Evaluation method, evaluation device, and program

Abstract

To provide an evaluation method, an evaluation device, and a program capable of improving efficiency of learning and reducing an evaluation period for a cognitive function.SOLUTION: A determination unit 213 makes a correct answer determination when a movement of an object animal 2 at a position associated with a correct answer is detected a first number of times of twice or more continuously. Alternatively, the determination unit makes an incorrect answer determination when a movement of the object animal 2 at a position associated with an incorrect answer is detected a second number of times of twice or more continuously. When the correct answer determination is made, a supply device 32 supplies a reward to the object animal, and when the incorrect answer determination is made, the object animal is caused to stand by, or unpleasant stimulation is supplied. Determination results are accumulated in a secondary storage device 23, and evaluation data 232 is generated.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present invention relates to an evaluation method, an evaluation apparatus, and a program.

Background Art

[0002] Cognitive function tests using experimental animals are widely conducted in preclinical drug development for mental or neurological diseases, etc., or in brain science research. A test that makes experimental animals perform an operant learning task, which is a type of cognitive function test, is known to be able to examine complex cognitive functions (for example, Patent Document 1, Non-Patent Document 1).

[0003] The animal learning support apparatus described in Patent Document 1 supplies a reward to a test animal when the operation performed by the test animal on the operation unit is correct when a predetermined stimulus is given to the test animal in the cage. It is explained that in this way, the test animal can be made to learn using various patterns of tasks in a state where it is not restrained and can move freely.

[0004] Non-Patent Document 1 discloses a method of repeating original learning in which a correct figure and an incorrect figure are displayed and a reward is supplied when the correct figure is selected to measure the flexibility of cognitive function, and reversal learning in which the correct figure and the incorrect figure are swapped.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Documents

[0006]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] Tests of the flexibility of cognitive functions that repeatedly perform original learning and reversal learning of operant learning tasks are considered to be highly reliable and reproducible. On the other hand, when this test is used for efficacy tests in preclinical trials of drug discovery, etc., there is a problem that it takes a long time until the correct response rate of operant learning reaches a certain level or more, and the test takes a long time.

[0008] The present invention has been made in view of the above circumstances, and an object thereof is to provide an evaluation method, an evaluation device, and a program that can improve the efficiency of learning and shorten the evaluation period of cognitive functions or learning functions.

Means for Solving the Problems

[0009] (Evaluation Method) The evaluation method described in this specification is a determination step of determining a correct answer when the action of the target animal at a position associated with the correct answer is detected continuously for a first number of times or more, or determining an incorrect answer when the action of the target animal at a position associated with the incorrect answer is detected continuously for a second number of times or more; a supply step of supplying a reward or aversive stimulus according to the determination result of the determination step, and preferably, further includes an evaluation data generation step of accumulating the determination result of the determination step to generate evaluation data.

[0010] For example, the evaluation method described in this specification further includes a display step of simultaneously displaying a correct figure and one or more incorrect figures in two or more display areas of a display device, and in the determination step, a correct answer may be determined when contact of the target animal at a position corresponding to the correct figure is detected continuously for the first number of times, or an incorrect answer may be determined when contact of the target animal at a position corresponding to any one of the one or more incorrect figures is detected continuously for the second number of times.

[0011] When the evaluation method described in this specification includes a display step, it further includes a contact detection step of detecting contact of the target animal at positions corresponding to the correct figure and the one or more incorrect figures, and in the determination step, a correct answer may be determined when contact at a position corresponding to the correct figure, which is a correct action, is detected continuously for the first number of times in the contact detection step, and an incorrect answer may be determined when contact at a position corresponding to any one of the one or more incorrect figures, which is an incorrect action, is detected continuously for the second number of times in the contact detection step.

[0012] The evaluation data may include a correct answer rate for all the determination results for the determination results of the determination step for a predetermined number of times or more or the determination results of the determination step for a plurality of times within a certain period of time.

[0013] The evaluation data may include information indicating the cognitive function or learning function of the target animal derived based on the correct answer rate or the time change of the correct answer rate.

[0014] The evaluation data may include a determination result of reversal learning when the figure set for the correct figure and any one of the one or more incorrect figures are swapped with each other.

[0015] ​The evaluation data may include information indicating the flexibility of the cognitive function or learning function of the target animal, which is derived based on the correct answer rate for all the determination results of the above-described determination steps for a predetermined number of times of two or more times or the determination steps for a plurality of times within a certain period of time regarding the reverse learning, or the time change of the correct answer rate.

[0016] In the determination step, when the contact of the target animal at a position corresponding to any one of the one or more incorrect figures is detected continuously for the second number of times, a determination of an incorrect answer is made, and a light color may be displayed in the display area where the correct figure or the incorrect figure was displayed.

[0017] The first number of times and the second number of times are predetermined numbers of times according to the type of the target animal, and the first number of times and the second number of times may be the same number of times as each other.

[0018] The evaluation data generated after administering a drug to a model animal or a wild-type animal with a low cognitive function or learning function is compared with the evaluation data generated for the same animal or an animal of the same species as the model animal or the wild-type animal before administering the drug, and a drug evaluation step of evaluating the influence of the drug on the cognitive function or learning function may be further provided.

[0019] (Evaluation device) The evaluation device described in this specification A determination unit that makes a determination of a correct answer when the action of the target animal at a position associated with the correct answer is detected continuously for the first number of times of two or more times, or makes a determination of an incorrect answer when the action of the target animal at a position associated with the incorrect answer is detected continuously for the second number of times of two or more times, A supply device that supplies a reward or supplies an aversive stimulus according to the determination result of the determination unit.

[0020] (Program) The program described in this specification Causes a computer When the movement of the target animal at the position associated with the correct answer is detected continuously for the first number of times or more than two times, a correct answer determination is made, or when the movement of the target animal at the position associated with the incorrect answer is detected continuously for the second number of times or more than two times, an incorrect answer determination is made by a determination unit. A supply instruction unit that supplies a reward or supplies an aversive stimulus according to the determination result of the determination unit. It functions as a storage unit that stores the determination result of the determination unit as evaluation data.

Effect of the Invention

[0021] According to the present invention, the learning efficiency can be improved and the evaluation period of the cognitive function or the learning function can be shortened.

Brief Description of the Drawings

[0022]

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Mode for Carrying Out the Invention

[0023] Embodiments of the present invention will be described with reference to the drawings. Note that the present invention is not limited by the following embodiments and drawings. In the following embodiments, expressions such as "having", "including", or "containing" also include the meaning of "consisting of" or "composed of".

[0024] (Embodiment 1) The evaluation method according to the present embodiment is a method for evaluating the cognitive function or learning function of a target animal by having the target animal perform an operant learning task. The operant learning task in the present embodiment is a task of graphic discrimination learning for discriminating graphics. FIG. 1 is a block diagram showing an example of the hardware configuration of an evaluation apparatus 1 using the evaluation method according to the first embodiment.

[0025] As shown in FIG. 1, the evaluation device 1 consists of an information processing device 20 and an animal chamber 30. On one side of the inner wall of the animal chamber 30, a touch panel 31 is provided, and further, a supply device 32 for supplying food pellets is provided at a position away from the touch panel 31 of the animal chamber 30.

[0026] The information processing device 20 is an arbitrary computer installed with programs such as graphic discrimination learning evaluation processing, and may be a general-purpose information processing terminal such as a personal computer, a smartphone, or a tablet-type terminal, or a dedicated terminal. The information processing device 20 includes, for example, as shown in FIG. 1, a processor 21, a primary storage device 22, a secondary storage device 23, a communication interface 24, and an input unit 25.

[0027] The processor 21 of the information processing device 20 consists of, for example, a CPU (Central Processing Unit), and by executing the programs stored in the secondary storage device 23, executes each process including the graphic discrimination learning evaluation process. The primary storage device 22 is a memory capable of reading and writing data at high speed, such as a RAM (Random Access Memory), and temporarily stores programs, image data, etc. read from the secondary storage device 23 for the arithmetic processing executed by the processor 21. The secondary storage device 23 is a large-capacity storage device, composed of a flash memory or the like, and stores programs, setting values, image data, etc. of the processes executed by the processor 21.

[0028] The communication interface 24 is an interface for transmitting and receiving data with the touch panel 31 and the supply device 32. The communication method of the communication interface 24 is arbitrary, and for example, wireless communication such as wireless LAN or short-range wireless communication or wired communication such as USB is performed. The input unit 25 receives the operation of the operator and outputs the input signal to the processor 21. The input unit 25 consists of, for example, input buttons, a keyboard, a pointing device, etc.

