Method for detecting cognitive disorders in white rats

FIELD: medicine.

SUBSTANCE: single-step testing of white rats is carried out in an open field facility. The total length of locomotion, sniffing, and sitting actions as well as the number of upright postures and freezing acts are recorded. Prognostic coefficients F1 and F2 are determined by formulas and compared. If F2 is more than F1, cognitive disorders are stated in experimental animals, and if F1 is more than F2, the above are stated to be absent. That is followed by calculating a prognostic index (PI), which is used to determine an intensity of the cognitive disorders: low, moderate and high.

EFFECT: method enables detecting the presence of the cognitive disorders in the rats by using the values of motor and investigatory activity and anxiety.

2 cl, 2 tbl, 4 ex

 

The invention relates to medicine, specifically to experimental medicine, and can be used to study the cognitive performance of white rats in norm and at a pathology of various origins.

Known methods for performance evaluation of cognitive functions by testing experimental animals in tests "radial maze, maze Morris", "T-maze" [2, 5]. The main characteristic of these methods is the long period of training animals, an average of from 8 to 15 days and more.

The closest way to study the cognitive animal performance (prototype) is a method of studying the peculiarities of higher nervous activity, consisting in the development of conventional drinking reflex in the T-shaped maze [3]. However, this method is rather time-consuming and of a conditioned reflex in animals requires a long period of time (10 days). When planning experimental studies arises the need for a preliminary assessment of the cognitive capacities of animals, which will allow you to expand or narrow the set of experimental methods of research in the future.

The problem solved by this invention is to develop a way of identifying cognitive impairment in white rats, allowing to reduce the complexity and time is of atrati on the experiment.

This object is achieved in that conduct testing of white rats in open field: for 3 minutes record the following indicators: total duration acts "locomotion", "obnyukhivanie", "sitting"; the number of vertical columns; the number of acts "freezing". Expect prognostic factors according to the formula:

F1=-20,94+0,28×a1+0,20×a2+0,28×a3+1,23×a4+0,47×a5,

F2=-28,02+0,03×a1+0,39×a2+0,39×a3+4,15×a4+2,08×a5,

where F1and F2- prognostic factors, a1- the total duration of the act of "obnyukhivanie" (C), a2- the total duration of the act of "sitting" (C), a3- the total duration of the act of "locomotion" (C), a4- the number of vertical racks, a5the number of acts "freezing".

If F1more F2make a conclusion about the absence of cognitive impairment in experimental animals, and when F2more F1- make a conclusion about the presence of cognitive impairment in experimental animals and determine their severity using a prognostic index (PI), which is calculated by the formula:

PAnd=11+e-(F2-F1),

where e is the base of natural logarithm (2,72...).

If PI is more than 0.5 and less of 0.64, the severity of cognitive impairment is defined as low, if PI is more of 0.65 and less 0,84 medium, when PI is more of 0.85 as high.

New in the present invention is that the test results in the "open field" in terms of motor and orienting-exploratory activity and anxiety it is possible to detect the presence of these individuals impaired cognitive functions such as learning ability and spatial orientation, as well as violation of the processes of working memory. Moreover, when calculating the prognostic index is determined by the severity of cognitive impairment in animals.

The authors are not found in the analyzed literature way of identifying cognitive impairment in white rats on the performance of their behavior in the open field.

Comparison of the invention with existing methods of assessment of cognitive abilities of white rats showed that for the first time proposed to establish the presence and assess the degree of cognitive impairment in rats by recording their behavior in open-field test.

Thus, the claimed invention meets the criteria of the invention of "Novelty" and "Inventive step", as it is the main way is not necessary for the expert from the prior art. The present invention meets the criterion of "Industrial applicability" because it can be used in experimental medicine, physiology, pathological physiology, pharmacology to identify the cognitive animal performance and when planning the design of experimental research.

In numerous studies the method of "open field" is used to assess the condition of the Central nervous system of animals [1, 4]. Recorded in this test the performance behavior characterized by orienting-investigative behavior (obnyukhivanie), motor activity (locomotion, sitting) and anxiety (freezing). Orienting-investigative activity, as a manifestation of the higher nervous activity, is one of the most important types of behavior by which animals acquire knowledge about the environment and demonstrate reasoning. In pharmacology increasing locomotor and orienting-exploratory activity of the animals of the experimental groups when compared to control indicates the presence of a possible neuroprotective effect of the studied compounds [4, 5]. At the same time to assess these metrics cognitive functions of animals, such as working memory, learning ability and spatial orientation, it is necessary to conduct to olitely studies using standard techniques, such as a conditional reflex active and passive avoidance (passive avoidance reaction and AVOIDANCE), T-maze, radial maze, water maze Morris, etc.

