Evaluation method, evaluation device, program, method for producing trained non-human animal, and non-human animal

Abstract

A determination unit (213): determines that an answer is correct when movement of an object animal at a position associated with a correct answer is detected continuously for a first number of times, which is two or more times; or determines that the answer is incorrect when movement of the object animal at a position associated with an incorrect answer is detected continuously for a second number of times, which is two or more times. When the answer is determined to be correct, a supply device (32) supplies a reward, and when the answer is determined to be incorrect, the supply device causes the object animal to stand by, or supplies a dislike stimulus. The determination results are accumulated in a secondary storage device (23), and evaluation data (232) is generated.

Description

Evaluation method, evaluation device, program, method for producing trained non-human animal, and non-human animal

[0001] The present invention relates to an evaluation method, an evaluation device, a program, a method for producing a trained non-human animal, and a non-human animal.

[0002] Cognitive function tests using laboratory animals are widely conducted in preclinical trials of drug discovery targeting psychiatric or neurological disorders, or in neuroscience research. One type of cognitive function test, in which laboratory animals are asked to perform operant learning tasks, is known to be capable of examining complex cognitive functions (e.g., Patent Document 1, Non-Patent Document 1).

[0003] The animal learning support device described in Patent Document 1 provides a subject animal in a cage with a predetermined stimulus, and if the subject animal performs a correct operation on an operating unit, it provides the subject animal with a reward. It is explained that this allows the subject animal to learn using a variety of task patterns while being unrestrained and able to move freely.

[0004] Non-Patent Document 1 discloses a method for measuring the flexibility of cognitive functions by repeating original learning, in which correct and incorrect figures are displayed and a reward is given when the correct figure is selected, and reversal learning, in which the correct and incorrect figures are swapped.

[0005] JP 2015-65939 A

[0006] Tatsuhiro Ayabe, 2 others, “Hop-Derived Iso-α-Acids in Beer Improve Visual Discrimination and Reversal Learning in Mice as “Assessed by a Touch Panel Operant System”, Frontiers in Behavioral Neuroscience, April 2019, Vol. 13, Article 67

[0007] The cognitive flexibility test, which involves repeated original learning and reversal learning of operant learning tasks, is considered to be highly reliable and reproducible. However, when this test is used for efficacy testing in preclinical drug discovery trials, it takes a long time for the operant learning accuracy rate to reach a certain level, which is a problem.

[0008] The present invention has been made in consideration of the above-mentioned circumstances, and aims to provide an evaluation method, evaluation device, program, method for producing a trained non-human animal, and non-human animal that can improve learning efficiency and shorten the evaluation period for cognitive function or learning function.

[0009] (Evaluation method) The evaluation method described in this specification includes a judgment step of determining that the answer is correct when the movement of the target animal is detected at a position corresponding to the correct answer a first number of times, which is two or more consecutive times, or determining that the answer is incorrect when the movement of the target animal is detected at a position corresponding to the incorrect answer a second number of times, which is two or more consecutive times, and a supply step of supplying a reward or an aversive stimulus depending on the judgment result of the judgment step, and preferably further includes an evaluation data generation step of accumulating the judgment results of the judgment step and generating evaluation data.

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

[0011] Furthermore, when the evaluation method described in this specification includes a display step, it may further include a contact detection step of detecting contact of the target animal at a position corresponding to the correct figure and one or more of the incorrect figures, and in the judgment step, a correct answer may be judged if contact at a position corresponding to the correct figure, which is correct behavior, is detected the first number of times in succession in the contact detection step, and an incorrect answer may be judged if contact at a position corresponding to one of the one or more incorrect figures, which is incorrect behavior, is detected the second number of times in succession in the contact detection step.

[0012] The evaluation data may include a rate of correct answers for all of the judgment results obtained from two or more predetermined number of judgment steps, or for a plurality of judgment steps performed 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 a change in the correct answer rate over time.

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

[0015] The evaluation data may include information indicating the flexibility of the cognitive or learning function of the target animal, derived based on the correct answer rate or the change in the correct answer rate over time for all of the judgment results of two or more predetermined number of judgment steps, or multiple judgment steps within a certain period of time, for the reversal learning.

[0016] In the judgment step, if contact of the target animal is detected at a position corresponding to one or more of the incorrect figures for the second number of consecutive times, an incorrect answer is judged, and a bright 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 depending on 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.

[0018] The method may further include a drug evaluation step of evaluating the effect of the drug on cognitive or learning function by comparing the evaluation data generated after administering a drug to a model animal or wild-type animal with low cognitive or learning function with evaluation data generated for the model animal before administration of the drug, or for the same animal or animal of the same species as the model animal or wild-type animal without administration of the drug.

[0019] (Evaluation device) The evaluation device described in this specification comprises a judgment unit that judges a correct answer when it detects the movement of a target animal at a position associated with a correct answer a first number of times, which is two or more consecutive times, or judges a wrong answer when it detects the movement of the target animal at a position associated with an incorrect answer a second number of times, which is two or more consecutive times, and a supply device that supplies a reward or an aversive stimulus depending on the judgment result of the judgment unit.

[0020] (Program) The program described in this specification causes a computer to function as: a judgment unit that determines that the answer is correct when the movement of the target animal is detected at a position corresponding to the correct answer a first number of times, which is two or more consecutive times, or that the answer is incorrect when the movement of the target animal is detected at a position corresponding to the incorrect answer a second number of times, which is two or more consecutive times; a supply instruction unit that supplies a reward or an aversive stimulus depending on the judgment result of the judgment unit; and a memory unit that stores the judgment result of the judgment unit as evaluation data.

[0021] (Method for producing a trained non-human animal) The method for producing a trained non-human animal described in this specification includes repeatedly performing a determination step in which a correct answer is determined when a movement of a target animal, which is a non-human animal, is detected at a position corresponding to a correct answer a first number of times, which is two or more consecutive times, or a determination in which an incorrect answer is determined when a movement of the target animal is detected at a position corresponding to an incorrect answer a second number of times, which is two or more consecutive times, and a supply step in which a reward is supplied to the target animal or an aversive stimulus is supplied depending on the determination result of the determination step.

[0022] (Non-human Animal) The non-human animal described herein is a non-human animal that has a higher rate of correct answers in a determination in which a predetermined action of the non-human animal at a position associated with a correct answer is judged to be correct two or more times in a first consecutive number of times, and / or a predetermined action of the non-human animal at a position associated with an incorrect answer is judged to be incorrect two or more times in a second consecutive number of times, than a non-human animal of the same species that has not undergone learning training, and is preferably a non-human animal produced by the method for producing a trained non-human animal described herein. For example, the non-human animal of the present invention can be used for evaluating cognitive / learning functions.

[0023] According to the present invention, it is possible to improve the efficiency of learning and shorten the evaluation period of cognitive function or learning function.

[0024] 1 is a block diagram showing an example of the hardware configuration of an evaluation device according to a first embodiment of the present invention. FIG. 2 is a schematic diagram showing an animal chamber. FIG. 3 is a functional block diagram showing the functional configuration of an evaluation device. FIG. 4 is a flowchart showing a process for evaluating figure discrimination learning according to the first embodiment. FIG. 5 is a diagram showing the movement of a mouse when a correct behavior is performed. FIG. 6 is a diagram showing the movement of a mouse when a correct behavior is performed and a reward is given. FIG. 7 is a diagram showing the movement of a mouse when an incorrect behavior is performed. FIG. 8 is a diagram showing the movement of a mouse when an incorrect behavior is performed and a reward is not given. FIG. 9 is a diagram showing the movement of a mouse when an incorrect behavior is performed and an aversive stimulus is given. FIG. 10 is a diagram showing another example of mouse movement. FIG. 11 is a diagram showing examples of one pair of figures and three pairs of figures. FIG. 12 is a flowchart showing a process for evaluating reversal learning according to a second embodiment of the present invention. FIG. 13 is a flowchart of a process for evaluating figure discrimination learning according to a first modification. FIG. 14 is a diagram showing the movement of a mouse when an incorrect behavior is performed in the second modification. FIG. 15 is a diagram showing the movement of a mouse when an incorrect behavior is performed and a reward is not given in the second modification. FIG. 16 is a diagram showing an example of display of a correct figure and an incorrect figure in the third modification. FIG. 17 is a diagram showing an example of display of a correct figure and an incorrect figure in the third modification. 10 is a diagram showing mouse movements when incorrect behavior is performed in position discrimination learning according to Modification 4. FIG. 11 is a diagram showing another example of display in position discrimination learning according to Modification 4. FIG. 12 is a graph showing the correct answer rates for the one-touch method and the two-touch method in Example 1. FIG. 13 is a graph showing the correct answer rates for reversal learning in Example 2. FIG. 14 is a graph showing the correct answer rates for wild-type mice and autism model mice in Example 3. FIG. 15 is a graph showing the correct answer rates for the two-touch method and the three-touch method in Example 4. FIG. 16 is a graph showing the correct answer rates for Modifications 1 and 2 in Example 5. FIG. 17 is a graph showing the correct answer rates for a combination of Modification 1 (three-touch method) and Modification 2 in Example 6.

[0025] Embodiments of the present invention will be described with reference to the drawings. Note that the present invention is not limited to the following embodiments and drawings. Note that in the following embodiments, the expressions "have," "include," or "contain" also include the meaning of "consisting of" or "consisting of."