[0029] Figure 2 is a schematic diagram showing the animal chamber 30. The animal chamber 30 shown in Figure 2 has a touch panel 31 and a supply device 32, and is a chamber that surrounds the outer periphery with the touch panel 31 as one side. The target animal 2 can move freely within the animal chamber 30. In Figure 2, among the outer peripheral surfaces of the animal chamber 30, the surfaces other than the touch panel 31 are omitted.

[0030] The display device 311 of the touch panel 31 is an arbitrary display device that displays the image sent from the information processing device 20, and is, for example, a liquid crystal display or an organic EL (Electro-Luminescence) display. The image displayed by the display device 311 is, as shown in Figure 2, an image in which two figures used for figure discrimination learning are arranged side by side on the left and right. That is, two figures are respectively displayed in two predetermined display areas 313 and 314 of the display device 311. The touch sensor 312 of the touch panel 31 is arranged on the front surface of the display device 311, and outputs a detection signal when the contact of the target animal 2 is detected in the display areas 313 and 314 of the display device 311.

[0031] On the front surface of the touch panel 31, a black plastic plate having two windows is installed, and the positions of the two windows generally coincide with the display areas 313 and 314 respectively. The size of the window, that is, the size of the two display areas 313 and 314, is, for example, 6 cm in length and 6 cm in width. The target animal 2 can touch the screen only through the two windows arranged on the left and right. That is, the touch sensor 312 can detect that it has touched one of the positions corresponding to each of the two figures.

[0032] The supply device 32 provided in the animal chamber 30 is a device that supplies food pellets as a reward, and supplies a predetermined amount of food pellets to the food dish 322 for the correct actions in succession for two or more first times of the target animal 2. The supply device 32 and the food dish 322 are preferably located on the opposite side of the touch panel 31. The animal chamber 30 may further include a water bottle provided so that the target animal 2 can freely drink water. Also, a speaker may be provided inside or on the outer periphery of the animal chamber 30. In that case, the animal chamber 30 may be provided in a soundproof box.

[0033] By executing the program of the graphic discrimination learning evaluation process stored in the secondary storage device 23, the processor 21 functions as a graphic acquisition unit 211, a display control unit 212, a determination unit 213, and a supply instruction unit 214 as shown in FIG. 3. FIG. 3 is a functional block diagram showing a functional configuration example of the evaluation device 1.

[0034] The graphic acquisition unit 211 selects and acquires an image of a pair of graphics from the graphic images 231 stored in the secondary storage device 23, and outputs it to the display control unit 212. More specifically, a plurality of pairs of images of corresponding graphics are stored in the secondary storage device 23. The graphics are, for example, pattern graphics as shown in FIG. 2. In the present embodiment, one of the images of the corresponding graphics is set as the correct graphic, and the other is set as the incorrect graphic. The graphic acquisition unit 211 acquires a pair of graphics that have been pre-selected or randomly selected based on the operation of the operator from the graphic images 231 stored in the secondary storage device 23, and outputs it to the display control unit 212.

[0035] The display control unit 212 displays the correct graphic in one of the display areas 313 and 314 arranged on the left and right that has been designated in advance, and displays the incorrect graphic in the other. Also, the display control unit 212 outputs information indicating the display area of the correct graphic or the incorrect graphic to the determination unit 213.

[0036] The determination unit 213 makes a correct answer determination when it continuously detects the movement of the target animal 2 (preferably, the contact of the target animal 2 at the position corresponding to the correct figure, for example, the contact of the target animal 2 in the display area where the correct figure is displayed) at the position corresponding to the correct figure for 2 or more first times. Further, the determination unit 213 makes an incorrect answer determination when it continuously detects the movement of the target animal 2 (preferably, the contact of the target animal 2 at the position corresponding to the incorrect figure, for example, the contact of the target animal 2 in the display area where the incorrect figure is displayed) at the position corresponding to the incorrect figure for 2 or more second times. In the present embodiment, a case will be described where the determination unit 213 makes a correct answer determination when it continuously detects the contact of the target animal 2 in the display area where the correct figure is displayed twice, and makes an incorrect answer determination when it continuously detects the contact of the target animal 2 in the display area where the incorrect figure is displayed twice.

[0037] First, when the contact sensor 312 detects the contact of the target animal 2 with the touch panel 31, the determination unit 213 acquires information indicating which of the display areas 313 and 314 the detected contact position is in. When the display area where the contact is detected matches the display area where the display control unit 212 displays the correct figure, the determination unit 213 determines that the correct action has been performed. On the other hand, when the display area where the contact is detected matches the display area where the display control unit 212 displays the incorrect figure, the determination unit 213 determines that the incorrect action has been performed.

[0038] When the determination unit 213 determines that the correct action has been performed twice in a row, it outputs the correct answer determination result to the secondary storage device 23, which is the storage unit, and adds it to the evaluation data 232. On the other hand, when the determination unit 213 determines that the incorrect action has been performed twice in a row, it outputs the incorrect answer determination result to the secondary storage device 23, which is the storage unit, and adds it to the evaluation data 232. The evaluation data 232 accumulated in the storage unit in this way may include statistical data such as the correct answer rate calculated from the determination results and the time change of the correct answer rate.

[0039] The determination unit 213 outputs the determination result to the display control unit 212 and the supply instruction unit 214. When the determination is a correct answer, the display control unit 212 turns off the graphics in all the display areas, and the supply instruction unit 214 instructs the supply device 32 to supply food pellets. The target animal 2 eats the food pellets supplied to the food dish 322. In this way, the target animal 2 repeatedly experiences that a reward in the form of food pellets is given when it performs the correct action twice in a row, learns the action that can obtain the reward, and intentionally performs the correct action twice in a row.

[0040] The operation of the evaluation device 1 configured as described above will be described with reference to the flowchart of FIG. 4. FIG. 4 is a flowchart of the graphic discrimination learning evaluation process executed by the processor 21 of the information processing device 20.

[0041] The target animal 2 is an arbitrary animal used in the behavior experiment, for example, a mouse. In the present embodiment, the case where a mouse is used as the target animal 2 will be described. The mouse, which is the target animal 2, is placed in the animal chamber 30 and performs the task of graphic discrimination learning. In order to enhance the motivation of the mouse to perform the task, food restriction may be imposed on the mouse during the task execution period. The animal chamber 30 is preferably provided in a soundproof box at a constant temperature in order to eliminate the influence of other environmental factors. The temperature is maintained at, for example, 23 ± 1°C.

[0042] The graphic discrimination learning evaluation process shown in the flowchart of FIG. 4 is performed on a mouse that has been trained in advance. As the prior training, first, habituation training is performed to make the mouse get used to the flow of food pellet supply. Food pellets are placed in the food dish 322 and fed to the mouse to let it remember the relationship between the food dish 322 and the food pellets. Furthermore, a beep sound is emitted from the speaker 323 at the timing of feeding. The mouse eats the food pellets supplied together with the beep sound repeatedly, and remembers that the food pellets are supplied together with the beep sound over a period of 1 day to 1 week, typically over several days.

[0043] After training, shaping is performed to make the mouse learn the process of supplying food pellets when it touches a figure. Specifically, the process of supplying food pellets when the mouse's nose tip, body, forelimb, etc. touch the figure displayed on the touch panel 31 is repeated. Here, at the timing of supplying the food pellets, the beep sound used for training is also sounded. First, the shaping where all the figures in the display area are turned off and food pellets are supplied when there is one contact is performed over 1 day to 1 week, typically over several days. Next, the shaping where all the figures in the display area are turned off and food pellets are supplied when there are two contacts is performed. As a result, the mouse learns the relationship that food pellets are supplied when it touches the figure displayed on the touch panel 31 twice over 1 day to 1 week, typically over several days.

[0044] For the mouse that has completed the prior training, this evaluation is started by the figure discrimination learning evaluation process shown in the flowchart of FIG. 4. First, the processor 21 designates a pair of figures from the figure images stored in the secondary storage device 23 based on the operation of the operator or randomly, and also designates the display areas for displaying the correct figure and the incorrect figure respectively (step S101). More specifically, in step S101, the display area for displaying the correct figure and the display area for displaying the incorrect figure are designated among the display areas 313 and 314 existing at the positions of the windows arranged on the left and right. The figure acquisition unit 211 acquires the pair of correct figure and incorrect figure designated in step S101.

[0045] Thereafter, with the trained mouse in the animal chamber 30, the display control unit 212 displays a pair of figures in the two display areas 313 and 314 of the display device 311 (step S102: display step). Also, the display control unit 212 passes the information of the display areas 313 and 314 where the correct figure or the incorrect figure is displayed to the determination unit 213.

