JP2015195835A - Evaluation value calculation method of hippocampus function, evaluation value calculation system of hippocampus function, evaluation method of hippocampus function, and test item set - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an evaluation value calculation method of a hippocampus function capable of easily and reliably evaluating a hippocampus function of a subject.SOLUTION: An evaluation value of a hippocampus function is calculated by the following processes: a process in which trials to sequentially present a plurality of test items to a subject are repeated; a process in which, after each trial is finished in the above process, the subject is caused to answer which of (A) a test item first presented, (B) a test item similar to, but different from, a test item presented in a previous trial, and (C) a test item the same as the test item presented in a previous trial is the test item presented in the trial; a correctness determination process in which the test item presented in the trial process is compared with the answer result acquired in the answering process, and the correctness of the answer result for each trial is determined; and an evaluation value calculation process in which the result acquired in the correctness determination process is summed up, a correct answer rate for each pattern of the (A), (B), and (C) is calculated, and the correct answer rate is determined as an evaluation value of the hippocampus function.

Description

  The present invention relates to a hippocampal function evaluation value calculation method, a hippocampal function evaluation value calculation system, a hippocampal function evaluation method, and a test item set.

  The hippocampus is known to play an important role in learning and memory, and various studies have been conducted on its function.

  For example, Non-Patent Document 1 describes that genetically modified animals are involved in recognition (pattern separation) of things that are similar but slightly different in the NMDA receptor of the hippocampal dentate gyrus. Non-Patent Document 2 describes that neoplastic neurons are involved in pattern separation and mature neurons are involved in pattern completion (recognition of the shape of a similar object).

  On the other hand, Patent Document 1 discloses a brain function measurement method in which a subject is asked whether a primary image and a secondary image displayed on a display are the same or different, and the activity of the brain function is measured from the answer result. Have been described. More specifically, in the method of Patent Document 1, primary images provided with a gaze area are automatically and sequentially displayed, and the image information in the gaze area is the same or different with respect to these primary images. Similarly, the secondary images are automatically and sequentially displayed, and the image in the designated gaze area is visually observed to answer whether the image is the same or different from the previously observed primary image. According to the method of Patent Document 1, it is said that the activity of a function such as a hippocampus can be easily measured without using an expensive apparatus such as a functional magnetic resonance image (fMRI).

JP 2005-192637

Science 317, 94-97, Jul6, 2007 Cell 149,188-201, March30,2012

  As described in Non-Patent Documents 1 and 2, in order to accurately evaluate the hippocampal function of a subject, it is important to grasp the state of the neonatal neurons of the hippocampus involved in pattern separation. However, since the brain function measuring method of Patent Document 1 is to determine whether the primary image and the secondary image provided with the gaze area are the same or different, the primary memory (the memory that enters first) is mainly used. Are only being examined. In addition, the method of Patent Document 1 has a problem that it is difficult to evaluate the hippocampal function because the attention function (frontal lobe function) whether or not the subject can confirm the gaze area greatly affects the answer result.

  The present invention has been made in view of the circumstances as described above. The hippocampal function evaluation value calculation method, the hippocampal function evaluation value calculation system, and the hippocampal function can easily and reliably evaluate the hippocampal function of the subject. The problem is to provide an evaluation method. It is also an object to provide test items used for the evaluation of hippocampal function.

In order to solve the above-mentioned problem, the hippocampal function evaluation value calculation method of the present invention is a method for calculating a hippocampal function evaluation value that serves as an index for determining the health of a subject's hippocampal function, Process of:
Trial process of repeatedly trying to present multiple test items to the subject sequentially;
After the end of each trial in the trial process, the test items presented in the trial to the subject are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Different kind of test item similar to the test item presented in the previous trial (C) Of the same test items as the test item presented in the previous trial Answering process to answer which of
The test item presented in the trial process and the answer result obtained in the answer process are compared to determine whether the answer result for each trial is correct or incorrect; and the results obtained in the correct / incorrect process are totaled And calculating an accuracy rate for each of the patterns (A), (B), and (C), and including an evaluation value calculation step of obtaining the accuracy rate as an evaluation value of the hippocampal function.