The experiment was carried out on outbred rats in the amount of 140 individuals weighing 180-240 g, obtained from own nursery Angarsk branch of the fgbi "wsnt EB" SB RAMS. Testing white rats was performed using a setup open field, representing a circular arena with a diameter of 97 cm, height of walls 42 cm, diameter of the holes in the floor - 2, see the Observation was made within 3 minutes with the registration of the following indicators: total duration acts "locomotion", "obnyukhivanie", "sitting"; the number of vertical columns; the number of acts "freezing".

The obtained results were processed using the SPT Statistica 6.0. (criteria Mann-Whitney, discriminant analysis, persons No. AXXR004E642326FA).

Table 1 allows us to draw conclusions regarding the statistical significance of each of the dependent variables included in the model is constructed. In this case, all the studied variables have a highly significant influence on the dependent variable (p<0,05). The significance level for the model was 0.0001.

Table 1
Indicators informative paragraph is Isakov, included in the linear discriminant functions
A variable in the modelLambda WilksFp-level
The total duration of Abdugani"0,4244,640,00001
The total duration of the "sitting"0,4141,370,0001
The total duration of "locomotion"0,2712,010,001
The number of vertical racks0,2610,180,0026
The number of act "rising"0,24of 7.360,0091

To confirm the cognitive status of white rats conducted an assessment of working memory, learning ability, spatial orientation and navigation learning when tested in the radial maze and a Morris water maze.

Table 2 presents the results of the test animals in the "open field", "radial is the labyrinth, a Morris water maze (data are presented as medians and interquartile scale).

Table 2
Performance testing of animals in the "open field", "radial maze, water maze Morris, Me (LQ; UQ)
IndicatorsOptions research
Group # 1 acute prenatal hypoxia"Group # 2 "chronic prenatal hypoxia"Group # 3 "toluene"Group # 4 "control"
Open field
The total duration of obnyukhivanie"46 (38; 51,5)31 (25; 37)*32,5 (28; 39)52 (42; 71)
The number of vertical racks4 (2; 6)2,5 (1; 4)*5 (4; 6)4 (3; 6)
The total duration of locomotion" 64 (21; 79)*77 (62; 95)97 (88; 106)*73 (61; 92)
The total duration of the "sitting"46 (23; 85)*43 (23; 56)*5 (4; 6)16 (7,5; 26)
The number of acts "rising"2 (1; 4)*1 (1; 2)*1 (0; 2)1 (0; 1)
Radial maze
The number of working memory errors (last test session)0 (0; 0,5)0,5 (0; 1)*0 (0; 0,5)0 (0; 0)
The number of consecutively visited hoses (last test session)3,5 (3; 4)2 (3; 3)*3 (3; 4)4 (3; 4)
Water maze Morris
The latent period of search for a hidden platform68,5 (40,5; 78,0)*59,5 (46,3; 7,8)* 51,3 (37-73,5)*42,7 (31,8; 61,5)
Note: * - the differences are statistically significant compared to control at p<0.05; number of animals in each group - 35

Example 1.

White rat exposed to chronic prenatal hypoxia. During examination in open field test revealed numeric values:

a1- the total duration of the act of "obnyukhivanie" - 32,5,

a2- the total duration of the act of "sitting" - 23,

a3- the total duration of the act of "locomotion" - 109.7 from,

a4- the number of vertical columns is 0,

a5the number of acts "rising" - 1.

The calculated prognostic factors F1and F2by the formulas:

F1=-20,94+0,28×32,5+0,20×23+0,28×109,7+1,23×0+0,47×1=23,63,

F2=-28,02+0,03×32,5+0,39×23+0,39×109,7+4,15×0+2,08×1=27,26.

F2more F1PI=0,97.