[0026] (Embodiment 1) An evaluation method according to this embodiment is a method for evaluating the cognitive function or learning function of a target animal that is a test subject by having the target animal perform an operant learning task. The operant learning task in this embodiment is a graphic discrimination learning task in which the target animal discriminates between graphics. Figure 1 is a block diagram showing an example of the hardware configuration of an evaluation device 1 that utilizes the evaluation method according to this embodiment 1.

[0027] 1, the evaluation device 1 comprises an information processing device 20 and an animal chamber 30. A touch panel 31 is provided on one surface of the inner wall of the animal chamber 30, and further, a feeder 32 is provided to feed food particles to a position of the animal chamber 30 away from the touch panel 31.

[0028] The information processing device 20 is any computer on which a program for evaluating graphic discrimination learning or the like is installed, and may be a general-purpose information processing terminal such as a personal computer, a smartphone, or a tablet terminal, or may be a dedicated terminal. The information processing device 20 includes, for example, a processor 21, a primary storage device 22, a secondary storage device 23, a communication interface 24, and an input unit 25, as shown in FIG.

[0029] The processor 21 of the information processing device 20 is, for example, a CPU (Central Processing Unit) and executes various processes, including the graphic discrimination learning evaluation process, by executing programs stored in the secondary storage device 23. The primary storage device 22 is, for example, a memory capable of high-speed data reading and writing, 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, such as a flash memory, and stores programs, setting values, image data, etc. for the processes executed by the processor 21.

[0030] The communication interface 24 is an interface for transmitting and receiving data to and from the touch panel 31 and the supply device 32. The communication method of the communication interface 24 is arbitrary, and may be, for example, wireless communication such as wireless LAN or short-range wireless communication, or wired communication such as USB. The input unit 25 accepts operations by the operator and outputs the input signal to the processor 21. The input unit 25 is composed of, for example, input buttons, a keyboard, a pointing device, etc.

[0031] Fig. 2 is a schematic diagram showing an animal chamber 30. The animal chamber 30 shown in Fig. 2 has a touch panel 31 and a supply device 32, and is a chamber whose periphery is surrounded by the touch panel 31 on one side. The target animal 2 can move freely inside the animal chamber 30. In Fig. 2, the outer periphery of the animal chamber 30 other than the touch panel 31 is omitted.

[0032] The display device 311 of the touch panel 31 is any display device that displays an image sent from the information processing device 20, such as a liquid crystal display or an organic EL (Electro-Luminescence) display. The image displayed by the display device 311 is an image in which two figures used for figure discrimination learning are arranged side by side, as shown in FIG. 2 . That is, the two figures are displayed in two predetermined display areas 313 and 314 of the display device 311. The contact sensor 312 of the touch panel 31 is disposed in front of the display device 311, and outputs a detection signal when contact of the target animal 2 with the display areas 313 and 314 of the display device 311 is detected.

[0033] A black plastic plate with two windows is installed on the front of the touch panel 31, and the positions of the two windows roughly coincide with the display areas 313 and 314, respectively. The size of the windows, i.e., the size of the two display areas 313 and 314, is, for example, 6 cm in height and 6 cm in width. The target animal 2 can only touch the screen through the two windows located on the left and right. In other words, the contact sensor 312 can detect contact with either of the positions corresponding to the two figures.

[0034] The feeder 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 a food tray 322 when the target animal 2 performs a first consecutive correct behavior two or more times. The feeder 32 and the food tray 322 are preferably located on opposite sides of the touch panel 31. The animal chamber 30 may further include a water bottle so that the target animal 2 can drink water freely. A speaker may also be provided inside or on the outer periphery of the animal chamber 30. In this case, the animal chamber 30 may be provided in a soundproof box.

[0035] The processor 21 executes a program for the graphic discrimination learning evaluation process stored in the secondary storage device 23, thereby functioning 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 an example of the functional configuration of the evaluation device 1.

[0036] The graphic acquisition unit 211 selects and acquires a pair of graphic images from the graphic images 231 stored in the secondary storage device 23, and outputs them to the display control unit 212. More specifically, a plurality of pairs of graphic images are stored in the secondary storage device 23. The graphics are, for example, patterned graphics as shown in FIG. 2. In this embodiment, one of the pair of graphic images is set as a correct graphic, and the other is set as an incorrect graphic. The graphic acquisition unit 211 acquires a pair of graphics that have been selected in advance based on an operation by the operator or randomly selected from the graphic images 231 stored in the secondary storage device 23, and outputs them to the display control unit 212.

[0037] The display control unit 212 displays the correct answer figure in a pre-designated one of the left and right display areas 313, 314, and displays the incorrect answer figure in the other. The display control unit 212 also outputs information indicating the display area of ​​the correct answer figure or the incorrect answer figure to the determination unit 213.

[0038] The determination unit 213 determines a correct answer when it detects a movement of the target animal 2 at a position corresponding to the correct answer figure two or more consecutive first times (preferably, contact of the target animal 2 at a position corresponding to the correct answer figure, for example, contact of the target animal 2 in the display area displaying the correct answer figure). Also, the determination unit 213 determines a wrong answer when it detects a movement of the target animal 2 at a position corresponding to the incorrect answer figure two or more consecutive second times (preferably, contact of the target animal 2 at a position corresponding to the incorrect answer figure, for example, contact of the target animal 2 in the display area displaying the incorrect answer figure). In this embodiment, a case will be described in which the determination unit 213 determines a correct answer when it detects contact of the target animal 2 in the display area displaying the correct answer figure two consecutive times, and determines a wrong answer when it detects contact of the target animal 2 in the display area displaying the incorrect answer figure two consecutive times.

[0039] First, when the contact sensor 312 detects contact of the target animal 2 with the touch panel 31, the determination unit 213 acquires information indicating whether the detected contact position is in the display area 313 or 314. When the display area where the contact was detected matches the display area in which the display control unit 212 has displayed the correct figure, the determination unit 213 determines that a correct behavior has been performed. On the other hand, when the display area where the contact was detected matches the display area in which the display control unit 212 has displayed the incorrect figure, the determination unit 213 determines that an incorrect behavior has been performed.

[0040] When the determination unit 213 determines that a correct action has been performed two consecutive times, it outputs the determination result of the correct answer 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 an incorrect action has been performed two consecutive times, it outputs the determination result of the incorrect answer to the secondary storage device 23, which is the storage unit, and adds it to the evaluation data 232. The evaluation data 232 thus accumulated in the storage unit may include statistical data such as the correct answer rate calculated from the determination results and changes in the correct answer rate over time. Throughout this specification, the term "correct answer rate" refers to the ratio of the number of correct answer determinations to the total number of determinations during a given period or number of times.

[0041] The determination unit 213 outputs the determination result to the display control unit 212 and the supply instruction unit 214. If the determination is correct, the display control unit 212 turns off the figures in all display areas, and the supply instruction unit 214 instructs the supply device 32 to supply food particles. The target animal 2 eats the food particles supplied to the food tray 322. In this way, the target animal 2 repeatedly experiences being given a reward in the form of food particles when it performs the correct behavior twice in a row, learns the behavior that will earn it a reward, and comes to intentionally perform the correct behavior twice in a row.

[0042] The operation of the evaluation device 1 configured as 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.

[0043] The subject animal 2 is any non-human animal used in behavioral experiments, such as a mouse. In this embodiment, a case where a mouse is used as the subject animal 2 will be described. The subject animal 2, that is, a mouse, is placed in an animal chamber 30 and performs a pattern discrimination learning task. To increase the mouse's motivation to perform the task, food may be restricted for the mouse during the task performance period. The animal chamber 30 is preferably placed in a soundproof box at a constant temperature to eliminate the influence of other environmental factors. The temperature is maintained at, for example, 23±1°C.

[0044] The process for evaluating graphic discrimination learning shown in the flowchart of Fig. 4 is performed on mice that have undergone prior training. As part of the prior training, first, habituation is performed to familiarize the mouse with the flow of food pellets. Food pellets are placed in a food dish 322 and the mouse is allowed to eat them, allowing the mouse to remember the relationship between the food dish 322 and the food pellets. Furthermore, a beep is sounded from a speaker 323 at the timing of feeding. By repeatedly eating the food pellets that are supplied with the beep, the mouse learns that food pellets are supplied with the beep over a period of one day to one week, typically several days.

[0045] After training, behavior shaping is performed to teach the mouse that touching a figure results in the provision of food particles. Specifically, the process of providing food particles when the mouse's nose, body, forelimbs, etc. touch the figure displayed on the touch panel 31 is repeated. At this point, the beep sound used in training is sounded at the timing of food provision. First, behavior shaping is performed over a period of one day to one week, typically several days, in which the figures in all display areas are turned off and food particles are provided upon one contact. Next, behavior shaping is performed over a period of one day to one week, typically several days, in which the figures in all display areas are turned off and food particles are provided upon a second contact (2-touches shaping). This allows the mouse to learn the relationship that touching a figure displayed on the touch panel 31 twice results in the provision of food particles over a period of one day to one week, typically several days.

[0046] For a mouse that has completed the preliminary training, the actual evaluation is started by the graphic discrimination learning evaluation process shown in the flowchart of Fig. 4. First, the processor 21 designates a pair of graphics from graphic images stored in the secondary storage device 23 based on the operator's operation or randomly, and also designates display areas in which to display the correct and incorrect graphics (step S101). More specifically, in step S101, the display areas in which to display the correct and incorrect graphics are designated from the display areas 313 and 314 located at the positions of the windows arranged on the left and right. The graphic acquisition unit 211 acquires the pair of correct and incorrect graphics designated in step S101.

