The monitoring apparatus comprises one or more units, each unit containing, depending on the type of unit one or more electrodes, sensors, cameras that capture measured data. The measured data component of each unit may or may not result from a processing of a signal captured by the one or more electrodes, sensors, cameras.
The monitoring apparatus may comprise an electroencephalogram (EEG) capturing unit. The response data i.e. measured data comprises outputted EEG data. The EEG capturing unit may comprise at least two (e.g. 2, 3, 4, 5 or more), preferably a plurality of electrodes configured for acquiring electrical activity data from the subject's brain. The electrodes may be configured for placement at predetermined positions across the subject's cephalic region; for instance to the frontal, parietal, and/or occipital region. An exemplary electrode configuration is 2 frontal electrodes, 2 lateral electrodes, 1 occipital electrode with respect to the head.
However, it is clear that alternative embodiments are possible comprising other electrodes at other scalp locations.
In a preferred configuration, the EEG capturing unit may comprise at least three electrodes:
The EEG capturing unit may further comprise a ground or reference electrode. This is situated away from the F-, P- or C-EEG electrode to allow spatial reconstruction. However according to alternative embodiments, the EEG capturing unit cold for example comprises only electrodes for capturing data at a single or two scalp locations.
The electrodes may be integrated into a wearable device e.g. a wearable headset. The electrodes may be fixed to or detachable from the wearable device. The electrodes may be dry-contact electrodes. The electrodes may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The electrodes may be reusable or one-time use. The electrodes may be integrated into a head-strap or fixing band. The electrodes may be integrated into a mask portion of a media renderer, as explained in further detail below. The electroencephalogram (EEG) capturing unit typically includes an amplifier for amplification of the detected signal. Signals are digitized for processing by a digital-to-analogue converter for processing by the processing unit. The sampling rate is typically at least 2.5 times higher than the highest frequency of interest. The digital-to-analogue converter may be separate or built into the processing unit.
According to an embodiment the monitoring apparatus may comprise a muscular movement data capturing unit, such as for example an electromyography (EMG) capturing unit. The response data i.e. measured data comprises outputted EMG data. The EMG capturing unit may comprise at least one (e.g. 1, 2, 3, 4, 5 or more), preferably a plurality of electrodes configured for acquiring electrical activity data from the subject muscle tissue. Where an EEG capturing unit is present, the EMG capturing unit may share at least one electrode with the EEG capturing unit. Similarly, where an EEG capturing unit is present, an ECG capturing unit may share at least one electrode with the EEG capturing unit. The electrodes may be configured for placement at predetermined positions across the subject's cranial and/or facial region; preferably to the frontal region. The electrodes may be integrated into a wearable device e.g. a wearable headset. The electrodes may be fixed to or detachable from the wearable device. The electrodes may be dry-contact electrodes. The electrodes may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The electrodes may be reusable or one-time use. The electrodes may be integrated into a head-strap or fixing band. The electrodes may be integrated into a mask portion of the media renderer. The EMG capturing unit typically includes an amplifier for amplification of the detected signal. Signals are digitized for processing by a digital-to-analogue converter for processing by the processing unit. The digital-to-analogue converter may be separate or built into the processing unit.
According to an embodiment, the monitoring apparatus may comprise a respiratory data (RD) capturing unit. The response data i.e. measured data comprises outputted respiratory data. RD capturing unit may comprise at least one (e.g. 1, 2, 3, 4, 5 or more) sensor(s) configured for acquiring RD from the subject. The respiratory data may comprise one or more of respiration rate, respiration rate variability, inhalation pressure. The RD capturing unit may comprise one or more photoplethysmogram (PPG) sensors. A PPG sensor detects blood volume changes in vasculature below the skin; the sensor is typically optical. The respiration rate and respiration rate variability may be determined from the PPG sensor. A PPG sensor may be placed at temple area and/or forehead area. The respiration rate and respiration rate variability may be determined from the PPG sensor. One or more of the sensor(s) may be configured for placement at predetermined positions across the subject's cranial and/or facial region. The sensor(s) may be integrated into a wearable device e.g. a wearable headset. The sensor(s) may be fixed to or detachable from the wearable device. According to an embodiment, the sensor(s) may be dry-contact sensor(s) and/or electrode(s). The sensor(s) may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The sensor(s) may be reusable or one-time use. The sensor(s) may be integrated into a head-strap or fixing band. The sensor(s) may be integrated into a mask portion of the media renderer e.g. so as to place PPG sensors at the forehead and/or temple region. The RD capturing unit may comprise a wearable chest band containing a force transducer that measures the expansion and contraction of the chest; the respiration rate and respiration rate variability may be determined from the wearable chest band sensor. The RD capturing unit may comprise an airways air pressure detector that measures the air pressure (e.g. during inhalation or exhalation). The RD capturing unit typically includes an amplifier for amplification of the detected signal. Signals are digitized for processing by a digital-to-analogue converter for processing by the processing unit. The digital-to-analogue converter may be separate or built into the processing unit.
