CN112205989B - Screening system for panic disorder patients - Google Patents

Screening system for panic disorder patients Download PDF

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CN112205989B
CN112205989B CN202011007464.7A CN202011007464A CN112205989B CN 112205989 B CN112205989 B CN 112205989B CN 202011007464 A CN202011007464 A CN 202011007464A CN 112205989 B CN112205989 B CN 112205989B
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CN112205989A (en
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李量
丁宇
曲天书
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Abstract

The invention discloses a panic disorder patient screening system which comprises a signal playing unit, a signal acquisition unit and a signal processing platform. Compared with the traditional startle reflex prepulse inhibition detection system, the prepulse stimulation played by the signal playing unit uses single-syllable or double-syllable voice signals for the first time, wherein the single-syllable or double-syllable voice signals comprise fear emotion voice, common negative voice and neutral word voice, and semantic processing on the prepulse stimulation signals is introduced for the first time; indexes calculated by the signal processing platform not only comprise the amplitude of the startle reflex and the prepulse inhibition thereof, but also give screening guidance suggestions of the panic disorder by investigating the generalization effect of fear emotion attention and space attention on PPI regulation. The method can be used for quickly, conveniently and objectively screening the panic disorder aiming at the major social events.

Description

Screening system for panic disorder patients
Technical Field
The invention belongs to the technical field of biology and new medicines, and particularly relates to a panic disorder screening means taking generalization of attention regulation of preplanning pulse inhibition as a key technical paradigm, which comprises a related technology of taking negative vocabulary audio as a stimulating material and taking orbicularis oculi myoelectricity as a key signal.
Background
A sudden occurrence of a strong sensory stimulus triggers a systemic reflex activity in the human or animal called startle reflex, which is the protective action of the human or animal against the threatening stimulus, but interrupts the ongoing cognitive activity, interfering with normal cognitive processing. However, if a weak stimulus not enough to cause a startle reflex (i.e., a pre-pulse stimulus) is present before the strong stimulus, suppression of the latter startle reflex occurs, which is called pre-pulse inhibition of the startle reflex (PPI). PPI is a widely used sensorimotor gating measurement model, wherein the core technology is to collect electromyographic signals of the orbicularis oculi muscles through a non-invasive acquisition device, process and identify the difference value of the peak value of the electromyographic signals caused by startle stimulation when the anterior pulse stimulation exists or not by a computer and carry out quotient with the peak value when the anterior pulse stimulation does not exist, and then convert the difference value into the output of the computer to finish the measurement of sensorimotor gating.
In a reverberant environment, when the time delay is short enough, a direct sound emitted by a sound source and a reflected sound thereof are perceptually fused, that is, a listener can only hear the direct sound and cannot perceive the reflected sound. This is called an auditory priority effect, and when the same sound is played to the subject using two earphones, the subject can be made to perceive only the sound of the leading earphone by changing the time difference between the two earphones. If two earphones play the target sound and the masking sound simultaneously, but the left earphone target sound leads and the right earphone masking sound leads, the listener perceives the target sound to be on the left and the masking sound to be on the right (or vice versa), and subjective spatial separation occurs. The existing sound space separation technology is objective sound separation, namely two loudspeakers play different sounds, and the separation mode causes different long-term pressure ratios of sound signals entering two ears and changes of perceptual density of sound images. The paradigm of subjective spatial separation used in the present invention can make the subject pay attention to the target sound signal spatially selectively without changing the characteristics (such as spectral characteristics, intensity and sound density) of the sound signal, thereby improving the recognition of the target sound. After the current impulsive sound is fear-conditioned to have ecological significance, the presence of the prepulse sound also draws the attention of the listener, and the presence of a masking noise disturbs the attention of the prepulse sound. In addition, the subjective spatial separation between the prepulse sounds and the masking noise based on the auditory precedence effect may enhance the spatially selective attention to the prepulse sounds, so that the PPI is further enhanced on the basis of the enhancement of the fear conditioning. The panic disorder patients have a higher amplitude of the startle reflex, a loss of gating function and show a generalized phenomenon of fear-provoking stimuli and events, i.e. some stimuli and events that are not directly related or ambiguous and are not yet fear-provoked in the normal healthy population, but a significant fear-emotional response in the panic disorder patients. Currently, an effective early diagnosis method for panic disorder is lacked, and the invention mainly screens and intervenes in panic disorder patients through the attention-regulated generalization of the inhibition of the pre-startle reflex pulse.