[0047] 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). The display control unit 212 also passes information on the display areas 313 and 314 in which the correct figure or the incorrect figure is displayed to the determination unit 213.

[0048] Specifically, as shown in Figures 5A, 5B, 6A, and 6B, the display control unit 212 displays a correct figure and an incorrect figure in the display areas 313 and 314 specified in step S101, respectively, so that a pair of figures can be seen through two windows. Figure 5A shows the movement of the mouse when a correct behavior is performed, and Figure 5B shows a state in which a food pellet is given to the mouse as a reward when the correct behavior is performed twice consecutively. Figure 6A shows the movement of the mouse when an incorrect behavior is performed, and Figure 6B shows a state in which the mouse is not given a reward when the incorrect behavior is performed twice consecutively. Figures 5A, 5B, 6A, and 6B show cases in which the left of two figures is a correct figure and the right is an incorrect figure.

[0049] When the contact sensor 312 detects contact with the mouse, the determination unit 213 acquires information about the contacted display area from the contact sensor 312 and determines whether or not a correct behavior has been performed (step S103). The determination unit 213 determines that a correct behavior has been performed when it detects that the mouse has contacted the display area 313 in which the correct figure is displayed as shown in Fig. 5A (contact detection step). Furthermore, the determination unit 213 determines that an incorrect behavior has been performed when it detects that the mouse has contacted the display area 314 in which the incorrect figure is displayed as shown in Fig. 6A (contact detection step).

[0050] When it is determined that a correct action has been taken with respect to 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).

[0051] When it is determined that the mouse has performed the correct behavior in response to the displayed figure in step S104 (step S105: Yes), the correct behavior is determined to be correct because it has been performed twice in a row (step S106: determination step). Then, as shown in Fig. 5B, a beep sounds from the speaker 323, the display control unit 212 turns off the figures in all display areas, and the supply instruction unit 214 controls the supply device 32 to supply food pellets as a reward (step S107: supply step). This allows the mouse to eat the food pellets.

[0052] When it is determined that an incorrect behavior has been performed with respect to 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).

[0053] When it is determined that an incorrect behavior has been performed on the displayed figure in step S108 (step S109: No), it is determined that the incorrect behavior has been performed twice in a row, resulting in an incorrect answer (step S110: determination step). When an incorrect answer is determined, the supply instruction unit 214 simply outputs a buzzer sound with a lower pitch than a beep from the speaker 323, as shown in FIG. 6B, without issuing a supply instruction, and waits for a predetermined time (step S111). At this time, all figures in the display area are turned off. The mouse hears the buzzer sound and waits without being able to eat the food pellets.

[0054] When the determination unit 213 determines that a correct behavior has been performed for 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, and when a correct behavior has been performed twice in a row (step S105: Yes), it is determined to be a correct response (step S106), a reward is provided (step S107), but when an incorrect behavior has been performed twice in a row (step S109: No), it is determined to be an incorrect response (step S110), and the process waits (step S111).

[0055] After a reward is provided in step S107 or after waiting in step S111, the determination unit 213 adds a record of the correct answer or incorrect answer to the evaluation data 232 of the secondary storage device 23 (step S112: evaluation data generation step). Thereafter, if the operator does not perform an end operation (step S113: No), the process returns to step S101. If the operator performs an end operation (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.

[0056] If the answer is determined to be incorrect in step S105 but correct in step S109, the graphic display in steps S104 and S108 and the correct / incorrect judgment in steps S105 and S109 are repeated, but an upper limit may be set for the time for repeating the process. In this case, the judgment unit 213 may judge the answer to be incorrect when the upper limit time has elapsed, and add the judgment result to the evaluation data 232.

[0057] The evaluation data 232 may include statistical data calculated from the judgment results accumulated after performing any number of judgment steps (steps S106 and S110), two or more times, or from the judgment results accumulated after performing multiple judgment steps within a certain period of time. The statistical data may include, for example, the correct answer rate, which is the ratio of correct answers to all accumulated judgment results, or the change in the correct answer rate over time. The number of judgment steps for calculating the correct answer rate is not particularly limited as long as it provides the desired evaluation result, but may be set to, for example, 20 to 200 times, 50 to 150 times, or 100 times. Furthermore, when performing the judgment steps within a certain period of time to calculate the correct answer rate, the time required for performing the judgment steps may be set to 10 minutes to 1 hour, 20 to 40 minutes, or 30 minutes. Furthermore, the set number or duration of trials may be considered one session, and the change in the correct answer rate over time may be calculated when one session is performed per day. Information indicating the cognitive or learning function of the target animal 2 can be derived from the change in the correct answer rate over time.

[0058] A high rate of correct answers is evaluated as having high cognitive function or learning function, and a low rate of correct answers is evaluated as having low cognitive function or learning function. When evaluating cognitive function or learning function using the change in correct answer rate over time as an index, for example, a high rate of increase in the rate of correct answers is evaluated as having high cognitive function or learning function, and a low rate of increase in the rate of correct answers is evaluated as having low cognitive function or learning function. The evaluation of the high or low rate of correct answer or rate of increase can be performed using the rate of correct answer or rate of increase obtained by performing the evaluation method of this embodiment on the same target animal 2 or different target animals 2 at different times and / or under different conditions as an index, or can be performed using the rate of correct answer or rate of increase obtained by simultaneously performing the same evaluation method on different target animals 2 under different conditions as an index.

[0059] For example, when examining the cognitive or learning function of a model animal, which is a non-human animal with a specific genetic modification or disease, as the subject animal 2, the correct answer rate or rate of increase can be measured using the model animal and a wild-type animal of the same species, and the cognitive or learning function of the model animal can be evaluated based on the correct answer rate or rate of increase of the model animal relative to the correct answer rate or rate of increase of the wild-type animal. In other words, if the correct answer rate or rate of increase is higher than that of a wild-type animal, it can be evaluated that the cognitive or learning function is improved, and if the correct answer rate or rate of increase is lower than that of a wild-type animal, it can be evaluated that the cognitive or learning function is decreased.

[0060] Furthermore, the evaluation method according to the present embodiment can be used to evaluate the effects of a drug on cognitive or learning function by comparing evaluation data generated after administering a drug to a model animal or wild-type animal, which is a non-human animal with low cognitive or learning function, with evaluation data generated for the same model animal or wild-type animal before drug administration, or for an animal of the same species but without drug administration (drug evaluation step). If the correct answer rate or rate of increase in the animal after drug administration is higher than that before or without drug administration, the drug can be determined to have the effect of improving cognitive or learning function. If the correct answer rate or rate of increase in the animal after drug administration is the same or lower than that before or without drug administration, the drug can be determined to not improve (or impair) cognitive or learning function.

[0061] The evaluation results may be, for example, those obtained by evaluating animals after administration of a food or drug. They may be qualitative, such as whether cognitive function or learning function was improved, had no effect, or was impaired, or quantitative, such as the rate of correct answers. For example, by using a normal non-human animal that has ingested a test food or test drug as a subject animal and evaluating its cognitive function or learning function using the evaluation method of this embodiment, it is possible to evaluate whether the test food or test drug improves, has no effect, or impairs cognitive function or learning function. Preferably, a normal non-human animal of the same species that has not ingested the test food or test drug may be used as a control subject animal to evaluate its cognitive function or learning function using the evaluation method described in this embodiment. The cognitive function or learning function of the control may be compared with that of a normal non-human animal that has ingested the test food or test drug to evaluate whether the test food or test drug improves, has no effect, or impairs cognitive function or learning function. Alternatively, model animals with poor learning ability that have been administered a test food or test drug can be used as subject animals to evaluate their cognitive and learning functions using the evaluation method of the present embodiment, thereby assessing whether the test food or test drug improves, has no effect on, or impairs the cognitive and learning functions of the model animals. Preferably, the cognitive and learning functions of the same species of normal non-human animal that has not been administered the test food or test drug (positive control) and / or the same species of model animal with poor learning ability (negative control) can be used as control subject animals to evaluate the cognitive and learning functions using the evaluation method of the present embodiment. The cognitive and learning functions of the control animals can be compared with those of normal non-human animals administered the test food or test drug to assess whether the test food or test drug improves, has no effect on, or impairs the cognitive and learning functions of the model animals.

[0062] The following describes the effect of the evaluation method according to this embodiment, in which a correct answer is determined to be correct if a correct action is performed multiple times, for example, two consecutive times, and an incorrect answer is determined to be incorrect if an incorrect action is performed multiple times, for example, two consecutive times. When a correct answer is determined based on a single correct action or an incorrect answer is determined based on a single incorrect action, even if the mouse accidentally touches the touch panel 31 unintentionally, it takes time to learn the relationship between the correct figure and the touch. In contrast, according to the evaluation method according to this embodiment, a correct answer or an incorrect answer is determined based on a correct or incorrect action performed multiple times, for example, two consecutive times, thereby reducing the influence of unintentional actions and improving learning efficiency.

[0063] In other words, a trained non-human animal that can correctly answer questions at a higher rate than non-trained non-human animals can be produced by a production method that repeatedly performs a determination step in which a correct response is determined when a correct response is observed multiple times, for example, two consecutive times, and an incorrect response is determined when an incorrect response is observed multiple times, for example, two consecutive times, and a supply step in which a reward or an aversive stimulus is provided depending on the determination result of the determination step. Training may take one to two sessions, where one trial is defined as the period from the display of a graphic to the provision of a reward or an aversive stimulus, and one session is defined as the completion of 100 trials or 30 minutes after the start of trials. The method for producing a trained non-human animal may also be a method for preparing a trained non-human animal.