According to an embodiment, the monitoring apparatus may comprise a cardiovascular data capturing unit, which according to an embodiment for example comprises a heart rate (HR) capturing unit. The response data i.e. measured data comprises outputted HR data. HR capturing unit may comprise at least one (e.g. 1, 2, 3, 4, 5 or more) sensor(s) and/or electrode(s) configured for acquiring heart data from the subject. The HR capturing unit may comprise one or more photoplethysmogram (PPG) sensors that detects blood volume changes vasculature below the skin; the sensor is typically optical. A PPG sensor may be placed at temple area and/or forehead area. The peaks of a captured PPG wave can be used to estimate the heart rate, heart rate variability as well as heartbeat interval, and blood pressure (two PPG sensors). The HR capturing unit may comprise one or more ECG electrodes, or any other suitable electrodes configured for acquiring electrical activity data from the subject heart. Where an EEG or EMG capturing unit is present, the HR capturing unit may share an electrode with the EEG or EMG capturing unit. One or more of the sensor(s) and/or electrode(s) may be configured for placement at predetermined positions across the subject's cranial and/or facial region; they may be placed bilaterally. Where the sensors are PPG sensors, they may be configured for placement at the forehead and/or temple region. The sensor(s) and/or electrode(s) may be integrated into a wearable device e.g. a wearable headset. The sensor(s) and/or electrode(s) may be fixed to or detachable from the wearable device. The sensor(s) and/or electrode(s) may be dry-contact sensor(s) and/or electrode(s). The sensor(s) and/or electrode(s) may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The sensor(s) and/or electrode(s) may be reusable or one-time use. The sensor(s) and/or electrode(s) may be integrated into a head-strap or fixing band. The sensor(s) and/or electrode(s) may be integrated into a mask portion of the media renderer e.g. so as to place PPG sensors at the forehead and/or temple region. The HR capturing unit typically includes an amplifier for amplification of the detected signal. Signals are digitized for processing by a digital-to-analogue converter for processing by the processing unit. The digital-to-analogue converter may be separate or built into the processing unit.
According to an embodiment, the monitoring apparatus may comprise an ocular movement data capturing unit, which according to an embodiment comprises an electrooculography (EOG) capturing unit. The response data i.e. measured data comprises outputted EOG data. EOG capturing unit may comprise at least one (e.g. 1, 2, 3, 4, 5 or more), preferably a plurality of electrodes configured for acquiring electrical activity data from around the subject eye. Where an EEG or EMG capturing unit is present, the EOG capturing unit may share an electrode with the EEG or EMG capturing unit. The electrode(s) may be configured for placement at predetermined positions across the subject's cranial and/or facial region; preferably to the around (e.g. above and below, to left and right of an eye). The electrode(s) may be integrated into a wearable device e.g. a wearable headset. The electrode(s) may be fixed to or detachable from the wearable device. The electrode(s) may be dry-contact electrode(s). The electrode(s) may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The electrode(s) may be reusable or one-time use. The electrode(s) may be integrated into a head-strap or fixing band. The electrode(s) may be integrated into a mask portion of the media renderer. The EOG capturing unit typically includes an amplifier for amplification of the detected signal. Signals are digitized for processing by a digital-to-analogue converter for processing by the processing unit. The digital-to-analogue converter may be separate or built into the processing unit.