[0046] Specifically, as shown in FIGS. 5 and 6, the display control unit 212 causes the correct figure and the incorrect figure to be respectively displayed in the display areas 313 and 314 specified in step S101, so that a pair of figures can be visually recognized from two windows. FIG. 5(a) is a diagram showing the movement of the mouse when the correct action is performed, and FIG. 5(b) is a diagram showing the state in which food pellets are given to the mouse as a reward when the correct action is performed twice in a row. FIG. 6(a) is a diagram showing the movement of the mouse when the incorrect action is performed, and FIG. 6(b) is a diagram showing the state in which no reward is given to the mouse when the incorrect action is performed twice in a row. FIGS. 5 and 6 show the case where the left side of the two figures is the correct figure and the right side is the incorrect figure.

[0047] When the contact sensor 312 detects the contact of the mouse, the determination unit 213 acquires information on the contacted display area from the contact sensor 312 and determines whether the correct action has been performed (step S103). As shown in FIG. 5(a), when the contact of the mouse is detected in the display area 313 where the correct figure is displayed (contact detection step), the determination unit 213 determines that the correct action has been performed. Further, as shown in FIG. 6(a), when the contact of the mouse is detected in the display area 314 where the incorrect figure is displayed (contact detection step), the determination unit 213 determines that the incorrect action has been performed.

[0048] When it is determined that the correct action has been performed on the figure displayed in step S102 (step S103: Yes), the display control unit 212 displays the same figures as those displayed in step S102 as the correct figure and the incorrect figure in the same display areas 313 and 314, respectively (step S104: display step).

[0049] When it is determined that the correct action has been performed on the figure displayed in step S104 (step S105: Yes), since the correct action has been performed twice in a row, it is determined as a correct answer (step S106: determination step). Then, as shown in FIG. 5(b), a beep sound is emitted from the speaker 323, the display control unit 212 turns off the figures in all the display areas, and the supply instruction unit 214 causes the supply device 32 to supply food pellets as a reward (step S107: supply step). Thereby, the mouse can eat the food pellets.

[0050] When it is determined that an incorrect action has been performed on the figure displayed in step S102 or step S104 (step S103 or step S105: No), the display control unit 212 displays the same figures as those displayed in step S102 as the correct figure and the incorrect figure in the same display areas 313 and 314, respectively (step S108).

[0051] When it is determined that an incorrect action has been performed on the figure displayed in step S108 (step S109: No), since the incorrect action has been performed twice in a row, it is determined as an incorrect answer (step S110: determination step). When it is determined as an incorrect answer, the supply instruction unit 214 only outputs a buzzer sound with a lower pitch than the beep sound from the speaker 323 as shown in FIG. 6(b), does not give a supply instruction, and waits for a predetermined time (step S111). At this time, the figures in all the display areas are turned off. The mouse hears the buzzer sound and waits in a state where it cannot eat the food pellets.

[0052] When it is determined by the determination unit 213 that the correct action has been performed on the figure displayed in step S108 (step S109: Yes), the process returns to step S104. Thereafter, the processes of steps S104, S105, S108, and S109 are repeated. When it is determined that the correct answer has been given due to the correct action being performed twice in a row (step S105: Yes) (step S106), a reward is supplied (step S107). When it is determined that the answer is incorrect due to the incorrect action being performed twice in a row (step S109: No) (step S110), the system waits (step S111).

[0053] After the reward is supplied in step S107 or after waiting in step S111, the determination unit 213 adds a record of the correct or incorrect answer to the evaluation data 232 in the secondary storage device 23 (step S112: evaluation data generation step). Thereafter, if there is no end operation by the operator (step S113: No), the process returns to step S101. If there is an end operation by the operator (step S113: Yes), the process ends. Hereinafter, the series of processes from step S101 to step S112 may also be referred to as a trial.

[0054] If it is determined as incorrect in step S105 and determined as correct in step S109, the figure display in steps S104 and S108 and the correctness determination in steps S105 and S109 will be repeated, but an upper limit may be set for the repetition time. In this case, the determination unit 213 may determine that it is an incorrect answer when the upper limit time is exceeded and add the determination result to the evaluation data 232.

[0055] The evaluation data 232 may include statistical data calculated from the determination results accumulated by performing the determination steps (steps S106 and S110) any number of times two or more times, or the determination results accumulated by performing the determination steps multiple times within a certain period of time. The statistical data is, for example, the correct answer rate which is the ratio of correct answer determinations for all the accumulated determination results, or the time change of the correct answer rate. The number of times of the determination steps for calculating the correct answer rate is not particularly limited as long as it gives the target evaluation result, but can be set, for example, to 20 to 200 times, 50 to 150 times, or 100 times. Also, when performing the determination steps within a certain period of time to calculate the correct answer rate, the time can be set to 10 minutes to 1 hour, 20 minutes to 40 minutes, or 30 minutes. Also, taking the trial of the set number of times or time as one session, the time change of the correct answer rate when performing one session per day may be calculated. Information indicating the cognitive function or learning function of the target animal 2 can be derived from the time change of the correct answer rate.

[0056] When the correct answer rate is high, it is evaluated that the cognitive function or learning function is high, and when the correct answer rate is low, it is evaluated that the cognitive function or learning function is low. When evaluating the cognitive function or learning function using the time change of the correct answer rate as an index, for example, when the increase rate of the correct answer rate is high, it is evaluated that the cognitive function or learning function is high, and when the increase rate of the correct answer rate is low, it is evaluated that the cognitive function or learning function is low. The evaluation of the high or low correct answer rate or increase rate can be based on the correct answer rate or increase rate obtained by implementing the evaluation method according to this embodiment for the same target animal 2 or different target animals 2 at different times or / and under different conditions, or can also be based on the correct answer rate or increase rate obtained by implementing the same evaluation method for different target animals 2 under different conditions at the same time.

[0057] For example, when examining the cognitive function or learning function of a model animal with specific gene modification or a diseased model animal as the target animal 2, the correct answer rate or increase rate is measured using the model animal and a wild-type animal of the same species, and the cognitive function or learning function of the model animal is evaluated based on the level of the correct answer rate or increase rate of the model animal relative to the correct answer rate or increase rate of the wild-type animal. That is, when the correct answer rate or increase rate is higher compared to the wild-type animal, it can be evaluated that the cognitive function or learning function has improved, and when the correct answer rate or increase rate is lower compared to the wild-type animal, it can be evaluated that the cognitive function or learning function has declined.

[0058] Also, using the evaluation method according to the present embodiment, by comparing the evaluation data generated after administering a drug to a model animal or a wild-type animal with low cognitive function or learning function with the evaluation data generated for the same animal before administering the drug or a wild-type animal of the same species without drug administration, the effect of the drug on the cognitive function or learning function can also be evaluated (drug evaluation step). When the correct answer rate or increase rate of the animal after drug administration is higher compared to the animal before drug administration or without drug administration, it is determined that the drug has the effect of improving the cognitive function or learning function, and when the correct answer rate or increase rate of the animal after drug administration is equal to or lower compared to the animal before drug administration or without drug administration, it can be evaluated that the drug does not improve (or decreases) the cognitive function or learning function.

[0059] In the evaluation method according to the present embodiment, the effect of determining a correct answer when there are correct answer behaviors multiple times, for example, two consecutive times, and determining an incorrect answer when there are incorrect answer behaviors multiple times, for example, two consecutive times, will be described. When determining a correct answer based on one correct answer behavior or an incorrect answer based on one incorrect answer behavior, even when the mouse accidentally touches the touch panel 31 unintentionally, a correct answer or incorrect answer is determined, so it takes time to learn the relevance between the correct figure and the contact. In contrast, according to the evaluation method according to the present embodiment, since a correct answer or incorrect answer is determined based on correct answer behaviors or incorrect answer behaviors multiple times, for example, two consecutive times, the influence of unintentional behaviors can be reduced, and the learning efficiency can be improved.

[0060] As described above, in the evaluation method according to the present embodiment, a correct figure and an incorrect figure are displayed in each of the display areas 313 and 314 of the display device 311, and when the contact of the target animal 2 with the correct figure is detected twice in a row, the determination unit 213 makes a positive determination. Then, when it is determined that the answer is correct, a reward is supplied and the determination result is accumulated as evaluation data 232. Thereby, it becomes possible to improve the learning efficiency and shorten the evaluation period of the cognitive function. Furthermore, by shortening the evaluation period, it becomes possible to apply it to preclinical trials of drug discovery targeting mental diseases or neurological diseases, etc.