[0064] Furthermore, non-human animals that have undergone training that includes a judgment step in which a correct response is judged to be correct if the correct response occurs multiple times, for example, two times in a row, and an incorrect response is judged to be incorrect if the incorrect response occurs multiple times, for example, two times in a row, and a supply step in which a reward or an aversive stimulus is supplied depending on the judgment result of the judgment step, are able to answer correctly at a higher rate than non-human animals that have not undergone training.

[0065] As described above, in the evaluation method according to this embodiment, a correct answer pattern and an incorrect answer pattern are displayed in the display areas 313, 314 of the display device 311, respectively, and when contact of the target animal 2 with the correct answer pattern is detected twice in a row, the determination unit 213 determines that the answer is correct. If the answer is determined to be correct, a reward is provided, and the determination result is stored as evaluation data 232. This makes it possible to improve learning efficiency and shorten the evaluation period for cognitive function. Furthermore, shortening the evaluation period makes it possible to apply the method to preclinical trials of drug discovery targeting psychiatric disorders, neurological disorders, etc.

[0066] In this embodiment, the evaluation device 1 provides a food pellet as a reward when correct behavior is detected twice consecutively. However, a liquid such as water, milk, or juice may also be used as a reward. Furthermore, as shown in FIGS. 7A and 7B , an aversive stimulus 324 may be provided to the target animal 2 when incorrect behavior is detected twice consecutively. The aversive stimulus 324 may be, for example, a weak current (e.g., approximately 0.2 mA) applied to a stainless steel grid installed on the floor, as shown in FIG. 7B . When the stainless steel grid comes into contact with the foot of the target animal 2, a weak current flows, resulting in an aversive stimulus known as a foot shock. In this case, a food pellet may be provided when correct behavior is detected twice consecutively, or the target animal may wait without providing any food pellet.

[0067] Furthermore, in the present embodiment, the correct or incorrect behavior is determined based on contact with the display areas 313, 314 that display the correct or incorrect symbol, but this is not limited to this. The correct or incorrect behavior may also be determined based on contact at any position associated with the correct or incorrect symbol. For example, as shown in FIG. 8, the correct or incorrect behavior may be determined based on contact with a push-button switch 325 provided directly below the display areas 313, 314 that display the correct or incorrect symbol.

[0068] Furthermore, in this embodiment, patterned figures are exemplified as the correct figure and the incorrect figure in FIG. 2 , but this is not limiting. The correct figure and the incorrect figure may be any figure as long as they are a pair of figures that are different from each other. For example, the correct figure and the incorrect figure may be a pair of figures that are different in brightness, and the target animal 2 may be made to perform a brightness discrimination learning task to distinguish between brightnesses. Furthermore, the correct figure and the incorrect figure may be a pair of figures that are different in color, and the target animal 2 may be made to perform a color discrimination learning task to distinguish between colors. Furthermore, the correct figure and the incorrect figure may be a pair of moving images in which the figures move in different directions, and the target animal 2 may be made to perform a movement direction discrimination learning task to distinguish between movement directions.

[0069] (Embodiment 2) Similar to Embodiment 1, the evaluation method according to Embodiment 2 is a method of having a target animal 2 perform an operant learning task and evaluating the cognitive function or learning function of the target animal 2. The hardware configuration of an evaluation device 1 using the evaluation method according to this embodiment is similar to that of Embodiment 1.

[0070] In the evaluation method according to this embodiment, the figure acquisition unit 211 acquires a pair of figures from the secondary storage device 23 based on the operator's operation or randomly designated, and the display control unit 212 displays a pair of correct and incorrect figures, and determines whether the target animal 2 is behaving correctly or incorrectly in response to these figures.

[0071] In the first embodiment, one of a pair of figures is set in advance as a correct figure and the other as an incorrect figure, but in the evaluation method according to the present embodiment, the display control unit 212 switches between the correct figure and the incorrect figure and displays them, and the determination unit 213 determines whether the target animal 2 behaves correctly or incorrectly in response to this display. Hereinafter, figure discrimination learning performed by switching between the correct figure and the incorrect figure and displaying them is also referred to as reversal learning.

[0072] The operation of the evaluation device 1 according to this embodiment will be described in detail with reference to Figures 9 and 10. Figure 9 shows an example of one pair of figures P and three pairs of figures A, B, and C. Note that, in this embodiment, a case will be described in which pattern figures are used as the correct and incorrect figures, but the figures are not limited to pattern figures and may be any mutually different figures that make up a pair. Figure 10 is a flowchart of the reversal learning evaluation process.

[0073] Before starting the actual evaluation, the target animal 2, a mouse, undergoes preliminary training such as habituation and behavior formation similar to that in Embodiment 1. In the behavior formation training, for example, a pair of figures P shown in Fig. 9 is used to teach the mouse the process of being supplied with food pellets by touching the figures displayed on the touch panel 31. After the training, the actual evaluation is started using the reversal learning evaluation process shown in the flowchart of Fig. 10.

[0074] In this embodiment, the figure discrimination learning evaluation is repeated by changing the pair of figures. The figure discrimination learning evaluation at each step in Fig. 10 is the same as that explained in the first embodiment using the flowchart in Fig. 4. First, processor 21 performs the figure discrimination learning evaluation shown in Fig. 4 using one pair P of figures, with the figure on the left in Fig. 9 as the correct figure and the figure on the right as the incorrect figure (step S201).

[0075] After a predetermined rate of correct answers is obtained in step S201, processor 21 performs a figure discrimination learning evaluation in the original phase using three pairs of figures A, B, and C (step S202). At this time, display control unit 212 sets the left figure of pair A, B, and C figures shown 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 in Fig. 4, processor 21 designates one pair of figures from pair A, B, and C based on an operation by the operator or randomly, and designates display areas 313 and 314 in which the correct figure and the incorrect figure are to be displayed, respectively.

[0076] Next, in step S102, the display control unit 212 displays the correct and incorrect symbols in the display areas 313 and 314 specified in step S101, and passes information about the display areas 313 and 314 in which the correct or incorrect symbol is displayed to the determination unit 213. In steps S104 and S108, the display control unit 212 displays the same symbols as those displayed in step S102 as the correct and incorrect symbols in the same display areas 313 and 314. Using the symbols displayed in this way, a determination is made in steps S103, S105, and S109 as to whether the behavior is correct or incorrect, and a determination is made that the behavior is correct if two consecutive correct answers are given, and an incorrect answer if two consecutive incorrect answers are given.

[0077] After a correct answer rate equal to or greater than a predetermined value is obtained in step S202, the processor 21 performs a reverse phase figure discrimination learning evaluation in which the correct and incorrect answer figures of the three pairs A, B, and C are swapped (step S203). At this time, the display control unit 212 sets the right figure of the figures in the pairs A, B, and C shown in Fig. 9 as the correct answer figure and the left figure as the incorrect answer figure, and performs the figure discrimination learning evaluation shown in Fig. 4. More specifically, in step S101 of the flowchart in Fig. 4, the processor 21 designates a pair of figures from the figures in the pairs A, B, and C based on the operator's operation or randomly, and designates display areas 313 and 314 in which the correct answer figure and the incorrect answer figure are to be displayed, respectively.

[0078] Next, in step S102, the display control unit 212 displays the correct and incorrect symbols in the display areas 313 and 314 specified in step S101, and passes information about the display areas 313 and 314 in which the correct or incorrect symbol is displayed to the determination unit 213. In steps S104 and S108, the display control unit 212 displays the same symbols as those displayed in step S102 as the correct and incorrect symbols in the same display areas 313 and 314. Using the symbols displayed in this way, a determination is made in steps S103, S105, and S109 as to whether the behavior is correct or incorrect, and a determination is made that the behavior is correct if two consecutive correct answers are given, and an incorrect answer if two consecutive incorrect answers are given.

[0079] After a predetermined percentage of correct answers is obtained in step S203, processor 21 performs a re-reversed phase of figure discrimination learning evaluation in which the correct and incorrect figures of the three pairs A, B, and C are swapped (step S204). That is, processor 21 performs the same figure discrimination learning evaluation as in the original phase of step S202.

[0080] After a predetermined percentage of correct answers is obtained in step S204, the processor 21 performs a third reversal phase of the figure discrimination learning evaluation in which the correct and incorrect figures of the three pairs 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. Thereafter, the processor 21 ends the process.

[0081] The judgment results obtained in each graphic discrimination learning are accumulated as evaluation data 232. The evaluation data 232 may include judgment results accumulated by performing any number of judgment steps (steps S106 and S110 in FIG. 4 ) (two or more times) in each graphic discrimination learning, or statistical data calculated from judgment results accumulated by performing multiple judgment steps within a certain period of time. The statistical data may include, for example, a correct answer rate, which is the ratio of correct answer judgments to all accumulated judgment results, or a change in the correct answer rate over time, or information indicating the flexibility of cognitive function or learning function derived based on the correct answer rate or a change in the correct answer rate over time.

[0082] The number of judgment steps for calculating the correct answer rate, or the time for which the judgment steps are performed within a certain time period for calculating the correct answer rate, can be set arbitrarily, as in embodiment 1. In each pattern discrimination learning, a set number of trials or time period may be considered as one session, and the change in the correct answer rate over time when one session is performed per day may be calculated. Information indicating the flexibility of the cognitive function or learning function of the target animal 2 can be derived from the change in the correct answer rate over time when reversal learning is performed.