The hippocampal function evaluation value calculation system of the present invention is a system for calculating an evaluation value of the hippocampal function, which is an index for judging the health of the hippocampal function of the subject,
A test item presenting means for repeatedly executing trials for sequentially presenting a plurality of test items to a subject;
A test item output means for outputting a test item to be presented in each trial to a test item presenting means;
After the end of each trial, the test items presented by the subject in each trial are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Another test item similar to the test item that was presented in the previous trial (C) The same test item as the test item presented in the previous trial An answer result input means for inputting an answer result as to which of the items,
Answer result storage means for storing the answer result input via the answer result input means;
Compare the test item in each trial output by the test item output means with the answer result stored in the answer result storage means, determine the correctness of the answer result for each trial, (A), (B), an evaluation value calculating means for calculating a correct answer rate for each pattern of (C), and obtaining the correct answer rate as an evaluation value of the hippocampal function,
It is characterized by including.

The hippocampal function evaluation method of the present invention is a hippocampal function evaluation method for evaluating the health of a subject's hippocampal function, and includes the following steps:
Trial process of repeatedly trying to present multiple test items to the subject sequentially;
After the end of each trial in the trial process, the test items presented in the trial to the subject are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Different kind of test item similar to the test item presented in the previous trial (C) Of the same test items as the test item presented in the previous trial Answering process to answer which of
A correct / incorrect determination step of comparing the test item presented in the trial step with the response result obtained in the response step to determine whether the response result for each trial is correct or incorrect;
Correct answer rate calculation step of calculating the correct answer rate for each of the patterns (A), (B), and (C) by counting the correctness of the answer results obtained in the answer step;
Comparing the correct answer rate of the pattern (B) of the subject calculated in the correct answer rate calculating step with (average ± standard deviation) of the correct answer rate of the pattern (B) of healthy subjects,
A hippocampal function evaluation process for evaluating that the hippocampus is diseased or damaged when the correct answer rate of the subject is at least twice the standard deviation of the correct answer rate of the pattern (B) of healthy subjects;
It is characterized by including.

  The test item set of the present invention is a set of test items used in the evaluation value calculation method for the hippocampal function, and is an item for which 85% to 98% of 30 or more healthy persons are determined to be the same The same test item set consisting of a group and the same test item set consisting of items judged that 40% to 50% of 30 or more healthy persons are similar to the same test item but different And a single test item set including a single test item group determined to be different from the test item set and the similar test item set.

  According to the hippocampal function evaluation value calculation method and hippocampal function evaluation value calculation system of the present invention, it is possible to simply and reliably calculate an evaluation value that is an index of the health of the subject's hippocampal function. In addition, according to the method for evaluating hippocampal function of the present invention, whether or not the subject's hippocampus has a disease or damage, the state of new nerve cells, the course of recovery of cognitive function after radiotherapy, endocrine metabolic disease, diabetes In addition, the cognitive ability (hippocampal newborn function) of obese patients can be easily and reliably evaluated. Furthermore, according to the test item of the present invention, the evaluation value of the hippocampal function can be easily obtained.

It is the figure which showed the specific example of "similar another kind of test item." It is the schematic which illustrated one Embodiment of the evaluation value calculation method of the hippocampal function of this invention. It is a figure which shows the result of the BOLD analysis of one healthy subject (25-year-old boy) and the evaluation value (New, Lure, Same correct rate (average value ± standard deviation)) of hippocampal function. It is a figure which shows the result of the correct answer rate of New, Lure, and Same of a healthy subject, a benign brain tumor patient, a malignant brain tumor patient, and a malignant brain tumor radiotherapy patient. It is a figure which shows the relationship between the radiation dose at the time of irradiating a hippocampus of a test subject with radiation, and a Lure correct answer rate. It is a figure which shows the relationship between the BOLD signal of a hippocampus, and a Lure correct answer rate. It is a figure which shows the correct answer rate and BOLD signal of New, Lure, and Same in the example which performed radiation chemotherapy with respect to the patient of atypical meningioma. It is a figure which shows the correct answer rate and BOLD signal of New, Lure, and Same in the example which performed the radiochemotherapy with respect to the patient of a malignant brain tumor (glioma). It is a figure which shows the change of the correct answer rate of New, Lure, and Same in the example which performed the therapeutic intervention by the medicine after performing radiation chemotherapy for the patient of the left temporal lobe glioblastoma.

The evaluation value calculation method for hippocampal function according to the present invention is a method for calculating an evaluation value for hippocampal function, which is an index for determining the health of the hippocampal function of a subject, and includes the following steps:
Trial process of repeatedly trying to present multiple test items to the subject sequentially;
After the end of each trial in the trial process, the test items presented in the trial to the subject are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Different kind of test item similar to the test item presented in the previous trial (C) Of the same test items as the test item presented in the previous trial Answering process to answer which of
A correct / incorrect determination step of comparing the test item presented in the trial step with the response result obtained in the response step to determine whether the response result for each trial is correct or incorrect;
The correctness / incorrectness of the answer results obtained in the answering process is totaled, the correct answer rate is calculated for each of the patterns (A), (B), and (C), and the correct answer rate is obtained as an evaluation value of the hippocampal function. Process;
including.