[0061] In the present embodiment, the evaluation device 1 gives food pellets as a reward when a correct action is detected twice in a row, but a liquid such as water, milk or juice may be used as a reward. Also, as shown in FIGS. 7(a) and 7(b), when an incorrect action is detected twice in a row, an aversive stimulus 324 may be given to the target animal 2. The aversive stimulus 324 is, for example, a weak current (for example, about 0.2 mA) flowing through a stainless steel grid installed on the floor surface as shown in FIG. 7(b). When the stainless steel grid contacts the foot of the target animal 2, a weak current flows, which becomes an aversive stimulus called a foot shock. In this case, food pellets may be given when a correct action is detected twice in a row, or it may wait without giving anything.

[0062] Also, in the present embodiment, a correct action or an incorrect action is determined based on the contact with the display areas 313 and 314 that display the correct figure or the incorrect figure, but it is not limited to this. A correct action or an incorrect action may be determined based on the contact at an arbitrary position associated with the correct figure or the incorrect figure. For example, as shown in FIG. 8, a correct action or an incorrect action may be determined based on the contact with a push-type button switch 325 provided directly below the display areas 313 and 314 where the correct figure or the incorrect figure is displayed.

[0063] In addition, in the present embodiment, although pattern figures are exemplified in FIG. 2 as the correct figure and the incorrect figure, the present invention is not limited to this. The correct figure and the incorrect figure may be any figures as long as they are a pair of different figures. For example, the correct figure and the incorrect figure may be a pair of figures with different brightnesses, and the target animal 2 may be made to perform a brightness discrimination learning task for distinguishing the brightnesses. Further, the correct figure and the incorrect figure may be a pair of figures with different colors, and the target animal 2 may be made to perform a color discrimination learning task for distinguishing the colors. Further, the correct figure and the incorrect figure may be a pair of moving images with different moving directions of the figures, and the target animal 2 may be made to perform a motion direction discrimination learning task for distinguishing the motion directions.

[0064] (Embodiment 2) The evaluation method according to the present Embodiment 2 is a method for evaluating the cognitive function or learning function of the target animal 2 by making the target animal 2 perform an operant learning task, similar to Embodiment 1. The hardware configuration of the evaluation apparatus 1 using the evaluation method according to the present embodiment is the same as that of Embodiment 1.

[0065] Also in the evaluation method according to the present embodiment, the figure acquisition unit 211 acquires a pair of figures specified based on the operation of the operator or randomly from the secondary storage device 23, and the display control unit 212 displays a pair of correct figures and incorrect figures, and determines the correct behavior or incorrect behavior of the target animal 2 with respect to this.

[0066] In Embodiment 1, one of the pair of figures was set as the correct figure and the other was set as the incorrect figure in advance. However, in the evaluation method according to the present embodiment, the display control unit 212 displays the figure as the correct figure and the figure as the incorrect figure by swapping them with each other, and the determination unit 213 determines the correct behavior or incorrect behavior of the target animal 2 with respect to this display. Hereinafter, the figure discrimination learning performed by swapping the figure as the correct figure and the figure as the incorrect figure with each other is also called reversal learning.

[0067] The operation of the evaluation device 1 according to this embodiment will be described in detail with reference to FIGS. 9 and 10. FIG. 9 is a diagram showing examples of the figures of a pair P and the figures of three pairs A, B, and C. In this embodiment, the case where pattern figures are used as the correct figure and the incorrect figure will be described. However, the figures are not limited to pattern figures, and any different figures that form a pair may be used. FIG. 8 is a flowchart of the reversal learning evaluation process.

[0068] Before entering this evaluation, the mouse, which is the target animal 2, undergoes preliminary training such as training and behavior formation similar to those in Embodiment 1. In the training of behavior formation, for example, using a pair of figures of a pair P as shown in FIG. 9, the mouse is made to remember the process in which food pellets are supplied by touching the figure displayed on the touch panel 31. This evaluation is started using the trained mouse by the reversal learning evaluation process shown in the flowchart of FIG. 10.

[0069] In this embodiment, the figure discrimination learning evaluation is repeated by changing the pair of figures. The figure discrimination learning evaluation in each step of FIG. 10 is the same as that described using the flowchart of FIG. 4 in Embodiment 1. First, the processor 21 performs the figure discrimination learning evaluation shown in FIG. 4, using a pair of figures of a pair P, with the left figure in FIG. 9 as the correct figure and the right figure as the incorrect figure (step S201).

[0070] After obtaining the predetermined correct answer rate in step S201, the processor 21 performs the figure discrimination learning evaluation of the original phase using the three pairs of figures A, B, and C (step S202). At this time, the display control unit 212 sets the left figure among the pair A, B, C figures illustrated in FIG. 9 as the correct figure and the right figure as the incorrect figure, and performs the figure discrimination learning evaluation shown in FIG. 4. More specifically, in step S101 of the flowchart of FIG. 4, the processor 21 designates a pair of figures from the figures of pairs A, B, and C based on the operation of the operator or randomly, and designates the display areas 313 and 314 for displaying the correct figure and the incorrect figure, respectively.

[0071] Next, in step S102, the display control unit 212 causes the correct figure and the incorrect figure to be displayed in the display areas 313 and 314 specified in step S101, and passes the information on the display areas 313 and 314 in which the correct figure or the incorrect figure is displayed to the determination unit 213. In steps S104 and S108, the display control unit 212 displays the same figures as those displayed in step S102 as the correct figure and the incorrect figure in the same display areas 313 and 314, respectively. Using the figures thus displayed, it is determined in steps S103, 105, and 109 whether it is a correct action or an incorrect action, and a correct answer determination is made if the correct answer is given twice in a row, and an incorrect answer determination is made if the incorrect answer is given twice in a row.

[0072] After a correct answer rate equal to or higher than a predetermined value is obtained in step S202, the processor 21 performs figure discrimination learning evaluation in a reverse phase in which the correct figures and the incorrect figures of three pairs A, B, and C are interchanged (step S203). At this time, the display control unit 212 sets the figure on the right side among the figures of pairs A, B, and C illustrated in FIG. 9 as the correct figure, sets the figure on the left side as the incorrect figure, and performs figure discrimination learning evaluation shown in FIG. 4. More specifically, in step S101 of the flowchart of FIG. 4, the processor 21 designates one pair of figures from the figures of pairs A, B, and C based on the operation of the operator or randomly, and designates the display areas 313 and 314 for displaying the correct figure and the incorrect figure, respectively.

[0073] Next, in step S102, the display control unit 212 causes the correct figure and the incorrect figure to be displayed in the display areas 313 and 314 specified in step S101, and passes the information on the display areas 313 and 314 in which the correct figure or the incorrect figure is displayed to the determination unit 213. In steps S104 and S108, the display control unit 212 displays the same figures as those displayed in step S102 as the correct figure and the incorrect figure in the same display areas 313 and 314, respectively. Using the figures thus displayed, it is determined in steps S103, 105, and 109 whether it is a correct action or an incorrect action, and a correct answer determination is made if the correct answer is given twice in a row, and an incorrect answer determination is made if the incorrect answer is given twice in a row.

[0074] After the predetermined correct answer rate is obtained in step S203, the processor 21 performs a figure discrimination learning evaluation in a re-reversal phase in which the correct and incorrect figures of the three pairs of A, B, and C are swapped (step S204). That is, the processor 21 performs the same figure discrimination learning evaluation as in the original phase of step S202.

[0075] After the predetermined correct answer rate is obtained in step S204, the processor 21 performs a figure discrimination learning evaluation in a re-re-reversal phase in which the correct and incorrect figures of the three pairs of A, B, and C are swapped (step S205). That is, the processor 21 performs the same figure discrimination learning evaluation as in the reversal phase of step S203. Then, the processor 21 ends the process.

[0076] The determination results obtained in each figure discrimination learning are stored as evaluation data 232. The evaluation data 232 may include the determination results accumulated by performing the determination steps (steps S106 and S110 in FIG. 4) any number of times two or more times in each figure discrimination learning, or the statistical data calculated from the determination results accumulated by performing the determination steps a plurality of times within a certain period of time. The statistical data may include, for example, the correct answer rate, which is the ratio of the correct answer determinations to all the accumulated determination results, or the time change of the correct answer rate, or the information indicating the flexibility of the cognitive function or learning function derived based on the correct answer rate or the time change of the correct answer rate.

[0077] The number of determination steps for calculating the correct answer rate, or the time when the determination steps are performed within a certain period of time to calculate the correct answer rate, can be arbitrarily set in the same manner as in the first embodiment. In each figure discrimination learning, the trials for the set number or time can be regarded as one session, and the time change of the correct answer rate when one session is performed per day can be calculated. Information indicating the flexibility of the cognitive function or learning function of the target animal 2 can be derived from the time change of the correct answer rate when reverse learning is performed.

[0078] Here, the flexibility of the cognitive function or learning function is an index of the ability to flexibly change one's way of thinking in response to changes from the external environment. When one can quickly recognize that the problem has been reversed and can flexibly answer the problem correctly, it can be evaluated that the flexibility is high.