Conclusion: the presence of a given individual cognitive impairment high degree. The testing results of the water and the radial maze showed that this animal indicators of cognitive abilities significantly reduced compared with the control group. Thus, the latent period locate a hidden platform in the water maze in a given individual was 61,9 C, considerably higher than the average of the control group (427 (31,8; 61,5) C. When learning in the radial maze, the number of working memory errors (2 errors) in the last training session, this individual was higher than control group 0 (0; 0). The number of consecutively visited backed by arms of the maze in a given individual (2) was significantly lower than the control group 4 (3; 4) (table.2).

Example 2.

The white rat, subjected to inhalation exposure to toluene. During examination in open field test revealed numeric values:

a1- the total duration of the act of "obnyukhivanie" - 55,

a2- the total duration of the act of "sitting" - 19,5 with,

a3- the total duration of the act of "locomotion" - 79,7 with,

a4- the number of vertical racks - 1,

a5the number of acts "rising" - 3.

The calculated prognostic factors F1 and F2 by the formulas:

F1=-20,94+0,28×55+0,20×19,5+0,28×79,7+1,23×1+0,47×3=23,09;

F2=-28,02+0,03×55+0,39×19,5+0,39×79,7+4,15×1+2,08×3=23,12.

F2more F1PI=0,51.

Conclusion: the presence of a given individual cognitive impairment low severity. The examination of water and radial mazes confirmed the presence of cognitive impairment from this animal. This individual was observed the increase of the latent period locate a hidden platform in a water maze, which amounted to 57.2 from and far above the average indicators of the group I control (42,7 (31,8; 61,5) C. When learning in the radial maze obvious violations of working memory have been identified (table.2).

Example 3.

The white rat, subjected to acute prenatal hypoxia. During examination in open field test revealed numeric values:

a1- the total duration of the act of "obnyukhivanie", 57 p,

a2- the total duration of the act of "sitting" - 23,

a3- the total duration of the act of "locomotion" - 85,

a4- the number of vertical racks - 1,

a5the number of acts "rising" - 2.

The calculated prognostic factors F1and F2by the formulas:

F1=-20,94+0,28×57+0,20×23+0,28×85+1,23×1+0,47×2=25,34,

F2=-28,02+0,03×57+0,39×23+0,39×85+4,15×1+2,08×2=24,56.

F2more F1PI=0,68.

Conclusion: the presence of a given individual cognitive impairment moderate severity. When tested in water and the radial maze were confirmed by the results obtained. This animal was observed the increase of the latent period locate a hidden platform in the water maze (69,1) and the number of working memory errors when learning in the radial maze (3) compared with the average performance of the control group (table.2).

Example 4.

White rat from the control group. During examination in open field test revealed numeric values:

a1- the sum of the Naya duration of the act of "obnyukhivanie" - 59,2 with,

a2- the total duration of the act of "sitting" - 27,9 with,

a3- the total duration of the act of "locomotion" - 73.2 C,

a4- the number of vertical columns is 0,

a5the number of acts "rising" - 1.

The calculated prognostic factors F1 and F2 by the formulas:

F1=-20,94+0,28×59,2+0,20×27,9+0,28×73,2+1,23×0+0,47×1=21,95,

F2=-28,02+0,03×59,2+0,39×27,9+0,39×73,2+4,15×0+2,08×1=15,68.

F1more F2.

Conclusion: there are no cognitive impairment in a given individual. Testing in water and radial mazes confirmed the results obtained. Violations ability to navigation to learning and change processes spatial and working memory were observed. Indicators of cognitive abilities of the species - the latent period locate a hidden platform (35), the number of working memory errors (0) and the number of consecutively visited reinforced sleeve radial maze in the last test session (4) were within the average of the control group (table.2).

Thus, the proposed method is less time-consuming and requires less time to experiment.

Literature

1. Training in a Morris water maze females and male rats exposed to hypoxia in different periods of prenatal development period / O. I. Wateva [and other] // Journal of evolutionary biokhimiia physiology. - 2005. - T. 41, No. 6. - S. 530-533.

2. Samostroev M. A. Experimental models of behavior / M. A. Samostroev, D. L. Warm, And. And. Tyurenkov // science. - 2009. No. 2. - S. 140-152.

3. Pershina O. C., Suslov N. And., Litvinenko C. I., Popov, Etc., the Effects of an extract from the aerial parts of Scutellaria baicalensis Georgi on the production and reproduction of conventional drinking reflex in intact animals and animals with alcohol intoxication // Plant resources. - 2000. - Vol.2. - S. 120-124.