[0083] Here, flexibility of cognitive or learning functions is an indicator of the ability to flexibly change one's way of thinking in response to changes in the external environment, and a person can be evaluated as having high flexibility when they are able to quickly recognize that they have reversed the task and flexibly answer the task correctly.

[0084] For example, in this embodiment, if the rate of increase in the rate of correct answers within a certain period of time after swapping the correct and incorrect figures is high, the flexibility of the cognitive function or learning function is evaluated as high, and if the rate of increase in the rate of correct answers is low, the flexibility of the cognitive function or learning function is evaluated as low. The level of the rate of increase in the rate of correct answers can be evaluated using as an index the rate of increase in the rate of correct answers obtained by performing the evaluation method of this embodiment on the same target animal 2 or different target animals 2 at different times and / or under different conditions, or the rate of increase in the rate of correct answers obtained by simultaneously performing the same evaluation method on different target animals 2 under different conditions.

[0085] For example, when examining the flexibility of the cognitive or learning function of a model animal with a specific genetic modification or disease as the subject animal 2, the rate of increase in the correct answer rate can be measured using the model animal and a wild-type animal of the same species, and the level of the flexibility of the cognitive or learning function of the model animal can be evaluated based on the level of the increase in the correct answer rate of the model animal relative to the increase in the correct answer rate of the wild-type animal. In other words, if the rate of increase in the correct answer rate within a certain period of time after swapping the correct and incorrect figures is high compared to wild-type animals, the flexibility of the cognitive or learning function can be evaluated as high, and if the rate of increase in the correct answer rate is low compared to wild-type animals, the flexibility of the cognitive or learning function can be evaluated as low.

[0086] Furthermore, the evaluation method according to this embodiment can also be used to evaluate the effect of a drug on the flexibility of cognitive or learning functions by comparing evaluation data generated after administering a drug to a model animal or wild-type animal with low flexibility of cognitive or learning functions with evaluation data generated for the same animal or animal of the same species as the model animal or wild-type animal before administration of the drug (drug evaluation step).

[0087] In the evaluation method according to the present embodiment, correct or incorrect answers are determined based on two consecutive correct or incorrect actions, which improves the learning efficiency of each pattern discrimination learning task and significantly shortens the overall evaluation period.

[0088] In this embodiment, the figure discrimination learning evaluation is performed in the order of the original phase, the reversed phase, the second reversed phase, and the third reversed phase, but the number of times the correct and incorrect figures are reversed is arbitrary. Only the original phase and the reversed phase may be performed, or the third reversed phase may be followed by a further reversed figure discrimination learning evaluation.

[0089] As described above, in the evaluation method according to this embodiment, graphic discrimination learning is performed using multiple pairs of correct and incorrect figures, then graphic discrimination learning is performed using reversed correct and incorrect figures, and then reversal learning is repeatedly performed. This makes it possible to improve learning efficiency and shorten the evaluation period even in the evaluation of the flexibility of cognitive function or learning function. Furthermore, shortening the evaluation period makes it possible to apply this method to preclinical trials of drug discovery targeting psychiatric disorders, neurological disorders, etc.

[0090] Various modifications are possible to the above-described first and second embodiments, and modifications will be described with reference to the drawings.

[0091] (Modification 1) The hardware configuration and functional configuration of the evaluation device 1 using the evaluation method according to Modification 1 are the same as those in Embodiment 1. In the above-described Embodiment 1, the determination unit 213 determines whether the answer is correct or incorrect when a correct or incorrect action is performed twice consecutively, but in this modification, the determination unit 213 determines whether the answer is correct or incorrect when a correct or incorrect action is performed three times consecutively.

[0092] 11 is a flowchart of the graphic discrimination learning evaluation process according to this modified example. After preliminary training similar to that of the first embodiment, the actual 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 graphic images stored in the secondary storage device 23 based on the operator's operation or randomly, and also designates display areas in which to display the correct and incorrect graphics (step S101). More specifically, in step S101, the processor 21 designates a display area in which to display the correct and incorrect graphics from among the display areas 313 and 314 located at the positions of the windows on the left and right. The graphic acquisition unit 211 acquires the pair of correct and incorrect graphics designated in step S101.

[0093] Thereafter, the display control unit 212 displays the pair of correct and incorrect figures acquired by the figure acquisition unit 211 in the display areas 313 and 314 specified in step S101 (step S102: display step).

[0094] When the contact sensor 312 detects contact with the mouse, the determination unit 213 acquires information about the contacted display area from the contact sensor 312 and determines whether the correct action has been taken (step S103). When it is determined that the correct action has been taken with respect to 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).

[0095] When the mouse performs a correct behavior 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 and incorrect figures in the same display areas 313 and 314, respectively (step S304). When it is determined that the mouse has performed a correct behavior on the figure displayed in step S304 (step S305: Yes), the mouse is determined to have performed the correct behavior three times in a row, resulting in a correct response (step S106). Thereafter, the supply instruction unit 214 sounds a beep from the speaker 323 and controls the supply device 32 to supply food pellets as a reward (step S107). This allows the mouse to eat the food pellets.

[0096] When it is determined that an incorrect behavior has been performed with respect to 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 in the same display areas 313 and 314, respectively (step S108).

[0097] When it is determined that an incorrect behavior has been performed with respect to the displayed figure in step S108 (step S109: No), the display control unit 212 displays the same figures as those displayed in step S102 as the correct and incorrect figures in the same display areas 313 and 314, respectively (step S308). When it is determined that an incorrect behavior has been performed with respect to the displayed figure in step S308 (step S309: No), it determines that an incorrect response has been made because the incorrect response has been performed three times in a row (step S110). When it determines that an incorrect response has been made, the supply instruction unit 214 simply outputs a buzzer sound with a lower pitch than a beep from the speaker 323, does not issue a supply instruction, and waits for a predetermined time (step S111). The mouse listens to the buzzer sound and waits without being able to eat the food pellets.

[0098] When the determination unit 213 determines that a correct behavior has been performed for 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, and when a correct behavior has been performed three times in a row (step S305: Yes), it is determined to be a correct response (step S106), and a reward is provided (step S107). When an incorrect behavior has been performed three times in a row (step S309: No), it is determined to be an incorrect response (step S110), and the process waits (step S111).

[0099] After the reward is provided in step S107 or after waiting in step S111, the determination unit 213 adds a record of the correct answer or incorrect answer to the evaluation data 232 of the secondary storage device 23 (step S112). 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.

[0100] If the answer is determined to be incorrect in step S105 or step S305 and to be correct in step S109 or step S309, the graphic display in steps S104, S304, S108, and S308 and the correct / incorrect judgment in steps S105, S305, S109, and S309 are repeated, but an upper limit may be set for the time for repeating the process. In this case, if the upper limit time is exceeded, the answer is determined to be incorrect, and the judgment result may be added to the evaluation data 232.

[0101] As described above, according to the determination method of this modified example, in which a correct answer is determined if there are three consecutive correct actions, and an incorrect answer is determined if there are three consecutive incorrect actions, the influence of unintentional actions such as accidentally touching the touch panel 31 can be reduced compared to when determining whether an answer is correct or incorrect based on a single correct or incorrect action, thereby improving learning efficiency.

[0102] In addition, the first number of times, which is the number of consecutive correct behaviors, and the second number of times, which is the number of consecutive incorrect behaviors, for determining whether an answer is correct or incorrect are set to two in the first embodiment and three in this modification, but may be set to four or more. The first number and the second number of times may be determined depending on the type of target animal 2. For example, when an animal with a more cognitive function than a mouse is used as the target animal 2, any number of times equal to or greater than three may be selected.

[0103] Furthermore, in the evaluation method according to the second embodiment, the first number of consecutive correct behaviors or the second number of consecutive incorrect behaviors may be three or more to determine whether a response is correct or incorrect. Furthermore, the first number of consecutive correct behaviors and the second number of consecutive incorrect behaviors may be the same as in the first and second embodiments and this modification, or may be different numbers. That is, the determination unit 213 may determine a response as correct when detecting two or more consecutive correct behaviors the first number of times, and may determine a response as incorrect when detecting two or more consecutive incorrect behaviors the second number of times. The first and second numbers can be set appropriately depending on the type of target animal 2, and may be, for example, two, three, four, five, or six times. Note that a larger number of times is not necessarily better; it is preferable that the number of times be within a range that allows the target animal 2 to recognize that it has come into contact multiple times.

[0104] (Variation 2) The hardware configuration and functional configuration of the evaluation device 1 using the evaluation method according to Variation 2 are the same as those of Embodiment 1. In the above-described Embodiment 1 or Variation 1, the determination unit 213 determines an incorrect answer when an incorrect action is performed a second number of times (two or more times consecutively), and then sounds a buzzer and waits. In contrast, in this variation, as shown in FIG. 12A , when an incorrect action is detected a second number of times consecutively and a wrong answer is determined, no reward is provided as shown in FIG. 12B , and the display control unit 212 displays a white color in the display areas 313 and 314 that previously displayed a pair of figures, instead of turning off all figures in the display areas. When the display control unit 212 displays a white color, the supply instruction unit 214 may or may not sound a buzzer. Furthermore, the displayed color may be any light color other than white.