Disclosure of Invention
The invention aims to establish a screening system for patients with panic disorder based on subjective spatial separation and fear generalization by utilizing attention regulation of prepulse inhibition before startle reflex.
The technical scheme of the invention is as follows:
a panic disorder patient screening system based on attention regulation generalization of preplanning pulse suppression comprises a signal playing unit, a signal acquisition unit and a signal processing platform. Compared with the traditional startle reflex prepulse inhibition detection system, the invention has the technical innovation that the prepulse stimulation played by the signal playing unit uses single-syllable or double-syllable voice signals for the first time, the single-syllable or double-syllable voice signals comprise fear emotion voice, common negative voice and neutral word voice, and semantic processing on the prepulse stimulation signals is introduced for the first time. Another technical innovation of the method is that the indexes calculated by the signal processing platform not only comprise the amplitude of the startle reflex and the prepulse inhibition thereof, but also give a screening guidance suggestion of the panic disorder by observing the generalization of fear emotional attention and spatial attention on PPI regulation (corresponding to the part c-f in the signal processing platform).
Specifically, the method comprises the following steps:
and the signal playing unit is used for playing the sound analog signals of the startle stimulus, the prepulse stimulus and the background noise.
And the signal acquisition unit is used for acquiring myoelectric signals of orbicularis oculi muscles of a tested person and sending the myoelectric signals to the signal processing platform.
And the signal processing platform is used for calculating the frightened reflex amplitude and the PPI value and giving a conclusion.
Further, the startle played by the signal playing unit is white noise (100dB SPL) with a duration of 40 ms.
Further, the prepulse stimulus played by the signal playing unit is a double syllable speech signal (70dB SPL) which is read by young women with single voice. It can be divided into: (1) negative voice signals (which can be combined with facts such as 'virus' and 'pneumonia') related to frightening are called frightening prepulse for short; (2) negative voice signals (such as 'gauze' and 'garbage') irrelevant to panic are called negative prepulse for short; (3) the Chinese word speech (such as "tree" and "building") is called neutral pre-pulse for short.
Furthermore, the prepulse stimulus played by the signal playing unit is divided into three cases of leading 3ms at the left side, leading 3ms at the right side and simultaneously presenting at both sides.
Further, the background noise played by the signal playing unit is a background masking speech stimulus, and is composed of meaningless sentences (60dB SPL) read by voices of two young women, and the sentences are divided into 3ms ahead on the left side or 3ms ahead on the right side.
Further, the direction of the background noise is consistent with the leading direction of the pre-pulse sound (both the background noise and the pre-pulse sound are left leading or right leading), which is the subjective spatial coincidence, and the direction of the leading is inconsistent (the background noise is left leading or right leading, which is the front pulse stimulates the headphones on both sides to play at the same time), which is the subjective spatial separation (as shown in fig. 1).
Further, the signal acquisition unit sends the myoelectric signal of the orbicularis oculi muscle of the subject to the signal processing platform.
Further, the signal processing platform takes the difference (uV) between the maximum peak value and the baseline value in the time window range of 20ms-120ms after the startle stimulus is played as the amplitude H of the startle reflex under all conditions. The effective startle reflection amplitude that has proven to be detectable in this time range. The baseline value is the mean value of the electromyographic signals within the first 5ms after the data start to be collected, and the maximum peak value is the absolute value of the maximum electromyographic value generated by startle reflex.