[0079] For example, in this embodiment, when the increase rate of the correct answer rate within a certain time after swapping the correct figure and the incorrect figure is high, it is evaluated that the flexibility of the cognitive function or learning function is high. When the increase rate of the correct answer rate is low, it is evaluated that the flexibility of the cognitive function or learning function is low. The evaluation of the high or low increase rate of the correct answer rate can be based on the increase rate of the correct answer rate obtained by implementing the evaluation method according to this embodiment for the same target animal 2 or different target animals 2 at different times or / and under different conditions. It can also be based on the increase rate of the correct answer rate obtained by implementing the same evaluation method for different target animals 2 under different conditions at the same time.

[0080] For example, when examining the flexibility of the cognitive function or learning function of a specific genetically modified or diseased model animal as the target animal 2, the increase rate of the correct answer rate is measured using the model animal and a wild-type animal of the same species. The flexibility of the cognitive function or learning function of the model animal can be evaluated based on the high or low increase rate of the correct answer rate of the model animal with reference to the increase rate of the correct answer rate of the wild-type animal. That is, compared with the wild-type animal, when the increase rate of the correct answer rate within a certain time after swapping the correct figure and the incorrect figure is high, it can be evaluated that the flexibility of the cognitive function or learning function is high. When the increase rate of the correct answer rate is low compared with the wild-type animal, it can be evaluated that the flexibility of the cognitive function or learning function is low.

[0081] Also, by using the evaluation method according to this embodiment, the evaluation data generated after administering a drug to a model animal or a wild-type animal with low flexibility of the cognitive function or learning function is compared with the evaluation data generated for the same animal or an animal of the same species as the model animal or wild-type animal before administering the drug, so as to evaluate the influence of the drug on the flexibility of the cognitive function or learning function (drug evaluation step).

[0082] Also in the evaluation method according to the present embodiment, since the correct answer or incorrect answer is determined based on the correct action or incorrect action performed twice in a row, the learning efficiency of each shape discrimination learning can be improved, and the evaluation period can be significantly shortened as a whole.

[0083] In the present embodiment, the shape discrimination learning evaluation was performed in the order of the original phase, the reversal phase, the re-reversal phase, and the re-re-reversal phase. However, the number of times of reversing the correct shape and the incorrect shape is arbitrary. Only the original phase and the reversal phase may be performed, or after the re-re-reversal phase, the shape discrimination learning evaluation with further reversed shapes may be performed.

[0084] As described above, in the evaluation method according to the present embodiment, shape discrimination learning is performed using a plurality of pairs of correct shapes and incorrect shapes, and then shape discrimination learning is performed using the correct shape and the incorrect shape that are reversed. After that, repeated reversal learning is performed. As a result, it is possible to improve the learning efficiency also in the evaluation of the flexibility of the cognitive function or the learning function, and shorten the evaluation period. Furthermore, by shortening the evaluation period, it becomes possible to apply it to the preclinical trials of drug discovery targeting mental diseases or neurological diseases.

[0085] The above-described Embodiments 1 and 2 can be variously modified. A modification will be described with reference to the drawings.

[0086] (Modification 1) The hardware configuration and functional configuration of the evaluation device 1 using the evaluation method according to the present Modification 1 are the same as those in Embodiment 1. In Embodiment 1 above, when the correct action or incorrect action was performed twice in a row, the determination unit 213 determined the correct answer or incorrect answer. However, in this modification, when the correct action or incorrect action is performed three times in a row, the correct answer or incorrect answer is determined.

[0087] FIG. 11 is a flowchart of the graphic discrimination learning evaluation process according to this modified example. After the same prior training as in the first embodiment, this evaluation is started by the graphic discrimination learning evaluation process shown in the flowchart of FIG. 11. First, the processor 21 designates a pair of graphics from the graphic images stored in the secondary storage device 23 based on the operation of the operator or randomly, and also designates a display area for displaying each of the correct graphic and the incorrect graphic (step S101). More specifically, in step S101, the display areas 313 and 314 located at the positions of the windows arranged on the left and right are designated as the display area for displaying the correct graphic and the display area for displaying the incorrect graphic. The graphic acquisition unit 211 acquires the pair of correct graphic and incorrect graphic designated in step S101.

[0088] Thereafter, the display control unit 212 displays the pair of correct graphic and incorrect graphic acquired by the graphic acquisition unit 211 in the display areas 313 and 314 designated in step S101, respectively (step S102: display step).

[0089] When the contact sensor 312 detects the contact of the mouse, the determination unit 213 acquires the information of the contacted display area from the contact sensor 312 and determines whether a correct action has been performed (step S103). When it is determined that a correct action has been performed on the graphic displayed in step S102 (step S103: Yes), the display control unit 212 displays the same graphics as those displayed in step S102 as the correct graphic and the incorrect graphic in the same display areas 313 and 314, respectively (step S104).

[0090] When a correct action is performed on the figure displayed in step S104 (step S105: Yes), the display control unit 212 displays the same figures as those displayed in step S102 as the correct figure and the incorrect figure, respectively, in the same display areas 313 and 314 (step S304). When it is determined that a correct action has been performed on the figure displayed in step S304 (step S305: Yes), it is determined as a correct answer because a correct action has been performed three times in a row (step S106). Thereafter, the supply instruction unit 214 sounds a beep from the speaker 323 and causes the supply device 32 to supply food pellets as a reward (step S107). As a result, the mouse can eat the food pellets.

[0091] When it is determined that an incorrect action has been performed on the figure displayed in step S102, step S104, or step S304 (step S103, step S105, or step S305: No), the display control unit 212 displays the same figures as those displayed in step S102 as the correct figure and the incorrect figure, respectively, in the same display areas 313 and 314 (step S108).

[0092] When it is determined that an incorrect action has been performed on the figure displayed in step S108 (step S109: No), the display control unit 212 displays the same figures as those displayed in step S102 as the correct figure and the incorrect figure, respectively, in the same display areas 313 and 314 (step S308). When it is determined that an incorrect action has been performed on the figure displayed in step S308 (step S309: No), it is determined as an incorrect answer because an incorrect action has been performed three times in a row (step S110). When an incorrect answer is determined, the supply instruction unit 214 only outputs a buzzer sound with a lower pitch than the beep from the speaker 323, does not give a supply instruction, and waits for a predetermined time (step S111). The mouse hears the buzzer sound and waits in a state where it cannot eat the food pellets.

[0093] When it is determined by the determination unit 213 that the correct action has been performed on the figure displayed in step S108 or step S308 (step S109 or step S309: Yes), the process returns to step S104. Thereafter, the processes of steps S104, S105, S304, S305, S108, S109, S308, and S309 are repeated. When it is determined that the correct answer has been given due to the correct action being performed three times in a row (step S305: Yes), if it is determined that the answer is correct (step S106), a reward is supplied (step S107). When it is determined that the answer is incorrect due to the incorrect action being performed three times in a row (step S309: No), if it is determined that the answer is incorrect (step S110), the system waits (step S111).

[0094] After the reward is supplied in step S107 or after waiting in step S111, the determination unit 213 adds a record of the correct or incorrect answer to the evaluation data 232 of the secondary storage device 23 (step S113). Thereafter, if there is no end operation by the operator (step S113: No), the process returns to step S101. If there is an end operation by the operator (step S113: Yes), the process ends.

[0095] In addition, if it is determined as incorrect in step S105 or step S305 and determined as correct in step S109 or step S309, the figure display in steps S104, S304, S108, and S308 and the correctness determination in steps S105, S305, S109, and S309 will be repeated, but an upper limit may be set for the repetition time. In this case, if the upper limit time is exceeded, it may be determined that the answer is incorrect and the determination result may be added to the evaluation data.

[0096] As described above, according to the determination method according to this modification example, in which it is determined that the answer is correct when there are three consecutive correct actions and it is determined that the answer is incorrect when there are three consecutive incorrect actions, compared to the case of determining the correct or incorrect answer based on a single correct or incorrect action, it is possible to reduce the influence of unintentional actions such as accidentally touching the touch panel 31, and it is possible to improve the learning efficiency.

[0097] Note that, in order to determine a correct answer or an incorrect answer, the first number of times of continuously performing a correct action or the second number of times of performing an incorrect action, which is set to 2 times in the first embodiment and 3 times in this modified example, may be 4 times or more. The first number of times and the second number of times may be determined according to the type of the target animal 2. For example, when an animal with a cognitive function superior to that of a mouse is used as the target animal 2, any number of times of 3 times or more may be selected.