[0105] According to this modified example, by performing the incorrect behavior a second number of times (two or more times) in succession, it becomes easier for the target animal 2 to visually recognize that it has been judged to have given an incorrect response, and since small animals such as mice have a tendency to avoid bright illumination inside the chamber caused by a white display, the learning effect is improved.

[0106] (Variation 3) In the above-described embodiments 1 and 2 and variations 1 and 2, the determination unit 213 determines a correct answer when the target animal 2 contacts a position corresponding to one correct answer figure a first number of times in a row (two or more times), and determines a wrong answer when the target animal 2 contacts a position corresponding to one incorrect answer figure a second number of times in a row (two or more times), but this is not limited to this. In this variation 3, there are two or more incorrect answer figures, and the determination unit 213 determines a correct answer when the target animal 2 contacts a position corresponding to one correct answer figure a first number of times in a row, and determines a wrong answer when the target animal 2 contacts a position corresponding to one of two or more incorrect answer figures a second number of times in a row. Figure 13A is a display example in which one correct answer figure and two incorrect answer figures are displayed, and Figure 13B is a display example in which one correct answer figure and four incorrect answer figures are displayed.

[0107] 13A and 13B, in steps S102, S104, S108, S304, and S308 of Figures 4 and 11, the display control unit 212 displays one correct answer figure and two or more incorrect answer figures in three or more display areas 315. At this time, a black plastic plate having the same number of windows as the number of display areas 315 is installed on the front of the touch panel 31, and the one correct answer figure and two or more incorrect answer figures are displayed in the display areas 315 located in each window.

[0108] In this state, the contact sensor 312 detects contact of the target animal 2 at positions corresponding to one correct figure and two or more incorrect figures. The determination unit 213 then determines that a correct behavior has been performed when the contact sensor 312 detects contact at a position corresponding to the correct figure (steps S103, S105, S109, S305, S309: Yes). On the other hand, the determination unit 213 determines that an incorrect behavior has been performed when the contact sensor 312 detects contact at a position corresponding to one of two or more incorrect figures (steps S103, S105, S109, S305, S309: No). Other processing is the same as in the first and second embodiments or the first and second modifications.

[0109] In this way, in this modified example, cognitive function can be evaluated using a task in which the correct figure is selected from a choice of three or more figures.

[0110] (Variation 4) In the above-described embodiments 1 and 2 and variations 1-3, the target animal 2 performs figure discrimination learning, and the determination unit 213 determines a correct answer when it detects contact of the target animal 2 at a position corresponding to the correct answer figure a first number of times in a row, two or more times in a row, and determines a wrong answer when it detects contact of the target animal 2 at a position corresponding to one or more incorrect answer figures a second number of times in a row, but this is not limited to this. In this variation 4, the target animal 2 performs position discrimination learning to select a position according to the displayed figure. That is, the determination unit 213 determines a correct answer when it detects contact of the target animal 2 at a position corresponding to the correct answer a first number of times in a row, and determines a wrong answer when it detects contact of the target animal 2 at a position corresponding to the incorrect answer a second number of times in a row.

[0111] For example, when a pre-specified figure is displayed in two left and right display areas 313, 314, one of the display areas may be associated with the correct answer, and the other display area may be associated with the incorrect answer. Alternatively, as shown in Figures 14A, 14B, and 14C, when a pre-specified figure is displayed in three left, center, and right display areas 316, one of the display areas 316 may be associated with the correct answer, and the remaining display areas 316 may be associated with the incorrect answer. Alternatively, for two top and bottom display areas or three top, middle, and bottom display areas, one of the display areas may be associated with the correct answer, and the remaining display areas may be associated with the incorrect answer.

[0112] As shown in Figures 14A, 14B, and 14C, the same figure is simultaneously displayed in each display area 316. When the central display area 316 is associated with the correct answer for the displayed figures in Figures 14A and 14B, it is determined that a correct behavior has been performed in the case of Figure 14A where contact is detected in the central display area 316, and it is determined that an incorrect behavior has been performed in the case of Figure 14B where contact is detected in the right display area 316. When the right display area 316 is associated with the correct answer for the displayed figure in Figure 14C, it is determined that a correct behavior has been performed in the case of Figure 14C where contact is detected in the right display area 316. This allows position discrimination learning to be performed.

[0113] Furthermore, the motion at the positions associated with the correct and incorrect answers may be any motion other than contact. For example, instead of the contact sensor 312, a pressure sensor or the like may be provided to detect the motion of pressing the positions associated with the correct or incorrect answers. Furthermore, when the positions associated with the correct and incorrect answers are placed on the floor, the motion of staying at the positions associated with the correct or incorrect answers may be detected. That is, the determination unit 213 determines the answer as correct when it detects a predetermined motion of the target animal 2 at the position associated with the correct answer a first number of times in a row, and determines the answer as incorrect when it detects a predetermined motion of the target animal 2 at the position associated with the incorrect answer a second number of times in a row.

[0114] In this way, in this modified example, cognitive function can be evaluated using a task in which an arbitrary movement is performed at a position associated with a correct or incorrect answer.

[0115] The hardware configurations, functional configurations, and flowcharts shown in the first and second embodiments and modifications 1 to 4 are merely examples, and can be modified and applied as desired.

[0116] For example, in the above-mentioned embodiments 1 and 2 and variant 1-4, in step S101 of the figure discrimination learning evaluation process shown in FIG. 4, a pair of figures and a display area for displaying the correct and incorrect figures are designated based on the operator's operation or randomly, but the same pair of figures may be designated repeatedly in step S101.

[0117] Furthermore, in the above embodiments 1 and 2 and variants 1-4, the correct answer figure and one or more incorrect answer figures are simultaneously displayed in two or more display areas of one display device 311, but it is also possible to provide two or more display devices 311 and display the correct answer figure and one or more incorrect answer figures on each display device 311.

[0118] The evaluation methods according to the above-described embodiments 1 and 2 and modifications 1-4 can be used as methods for evaluating cognitive function or learning function depending on the purpose. Furthermore, the evaluation methods according to the above-described embodiments 1 and 2 and modifications 1-4 may include, prior to the evaluation step, a training step in which a method similar to the evaluation method is performed for a certain period of time or a certain number of trials. Alternatively, the above-described method for producing a trained non-human animal can be performed using a target animal that has been trained in advance by performing the method for producing a trained non-human animal for a certain period of time or a certain number of trials. For example, if one trial is defined as the time from when a graphic is displayed until a pellet of food is dispensed, and one session is defined as the completion of 100 trials or 30 minutes after the start of trials, the training may last for one to two sessions.

[0119] In the evaluation methods, evaluation devices, and programs according to the above-described first and second embodiments and modifications 1-4, the subject animal used is not particularly limited as long as it is a non-human animal. Examples of non-human animals that can be used include normal non-human animals, wild-type non-human animals, non-human model animals with low cognitive or learning functions, and non-human model animals with high cognitive or learning functions. Non-human animals may be, for example, rodents such as mice, rats, and guinea pigs, or non-rodents such as dogs, marmosets, and monkeys. Furthermore, in the evaluation methods, evaluation devices, and programs according to the above-described first and second embodiments and modifications 1-4, the subject animal used may be a non-human animal that has undergone the training described in the above-described embodiments and modifications, or a non-human animal that has not undergone such training.

[0120] The functions realized by the processor 21 of the information processing device 20 according to the first and second embodiments and modifications 1 to 4 can be realized by using a normal computer system, not a dedicated system.

[0121] For example, a computer capable of realizing each function may be configured by distributing a program for executing the operations of the above-described embodiments and modifications on a computer-readable recording medium such as a CD-ROM (Compact Disc Read-Only Memory), a DVD (Digital Versatile Disc), an MO (Magneto Optical Disc), or a memory card, and installing the program on the computer. If each function is realized by sharing the work between an OS (Operating System) and an application, or by cooperation between the OS and an application, only the parts other than the OS may be stored on the recording medium.

[0122] The present invention will be explained in more detail with reference to the following examples, but the present invention is not limited to these examples.

[0123] Example 1 C57BL / 6 mice were used as the subject animals 2. To increase their motivation to perform the task, the mice were subjected to food restriction during the task performance period. The mice were 10 weeks or older at the start of food restriction. The mice, which had been fed ad libitum, were housed individually and, from the second day of breeding, were given a set amount of food while their weights were measured. Food restriction was performed so that the mice's weights were within 85% to 90% of their weights at the ad libitum feeding level before individual breeding. Mice that had reached the target weight after food restriction were subjected to graphic discrimination learning using the evaluation device 1 according to embodiment 1, and the learning state was evaluated. A modified version of a touch panel operant experimental device manufactured by Ohara Medical Industries Co., Ltd. was used as the evaluation device 1.

[0124] The feed pellets supplied by the feeder 32 were 10 g of TestDiet feed pellets (AIN-76A Rodent Tablet; TestDiet, St. Louis, MO, USA). The animal chamber 30 was housed in a soundproof box, and a speaker 323 was installed inside the soundproof box. The temperature inside the animal chamber 30 was set to 23±1°C.

[0125] 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 lasted 30 minutes, and the mouse was allowed to eat 10 food pellets from the food dish during the first 15 minutes to learn the relationship between the food dish and the food pellets. During the last 15 minutes, one food pellet was provided every 30 seconds accompanied by a short beep. This allowed the mouse to learn that food pellets were provided along with the beep. By repeating one 30-minute session two or three times a day, the mouse learned to eat all of the food pellets without leaving any behind. The habituation process was completed when the mouse learned to eat all of the food pellets without leaving any behind.