  Hereinafter, each process of the hippocampal function evaluation calculation method of the present invention will be described. In the present invention, “hippocampus” includes dentate gyrus.

  The trial process is a process of repeatedly performing trials to sequentially present a plurality of test items to the subject.

  The test item refers to an item for which the subject should visually store a symbol or the like. Examples of the test item include a card on which the symbol is represented, a three-dimensional object, and an image on the screen. Accordingly, the method and means for presenting the test item to the subject can also be appropriately set in consideration of the type of the test item, the state of the subject, and the like. Specifically, for example, when the test item is a card on which a symbol is represented, a method of sequentially presenting cards to the subject one by one can be employed. It is preferable to use a test item set in which a plurality of such test items are combined.

  The number of trials in the trial process (the number of test item presentations), the test item presentation time, the time interval between trials, and the like are not particularly limited as long as the conditions of the subject to be compared are the same. For example, the number of trials (the number of times the test item is presented) can be exemplified by a range of, for example, about 30 to 150 times in consideration of the state of the subject and the degree of difficulty.

In the answering process, after the end of each trial in the trial process (after the presentation of one test item), the test items presented to the subject in the trial are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Different kind of test item similar to the test item presented in the previous trial (C) Of the same test items as the test item presented in the previous trial Let me answer which one of them.

  That is, in order for the subject to answer correctly in the answering process, all the contents of the test items (designs, etc.) presented in the previous trial are memorized and compared with the currently presented test items (A) to (A It is necessary to select and answer the pattern of C). Therefore, as the number of trials (the number of test items presented) increases, the types of test items that should be memorized by the subject increase, and the difficulty of answering increases. In addition, since the difficulty of responses may vary depending on the similarity of test item designs and the order in which test items are presented, the test item presentation conditions in the trial process are standardized, and the correct answer of the normal healthy subject in advance It is necessary to obtain the average value of the rate.

  The answer format in the answering process is not particularly limited, and a third party may record the verbal answer of the subject, let the subject himself fill in the answer sheet, or enter the answer into the computer, etc. Also good.

  For example, in the case of a test item in which a pattern is represented, a part of the pattern is compared to the pattern of the test item presented in the previous trial. Can be exemplified such that the symbol is missing or added, the outer shape of the symbol is the same, but the color is different, and the symbol is symmetrically represented. Therefore, a test item set including a plurality of such test items is, for example, the same test item set consisting of items determined to be the same by 85% to 98% of 30 or more healthy persons, and 30 40% to 50% of the above healthy subjects are judged to be similar to the same test item but similar test item set consisting of items judged to be different from the same test item set and similar test item set It can be constituted by a single test item set consisting of a single test item group. About the similarity of a test item, what was created based on such a standard can be used. The term “healthy person” as used herein refers to a person whose brain hippocampal function has not been confirmed to be impaired due to disease or injury.

  FIG. 1 is a diagram showing a specific example of “similar types of test items”. In the left and right symbols of the card as the test item illustrated in FIG. 1A, the direction of the shisa and the opening / closing state of the mouth are different, and the cards having both symbols are designed as test items similar to each other. In addition, in the card design illustrated in FIG. 1B, the flowers have substantially the same shape, but the colors are different, and the cards having both designs are designed as test items similar to each other.

  In the correctness determination process, the test item presented in the trial process is compared with the response result obtained in the response process to determine the correctness of the response result for each trial. A method for determining whether the answer result is correct or not is not particularly limited. For example, a third party may determine whether the test subject's answer is correct, or the computer may automatically determine whether the answer is correct. In the correctness / incorrectness determination process, it is only necessary to check whether the test item pattern (A), (B), and (C) presented in the trial process match the test subject's response in the response process. Is easy to determine.

  Furthermore, the trial process, the reply process, and the correctness determination process in the hippocampal function evaluation value calculation method of the present invention will be described with reference to a specific example shown in FIG. FIG. 2 is a schematic diagram illustrating an embodiment of a method for calculating an evaluation value of a hippocampal function according to the present invention, and illustrates an embodiment using a card on which a symbol is represented as a test item.

  For convenience, (A) Test item presented for the first time is “New”, (B) Another test item similar to the test item presented in the previous trial is “Lure”, (C) Previous trial The same test item as the card that has been presented in is described as “Same”.