[0098] Also, in the evaluation method according to the second embodiment, in order to determine a correct answer or an incorrect answer, the first number of times of continuously performing a correct action or the second number of times of performing an incorrect action may be set to 3 times or more. Also, the first number of times of continuously performing a correct action and the second number of times of performing an incorrect action may be the same as each other as in the first and second embodiments and this modified example, or may be different from each other. That is, the determination unit 213 may perform a correct answer determination when detecting a correct action continuously for only the first number of times of 2 times or more, and may perform an incorrect answer determination when detecting an incorrect action continuously for only the second number of times of 2 times or more. The first number of times and the second number of times can be appropriately set according to the type of the target animal 2, but can be, for example, 2 times, 3 times, 4 times, 5 times, or 6 times. Note that it is not the case that the larger the number of times, the better, and it is preferable to be within the range of the number of times that the target animal 2 can recognize having contacted a plurality of times.

[0099] (Modified Example 2) The hardware configuration and functional configuration of the evaluation device 1 using the evaluation method according to the second modification example are the same as those in the first embodiment. In the above-described first embodiment or the first modification example, the determination unit 213 determines an incorrect answer when incorrect actions are continuously performed a second number of times or more, and then sounds a buzzer and waits. In contrast, in this modification example, as shown in Fig. 12(a), when incorrect actions are continuously detected a second number of times and an incorrect answer is determined, no reward is given as shown in Fig. 12(b), and the display control unit 212 causes white to be displayed instead of turning off the figures in all the display areas 313 and 314 where a pair of figures are being displayed. When the display control unit 212 displays white, the supply instruction unit 214 may or may not sound a buzzer. Also, the color to be displayed may be any light color other than white.

[0100] According to this modification example, by continuously performing incorrect actions a second number of times or more, it becomes easier for the target animal 2 to visually recognize that an incorrect answer has been determined. Also, since small animals such as mice tend to avoid having the chamber brightly illuminated by white display, an effect of improving the learning effect can be obtained.

[0101] (Modification Example 3) In the above-described first and second embodiments and the first and second modification examples, the determination unit 213 determines a correct answer when the target animal 2 contacts a position corresponding to one correct figure continuously a first number of times or more, and determines an incorrect answer when the target animal 2 contacts a position corresponding to one incorrect figure continuously a second number of times or more. However, the present invention is not limited to this. In this modification example 3, there are two or more incorrect figures, and the determination unit 213 determines a correct answer when the target animal 2 contacts a position corresponding to one correct figure continuously a first number of times, and determines an incorrect answer when the target animal 2 contacts a position corresponding to any one of two or more incorrect figures continuously a second number of times. Fig. 13(a) is a display example when one correct figure and two incorrect figures are displayed, and Fig. 13(b) is a display example when one correct figure and four incorrect figures are displayed.

[0102] More specifically, as shown in FIGS. 13(a) and (b), in steps S102, S104, S108, S304, and S308 of FIGS. 4 and 11, the display control unit 212 causes one correct figure and two or more incorrect figures to be displayed in three or more display areas 315. At this time, on the front surface of the touch panel 31, a black plastic plate having the same number of windows as the number of display areas 315 is installed, and one correct figure and two or more incorrect figures are displayed in the display areas 315 located in each window.

[0103] In this state, the contact sensor 312 detects the contact of the target animal 2 at positions corresponding to one correct figure and two or more incorrect figures. Then, when the contact sensor 312 detects contact at a position corresponding to the correct figure, the determination unit 213 determines that the correct behavior has been performed (steps S103, S105, S109, S305, S309: Yes). On the other hand, when contact at a position corresponding to any of the two or more incorrect figures is detected, it is determined that an incorrect behavior has been performed (steps S103, S105, S109, S305, S309: No). Other processes are the same as those in Embodiments 1 and 2 or Modification Examples 1 and 2.

[0104] In this way, in this modification example, the cognitive function can be evaluated using the task of selecting the correct figure from among three or more figure options.

[0105] (Modification Example 4) In the above-described Embodiments 1 and 2 and Modification Examples 1 to 3, the target animal 2 performs figure discrimination learning, and the determination unit 213 determines that it is a correct answer when the contact of the target animal 2 at a position corresponding to the correct figure is detected continuously for two or more first times, and determines that it is an incorrect answer when the contact of the target animal 2 at a position corresponding to any of one or more incorrect figures is detected continuously for two or more second times. However, the present invention is not limited to this. In this Modification Example 4, the target animal 2 performs position discrimination learning in which it selects a position corresponding to the displayed figure. That is, the determination unit 213 determines that it is a correct answer when the contact of the target animal 2 at a position associated with the correct answer is detected continuously for the first time, and determines that it is an incorrect answer when the contact of the target animal 2 at a position associated with the incorrect answer is detected continuously for the second time.

[0106] For example, when predetermined figures are displayed in the two display areas 313 and 314 on the left and right, one of the display areas at either position may be associated with the correct answer, and the display area at the other position may be associated with the incorrect answer. Alternatively, as shown in FIGS. 14(a), (b), and (c), when predetermined figures are displayed in the three display areas 316 on the left, in the center, and on the right, one of the display areas 316 at any one position may be associated with the correct answer, and the remaining display areas 316 at the other positions may be associated with the incorrect answer. Or, for the two display areas above and below or the three display areas above, in the middle, and below, one of the display areas at any one position may be associated with the correct answer, and the remaining display areas at the other positions may be associated with the incorrect answer.

[0107] As shown in FIGS. 14(a), (b), and (c), the same figure is simultaneously displayed in each display area 316. For the display figures in FIGS. 14(a) and (b), when the central display area 316 is associated with the correct answer, in the case of FIG. 14(a) where contact in the central display area 316 is detected, it is determined that the correct action has been taken, and in the case of FIG. 14(b) where contact in the right display area 316 is detected, it is determined that the incorrect action has been taken. For the display figure in FIG. 14(c), when the right display area 316 is associated with the correct answer, in the case of FIG. 14(c) where contact in the right display area 316 is detected, it is determined that the correct action has been taken. Thereby, position discrimination learning can be performed.

[0108] Also, the actions at the positions associated with the correct answer and the incorrect answer may be any actions other than contact. For example, instead of the contact sensor 312, a pressure sensor or the like may be arranged to detect an action of pressing the position associated with the correct answer or the incorrect answer. Also, when the positions associated with the correct answer and the incorrect answer are arranged on the floor, an action of staying at the position associated with the correct answer or the incorrect answer may be detected. That is, the determination unit 213 determines that it is a correct answer when it detects a predetermined action of the target animal 2 at the position associated with the correct answer continuously for the first number of times, and determines that it is an incorrect answer when it detects a predetermined action of the target animal 2 at the position associated with the incorrect answer continuously for the second number of times.

[0109] Thus, in this modified example, the evaluation of the cognitive function can be performed using a task of performing an arbitrary operation at a position associated with a correct answer or an incorrect answer.

[0110] The hardware configurations, functional configurations, and flowcharts shown in the above-described Embodiments 1 and 2 and Modified Examples 1 to 4 are examples, and can be arbitrarily changed and applied.

[0111] For example, in the above-described Embodiments 1 and 2 and Modified Examples 1 to 4, in step S101 of the graphic discrimination learning evaluation process shown in FIG. 4, based on the operation of the operator or randomly, a pair of graphics, a display area for displaying a correct graphic and an incorrect graphic, were specified. However, the same pair of graphics may be repeatedly specified in step S101.

[0112] Also, in the above-described Embodiments 1 and 2 and Modified Examples 1 to 4, it was assumed that the correct graphic and one or more incorrect graphics were simultaneously displayed in two or more display areas of one display device 311. However, two or more display devices 311 may be provided, and the correct graphic and one or more incorrect graphics may be displayed on each display device 311.

[0113] Each function realized by the processor 21 of the information processing apparatus 20 according to the above-described Embodiments 1 and 2 and Modified Examples 1 to 4 can be realized using a normal computer system, not a dedicated system.

[0114] For example, a program for executing the operations of the above-described embodiments and modification examples may be stored and distributed on a computer-readable recording medium such as a CD-ROM (Compact Disc Read-Only Memory), DVD (Digital Versatile Disc), MO (Magneto Optical Disc), memory card, etc., and a computer capable of realizing each function may be configured by installing the program in the computer. And when each function is realized by the division of labor between the OS (Operating System) and the application, or the cooperation between the OS and the application, only the part other than the OS may be stored on the recording medium.

[0115] The present invention will be described more specifically by the following examples, but the present invention is not limited by the examples.