According to an embodiment, the monitoring apparatus may comprise an electrodermal activity (EDA) capturing unit. The response data i.e. measured data comprises outputted EDA data. EDA capturing unit may comprise at least one (e.g. 1, 2, 3, 4, 5 or more), preferably a plurality of electrodes configured for acquiring electrical activity data from the subject skin tissue. Where an EEG or EMG capturing unit is present, the EDA capturing unit may share an electrode with the EEG or EMG capturing unit. The electrode(s) may be configured for placement at predetermined positions across the subject's cranial and/or facial region; preferably to the frontal region.
The electrode(s) may be integrated into a wearable device e.g. a wearable headset. The electrode(s) may be fixed to or detachable from the wearable device. The electrode(s) may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The electrode(s) may be reusable or one-time use. The electrode(s) may be integrated into a head-strap or fixing band. The electrode(s) may be integrated into a mask portion of the media renderer. The EDA capturing unit typically includes an amplifier for amplification of the detected signal. Signals are digitized for processing by a digital-to-analogue converter for processing by the processing unit. The digital-to-analogue converter may be separate or built into the processing unit.
According to an embodiment, the EDA capturing unit may be configured for measurement of galvanic skin response. The response data i.e. measured data comprises outputted GSR data. EDA capturing unit may comprise at least one (e.g. 1, 2, 3, 4, 5 or more), preferably a plurality of GSR electrodes configured for acquiring galvanic skin response. Where an EEG or EMG capturing unit is present, the EDA capturing unit may share a localized or reference electrode with the EEG or EMG capturing unit for acquiring galvanic skin response. The electrode(s) may be configured for placement at predetermined positions across the subject's cranial and/or facial region; preferably to the frontal or forehead region. The GSR electrode(s) may be integrated into a wearable device e.g. a wearable headset. The GSR electrodes may be fixed to or detachable from the wearable device. The GSR electrodes may be dry-contact electrode(s). The GSR electrode(s) may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The GSR electrode(s) may be reusable or one-time use. The GSR electrode(s) may be integrated into a head-strap or fixing band. The GSR electrode(s) may be integrated into a mask portion of the media renderer.
According to an embodiment, the monitoring apparatus may comprise an electrocardiogram (ECG) capturing unit. The response data i.e. measured data comprises outputted heart rate or ECG data. ECG capturing unit may comprise at least one (e.g. 1, 2, 3, 4, 5 or more), preferably a plurality of electrodes configured for acquiring electrical activity data from the subject heart. Where an EEG, EMG, or EDA capturing unit is present, the ECG capturing unit may share an electrode with the EEG, EMG, or EDA capturing unit. The electrodes being configured for placement at predetermined positions across the subject's chest, or any other suitable location where the heart ECG data can be captured. The electrodes may be integrated into a wearable device e.g. a wearable headset. The electrodes may be fixed to or detachable from the wearable device. The electrodes may be held in place by gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The electrodes may be reusable or one-time use. An electrode may be integrated into a head-strap or fixing band. An electrode may be integrated into a portion of the media renderer.
According to an embodiment, the monitoring apparatus may further comprise a physiological monitoring unit. The response data i.e. measured data comprises outputted physiological data. The physiological monitoring unit may comprise at least one (e.g. 1, 2, 3, 4 or more) sensor for acquiring subject's physiological data, in particular a component of the physiological data. The physiological data may relate to one or more of the following: pulse rate, heart rate, heart rate variation, blood pressure, respiration rate, respiration rate variability, inhalation pressure, exhalation pressure, brain oxygenation, blood O2 saturation (SpO2), regional and/or central blood O2 saturation, skin conductance, galvanic skin response, body temperature. The physiological data may relate to one or more of the following: respiration rate, respiration rate variability, inhalation pressure, heart rate.
According to an embodiment, the monitoring apparatus may comprise a SpO2 capturing unit. The response data i.e. measured data comprises outputted SpO2 data. SpO2 capturing unit capturing unit may comprise at least one (e.g. 1, 2, 3, 4, 5 or more) sensor(s) configured for capturing SpO2 (blood oxygen saturation) data from the subject. The SpO2 data capturing unit may comprise one or more sensors e.g. photoplethysmogram (PPG) sensor; the sensor is typically optical. A sensor may be placed at temple area and/or forehead area. The sensor may be configured for placement at the forehead and/or temple region. The sensor(s) may be integrated into a wearable device e.g. a wearable headset. The sensor(s) may be fixed to or detachable from the wearable device. The sensor(s) may be dry-contact sensor(s). The sensor(s) may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The sensor(s) may be reusable or one-time use. The sensor(s) may be integrated into a head-strap or fixing band. The sensor(s) may be integrated into a mask portion of the media renderer e.g. so as to place sensor(s) at the forehead and/or temple region. The SpO2 capturing unit capturing unit typically includes an amplifier for amplification of the detected signal. Signals are digitized for processing by a digital-to-analogue converter for processing by the processing unit. The digital-to-analogue converter may be separate or built into the processing unit.