  As shown in FIG. 2, various symbols are drawn on the card presented to the subject in the trial process, and constitute a set of test item sets.

  In the first trial, the card 1 in FIG. 2 is presented. A shamisen diagram is drawn on the card 1, and the subject memorizes this symbol. Since this is the first trial, the subject is required to answer “New”.

  In the second trial, the card 2 in FIG. 2 is presented. The card 2 has a drawing of a beverage can, and the subject memorizes this symbol. Since this symbol is a new one different from the symbol of the card presented in the first trial, the subject is required to answer “New”.

  In the third trial, the card 3 in FIG. 2 is presented. On the card 3, a blue hibiscus figure is drawn, and the subject memorizes this symbol. Since this symbol is a new one different from the symbol of the card presented in the first and second trials, the subject is required to answer “New”.

  In the fourth trial, the card 4 in FIG. 2 is presented. On the card 4, a figure of Shisa facing right and closing his mouth is drawn, and the subject memorizes this symbol. Since this symbol is a new one different from the symbol of the card presented in the first to third trials, the subject is required to answer “New”.

  In the fifth trial, the card 5 in FIG. 2 is presented. An apple figure is drawn on the card 5, and the subject memorizes this symbol. Since this symbol is a new one different from the symbol of the card presented in the first to fourth trials, the subject is required to answer “New”.

  In the sixth trial, the card 6 in FIG. 2 is presented. Since the same shamisen diagram as the card 1 of the first trial is drawn on the card 6, the subject is required to answer “Same”.

  In the seventh trial, the card 7 in FIG. 2 is presented. On the card 7, a figure of a glass container is drawn, and the subject memorizes this design. Since this symbol is a new one different from the symbol of the card presented in the first to sixth trials, the subject is required to answer “New”.

  In the eighth trial, the card 8 in FIG. 2 is presented. Since the card 8 is drawn with the same apple figure as the card 5 of the fifth trial, the subject is required to answer “Same”.

  In the ninth trial, the card 9 in FIG. 2 is presented. Since the card 9 has a hibiscus figure with the same outline as the card 3 of the third trial but with a red color, the subject is required to answer “Lure”.

  In the tenth trial, the card 10 in FIG. 2 is presented. On the card 10, a figure of bitter gourd is drawn, and the subject memorizes this symbol. Since this symbol is a new one different from the symbol of the card presented in the first to ninth trials, the subject is required to answer “New”.

  In the 11th trial, the card 11 in FIG. 2 is presented. A hydrangea figure is drawn on the card 11, and the subject memorizes this symbol. Since this symbol is a new one different from the symbol of the card presented in the first to tenth trials, the subject is required to answer “New”.

  In the 12th trial, the card 12 in FIG. 2 is presented. Since the card 12 has a different orientation from the Shisa of the card 4 in the fourth trial, and a diagram of the Shisa with an open mouth is drawn, the subject is required to answer “Lure”.

  In the evaluation value calculation method of the hippocampal function of the present invention, such trials are repeatedly performed (trial process), and the answer of each trial is given to the subject by pattern (A): New, pattern (B): Lure, pattern (C) : Let me answer in any of the same (answer process), and make a correct / incorrect determination of the answer result (correct / incorrect determination process).

  Furthermore, in the evaluation value calculation step, the correctness / incorrectness of the answer results obtained in the correctness / incorrectness determination step is totaled, and the correct answer rate is calculated for each pattern of (A), (B), (C), and the correct answer rate is calculated. Obtained as an evaluation value of hippocampal function.

  The correct answer rate (%) is calculated by dividing the number of correct answers for each pattern of (A), (B), and (C) by the number of presentations for each pattern, and this number is the evaluation value for hippocampal function. . When calculating the average of correct answer rate (evaluation value of hippocampal function) of healthy persons, it can be expressed as “average value ± standard deviation”.

  In the hippocampal function evaluation method of the present invention, the average of the evaluation values of the hippocampal function of healthy subjects (the correct answer rate for each pattern of (A), (B), (C)) is obtained in advance by experiment, and this evaluation is performed. By comparing the value (correct answer rate) with the evaluation value (correct answer rate) of the subject's hippocampal function, the soundness of the subject's hippocampal function can be evaluated.

  In the hippocampal function evaluation method of the present invention, in addition to the above-described hippocampal function evaluation value calculation method, the correct answer rate of the pattern (B) of the subject is the average (average value ± standard) of the correct answer rate of the pattern (B) of healthy subjects. When the subject's correct answer rate is lower than the standard deviation (2SD) of the correct answer rate of the healthy person's pattern (B) by 2 SD or more, it is evaluated that the hippocampus is diseased or damaged. Process.