Example

[0116] [Example 1] As the target animal 2, C57BL / 6 strain mice were used. In order to enhance the motivation to perform the task, food restriction was imposed on the mice during the task execution period. The age of the mice was 10 weeks or older at the start of food restriction. Mice that had been freely fed were individually housed, and a fixed amount of food was given while measuring their body weight from the second day of housing. Food restriction was performed so that the body weight of the mice would be about 85% of that during free feeding before individual housing. Using the mice that had undergone food restriction and reached the target body weight, figure discrimination learning was performed with the evaluation apparatus 1 according to Embodiment 1, and the learning state was evaluated. As the evaluation apparatus 1, a touch panel operator experimental apparatus manufactured by Ohara Medical Industry Co., Ltd. was modified and used.

[0117] As the food pellets supplied by the supply device 32, 10 g food pellets (AIN-76A Rodent Tablet; TestDiet, St. Louis, MO, USA) from TestDiet were used. The animal chamber 30 was housed in a soundproof box, and a speaker 323 was installed in the soundproof box. The temperature inside the animal chamber 30 was set to 23 ± 1°C.

[0118] First, in the habituation process, 10 food pellets were placed in the food dish of the evaluation device 1, and the mouse was placed in the animal chamber 30. One session was set for 30 minutes. In the first half of 15 minutes, the mouse was allowed to eat the 10 food pellets in the food dish to let it remember the relationship between the food dish and the food pellets. In the second half of 15 minutes, one food pellet was supplied at a time every 30 seconds along with a short beep sound. As a result, the mouse learned that food pellets were supplied along with the beep sound. When the mouse ate all the food pellets without leaving any in a 30-minute session per day, the habituation process was terminated.

[0119] After the habituation ended, it shifted to the shaping process. In this process, the same figure was displayed in the two display areas 313 and 314 of the display device 311. When the tip of the mouse's nose, body, or forelimb touched either of the display areas 313 and 314, one food pellet was supplied along with the beep sound used in the habituation. First, the shaping was carried out such that a food pellet was supplied when there was one contact, and then the shaping was carried out such that a food pellet was supplied when there were two contacts. As a result, the mouse learned the relationship that a food pellet was supplied when it touched the displayed figure twice.

[0120] One trial was defined as the period from when the figure was displayed until the food pellet appeared. When 100 trials were completed or 30 minutes had elapsed, it was considered the end of one session. The mouse received training for one session per day. When the mouse was able to complete 100 trials within 30 minutes of one session and eat 100 food pellets, the shaping process was terminated.

[0121] For the mice in which the behavior formation had ended, evaluation was performed using the evaluation method according to Embodiment 1. In all the trials of this example, the figure displayed by the display device 311 was the pair P shown in FIG. 9. FIG. 15 is a graph showing the correct answer rate when a mouse was trained to discriminate figures using the evaluation method according to Embodiment 1 (hereinafter also referred to as the two-touch method). For comparison, FIG. 15 also shows the results of evaluation using a method in which a correct answer is determined by one correct behavior or an incorrect answer is determined by one incorrect behavior (hereinafter also referred to as the one-touch method). When evaluating using the one-touch method for comparison, in the behavior formation before evaluation, only the training in which food pellets were supplied by one contact was performed, and the training in which food pellets were supplied by two contacts was omitted.

[0122] In FIG. 15, the session on the horizontal axis is defined as one session when 100 trials for determining a correct answer or an incorrect answer are performed or when 30 minutes have elapsed after the start of the trial and the trial ends. The horizontal axis represents the progress of the session when one session is performed per day. The vertical axis is the correct answer rate for one session. Each value and error bar shown in the graph of FIG. 15 represent the average value of nine mice and the 95% confidence interval.

[0123] As is clear from FIG. 15, in the evaluation method of the one-touch method, the correct answer rate was still below 60% even at the sixth session. On the other hand, according to the two-touch method evaluation method according to Embodiment 1, the correct answer rate could exceed 80% at the sixth session. Thus, according to the evaluation method according to Embodiment 1, the learning efficiency could be significantly improved.

[0124] [Example 2] Using the evaluation method according to Embodiment 2, evaluation was performed on mice that had undergone the same preliminary training as in Example 1. According to the flowchart of FIG. 10, first, a figure discrimination learning evaluation using a pair of figures was performed (step S201). As the pair of figures at this time, the figures of pair P shown in FIG. 9 were used. The figure with vertical stripes on the left was set as the correct figure, and the figure with horizontal stripes on the right was set as the incorrect figure. One session of the figure discrimination learning evaluation ended when 100 trials or 30 minutes had elapsed. One session was performed per day, and it was continued until the correct answer rate of 80% or more continued for several days.

[0125] Next, a figure discrimination learning evaluation of three pairs was performed (step S202). As the three pairs of figures at this time, pairs A, B, and C shown in FIG. 9 were used. As the combination in the original phase, the figure on the left was set as the correct figure and the figure on the right was set as the incorrect figure. One session of the figure discrimination learning evaluation of three pairs ended when 150 trials or 45 minutes had elapsed. One session was performed per day, and it was continued until the correct answer rate of 80% or more continued for several days.

[0126] Next, a figure discrimination learning evaluation in the reverse phase with the correct and incorrect figures swapped was performed (step S203). The learning process was the same as in step S202. Next, a figure discrimination learning evaluation in the re-reverse phase with the correct and incorrect figures swapped again was performed (step S204), and finally, a figure discrimination learning evaluation in the re-re-reverse phase with the correct and incorrect figures swapped again was performed (step S205).

[0127] FIG. 16 shows the correct answer rate when a mouse was trained in figure discrimination learning using the evaluation method (two-touch method) according to Embodiment 2. For comparison in FIG. 16, the results of evaluation using the method (one-touch method) of determining a correct answer with one correct action or an incorrect answer with one incorrect action are also shown. When evaluating using the one-touch method for comparison, in the action formation before evaluation, only the training in which food pellets were supplied with one contact was performed, and the training in which food pellets were supplied with two contacts was omitted.

[0128] In FIG. 16, the horizontal axis represents the progress of the session when one session is conducted per day. The vertical axis represents the correct answer rate for 150 trials in one session. Each value and error bar shown in the graph of FIG. 16 represents the average value of nine mice and the 95% confidence interval.

[0129] As shown in FIG. 16, in the re-reversal phase, a significant difference appeared between the one-touch method and the two-touch method. In the evaluation method of the one-touch method, in the re-reversal phase, the correct answer rate was less than 60% even at the 12th session and could not reach 80% even at the 20th session. On the other hand, according to the evaluation method of the two-touch method according to the second embodiment, in the re-reversal phase, the correct answer rate could exceed 80% at the 12th session. Thus, according to the evaluation method according to the second embodiment, the learning efficiency can be significantly improved, and the flexibility of the cognitive function or learning function can also be evaluated. The short-term evaluation of the flexibility of the cognitive function or learning function can also be applied to the preclinical trials of drug discovery targeting mental diseases or neurological diseases.

[0130] [Example 3] Using the evaluation method according to the second embodiment, an evaluation was performed using an autism model mouse (Pat / Dp mouse), which is known to have low flexibility of cognitive function or learning function, and a wild-type mouse as the target animal 2. After performing the same preliminary training as in Example 1 on both mice, the evaluation was conducted. According to the flowchart of FIG. 10, first, a figure discrimination learning evaluation using a pair of figures was performed (step S201). As the pair of figures at this time, the figures of pair P shown in FIG. 9 were used, the figure with vertical stripes on the left was used as the correct figure, and the figure with horizontal stripes on the right was used as the incorrect figure. One session of the figure discrimination learning evaluation ended when 100 trials or 30 minutes had elapsed. One session was conducted per day, and it was continued until the correct answer rate of 80% or more continued for several days.

[0131] Next, three pairs of figure discrimination learning evaluations were conducted (step S202). As the three pairs of figures at this time, pairs A, B, and C shown in FIG. 9 were used. As the combination in the original phase, the left figure was set as the correct figure and the right figure was set as the incorrect figure. One session of the three pairs of figure discrimination learning evaluations ended when 150 trials or 45 minutes had elapsed. One session was conducted per day and continued until the correct answer rate of 80% or more continued for several days. Next, a figure discrimination learning evaluation in the reverse phase with the correct and incorrect figures swapped was conducted (step S203). The learning process was the same as in step S202.

[0132] FIG. 17 shows the results of conducting the figure discrimination learning evaluations in the last three sessions of the original phase and the reverse phase. Each value and error bar of the correct answer rate of wild-type mice represent the average value of 9 mice and the 95% confidence interval. Each value and error bar of the correct answer rate of autism model mice represent the average value of 6 mice and the 95% confidence interval.

[0133] As shown in FIG. 17, the result was obtained that the correct answer rate of the autism model mice up to the first five sessions in the initial stage of the reverse phase was lower than that of the wild-type mice. Thereby, it was possible to capture the cognitive flexibility disorder of the autism model mice, which was difficult to detect by operant learning in the past. According to the evaluation method according to Embodiment 2, it is also possible to apply it to preclinical trials of drug discovery targeting autism and the like.