4. Ivanov D., the Relationship between the metabolism of collagen and behavior of rats in the open-field test / A., Ivanov, V., Podkovkin // Successes of modern natural science. - 2010. No. 5. - S. 16-20.

5. Podkovkin Century, the Influence of short-term isolation on the behavior of rats in the open-field test / Century, Podkovkin, D., Ivanov / Successes of modern natural science. - 2009. No. 6. - S. 12-16.

1. How to detect cognitive impairment in white rats, which consists in studying the behavior of animals, wherein the animals are examined in open-field test, within three minutes, record the total duration acts "Obrucheva", "sitting", "locomotion", the number of act "rising" and the number of vertical pillars, determine prognostic factors F1and F2formula:
F1=-20,94+0,28×a1+0,20×a2+0,28×a3+1,23×a4+0,47×a5,
F2=-28,02+0,03×a1+0,39×a2 3+4,15×a4+2,08×a5,
where F1and F2- prognostic factors, a1- the total duration of the act of "obnyukhivanie" (C), a2- the total duration of the act of "sitting" (C), a3- the total duration of the act of "locomotion" (C), a4- the number of vertical racks, a5the number of acts "freezing", and when F1 is greater F2, make a conclusion about the absence of cognitive impairment in experimental animals, and if F2 is greater F1 ascertain the presence of cognitive impairment in experimental animals.

2. The method according to p. 1, characterized in that in the presence of cognitive impairment in experimental animals to assess the degree of their intensity according to the formula:
PAnd=11+e-(F2-F1),
where PI is the prognostic index,
e - base of natural logarithm (2,72...),
F1and F2- prognostic factors
when PI is more than 0.5 and less than 0.64 severity of cognitive impairment is defined as low, if PI is more of 0.65 and less 0,84 medium, when PI is greater 0,85 - like high.



 

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12 dwg, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and can be used for the correction of gynoid obesity. That is ensured by typing an eating disorder to be psychologically corrected. A diet therapy is prescribed with a caloric value determined by reducing a patient's habitual daily average caloric requirement per a percent equal to the patient's body weight index. That is combined with a low-carbohydrate diet with the carbohydrate content reduced to 40-60 g/day for 2 weeks. That is followed by prescribing a low-fat diet with the fat content reduced to 40-60 g/day for 10 weeks with avoiding fast assimilated carbohydrates having a glycaemic index of more than 50. The diet therapy cycle is repeated. That is combined with graduated aerobic physical exercises with no weight and resistance for the muscle groups of the lower body. There are also performed muscle-strengthening load exercises for the muscle group of the upper body promoting muscle fatigue. Between and after the graduated physical exercises, there are performed prolonged aerobic physical loads at least 5 days a week for 40-60 minutes. That is combined with the drug-free procedures aiming at improving the regional blood flow, increasing gluteofemoral and lower extremities muscle tonus. The low-fat diet involves administering health aids from the group of intestinal membrane-bound alpha-glucosidase and pancreatic alpha-amylase inhibitors. The course of the obesity correction involves administering catechin-containing preparations or biologically active additives. From the second month from the beginning of the obesity correction, the patient's face is exposed to full-spectrum natural or artificial light at intensity of not less than 2,000 lux for 1-2 hours a day simultaneously or alternatively with the physical loads.

EFFECT: method provides the effective weight reduction in the patients with gynoid obesity with reducing side effects.

5 cl, 8 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, forensic medicine, diagnostic measurements, including in investigative practice. An interactive psychophysiological testing (PPT) involves presenting a person being tested test questions, determining, analysing the psychogenesis parameters with using the person's physical parameter sensors, indicating the results and estimating. The test questions are typed as follows: first-version questions Q1, second-version questions Q2, neutral questions N. The questions Q1 and Q2 have an alternative meaning and equal power and are characterised by an equal presentation time, a consistency of comparing the questions according to the alternative versions, a minimised subjective personal effect of the PPT test expert by sound colour and level, an unconscious emotional support on the person's question perception, as well as an identity of putting the questions to be compared, their length and a fixation of the meaningful word and/or word combination in similar segments of both questions to be compared. The test is put in accordance with a concatenation as follows X:0→C,…,C→Q11.Q21→N→ →Q21.Q22→N→…→Q1n.Q2n→N, wherein X is a person's identification index; 0 is a non-estimated zero question; C is a question relieving an expectation stress; Q1i is the first-version question, wherein i=1, 2,…, n; Q2i is the second-version question, wherein i=1, 2,…, n; N is a neutral question; n is a number of specific circumstances of the event or action; ":", "→", "." are devisors. The questions are put taking into account the staging of the tested event, including the confirmed facts or data only and excluding the expert's conjectures or versions. The results are used to state one of the two alternative versions and to estimate the respective status of the person being tested. The psychogenesis is determined and analysed with using a polygraph, while putting the questions of the two alternative versions, indicating and processing the PPT data are conducted with a computer with relevant software.