  In the verification by the present inventor, the evaluation value of the hippocampal function obtained by the method for calculating the evaluation value of hippocampal function of the present invention is the evaluation value (average value ± standard deviation (SD)) of the pattern (A) in healthy subjects is 96 ±. 3. The evaluation value of pattern (B) is 47 ± 19, and the evaluation value of pattern (C) is 89 ± 10. In this case, for example, in the case where each evaluation value is lower than the average by 2SD (twice the standard deviation SD) or more (for example, when the evaluation value of the pattern (B) is less than 10), the hippocampal nerve It can be evaluated as a neoplastic disorder. Similarly, when the evaluation value of the pattern (C) is 70 or less, it can be evaluated as a hippocampal neurogenesis disorder for several weeks. Furthermore, when the evaluation value of the pattern (A) is less than 90, it can be evaluated that the disorder of hippocampal neurogenesis lasts for one month or more.

  In hippocampal neurons, cells that are renewed in the dentate gyrus (young neuron) are identified as similar, so if there is a tendency to decrease the neoplastic function in hippocampal neurons, the pattern (B ) Is confirmed to decrease. Neonatal hippocampal neurons differentiate into mature neurons in a few weeks and become young adult neurons. This cellular function is reflected in the evaluation value of pattern (C). Furthermore, if the neonatal function in hippocampal neurons continues to be injured for more than 1 month, the dysfunction of the old neuron will cause dysfunction, leading to a decrease in the evaluation value of pattern (A).

  According to the evaluation value obtained by the method for calculating the evaluation value of hippocampal function of the present invention, it is possible to simply and reliably evaluate a disease or environment affecting the hippocampal function without using an apparatus such as fMRI. Specifically, according to the evaluation value obtained by the hippocampal function evaluation value calculation method of the present invention, stroke, head injury, Huntington's disease, stress, depression, Parkinson's disease, schizophrenia, Alzheimer type dementia The pathological conditions such as can be easily evaluated in real time. Therefore, it is useful for the degree of progression of brain diseases, determination of therapeutic effects, discrimination, and the like. Since such an evaluation can be performed based on the quantified evaluation value of the hippocampal function (the correct answer rate), it does not necessarily require specialized knowledge and techniques by the medical staff.

  Furthermore, the present inventors have newly found that a decrease in hippocampal function is confirmed even in obesity, diabetes and endocrine diseases. Therefore, by comparing the evaluation value of the subject obtained by the method for calculating the evaluation value of hippocampal function of the present invention with the evaluation value of hippocampal function of a healthy person, the cognitive ability of obese patients, diabetes, treatment of endocrine metabolic diseases and It can be used effectively for management.

  Further, the present inventor has induced cognitive dysfunction in a patient who has been subjected to radiation therapy, and the evaluation value of the subject obtained by the hippocampal function evaluation value calculation method of the present invention is used to determine the hippocampal neogenesis function by therapeutic intervention. It has been confirmed that the recovery process can be evaluated.

  Next, the evaluation value calculation system for the hippocampal function of the present invention will be described. The hippocampal function evaluation value calculation system of the present invention automates the hippocampal function evaluation value calculation method of the present invention. Therefore, the description common to the above hippocampal function evaluation value calculation method is omitted.

The hippocampal function evaluation value calculation system of the present invention is a system for calculating an evaluation value of the hippocampal function, which is an index for judging the health of the hippocampal function of the subject,
A test item presenting means for repeatedly executing trials for sequentially presenting a plurality of test items to a subject;
A test item output means for outputting a test item to be presented in each trial to a test item presenting means;
After the end of each trial, the test items presented by the subject in each trial are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Another test item similar to the test item that was presented in the previous trial (C) The same test item as the test item presented in the previous trial An answer result input means for inputting an answer result as to which of the items,
Answer result storage means for storing the answer result input via the answer result input means;
Compare the test item in each trial output by the test item output means with the answer result stored in the answer result storage means, determine the correctness of the answer result for each trial, (A), (B), an evaluation value calculating means for calculating a correct answer rate for each pattern of (C), and obtaining the correct answer rate as an evaluation value of the hippocampal function,
including.

  The test item presenting means can exemplify a display, for example, and can exemplify a form in which the test item is displayed by an image displayed on the display.

  The test item output means outputs the test item presented in each trial to the test item presentation means and displays it. The test item output means can exemplify a system for executing and displaying a preset test item presentation pattern.