According to an embodiment, the one or more sensors may be integrated into a wearable device e.g. a wearable headset. The one or more sensors may be fixed to or detachable from the wearable device. The one or more sensors may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The one or more sensors may be reusable or one-time use. The one or more sensors may be integrated into a head-strap. The sensors may be integrated into a mask portion of a media renderer as explained in further detail below.
According to an embodiment, the monitoring apparatus may further comprise a body motion tracking unit. The response data i.e. measured data comprises outputted body motion tracking data. The body motion tracking unit may comprise at least one (e.g. 1, 2, 3, 4 or more) motion sensor for acquiring subject's body motion, in particular a component of the body motion tracking data. Examples of motion sensors include a 2- or 3-axis accelerometer, a gyroscope, one or more cameras, magnetic/induction transducers. The body motion includes movements of the head, limb (arms, legs, hands, knee, elbow). The body motion tracking unit may be a head movement tracking unit.
According to an embodiment, the one or more motion sensors may be integrated into a wearable device e.g. a wearable headset. The one or more motion sensors may be fixed to or detachable from the wearable device. The one or more motion sensors may be held in place be gravity, or by a force (e.g. applied by a spring or elastic) or by adhesive. The one or more motion sensors may be reusable or one-time use. The one or more motion sensors may be integrated into a head-strap. The motion sensors may be integrated into a mask portion of the media renderer.
According to an embodiment, the monitoring apparatus may further comprise an eye-tracking unit. The response data i.e. measured data comprises outputted eye tracking data. The eye tracking unit may comprise at least one (e.g. 1, 2, 3, 4 or more) camera for monitoring movement of one or both eyes of the subject. The eye tracking unit may comprise at least one light source (e.g. visible, infrared) configured to illuminate the eye. Captured images may be analyzed using eye tracking software to determine subject's focus of attention, drowsiness, consciousness or other mental states.
According to an embodiment, the one or more cameras may be integrated into a wearable device e.g. a wearable headset. The one or more cameras may be fixed to or detachable from the wearable device. The one or more cameras may be integrated into a mask portion of the media renderer.
According to an embodiment, the monitoring apparatus may further comprise a facial expression capturing unit. The response data i.e. measured data comprises outputted facial expression data—e.g. emotions, nociception. The facial expression capturing unit may comprise at least one (e.g. 1, 2, 3, 4 or more) camera for monitoring facial expressions of the subject. The facial expression capturing unit may comprise at least one light source (e.g. visible, infrared) configured to illuminate the face. Captured images may be analyzed using facial expression recognition software to determine subject's facial expressions and responses, e.g. pain or (dis)comfort. The one or more cameras may be integrated into a wearable device e.g. a wearable headset. The one or more cameras may be fixed to or detachable from the wearable device. The one or more cameras may be integrated into a portion of the media renderer.
According to an embodiment the monitoring apparatus may comprise an EEG capturing unit, an EMG capturing unit, an EDA capturing unit, an ECG capturing unit, a physiological monitoring unit, a head tracking unit, an eye tracking unit and a face capturing unit. The monitoring apparatus may comprise an EEG capturing unit, an EMG capturing unit, a HR capturing unit, and/or a respiratory data capturing unit.
According to a particular embodiment, in which the system is used during a non-pharmacological treatment session, the system may further comprise a media renderer that presents a treatment session to the subject. The treatment session may contain hypnosis and/or other evidence-based psychological and/or mind/body intervention. The media renderer may comprise a screen (e.g. LED, LCD, projector) on which moving images are displayed. The images immerse the attention of the subject and/or control the subject's experience and physiological response. The media renderer may comprise a sound transducer (e.g. earphone, headphone, speaker) to which audio is passed (e.g. music, dialogue, sound effects).