Further, the value of the inhibition of the pre-startreflex pulse (PPI) is calculated according to the average of the startreflexive amplitudes H1 under several pre-pulse stimulation conditions and the average of the startreflexive amplitudes H2 under the startreflexive stimulation only condition, and the calculation formula is as follows:
PPI (%) - (H2 mean-H1 mean)/(H2 mean) × 100%
a) The signal processing platform obtains the maximum peak value and the baseline value within the time window range of 20ms-120ms after the startle stimulation is played according to the electromyographic signals under the condition of playing the startle stimulation, and then the difference between the maximum peak value and the baseline value is used as the startle reflection amplitude H under the condition of playing the startle stimulationSurprise thatThe condition is played for 5 times, and H is taken for 5 timesSurprise thatTo obtain HSurprise thatMean value;
b) the signal processing platform obtains the maximum peak value and the baseline value within the time window range of 20ms-120ms after the startle stimulation is played according to the electromyographic signals under the condition of the pre-startle pulse stimulation, and then the difference between the maximum peak value and the baseline value is used as the startle reflex amplitude H under the condition of the pre-startle pulse stimulationPanic attackThe condition is played for 5 times, and H is taken for 5 timesPanic attackTo obtain HPanic attackMean value; the PPI induced by the pre-panic pulse is then calculated and labeled PPIPanic attack＝(HSurprise thatMean value-HPanic attackMean value)/HSurprise thatMean value is multiplied by 100%;
c) the signal processing platform obtains the maximum peak value and the baseline value within the time window range of 20ms-120ms after the startle stimulation is played according to the electromyographic signals under the condition of the negative pre-pulse stimulation, and then the difference between the maximum peak value and the baseline value is used as the startle reflection amplitude H under the condition of the negative pre-pulse stimulationNegativity of reactionThe condition is played for 5 times, and H is taken for 5 timesNegativity of reactionTo obtain HNegativity of reactionMean value; the PPI induced by the negative pre-pulse is then calculated and labeled PPINegativity of reaction＝(HSurprise thatMean value-HNegativity of reactionMean value)/HSurprise thatMean value is multiplied by 100%;
d) the signal processing platform obtains the maximum peak value and the baseline value within the time window range of 20ms-120ms after the startle stimulation is played according to the electromyographic signals under the condition of neutral pre-pulse stimulation, and then the difference between the maximum peak value and the baseline value is used as the startle reflection amplitude H under the condition of neutral pre-pulse stimulationNeutral propertyThe condition is played for 5 times, and H is taken for 5 timesNeutral propertyTo obtain HNeutral propertyMean value; the PPI induced by the neutral prepulse is then calculatedMarked PPINeutral property＝(HSurprise thatMean value-HNeutral propertyMean value)/HSurprise thatMean value is multiplied by 100%;
e) the signal processing platform calculates the startle enhancement amplitude PPIPanic attack-PPINeutral propertyNegative enhancement amplitude is PPINegativity of reaction-PPINeutral propertyIf the frightening enhancement amplitude is larger than the set threshold, performing step f), otherwise, judging that the emotional attention effect of the subject is not obvious;
f) if the negative enhancement amplitude is larger than the set threshold value, the emotional attention of the tested person is determined to be generalized, and a conclusion that the possibility of panic disorder of the tested person is high is output.
Further, PPIs induced by the panic pre-pulse, the negative pre-pulse and the neutral pre-pulse are labeled PPI respectivelyPanic attack、PPINegativity of reactionAnd PPINeutral propertyThe extent of the increase in panic is PPIPanic attack-PPINeutral propertyNegative enhancement amplitude is PPINegativity of reaction-PPINeutral propertyIf the panic enhancing amplitude is larger than 10%, the emotional attention enhancing effect of the testee is obvious, the next calculation is carried out, otherwise, the testee with the unobvious emotional attention effect is judged, and other diagnosis means are suggested.
Further, if the negative enhancement range is also larger than 10%, it is determined that the subject has generalized emotional attention, and a conclusion "the subject has a high possibility of panic disorder" is output.
Further, the panic enhancement amplitude and the negativity enhancement amplitude are compared respectively under two conditions of subjective spatial separation and coincidence of background noise and prepulse stimulation, and a result is output to be referred and judged by an experimenter or a doctor.
Compared with the prior art, the invention has the following positive effects:
based on the auditory priority effect, the invention uses the paradigm of subjective spatial separation to enable the subject to pay attention to the target sound signal spatially selectively on the premise of not changing the characteristics (such as spectral characteristics, intensity, sound density and the like) of the sound signal, thereby improving the identification of the target sound and finally introducing attention to the regulation of PPI. The present invention relates to the early diagnosis and intervention of panic disorder. The present invention does not require oral reporting and diagnoses from the subject's increased startle reflex, decreased PPI, attention to the generalization of PPI modulation. Is expected to play an important role in patients with language disorders and deliberately concealed conditions.
Drawings
Fig. 1 is a graph of the spatial relationship between pre-pulse stimulation and masking stimulation. Wherein the note represents the pre-pulse stimulus, the wavy line represents the background noise, the relative size of the graph represents the leading direction (rather than the sound intensity), when the front pulse stimulus is played simultaneously by the two-sided earphone, the subject will perceive the pre-pulse stimulus as coming from the front, and the background noise as coming from the left or right, thereby generating subjective spatial separation.
FIG. 2 is a diagram showing the relationship between units according to the present invention.
Detailed Description
The present invention is described in further detail below with reference to specific examples.