  The answer result input means is a means for the subject to confirm the test item presented by the test item presenting means and to input the answer in light of his / her own memory. Although specific embodiment is not specifically limited, For example, what inputs a reply by pushing a button, what inputs in a touch panel form on a display (test item presentation means), etc. can be illustrated.

  The answer result storage means can exemplify a storage medium (memory) for storing the answer result input via the answer result input means.

  The evaluation value calculation means compares the test item in each trial output by the test item output means with the answer result stored in the answer result storage means, and automatically determines correctness (A), ( The correct answer rate is calculated for each pattern of B) and (C), and a known arithmetic processor or the like can be exemplified.

  According to such an evaluation value calculation system for hippocampal function, the evaluation value of the hippocampal function of the subject can be automatically obtained, which is extremely simple.

  The hippocampal function evaluation value calculation method, hippocampal function evaluation value calculation system, hippocampal function evaluation method, and test item set according to the present invention are not limited to the above embodiments.

  Hereinafter, the hippocampal function evaluation value calculation method and the hippocampal function evaluation method of the present invention will be described in more detail together with examples. The hippocampal function evaluation value calculation method and the hippocampal function evaluation method of the present invention are described below. It is not limited to examples.

<Embodiment 1> Hippocampal function evaluation value calculation (1) Procedure Prepare 108 cards (test items) on which a pattern is drawn and repeat the trial of presenting them one by one to each subject. , "What was presented for the first time (New)", "Similar to what was previously presented, but different (Lure)", "Same as previously presented (Same ) ". Subject's responses were “new for the first time (New)”, “similar to what was previously presented but different (Lure)”, “what was previously presented Three types of answer cards, “Same”, were pointed and selected, and the selected answers of the subjects were entered on the record sheet. This record sheet has columns for entering the card presentation order, card type, correct answer card (Correct answer), and the subject's response, and it is easy to determine which card the subject gave the correct or incorrect answer. Recordable. At that time, there was no feedback on the correctness of the answers. Further, 108 cards were presented in a predetermined order, and the time required for all trials was set to about 7 minutes. In the following examples, the same procedure was used for experiments.

  The subjects were 36 healthy individuals, 31 benign brain tumor patients, 10 malignant brain tumor patients, and 13 malignant brain tumor radiotherapy patients. The therapeutic radiation dose for patients undergoing radiotherapy for malignant brain tumors was 22.7 ± 18.3 Gy (from 10 to 60 Gy).

Furthermore, the state of the subject's hippocampus was confirmed by BOLD (blood oxygenation level dependent) analysis by functional magnetic resonance imaging (fMRI). BOLD analysis can capture changes in magnetic susceptibility associated with changes in the amount of oxygen in the brain and evaluate changes in the hippocampus over time.
(2) Results FIG. 3 shows the results of BOLD analysis and hippocampal function evaluation values (New, Lure, Same correct answer rate (average value ± standard deviation)) of one healthy subject (25-year-old boy). As shown in FIG. 3, it is confirmed that the BOLD curve takes a downward peak at 2 seconds from the start and overshoots after taking the first upward peak at 5-6 seconds. Moreover, the correct answer rate of New, Lure, and Same of this healthy person was 93%, 44%, and 81%, respectively, and it was confirmed that it was in a normal range compared with the average value of other healthy persons.

  FIG. 4 shows the results of the correct answer rate of New, Lure, and Same for 36 healthy subjects, 31 benign brain tumor patients, 10 malignant brain tumor patients, and 13 malignant brain tumor radiotherapy patients.

  As shown in FIG. 4, the correct answer rate (average value ± standard deviation) of New, Lure, and Same of 36 healthy subjects was New: 96 ± 3, Lure: 47 ± 19, and Same: 89 ± 10. . The correct answer rate (mean ± standard deviation) of 31 patients with benign brain tumors was New: 93 ± 8, Lure: 43 ± 21, and Same: 86 ± 22. The correct answer rate (mean ± standard deviation) of 10 patients with malignant brain tumors was New: 95 ± 4, Lure: 38 ± 19, and Same: 86 ± 19. The correct answer rate (average ± standard deviation) of 13 patients with malignant brain tumor radiation therapy was New: 93 ± 8, Lure: 25 ± 27, and Same: 81 ± 26.

  Regarding the evaluation value of Lure, a significant difference was confirmed between 36 healthy subjects, 31 benign brain tumor patients, 10 malignant brain tumor patients, and 13 malignant brain tumor radiotherapy patients. Because patients with malignant brain tumor radiation therapy have reduced neonatal function of the hippocampus (hippocampal dentate gyrus), the Lure assessment value should reflect the ability or ability of the neurons in the hippocampal dentate gyrus to form Was confirmed.