Preferably the media renderer is integrated as a wearable device, e.g. headset. The media renderer may be provided as a virtual reality headset, as an augmented reality headset, or mixed reality headset. Most preferably the media renderer is integrated into a wearable device that provides virtual/augmented/mixed/etc. reality; which typically includes a display or projector, stereo sound (mono, stereo, multidimensional), and head motion tracking sensors (e.g. gyroscopes, accelerometers, structured light systems, etc.). Examples of suitable headsets are those supplied by Oculus (e.g. Oculus Rift, Oculus Go), Pico (e.g. G2 4K, G2 Pro), LG electronics (e.g. LG 360 VR), HTC (e.g. HTC Vive), Samsung (e.g. Samsung Gear VR), Google (e.g. Google Cardboard), Microsoft (Hololens), and other off-the-shelf or customized designs. The media renderer may be expanded by also rendering somatosensory content, such as vibrations (e.g. vibration modules equipped in a seat), and/or olfactory content (e.g. releasing one or more fragrances into the nasal cavity). Optionally, the media renderer may be equipped with a computing unit for executing or playing data, or it may receive data from an external media server (i.e. streaming).
As mentioned previously, the media renderer may be integrated into a wearable device, e.g. headset. The monitoring apparatus may be integrated into the wearable device. One or more electrodes and/or one or more sensors, and/or one or more cameras of the monitoring apparatus may be integrated into the wearable device
An exemplary embodiment of a wearable device is given in
However it is clear that the system and/or wearable device may make use of any other suitable configuration and/or arrangement of EEG electrodes, such as for example devices comprising one or more electrodes, for example two, three, four or more electrodes arranged at one or more scalp locations referred to in the international 10-20 system, or any other suitable device comprising one or more EEG electrodes. It is further also clear that the system and/or wearable device may make use of any other and/or further suitable configuration and/or arrangement of sensors and/or electrodes, such as for example a body temperature sensor, respiratory data sensor, etc.
According to an embodiment, the controller module may be configured for receiving measured data from the monitoring apparatus, and transforming the response data comprising the measured data into one or more of (N)LoA(I)(S), (N)LoP(I)(S), DoS(I)(S), DoD(I), DoH(I) . . . . The evaluation protocol may comprise use of one or more of a mathematical (e.g. statistical) model, trained machine-leaning model, mathematical index, reference data.
According to an embodiment, the controller module may be configured for receiving measured data from the monitoring apparatus, and transforming the response data comprising the measured data into the LoA, which is the level of anxiety as experienced by the subject, the LoPI, which is representing the level of pain as perceived by the subject, and/or a DoSI, DoDI and/or DoHI representing a measure of the non-pharmacological and/or pharmacological modified state of consciousness of the subject, using an evaluation protocol as described above. The evaluation protocol may for example comprise use of one or more of a mathematical (e.g. statistical) model, trained machine-leaning model, mathematical index, reference data.
According to an embodiment, the controller module typically comprises a circuit (e.g. microprocessor) configured to perform processing steps and memory. The controller module may or may not be integrated into a wearable device.
The method may be a computer implemented method.
There is further provided is a computing device or system configured for performing the method as described herein.
There is provided a computer program or computer program product having instructions which when executed by a computing device or system causing the computing device or system to perform the method as described herein.
There is provided a computer readable medium having stored thereon instructions which when executed by a computing device or system cause the computing device or system to perform the method as described herein.
There is provided a data stream which is representative of a computer program or computer program product having instructions which when executed by a computing device or system cause the computing device or system to perform the method as described herein.
The method and system described herein enable the therapist to quantify the patients level of anxiety, the level of pain as consciously perceived by the subject, and optionally a state of consciousness, a hypnotic state, . . . and/or enable optimal and potentially individual titration of initial dosages of analgesics, anesthetics, anxiolytics; . . . hypnotics, and/or optimize pharmacological and/or non-pharmacological sedation (VR therapy titration); and/or provide safer progress by Quantifying, Visualizing, Trending and potentially Predicting the patient's physiological reaction/consciously perceived level of pain during clinical, medical, surgical or therapeutic interventions; and/or increase subject safety; and/or increase subject amnesia of medical intervention.
Also provided is use of a computer-implement method described herein for determining a level of sedation of a subject induced pharmacologically and/or non-pharmacologically. The sedation may for example be for a surgical intervention and/or for example replacing and/or supplementing a pharmacological anesthetic with a non-pharmacological anesthetic.