[0126] After training was complete, the mouse moved on to the behavior shaping process. In this process, the same figure was displayed in two display areas 313 and 314 of the display device 311. When the mouse's nose, body, or forelimbs touched either display area 313 or 314, a beep sound, the same as used in training, was heard and one food pellet was delivered. First, the mouse was shaped to receive a food pellet upon one contact, and then to receive a food pellet upon two consecutive contacts (2-touches shaping). This allowed the mouse to learn the relationship that a food pellet would be delivered if it touched the displayed figure twice.

[0127] One trial was defined as the time from when the figure was displayed until the food pellets were dispensed, and one session ended when 100 trials had been completed or 30 minutes had passed. Mice underwent one training session per day. 100 trials were completed within 30 minutes of one session, and the behavioral formation process was completed when the mice were able to eat 100 food pellets. In this example, by conducting five or six sessions of training in which food pellets were dispensed upon one contact, the mice were able to complete 100 trials within 30 minutes. By conducting one or two subsequent sessions of training in which food pellets were dispensed upon two contacts, the mice were able to complete 100 trials within 30 minutes.

[0128] After completing the behavioral training, the mice were evaluated using the evaluation method according to embodiment 1. In all trials of this example, the figure displayed on the display device 311 was the pair P shown in FIG. 9 . FIG. 15 is a graph showing the accuracy rate when mice were trained to discriminate between figures using the evaluation method according to embodiment 1 (hereinafter referred to as the "two-touch method"). For comparison, FIG. 15 also shows the results of evaluation using a method in which a single correct response is determined as a correct response and a single incorrect response is determined as an incorrect response (hereinafter referred to as the "one-touch method"). Note that when evaluating using the one-touch method for comparison, only training in which food pellets are delivered with one touch was performed during behavioral training prior to evaluation; training in which food pellets are delivered with two touches was omitted.

[0129] In Figure 15, the horizontal axis indicates the number of sessions, with one session being defined as 100 trials in which correct or incorrect answers were judged, or as a trial that ended 30 minutes after the start of the trial. The horizontal axis represents the progress of one session per day. The vertical axis represents the percentage of correct answers per session. The values ​​and error bars shown in the graph in Figure 15 represent the average value for nine mice and the 95% confidence interval.

[0130] As is clear from Figure 15, with the one-touch evaluation method, the correct answer rate was below 60% even in the sixth session. On the other hand, with the two-touch evaluation method according to embodiment 1, the correct answer rate exceeded 80% in the sixth session. Thus, the evaluation method according to embodiment 1 significantly improved learning efficiency.

[0131] Example 2 Using the evaluation method according to embodiment 2, mice that had undergone the same pre-training as in Example 1 were evaluated. According to the flowchart in FIG. 10, first, a figure discrimination learning evaluation was performed using a pair of figures (step S201). The pair of figures used in this experiment was the pair P shown in FIG. 9, with the vertically striped figure on the left set as the correct figure and the horizontally striped figure on the right 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 continued until the correct answer rate was 80% or higher for several days.

[0132] Next, a three-pair figure discrimination learning evaluation was conducted (step S202). The three pairs of figures used in this evaluation were pairs A, B, and C shown in FIG. 9, and the left figure was designated as the correct figure and the right figure as the incorrect figure in the original phase combination. One session of the three-pair figure discrimination learning evaluation ended when 150 trials or 45 minutes had elapsed. One session was conducted per day, and continued until the correct answer rate was 80% or higher for several days.

[0133] Next, a reversal phase in which the correct and incorrect figures were swapped was performed to evaluate the figure discrimination learning (step S203). The learning flow was the same as in step S202. Next, a second reversal phase in which the correct and incorrect figures were swapped was performed again to evaluate the figure discrimination learning (step S204). Finally, a third reversal phase in which the correct and incorrect figures were swapped again was performed to evaluate the figure discrimination learning (step S205).

[0134] Figure 16 shows the percentage of correct answers when mice were trained to discriminate between shapes using the evaluation method (two-touch method) according to embodiment 2. For comparison, Figure 16 also shows the results of evaluation using a method in which a single correct action is judged as a correct answer and a single incorrect action is judged as an incorrect answer (single-touch method). Note that when evaluating using the single-touch method for comparison, only training in which food pellets are delivered with one touch was performed in the behavioral formation prior to evaluation, and training in which food pellets are delivered with two touches was omitted.

[0135] In Figure 16, the horizontal axis represents the progress of one session per day. The vertical axis represents the percentage of correct answers per 150 trials in one session. Each value and error bar in the graph in Figure 16 represents the average value for nine mice and the 95% confidence interval.

[0136] As shown in FIG. 16 , a significant difference was observed between the one-touch and two-touch methods in the third reversal phase. With the one-touch evaluation method, the correct answer rate was below 60% even in the 12th session during the third reversal phase, and failed to reach 80% even in the 20th session. On the other hand, with the two-touch evaluation method according to embodiment 2, the correct answer rate exceeded 80% in the 12th session during the third reversal phase. Thus, the evaluation method according to embodiment 2 can significantly improve learning efficiency and also evaluate the flexibility of cognitive function or learning function. Short-term evaluation of the flexibility of cognitive function or learning function can also be applied to preclinical trials of drug discovery targeting psychiatric disorders, neurological disorders, etc.

[0137] Example 3 Using the evaluation method according to embodiment 2, evaluation was performed using autism model mice (Pat / Dp mice), known to have low flexibility in cognitive or learning functions, and wild-type mice as the subject animals 2. Both mice underwent the same pre-training as in Example 1 before evaluation. Following the flowchart in FIG. 10 , a figure discrimination learning evaluation was first performed using a pair of figures (step S201). The pair of figures used in this experiment was the pair P shown in FIG. 9 , with the vertically striped figure on the left being the correct figure and the horizontally striped figure on the right being the incorrect figure. One session of the figure discrimination learning evaluation ended after 100 trials or 30 minutes had elapsed. One session was performed per day, and continued until a correct answer rate of 80% or more was maintained for several days.

[0138] Next, a three-pair figure discrimination learning evaluation was conducted (step S202). The three pairs of figures used in this study were pairs A, B, and C shown in FIG. 9, with the left figure being the correct figure and the right figure being the incorrect figure as the original phase combination. One session of the three-pair figure discrimination learning evaluation ended when 150 trials or 45 minutes had elapsed. One session was conducted per day, and continued until a correct answer rate of 80% or more was maintained for several days. Next, a reversed phase figure discrimination learning evaluation was conducted in which the correct and incorrect figures were swapped (step S203). The learning flow was the same as in step S202.

[0139] Figure 17 shows the results of the assessment of figure discrimination learning in the last three sessions of the original phase and the reversal phase. Each value and error bar for the correct response rate of wild-type mice represents the average value of nine mice and the 95% confidence interval. Each value and error bar for the correct response rate of autism model mice represents the average value of six mice and the 95% confidence interval.

[0140] As shown in Figure 17, the correct answer rate for the first five sessions of the reversal phase in the autism model mice was lower than that of wild-type mice. This demonstrated impaired cognitive flexibility in the autism model mice, which had previously been difficult to detect using operant learning. The evaluation method according to the second embodiment can also be applied to preclinical trials of drug discovery targeting autism, etc.

[0141] Example 4: Mice that had undergone pre-training were evaluated using the evaluation method according to Variation 1. The pre-training here was the same as in Example 1. However, when using the three-touch evaluation method, after habituation to learn the relationship between the food dish and the food pellets, behavioral shaping was performed in which food pellets were provided upon one contact, followed by behavioral shaping in which food pellets were provided upon three contacts (3-touches shaping). This allowed the mice to learn the relationship that food pellets would be provided upon three contacts with the displayed figure. In this example, after five or six sessions of training in which food pellets were provided upon one contact, the mice were able to complete 100 trials within 30 minutes. After one or two sessions of training in which food pellets were provided upon three contacts, the mice were able to complete 100 trials within 30 minutes.

[0142] According to the flowchart in Fig. 10, a figure discrimination learning evaluation was first performed using a pair of figures (step S201). The pair of figures used in this evaluation was the pair P shown in Fig. 9, with the vertically striped figure on the left being the correct figure and the horizontally striped figure on the right being 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 continued until the correct answer rate was 80% or higher for several days.

[0143] Next, a three-pair figure discrimination learning evaluation was conducted (step S202). The three pairs of figures used in this study were pairs A, B, and C shown in FIG. 9, with the left figure being the correct figure and the right figure being the incorrect figure as the original phase combination. One session of the three-pair figure discrimination learning evaluation was terminated when 150 trials or 45 minutes had elapsed. One session was conducted per day, and continued until a correct answer rate of 80% or more was maintained for several days. Next, a reversed phase figure discrimination learning evaluation was conducted in which the correct and incorrect figures were swapped (step S203). The learning flow was the same as in step S202.

[0144] 18 shows the results of evaluating the figure discrimination learning in the original phase and the reversed phase. The accuracy rate when mice were trained to discriminate figures using the evaluation method (two-touch method) according to embodiment 2 is shown. Each value and error bar indicates the average value for nine mice and the 95% confidence interval. The accuracy rate when mice were trained to discriminate figures using the evaluation method (three-touch method) according to modification 1 is shown. Each value and error bar indicates the average value for seven mice and the 95% confidence interval.