<Example 2> Hippocampal radiotherapy and Lure correct answer rate FIG. 5 shows the relationship between the radiation dose and the Lure correct answer rate when the left and right hippocampus of a subject is irradiated and treated. As shown in FIG. 5, in many subjects, the correct answer rate of Lure is reduced by hippocampal radiation therapy. That is, it was confirmed that the evaluation value of Lure reflects the neoplastic ability or neoplastic function of the hippocampal dentate gyrus.

<Example 3> Relationship between BOLD signal and Lure correct answer rate For 36 healthy subjects, 31 patients with benign brain tumor, 10 patients with malignant brain tumor, and 13 patients with malignant brain tumor radiation therapy in Example 1, fMRI was performed. The relationship between hippocampal BOLD signal and Lure correct answer rate was examined.

  The results are shown in FIG. As shown in FIG. 6, healthy subjects and benign brain tumor patients have a correlation between the BOLD signal and the Lure correct answer rate. The stronger the BOLD signal, the higher the Lure correct answer rate, and conversely, the weaker the BOLD signal, the more Lure. It was confirmed that the correct answer rate was low. On the other hand, for malignant brain tumor patients, the correlation trend was weakened, and it was confirmed that the correlation disappeared between the BOLD signal and the Lure correct response rate after irradiation (malignant brain tumor radiotherapy patients). That is, it was confirmed that the Lure correct answer rate reflects the state of the hippocampal function (the ability or function of the neuronal cells of the hippocampal dentate gyrus).

<Example 4> Specific examples of correct answer rate of New, Lure, Same and time axis change of BOLD signal (1) Fig. 7 shows radiation chemotherapy for a patient with atypical meningiomas (61 years old) The correct answer rate of New, Lure, and Same and the BOLD signal are shown. In this example, it is confirmed that the BOLD signal is normal, the Lure correct answer rate is high at 56.3%, and the hippocampal function is maintained almost normal before the radiation chemotherapy. After that, 14Gy radiotherapy caused the BOLD signal to decrease in the initial positive wave peak value, the Lure correct answer rate was 0%, and it was confirmed that the neonatal function of the hippocampus was suppressed, but before treatment Lure Since the correct answer rate was as high as 56.3%, the correct answer rate of New and Same does not decrease immediately. After 46Gy radiation therapy was completed, the Lure correct answer rate began to recover (Lure correct answer rate: 12.5%), and three months after radiation therapy, it was confirmed that the correct answer rate of New, Lure, and Same was normalized. The
(2) FIG. 8 shows the correct answer rate and BOLD signal of New, Lure, and Same in an example in which radiation chemotherapy was performed on a malignant brain tumor (glioma) patient (62 years old). In this example, the BOLD signal had a different image from that of healthy subjects in the previous stage of radiation chemotherapy, and the Lure correct answer rate was 6.3%, the Same correct answer rate was 0%, and the hippocampal function was very high. It turns out that it has fallen. After the start of radiochemotherapy (14 Gy), the BOLD signal was a biphasic negative wave, and the Lure correct answer rate was 0%. Therefore, when a drug that supports the neurogenesis function of the hippocampus was administered, 5 After a week, the BOLD signal normalized and the Lure correct answer rate normalized to 37.5% (neuromodulation by drugs). By giving chemotherapy three times after the end of radiotherapy, the BOLD signal again showed a different image from that of healthy subjects three months after the end of radiotherapy, and the Lure correct answer rate became 0% again. Because the hippocampal neonatal neurons at the time when the correct answer rate showed 37.5% (5 weeks after the start of radiation therapy) was responsible for the recognition of the same, it is considered that the Same correct answer rate was normalized.
(3) FIG. 9 shows the change in the correct answer rate of New, Lure, and Same in a case where a patient with left temporal lobe glioblastoma (aged 47 years) was administered radiochemotherapy and intervened with drugs. Yes. In this example, the Lure correct answer rate and the Same correct answer rate decline after surgery, and the Same correct rate recovers after 16 Gy radiotherapy, while the Lure correct answer rate declines. At this time, treatment intervention with a drug (memantate) was performed, and it was confirmed that the Lure correct answer rate was normalized.
(4) As described above, by using the evaluation value obtained by the method for calculating the evaluation value of the hippocampal function of the present invention, the state of cognitive function of the patient whose hippocampal function has been reduced by radiation therapy (recovery of the hippocampal neonatal function ) Can be easily diagnosed in real time.