1. Test preparation
In the preparation stage, the subject sits in a quiet environment (anechoic or shielded room is most desirable) and is fitted with electrodes (electrode 1. 10mm below the pupil; electrode 2: outside electrode 1 near the eye angle; ground electrode on the mastoid). After the electrodes were mounted, the sound was played for the trial through the headphones, while recording of EMG activity in the 500ms time window after the startle or pre-pulse stimulation occurred started.
2. Test flow
The subject first accommodated for background noise for 5 minutes. PPI testing is then performed. In general, the test was divided into two trials: prepulse stimulation + startle stimulation and only startle stimulation was played. For the pre-pulse + startle stimulation trials, 120ms after the onset of the pre-pulse stimulation, startle stimulation occurred, and the next trial occurred after an average of 15s (11-19 s). The pre-pulse stimulation can be divided into 2 types (subjective spatial separation, subjective spatial coincidence, see fig. 1) according to the subjective spatial relationship formed by the pre-pulse stimulation and the background noise. PPI tests are divided into two groups of tests in the leading direction of background noise. In the first set of tests, the background noise left headphone was leading by 3ms and the sound image of the noise appeared on the left side due to the precedence effect. The prepulse stimulation leads the left 3ms or the left and the right earphones are played simultaneously, so that two subjective feelings can be formed: the current pulse stimulation and the background noise are left leading for 3ms, the testee can subjectively perceive that the front pulse stimulation and the background noise come from the same direction, namely subjective space coincidence, on the contrary, when the background noise is left leading for 3ms, and the front pulse stimulation is played simultaneously by the left loudspeaker and the right loudspeaker, the testee can subjectively perceive that the front pulse stimulation and the background noise come from different directions, namely subjective space separation. Six prepulse stimuli (startle × split, negative × split, neutral × split, startle × coincidence, negative × coincidence, neutral × coincidence) + startle stimuli and trials presenting startle stimuli only were each presented randomly 5 times for a total of (6+1) × 5 ═ 35 trials, all trials being played randomly. In the second set of tests, the background noise right headphone leads by 3ms, and the noisy sound image appears on the right side due to the precedence effect. The prepulse stimulates the right earphone to lead 3ms or the left and right earphones to play simultaneously, and other conditions are the same as the first group of tests. The order of the two tests was randomized between subjects, with the test period taking approximately 20 minutes.
3. Data acquisition
As shown in fig. 2, the signal acquisition unit transmits the electromyographic signal of the orbicularis oculi muscle of the subject to the signal processing platform, and the startle reflex peak amplitude is defined as the difference (uV) between the maximum amplitude and the baseline amplitude within the time window of 20ms-120 ms. The effective startle reflection amplitude that has proven to be detectable in this time range. The PPI calculation and determination process is as described above, and the experimenter or the physician can take comprehensive consideration of the data.
4. Quality control
Eliminating invalid test times: (1) the maximum peak is located in the trial within 20ms after the appearance of the startle stimulus; (2) the maximum peak value is larger than 5 times of the mean value of the EMG reaction amplitude; (3) if the baseline value is more than 10uV in the waveform observation of the electromyographic signals, the obvious excessive head movement or spontaneous eye movement is considered to occur.
The present invention is not limited to the above embodiments, and those skilled in the art can implement the present invention in other various embodiments according to the disclosure of the present invention, so that all designs and concepts of the present invention can be changed or modified without departing from the scope of the present invention.