EFFECT: method provides higher information value, accuracy, reliability, objectiveness of the PPT results as compared to the previously known tests up to 90-95% with avoiding the distortion and ambivalence of the results.

5 cl, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to cardiology, and can be used for detecting individuals with a risk of the hypertensive disease. Regulatory relative risk of the disease, as well as standard multivariable personality test scores are determined for 10 years in apparently healthy males by the core examination, and a relation curve is plotted with using the scores: neurotic overcontrol - over 45 points, pessimistic attitude - over 49 points, rigidity - over 58 points, anxiety - over 67 points, and individuality - over 50 points. The scale scores are determined in the patient, and the curve is used to evaluate an individual relative risk of the hypertensive disease for the following 10 years in the patient.

EFFECT: method enables fast evaluation of the risk of this disease directly at the doctor's in a specific patient and detecting the individuals with the high risk of the hypertensive disease for the purpose of taking timely preventive measures.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to carrying out psychophysiological studies, e.g. analysing the individual's psychophysiological responses, and can be used in medical purposes, advertising industry, functional diagnostics, education science, psychology, judicial practice and criminal science. Current normal baseline physiological parameters of a person being tested are recorded by means of a polygraph. That is followed by forming a number of independent conceptual blocks of visual information to be presented to the person being tested on a demonstration monitor of an eye motion recording device to assess the subjective significance of the visual information. An eye position, motion, a path of motion and fixation lengths are recorded; zones of preferential passive concentration fixation are recorded. The derived data are analysed to select a primary gaze zone and to determine a gaze length. Visual information elements drawing much attention are determined; when presenting the visual information by means of the eye motion recording device, synchronous measurements of the physiological parameters of the person being tested are taken by using blood pressure contact sensors, photoplethysmographic measurement, galvanic skin response, upper and lower respiration pressure transducers, tremor sensors connected in turn to a sensor unit of a polygraph recording and processing the signals supplied from the sensors. The physiological parameter variations of the person being tested are assessed by comparing an excursion of their current values from the pre-recorded baseline values; the physiological parameter variations of the person being tested specific for perceiving the subjectively significant information and being simultaneous with the primary gaze moments are used to detect the visual information elements having the most emotional impact on the person being tested. Thereafter, the qualitative emotional assessment is ensured by distributing the detected visual information elements according to the pre-set parameters into a sequence with opposite coordinates in the form of verbal antonyms with using a semantic differential method.

EFFECT: method enables providing more accurate psychophysiological studies related to assessing the information perception, assessing the exposure of the visual information and its significance for the individual by recording the physiological parameters and using the semantic differential method.

FIELD: medicine.

SUBSTANCE: score rating of a medical history, neurological and psychiatric findings, and psychophysiological testing is carried out with assigning 0 points with no burdened medical history, focal symptoms and neurological clinical pattern of diseases, psychic diseases, unfavourable social environment observed. If observing one or two signs of mentioned above, 1 point is assigned. If more than three signs of mentioned above are observed, 2 points are assigned. A Luscher colour test is used to assess an autogenous norm, a vegetative and personal balance, a working capacity, a heteronomous or autonomous nature and a concentricity and excentricity. Emotionality, anger, joy and emotion control are measured by an emotional excitement scale. A degree of stress load is assessed by an Anderson life event scale. A simple hand-eye response is used to assess a functional level of the system, a response stability and a level of functionality. That is followed by detecting deviant trends by assigning 0, 1 or 2 points for each parameter depending on its value with all the points further summed up and no deviant trends in the behaviour diagnosed in case of 0 to 13 points collected; with a borderline case at 14-17 points; deviant trends in the behaviour at 18-26 points.