<Example 5> New, Lure, and Same correct answer rates of patients with pituitary adenoma and diabetic patients (1) The hippocampal function evaluation value was calculated by the method of the present invention for 9 patients with pituitary adenoma did. As a result, the correct answer rate (average value ± standard deviation) of New, Lure, and Same was New: 77 ± 32, Lure: 20 ± 17, and Same: 91 ± 9. In the case of a pituitary fibroma patient, the correct answer rate for New is 2 standard deviations and the correct answer rate for Lure is 1 standard deviation lower than the evaluation value (correct answer rate) of healthy subjects.
(2) Hippocampal function evaluation values were calculated by the method of the present invention for diabetic patients (including 6 obese patients). As a result, the evaluation values (New, Lure, Same correct rate (average value ± standard deviation)) were New: 93 ± 6, Lure: 23 ± 17, and Same: 80 ± 10. In the case of diabetic patients, the correct answer rate of Lure is 1 standard deviation lower than the evaluation value (correct answer rate) of healthy subjects.
(3) Thus, according to the evaluation value of the hippocampal function calculated by the method of the present invention, the cognitive ability (hippocampal neonatal function) of patients with endocrine metabolic diseases, diabetes, and obesity can be easily evaluated.

Claims (4)

A method for calculating an evaluation value of hippocampal function, which is an index for determining the health of the subject's hippocampal function, the following steps:
Trial process of repeatedly trying to present multiple test items to the subject sequentially;
After the end of each trial in the trial process, the test items presented in the trial to the subject are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Different kind of test item similar to the test item presented in the previous trial (C) Of the same test items as the test item presented in the previous trial Answering process to answer which of
The test item presented in the trial process and the answer result obtained in the answer process are compared to determine whether the answer result for each trial is correct or incorrect; and the results obtained in the correct / incorrect process are totaled And calculating an accuracy value for each of the patterns (A), (B), and (C), and including an evaluation value calculating step for obtaining the correct response rate as an evaluation value of the hippocampal function. Evaluation value calculation method. A system for calculating an evaluation value of hippocampal function, which is an index for determining the health of the hippocampal function of a subject,
A test item presenting means for repeatedly executing trials for sequentially presenting a plurality of test items to a subject;
A test item output means for outputting a test item to be presented in each trial to a test item presenting means;
After the end of each trial, the test items presented by the subject in each trial are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Different kind of test item similar to the test item presented in the previous trial (C) Of the same test items as the test item presented in the previous trial An answer result input means for inputting an answer result as to whether or not,
Answer result storage means for storing the answer result input via the answer result input means;
Compare the test item in each trial output by the test item output means with the answer result stored in the answer result storage means, determine the correctness of the answer result for each trial, (A), (B), an evaluation value calculating means for calculating a correct answer rate for each pattern of (C), and obtaining the correct answer rate as an evaluation value of the hippocampal function,
A system for calculating an evaluation value of hippocampal function, comprising: A method for evaluating hippocampal function for evaluating the health of a subject's hippocampal function, comprising the following steps:
Trial process of repeatedly trying to present multiple test items to the subject sequentially;
After the end of each trial in the trial process, the test items presented in the trial to the subject are the following patterns (A) to (C):
(A) Test item presented for the first time (B) Different kind of test item similar to the test item presented in the previous trial (C) Of the same test items as the test item presented in the previous trial Answering process to answer which of
An answering step for answering whether the test item presented in the trial step is the same test item as in the answering step;
A correct / incorrect determination step of comparing the test item presented in the trial step with the response result obtained in the response step to determine whether the response result for each trial is correct or incorrect;
Correct answer rate calculation step of calculating the correct answer rate for each of the patterns (A), (B), and (C) by counting the correctness of the answer results obtained in the answer step;
Comparing the correct answer rate of the pattern (B) of the subject calculated in the correct answer rate calculating step with the correct answer rate (average value ± standard deviation) of the pattern (B) of a healthy person,
A hippocampal function evaluation process for evaluating that the hippocampus is diseased or damaged when the correct answer rate of the subject is at least twice the standard deviation of the correct answer rate of the pattern (B) of healthy subjects;
A method for evaluating hippocampal function, comprising: The set of test items used in the hippocampal function evaluation value calculation method according to claim 1, wherein the same test is composed of an item group in which 85% to 98% of 30 or more healthy persons are determined to be the same. An item set, a similar test item set consisting of items that are judged to be similar to the same test item but 40% to 50% of 30 or more healthy persons are different, and the same test item set and similar A test item set including a single test item set consisting of a single test item group determined to be different from the test item set.