[0145] As shown in Figure 18, the learning efficiency of the three-touch method was significantly higher than that of the two-touch method during the reversal phase. More specifically, with the three-touch method, the correct answer rate exceeded 80% in the 12th session of the reversal phase. This makes it possible to further improve learning efficiency when conducting reversal learning to measure the flexibility of cognitive function or learning function. This enables the evaluation of the flexibility of cognitive function or learning function in a short period of time, and can also be applied to preclinical trials of drug discovery targeting psychiatric or neurological disorders, etc.

[0146] Example 5 Using the evaluation method according to Variation 1 of the three-touch method and the evaluation method according to Variation 2 in which white is displayed in the display areas 313 and 314 when an answer is determined to be incorrect using the three-touch method, a figure discrimination learning evaluation using a pair of figures was performed on mice that had undergone pre-training similar to that of Example 1. The pair of figures used in this experiment was the pair P shown in Figure 9, with the vertically striped figure on the left being the correct figure and the horizontally striped figure on the right being the incorrect figure. One session of the figure discrimination learning evaluation was terminated when 100 trials or 30 minutes had elapsed. One session was performed per day, and continued until the correct answer rate was 80% or higher for several days.

[0147] 19 shows the percentage of correct answers when pattern discrimination learning was performed using the evaluation methods according to Modification 1 and Modification 2. Each value and error bar in the evaluation method according to Modification 1 represents the average value of seven mice and the 95% confidence interval. Each value and error bar in the evaluation method according to Modification 2 represents the average value of six mice and the 95% confidence interval.

[0148] 19, the learning efficiency was further improved by adding a process for displaying white in the display areas 313 and 314 when an answer was determined to be incorrect. More specifically, the correct answer rate exceeded 90% in the fourth session, making it possible to further improve learning efficiency.

[0149] Example 6 Evaluation was performed on mice that had undergone pre-training using the evaluation methods according to Modifications 1 and 2. The pre-training here was the same as in Example 4. Following the flowchart in FIG. 10, the mice that had completed the pre-training were first subjected to a figure discrimination learning evaluation using a pair of figures (step S201). The pair of figures used in this evaluation was the pair P shown in FIG. 9. One session of the figure discrimination learning evaluation ended after 100 trials or 30 minutes. One session was performed per day, and all eight mice evaluated achieved a correct answer rate of 75% for two consecutive days over approximately 10 sessions.

[0150] Next, a three-pair figure discrimination learning evaluation was performed (step S202). The evaluation results are shown in FIG. 20. In this example, pairs A, B, and C shown in FIG. 9 were used as the three pairs of figures, and food pellets were provided when the mice contacted the correct figure three times in a row. One session of the three-pair figure discrimination learning evaluation was terminated when 150 trials or 45 minutes had elapsed. One session was performed per day, and the original phase figure discrimination learning evaluation was continued until all eight mice evaluated maintained a correct response rate of 75% or higher for two consecutive days.

[0151] Next, a reversal phase (Rev1) was conducted in which the correct and incorrect figures were swapped (step S203). When all eight mice in the reversal phase achieved a correct answer rate of 75% or higher for two consecutive days, a second reversal phase (Rev2, the same combination as in the original phase) was conducted in which the correct and incorrect figures were swapped. This swapping of the correct and incorrect figures was repeated 10 times, and the original phase and 10 reversal phases (Rev1 to Rev10) were completed in 114 sessions.

[0152] The number of sessions required to complete the evaluation of the original phase and the 10 reversal phases in this example was less than half that of the conventional evaluation method in which a single contact is used to determine correctness. Because the target animals, mice, begin to age and their cognitive abilities begin to decline after about six months of age, conventional evaluation methods may not have been able to provide a substantial evaluation. According to the present invention, by shortening the time required for evaluation, it is possible to evaluate substantial cognitive or learning functions.

[0153] In this specification, the methods, configurations, aspects, or interpretations of terms described in relation to any of the evaluation methods, evaluation devices, programs, methods for producing trained non-human animals, and non-human animals are intended to apply the same methods, configurations, aspects, or interpretations of terms to other methods, devices, and programs that do not have similar descriptions.

[0154] The present invention allows various embodiments and modifications without departing from the broad spirit and scope of the present invention. Furthermore, the above-described embodiments are intended to illustrate the present invention and do not limit the scope of the present invention. That is, the scope of the present invention is defined by the claims, not the embodiments. Various modifications made within the scope of the claims and the meaning of the invention equivalent thereto are considered to be within the scope of the present invention.

[0155] This application is based on Japanese Patent Application No. 2023-209598, filed on December 12, 2023. The entire specification, claims, and drawings of Japanese Patent Application No. 2023-209598 are incorporated herein by reference.

[0156] The present invention is suitable for testing non-human animals performing operant learning tasks.

[0157] 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 Determination unit, 214 Feeding instruction unit, 231 Graphic image, 232 Evaluation data, 311 Display device, 312 Contact sensor, 313, 314, 315, 316 Display area, 322 Feeding dish, 323 Speaker, 324 Aversive stimulus, 325 Button switch.

Claims

1. An evaluation method comprising: a determination step of determining that the answer is correct when the movement of a target animal is detected at a position corresponding to a correct answer a first number of times that is two or more consecutive times, or determining that the answer is incorrect when the movement of the target animal is detected at a position corresponding to an incorrect answer a second number of times that is two or more consecutive times; a supply step of supplying a reward or an aversive stimulus depending on the determination result of the determination step; and an evaluation data generation step of accumulating the determination results of the determination step and generating evaluation data.

2. The evaluation method of claim 1, further comprising a display step of simultaneously displaying a correct answer symbol and one or more incorrect answer symbols in each of two or more display areas of a display device, and in the judgment step, a correct answer is judged when contact of the target animal is detected at a position corresponding to the correct answer symbol the first number of consecutive times, or an incorrect answer is judged when contact of the target animal is detected at a position corresponding to any of one or more of the incorrect answer symbols the second number of consecutive times.

3. The evaluation method of claim 2, further comprising a contact detection step of detecting contact of the target animal at a position corresponding to the correct figure and one or more of the incorrect figures, wherein in the judgment step, if the contact detection step detects contact at a position corresponding to the correct figure, which is correct behavior, the first number of times in succession, a correct answer is judged, and if the contact detection step detects contact at a position corresponding to any of the one or more incorrect figures, which is incorrect behavior, the second number of times in succession, a wrong answer is judged.

4. The evaluation method according to claim 1, wherein the evaluation data includes a correct answer rate for all of the judgment results for two or more predetermined number of judgment steps, or for the judgment results for multiple judgment steps within a certain period of time.

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

6. The evaluation method according to claim 2, wherein the evaluation data includes a result of reversal learning when a figure set as the correct answer figure and a figure set as any one of the one or more incorrect answer figures are interchanged with each other.

7. The evaluation method of claim 6, wherein the evaluation data includes information indicating the flexibility of the cognitive or learning function of the target animal, derived based on the correct answer rate or the change in the correct answer rate over time for all of the judgment results for two or more predetermined number of judgment steps or multiple judgment steps within a certain period of time for the reversal learning.

8. The evaluation method of claim 2, wherein in the judgment step, if contact of the target animal is detected at a position corresponding to any one or more of the incorrect answer figures for the second consecutive number of times, an incorrect answer is judged to be present, and a bright color is displayed in the display area in which the correct answer figure or the incorrect answer figure was displayed.

9. The evaluation method according to claim 1, wherein the first number of times and the second number of times are predetermined numbers 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.

10. An evaluation method according to any one of claims 1 to 9, further comprising a drug evaluation step of evaluating the effect of the drug on cognitive or learning function by comparing the evaluation data generated after administering a drug to a model animal or a wild-type animal with low cognitive or learning function with evaluation data generated for the model animal before administration of the drug, or for the same animal or animal of the same species as the model animal or the wild-type animal to which the drug has not been administered.

11. An evaluation device comprising: a judgment unit that judges an answer to be correct when it detects the movement of a target animal at a position corresponding to a correct answer a first number of times or more consecutively, or judges an answer to be incorrect when it detects the movement of the target animal at a position corresponding to an incorrect answer a second number of times or more consecutively, and a supply device that supplies a reward or an aversive stimulus depending on the judgment result of the judgment unit.

12. A program for causing a computer to function as: a judgment unit that determines a correct answer when it detects the movement of a target animal at a position corresponding to a correct answer a first number of times or more consecutively, or that determines an incorrect answer when it detects the movement of the target animal at a position corresponding to an incorrect answer a second number of times or more consecutively; a supply instruction unit that supplies a reward or an aversive stimulus depending on the judgment result of the judgment unit; and a memory unit that stores the judgment result of the judgment unit as evaluation data.

13. A method for producing a trained non-human animal, comprising repeatedly carrying out a determination step of determining a correct answer when a movement of a target animal, which is a non-human animal, is detected at a position corresponding to a correct answer a first number of times that is two or more consecutive times, or determining an incorrect answer when a movement of the target animal is detected at a position corresponding to an incorrect answer a second number of times that is two or more consecutive times, and a supply step of supplying a reward or an aversive stimulus to the target animal depending on the determination result of the determination step.

14. A non-human animal that, in a judgment in which a predetermined movement of the non-human animal at a position corresponding to a correct answer is judged to be correct a first number of times or more consecutively, and / or a predetermined movement of the non-human animal at a position corresponding to an incorrect answer is judged to be incorrect a second number of times or more consecutively, has a higher rate of correct answers in said judgment than a non-human animal of the same species that has not been trained.

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