EFFECT: method enables objective assessment of the individual's behaviour by studying the neurological and psychiatric states and the psychological and psychophysiological findings.

6 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to gastroenterology, and can be used for providing the higher clinical effectiveness in the patients suffering dyspepsia syndrome combined with overweight. The method involves measuring an anxiety level (HARS) and a depression level (HDRS) according to Hamilton rating scales, assessing nutritional status by bioimpedancemetry, a degree of manifestation of sleep disorders, measuring glucose, testing glucose tolerance, immunoreactive insulin, cholesterol, high-density lipoprotein (HDLP), triglyceride in venous blood. If the patient is observed to suffer dyslipidemia and impaired glucose tolerance or variations of immunoreactive insulin, the preparation Dibikor is administered in a dose of 500 mg a day for three months. The patient suffering dyslipidemia and both of the disorders stated above requires administering Dibikor 1000 mg a day for three months. If the patient suffers an overweight with a body weight index falling within the range of 27 to 29.9 standard units and an active cell mass (ACM) percentage of 45 to 55 per cent as shown by bioimpedancemetry, the preparation Dietressa is administered in a dose of 1 tablet 3-4 times a day for three to six months. If the patient suffers an overweight with a body weight index falling within the range of 27 to 29.9 standard units and an active cell mass (ACM) percentage of 45 to 55 per cent as shown by bioimpedancemetry, the preparation Dietressa is administered in a dose of 2 tablet 3-4 times a day for three to six months. If the patient suffers mild and moderate sleep disorders and shows an emotive type of eating behaviour combined with mild affective disorders, the anti-depressant Valdoxane in a single dose of 25 mg a day for the night for two weeks. The course of the disease is followed by the anxiety and depression levels two weeks after the beginning of the therapy, with the positive progression of the diseases, the 25mg dose of Valdoxane remains unchanged to the end of the therapeutic course for three to six months. If no progression is exhibited, the dose is to be increased to 50 mg a day, and the therapy is continued from four to eight months. If the patient suffers severe sleep disorders and shows an emotive type of eating behaviour combined with moderate affective disorders, the anti-depressant Valdoxane in a single dose of 50 mg a day for the night for two to three months.

EFFECT: in each specific case, the method enables providing faster reduction of the clinical symptoms, including body fat weight reduction and active cell mass and water normalisation, normalising circadian rhythms of the vegetative balance, as well as prolonging the remission.

3 tbl, 2 ex

FIELD: physics.

SUBSTANCE: method employs a device in the form of a stand with two telescopic posts with induction sensors. A metal sphere moves on a channel at an angle of 5° and when the sphere passes the first induction sensor, an electrical signal is generated which triggers an electric stopwatch, and when the sphere passes the second induction sensor, the stopwatch stops. The second induction sensor is turned off and the test subject stops the stopwatch at the moment of seeing the sphere cross the finishing line by pressing a button. The reading of the stopwatch is the visual-motor reaction time. From 50 to 100 tests are carried out, which include recording all attempts by a test subject, including premature pressing of the button, constructing a personal bar chart for each test subject and selecting a standard criterion for evaluating and comparing the visual-motor reaction.

EFFECT: method increases accuracy and objectivity of evaluating visual-motor reaction to movement of an object in space.

4 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: method involves forming signals as tests requiring solution. The tests are shown with frequency changed proportionally to the frequency they are solved. The number of tests is set to be the same in the cases of recovered and tired state. General amount of time spent for finding solution for given number of tests and the number of tests having right solutions are determined in each state. Mental fatigue degree is evaluated from relative change of mean time needed for finding the right test solution using a relationship like (Tm.r- Tm.t)100%/Tm.t, where Tm.t = Tsum.t/Kr.t, Tm.r = Tsum.r/Kr.r, Tm.t is the time spent for finding the right answer in tired state, Tm.r is the time spent for finding the right answer in recovery state, Tsum.t is the total time spent to solve given number of tests in tired state, Tsum.r is the total time spent to solve given number of tests in recovered state, Kr.t is the number of right answers to the tests in tired state, Kr.r is the number of right answers to the tests in recovered state.

EFFECT: reliable estimation of fatigue degree.

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