[0134] [Example 4] Using the evaluation method according to Modification 1, an evaluation was performed on the mice that had undergone the same preliminary training as in Example 1. According to the flowchart of FIG. 10, first, a figure discrimination learning evaluation using one pair of figures was conducted (step S201). As the one pair of figures at this time, the figures of pair P shown in FIG. 9 were used, and the left vertical-striped figure was set as the correct figure and the right horizontal-striped figure was set as the incorrect figure. One session of the figure discrimination learning evaluation ended when 100 trials or 30 minutes had elapsed. One session was conducted per day and continued until the correct answer rate of 80% or more continued for several days.

[0135] Next, three pairs of shape discrimination learning evaluations were conducted (step S202). As the three pairs of shapes at this time, pairs A, B, and C shown in FIG. 9 were used. As the combination in the original phase, the left shape was set as the correct shape and the right shape was set as the incorrect shape. One session of the three pairs of shape discrimination learning evaluations was terminated when 150 trials or 45 minutes had elapsed. One session was conducted per day and continued until the correct answer rate of 80% or more continued for several days. Next, a shape discrimination learning evaluation in the reverse phase with the correct and incorrect shapes swapped was conducted (step S203). The learning process is the same as in step S202.

[0136] FIG. 18 shows the results of the shape discrimination learning evaluations in the original phase and the reverse phase. In the correct answer rate when the mouse was subjected to shape discrimination learning using the evaluation method (two-touch method) according to Embodiment 2, each value and the error bar indicate the average value of nine mice and the 95% confidence interval. In the correct answer rate when the mouse was subjected to shape discrimination learning using the evaluation method (three-touch method) according to Modification 1, each value and the error bar indicate the average value of seven mice and the 95% confidence interval.

[0137] As shown in FIG. 18, in the reverse phase, the learning efficiency of the three-touch method was significantly improved compared to that of the two-touch method. More specifically, in the case of the three-touch method, the correct answer rate exceeded 80% at the 12th session in the reverse phase. Thus, when performing reverse learning to measure the flexibility of the cognitive function or learning function, it is possible to further improve the learning efficiency by the three-touch method. It becomes possible to evaluate the flexibility of the cognitive function or learning function in a short period, and it can also be applied to preclinical trials of drug discovery targeting mental diseases or neurological diseases.

[0138] [Example 5] Using the evaluation method according to Modification Example 1 of the 3-touch method and the evaluation method according to Modification Example 2 of displaying white in the display areas 313 and 314 when a wrong answer is determined in the 3-touch method, a figure discrimination learning evaluation using a pair of figures was performed on a mouse that had undergone the same preliminary training as in Example 1. As the pair of figures at this time, the figures of pair P shown in FIG. 9 were used, with the figure with vertical stripes on the left as the correct figure and the figure with horizontal stripes on the right as the incorrect figure. One session of the figure discrimination learning evaluation was terminated when 100 trials were completed or 30 minutes had elapsed. One session was conducted per day, and it was continued until the correct answer rate of 80% or more continued for several days.

[0139] FIG. 19 shows the correct answer rate when figure discrimination learning is performed using the evaluation methods according to Modification Example 1 and Modification Example 2. Each value and error bar in the evaluation method according to Modification Example 1 indicates the average value of 7 mice and the 95% confidence interval. Each value and error bar in the evaluation method according to Modification Example 2 indicates the average value of 6 mice and the 95% confidence interval.

[0140] As shown in FIG. 19, by adding the process of displaying white in the display areas 313 and 314 when a wrong answer is determined, the learning efficiency was further improved. More specifically, the correct answer rate exceeded 90% in the fourth session, making it possible to further improve the learning efficiency.

[0141] The present invention can be implemented in various embodiments and modifications without departing from the broad spirit and scope of the present invention. Also, the above-described embodiments are for explaining the present invention and do not limit the scope of the present invention. That is, the scope of the present invention is indicated by the claims rather than the embodiments. And various modifications made within the scope of the claims and within the scope of the meaning of the invention equivalent thereto are considered to be within the scope of the present invention.

Industrial Applicability

[0142] The present invention is suitable for a test in which an operant learning task is performed on a target animal.

Explanation of Signs

[0143] 1 Evaluation device, 2 Target animal, 20 Information processing device, 21 Processor, 22 Primary storage device, 23 Secondary storage device, 24 Communication interface, 25 Input unit, 30 Animal chamber, 31 Touch panel, 32 Feeding device, 211 Graphic acquisition unit, 212 Display control unit, 213 Judgment unit, 214 Feeding instruction unit, 231 Graphic image, 232 Evaluation data, 311 Display device, 312 Contact sensor, 313, 314, 315, 316 Display area, 322 Food dish, 323 Speaker, 324 Aversive stimulus, 325 Button switch.

Claims

1. A determination step of making a correct answer determination when the actions of the target animal at positions associated with correct answers are detected continuously for a first number of times or more, or making an incorrect answer determination when the actions of the target animal at positions associated with incorrect answers are detected continuously for a second number of times or more; A supply step of supplying a reward or an aversive stimulus according to the determination result of the determination step; An evaluation data generation step of accumulating the determination results of the determination step to generate evaluation data, An evaluation method.

2. Further including a display step of simultaneously displaying a correct figure and one or more incorrect figures in two or more display areas of a display device, In the determination step, a correct answer determination is made when the contact of the target animal at the position corresponding to the correct figure is detected continuously for the first number of times, or an incorrect answer determination is made when the contact of the target animal at the position corresponding to any one of the one or more incorrect figures is detected continuously for the second number of times. The evaluation method according to Claim 1.

3. Further including a contact detection step of detecting the contact of the target animal at positions corresponding to the correct figure and the one or more incorrect figures, In the determination step, when the contact at the position corresponding to the correct figure, which is a correct action, is detected continuously for the first number of times in the contact detection step, a correct answer determination is made, and when the contact at the position corresponding to any one of the one or more incorrect figures, which is an incorrect action, is detected continuously for the second number of times in the contact detection step, an incorrect answer determination is made. The evaluation method according to Claim 2.

4. The evaluation data includes the correct answer rate for all the determination results for the determination results of the determination step for a predetermined number of times or more or the determination results of the determination step multiple times within a certain time period. The evaluation method according to Claim 1.

5. The evaluation data includes information indicating the cognitive function or learning function of the target animal derived based on the correct answer rate or the time change of the correct answer rate. The evaluation method according to Claim 4.

6. The evaluation data includes the determination result of reversal learning when the figure set for the correct figure and any one of the figures set for the one or more incorrect figures are swapped with each other. The evaluation method according to Claim 2.

7. The evaluation data is derived based on the correct answer rate for all the determination results of the above-mentioned determination steps for a predetermined number of times of two or more times or a plurality of times of the above-mentioned determination steps within a certain period of time, or the time change of the correct answer rate, and includes information indicating the flexibility of the cognitive function or learning function of the target animal. The evaluation method according to claim 6.

8. In the determination step, when contact of the target animal at a position corresponding to any one of the one or more incorrect figures is detected continuously for the second number of times, a determination of an incorrect answer is made, and a light color is displayed in the display area where the correct figure or the incorrect figure was displayed. The evaluation method according to claim 2.

9. The first number of times and the second number of times are predetermined numbers of times according to the type of the target animal, and the first number of times and the second number of times are the same number of times as each other. The evaluation method according to claim 1.

10. By comparing the evaluation data generated after administering a drug to a model animal or a wild-type animal with low cognitive function or learning function with the evaluation data generated for the same animal or an animal of the same species as the model animal or the wild-type animal before administering the drug, a drug evaluation step of evaluating the influence of the drug on the cognitive function or learning function is further provided. The evaluation method according to any one of claims 1 to 9.

11. A determination unit that makes a correct answer determination when detecting the movement of the target animal at a position associated with the correct answer continuously for two or more first numbers of times, or makes an incorrect answer determination when detecting the movement of the target animal at a position associated with the incorrect answer continuously for two or more second numbers of times. A supply device that supplies a reward or supplies an aversive stimulus according to the determination result of the determination unit. Evaluation device.

12. A computer A determination unit that makes a correct answer determination when detecting the movement of the target animal at a position associated with the correct answer continuously for two or more first numbers of times, or makes an incorrect answer determination when detecting the movement of the target animal at a position associated with the incorrect answer continuously for two or more second numbers of times. A supply instruction unit that causes a reward to be supplied or an aversive stimulus to be supplied according to the determination result of the determination unit. A storage unit that stores the determination result of the determination unit as evaluation data. A program for functioning as such.

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