Claims (5)

1. A panic disorder patient screening system is characterized by comprising a signal playing unit, a signal acquisition unit and a signal processing platform; wherein
The signal playing unit is used for playing sound analog signals of startle stimulation, prepulse stimulation or background noise; the prepulse stimulation is divided into the following components according to the content: (1) negative voice signals related to frightening, short pre-frightening pulses; (2) negative voice signals irrelevant to panic, called negative pre-pulses for short; (3) chinese word speech, called neutral prepulse for short; the signal playing unit firstly plays background noise for setting time length and then carries out PPI test on the frightened and reflected prepulse inhibition value; wherein the startle pre-pulse inhibition value PPI test is 7 trial random plays: 6 prepulse stimulation + startle stimulation tests and a test of only playing startle stimulation; the prepulse stimulation is divided into two modes of subjective space separation and subjective space superposition; different kinds of pre-pulse stimulation include frightened x separation, negative x separation, neutral x separation, frightened x coincidence, negative x coincidence, neutral x coincidence;
the signal acquisition unit is used for acquiring myoelectric signals of orbicularis oculi muscles of a tested person and sending the myoelectric signals to the signal processing platform;
the signal processing platform is used for calculating the startle reflex amplitude and the startle reflex prepulse inhibition value PPI of the testee according to the received electromyographic signals and giving a screening conclusion of the testee according to the calculation result; wherein:
a) the signal processing platform obtains the maximum peak value and the baseline value within the time window range of 20ms-120ms after the startle stimulation is played according to the electromyographic signals under the condition of playing the startle stimulation, and then the difference between the maximum peak value and the baseline value is used as the startle reflection amplitude H under the condition of playing the startle stimulationSurprise thatThe condition is played for a plurality of times to obtain HSurprise thatMean value;
b) the signal processing platform obtains the maximum peak value and the base line value within the time window range of 20ms-120ms after the startle stimulation is played according to the electromyographic signals under the condition of the pre-startle pulse stimulation, and then the maximum peak value and the base line value are obtainedThe difference between the large peak and baseline values is taken as the amplitude H of the startle reflex under the condition of the pre-startle pulse stimulationPanic attackThe condition is played for a plurality of times to obtain HPanic attackMean value; the prepulse inhibition value PPI of the startle reflex induced by the prepulse is then calculated, marked PPIPanic attack＝(HSurprise thatMean value-HPanic attackMean value)/HSurprise thatMean value is multiplied by 100%;
c) the signal processing platform obtains the maximum peak value and the baseline value within the time window range of 20ms-120ms after the startle stimulation is played according to the electromyographic signals under the condition of the negative pre-pulse stimulation, and then the difference between the maximum peak value and the baseline value is used as the startle reflection amplitude H under the condition of the negative pre-pulse stimulationNegativity of reactionThe condition is played for a plurality of times to obtain HNegativity of reactionMean value; the prepulse inhibition value PPI of the startle reflex induced by the negative prepulse is then calculated and labeled PPINegativity of reaction＝(HSurprise thatMean value-HNegativity of reactionMean value)/HSurprise thatMean value is multiplied by 100%;
d) the signal processing platform obtains the maximum peak value and the baseline value within the time window range of 20ms-120ms after the startle stimulation is played according to the electromyographic signals under the condition of neutral pre-pulse stimulation, and then the difference between the maximum peak value and the baseline value is used as the startle reflection amplitude H under the condition of neutral pre-pulse stimulationNeutral propertyThe condition is played for a plurality of times to obtain HNeutral propertyMean value; the prepulse inhibition value PPI of the startle reflex induced by the neutral prepulse is then calculated and labeled PPINeutral property＝(HSurprise thatMean value-HNeutral propertyMean value)/HSurprise thatMean value is multiplied by 100%;
e) the signal processing platform calculates the startle enhancement amplitude PPIPanic attack-PPINeutral propertyNegative enhancement amplitude is PPINegativity of reaction-PPINeutral propertyIf the frightening enhancement amplitude is larger than the set threshold, performing step f), otherwise, judging that the emotional attention effect of the subject is not obvious;
f) if the negative enhancement amplitude is larger than the set threshold value, the emotional attention of the tested person is determined to be generalized, and a conclusion that the possibility of panic disorder of the tested person is high is output.
2. The system of claim 1, wherein the startle stimulus played by the signal playing unit is white noise; the prepulse stimulation played by the signal playing unit is a double-syllable voice signal read by young women with single voice; the background noise played by the signal playing unit is background masking speech stimulation.
3. The system of claim 2, wherein the startle stimulus played by the signal playing unit is white noise with a duration of 40 ms; the prepulse stimulation played by the signal playing unit is divided into three conditions of leading the left side by 3ms, leading the right side by 3ms and simultaneously presenting the two sides; the background noise played by the signal playing unit is divided into a left side leading 3ms or a right side leading 3 ms.
4. A system according to claim 1, 2 or 3, wherein the magnitude of the panic enhancement and the magnitude of the negative enhancement are compared under two conditions of subjective spatial separation and coincidence of background noise and pre-pulse stimulation, respectively.
5. The system of claim 1, wherein the signal playback unit performs PPI testing of the pre-pulse suppression value of startle reflex in two groups according to the leading direction of background noise; in the first group of tests, the background noise left earphone leads Tms, the pre-pulse stimulates the left earphone to lead Tms or the left earphone and the right earphone play simultaneously; different prepulse stimulation, startle stimulation and test times only presenting startle stimulation are presented at random for N times respectively, and all test times are played at random; in the second set of tests, the background noise right earphone leads Tms, the pre-pulse stimulation right earphone leads Tms or the left and right earphones play simultaneously, and other conditions are the same as those in the first set of tests.
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