It is to be understood that this invention is not limited to particular systems and methods or combinations described, since such systems and methods and combinations may, of course, vary. It is also to be understood that the terminology used herein is not intended to be limiting, since the scope of the present invention is determined by the appended claims.
As used herein, the singular forms “a”, “an”, and “the” include both singular and plural referents unless the context clearly dictates otherwise.
The terms “comprising”, “comprises” and “comprised of” as used herein are synonymous with “including”, “includes” or “containing”, “contains”, and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps. It will be appreciated that the terms “comprising”, “comprises” and “comprised of” as used herein comprise the terms “consisting of”, “consists” and “consists of”.
The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within the respective ranges, as well as the recited endpoints.
The term “about” or “approximately” as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/−10% or less, preferably +/−5% or less, more preferably +/−1% or less, and still more preferably +/−0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier “about” or “approximately” refers is itself also specifically, and preferably, disclosed.
Whereas the terms “one or more” or “at least one”, such as one or more or at least one member(s) of a group of members, is clear per se, by means of further exemplification, the term encompasses inter alia a reference to any one of said members, or to any two or more of said members, such as, e.g., any ≥3, ≥4, ≥5, ≥6 or ≥7 etc. of said members, and up to all said members.
All references cited in the present specification are hereby incorporated by reference in their entirety. In particular, the teachings of all references herein specifically referred to are incorporated by reference.
Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.
In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.
Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the appended claims, any of the claimed embodiments can be used in any combination.
In the present description of the invention, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration only of specific embodiments in which the invention may be practiced. Parenthesized or emboldened reference numerals affixed to respective elements merely exemplify the elements by way of example, with which it is not intended to limit the respective elements. It is to be understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the present invention. The following detailed description, therefore, is not to be taken in a limiting sense, and the scope of the present invention is defined by the appended claims.
The inventors have found for the first time a strong association between response data in particular measured data collected from at least one EEG electrode, such as for example at least one of a frontal-EEG electrode, a parietal-EEG electrode and central-EEG electrode and the LoP of the subject and at an association between data from a parietal-EEG electrode and the LoA and an association between a frontal-EEG electrode and a level of modified consciousness, for example during a pharmacological and/or non-pharmacological treatment session to modify the state of consciousness of the subject. For the first time, an objective measure of a level of pain and/or a level of anxiety of the subject can be determined in real time. This is applicable in many situations, for instance, when a subject is undergoing a surgically invasive procedure under pharmacological and/or non-pharmacological sedation or any alternatively useful situations. In particular it is the first time that a combined measurement, by means of such response data is possible of both a LoA, LoP and/or DoS, particularly during non-pharmacological treatments such as for example hypnosis.
State of consciousness refers to a measurement of a subject's wakefulness and/or self-awareness as well as environmental awareness determining the subject's presence sensation, arousability (emotional response) and (physical) responsiveness to an internal or external stimulus or stimuli, characterized by the physiological activity and/or by a neurological signature.
In a specific modified state of consciousness, for example where the level of consciousness is different or modified with respect to a normal awake state, the subject is for example more relaxed, perceives less or no pain, experiences less or no anxiety, is more dissociated, is more prone to suggestions, and/or is optionally sedated. In such a specific modified state of consciousness, subject's cognitive functions may be absorbed in a specific task, and brain processes which usually happen together are separated. The creation of this specific state with reduced or no anxiety experienced by the subject, which is for example a state comprising a higher level of absorption and/or attention to a specific task, a dissociative state, or any other suitable state in which the level of consciousness is different and/or modified with respect to the normal awake state, allows a reduced perception of peripheral stimuli and a subject's modified perception of the self and the self in the environment. According to some embodiments of such a modified state of consciousness, the subject's physiology is usually modified (less involuntary movement i.e. swallowing, limb movement, eye blinking, higher stability of vital signs, larger respiratory patterns and improved oxygenation rates . . . ). In such a specific state with reduced or no experience of anxiety, such as for example a modified state of consciousness, a subject might experience partial or total catalepsy as well as disconnect from the environment (i.e. not hear/respond to verbal command). Senses may be under/overactivated according to requirements. However, according to alternative embodiments of a specific state with reduced or no experience of anxiety, for example involving a modified state of consciousness, a subject may be absorbed into and/or directing its attention to a specific task, or in other words in a state of a higher level of absorption and/or attention. Even further embodiments are possible, in which for example the subject is subjected to for example a mind/body exercise, etc. or any other suitable physiological intervention, in which the subject is subjected to for example a purely psychological treatment, such as for example cognitive behavioural therapy, etc. For example, a subject could be induced into such a specific modified state of consciousness, in which the dissociative state suppresses the experience of anxiety and/or the conscious perception of pain sufficiently so that it is possible to safely undergo a medical intervention, such as for example a surgical intervention, a medical intervention making use of local anaesthetics, etc.
The state of consciousness induced non-pharmacologically can be determined from one or more of a depth of dissociation (DoD) of the subject during the treatment session as discussed later below.
According to an embodiment a treatment session is applied to the subject to modify the state of consciousness of the subject. The treatment session may include one or more of hypnosis and/or other evidence-based psychological and/or mind/body intervention (i.e. non-pharmacological treatment), administration of active pharmacological ingredient (i.e. pharmacological treatment), other treatments (e.g. acupuncture, mechanical treatment, other non-pharmacological treatment). Preferably it comprises hypnosis. The degree to which the state of consciousness of the subject has been modified by hypnosis may be referred to as depth of hypnosis (DoH). The degree to which the state of consciousness of the subject has been modified by hypnosis or any other suitable non-pharmacological treatment and/or optionally by active pharmacological ingredient and optionally by other treatments may be referred to as depth of state (DoS).
In particular a non-pharmacological treatment includes for example hypnosis but also other treatments which are used to potentialize the hypnosis session and/or improve dissociation/a modified level of absorption, a modified state of consciousness/therapeutic impact, mind-body interventions, etc. It is clear that alternative non-pharmacological treatment sessions are possible. Examples of pharmacological treatment sessions may comprise administration of an anesthetic, analgesic and/or anxiolytic. Examples of anesthetics include:
Examples of anxiolytics include: Barbiturates, Benzodiazepines, Carbamates, Antihistamines, Opioids, Antidepressants, Sympatholytics, etc.
As used herein the term “subject” refers to the beneficiary of the therapeutic session. The “user” refers to a person or persons operating the method or system. The user may be a care provider such as a physician, or medical assistant, or non-medical assistant (e.g. friend, relative, helper) of the subject. In some circumstances, the user may be the subject, for instance, where a treatment is self-administered at home.
Hypnosis is one way of inducing an altered state of consciousness in a subject. The hypnosis therapy may be medical (clinical) hypnosis therapy, or home hypnosis therapy, or hypnosis therapy provided in any care or wellness environment. The hypnosis therapy may be extramural hypnosis therapy that is not provided in a care institution (i.e. not provided in a clinic, hospital, care center). While immersed in the altered state of consciousness, the subject's self-perception and the peripheral awareness are affected, changing the subject's experience of his/her sensation, perception, and thoughts, and making the subject prone to follow suggestions. Subject is absorbed and dissociated from reality.
An embodiment of a hypnotic treatment session typically comprises 4 sequential phases as exemplified in
The subject becomes prone to suggestive control during the (ii) phase, during which time the subject may be sedated, induced to relax, etc. Afterwards the subject is returned to a normal state of a consciousness by passing the (iii) and (iv) phases.
The phases are described in detail below, namely:
The hypnotic treatment session may be delivered by a hypnotist, more preferably it is presented using a media renderer such as a virtual reality head set for a fully immersive effect as described below in more detail. A stored hypnotic treatment session may be played through the media renderer, the content of the treatment session may be specific to the treatment goals.
While in such an altered state of consciousness, for example induced by treatments or activities inducing a higher level of absorption and/or attention, induced by hypnosis, or induced by any other suitable treatments, or alternatively any other suitable treatment not necessarily involving an altered state of consciousness, the subject can better manage anxiety and/or pain as well as other symptoms/issues. The subject can for example undergo medical interventions (e.g. invasive procedures) in the absence or with a lower dose of a pharmacological (anesthetic/analgesic/anxiolytic) agent.
| Number | Date | Country | Kind |
|---|---|---|---|
| 20191014.8 | Aug 2020 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2021/072568 | 8/13/2021 | WO |
