WO2014001271A2

WO2014001271A2 - Device for assessing the cognitive abilities of a patient

Info

Publication number: WO2014001271A2
Application number: PCT/EP2013/063168
Authority: WO
Inventors: Vincent Des Portes; Aurore CURIE; Anne CHEYLUS; Gérald BUSSY
Original assignee: Hospices Civils De Lyon; Université Lyon 1 Claude Bernard; Centre National De La Recherche Scientifique
Priority date: 2012-06-25
Filing date: 2013-06-24
Publication date: 2014-01-03
Also published as: FR2992158A1; FR2992158B1; WO2014001271A3

Abstract

The invention relates to a device (1) for assessing cognitive abilities, including: a display device (3); a testing device (2) configured to determine the location of the display device watched by an eye of the patient and to automatically carry out the following sequence: the display (3) of a test visual; the determination of the number of transitions of the gaze between a matrix and answer choices; and the repetition of the sequence for a plurality of test visuals.

Description

DEVICE FOR EVALUATING COGNITIVE CAPACITY OF A

PATIENT

The invention relates to the identification (phenotyping) and monitoring of pathologies altering the reasoning: neurodevelopmental disorders or neurodegenerative pathologies, with in particular the possibility of monitoring the cognitive capacities of a patient suffering from such a pathology, with a view to determine the effectiveness of a pharmacological treatment.

Among the known neurodevelopmental pathologies, mention may be made especially of intellectual disability: trisomy 21, mutation of the ARX gene or of the FMR1 gene (fragile syndrome syndrome). To date, the consequences of such pathologies are evaluated with methods comparable to methods of determining the intelligence quotient.

A method of analysis with a very good correlation with the intelligence quotient is in the Raven matrices. They evaluate inductive reasoning from an analog and non-verbal visual task. This is a multiple choice test. The matrices of Raven are in the form of matrices of nine cells (three by three). The order of the items is characterized by a growing difficulty level. Each item consists of 8 abstract figures presented in a square pattern whose ^9th element is missing but can be derived once we inferred the law that governs the series. The person must choose from the 8 answers proposed which she considers to be the correct answer.

The results obtained in these tests, for the pathologies of neurodevelopment mentioned above, are substantially similar, which corresponds to the finding that these tests do not allow to discriminate the cognitive level of these people.

A use of Raven's matrices is described in particular in the document "Solving the Raven Progressive Matrices by Adults with Intellectual Disability with / without Down Syndrome".

The use of these tests is similarly inconclusive to determine the evolution of the cognitive abilities of a patient, for example in the context of the study of a treatment.

The invention aims to solve one or more of these disadvantages.

The invention thus relates to a device for evaluating the cognitive capacities of a patient suffering from a neurodevelopmental or neurodegenerative pathology, as defined in the appended claims. Other characteristics and advantages of the invention will emerge clearly from the description which is given hereinafter, by way of indication and in no way limitative, with reference to the appended drawings, in which:

FIG. 1 represents examples of geometrical shapes that can be included in cognitive capacity evaluation test matrices according to the invention;

FIG. 2 illustrates the frame of a test display for the implementation of the invention;

FIGS. 3 to 7 illustrate various test visuals implemented according to the invention;

FIG. 8 is a schematic representation of an evaluation device according to an exemplary implementation of the invention;

Figures 9 to 12 illustrate test results for healthy subjects;

FIGS. 13 and 14 are comparative diagrams of the test results for healthy subjects and for several neurodevelopmental pathologies;

Figures 15 to 17 illustrate test results for healthy subjects;

Figures 18 to 20 are comparative diagrams of test results for healthy subjects and for patients with trisomy 21;

Figures 21 to 23 are comparative diagrams of test results for healthy subjects and for patients with Fragile Syndrome.

FIG. 1 represents examples of geometric shapes that are easily identifiable and dissociable by a patient presenting a pathology of neurodevelopment. Illustrated geometric shapes include a circle, a square, a triangle. These geometric shapes are in fact filled in their middle part. These forms are preferably simple and easily discriminable from each other.

FIG. 2 represents an example of a frame for a test display 5 for the implementation of the invention. The frame of the test display 5 includes a matrix

51, located in the upper part of the figure and a zone 52 at the bottom of the figure corresponding to the display of the proposed answers.

The matrix 51 comprises only four cells 531, 532, 533 and 534 arranged in the matrix along two lines and two columns. For reasons of readability, boxes 531 to 534 are here delimited by discontinuous lines.

Boxes 531 to 533 are intended to contain elements consisting of geometric shapes.

In order to make the test extremely simple, only two answers are proposed via frames 521 and 522; in box 52. Box 521 is intended to include an item corresponding to a bad answer in the examples that will be illustrated. The frame 522 is intended to include an item corresponding to a good answer in the examples which will be illustrated. However, in a succession of test visuals, the number of correct answers presented on the right and on the left is balanced.

As detailed below, boxes 531 to 533 include items

541 to 543 made of geometric shapes. The element, expected in box 534 according to a logical link, is missing. As detailed later, four parameters of the elements can be varied to create the matrices 51: the shape (for example round, square, triangle), the number (for example one or two), the color (for example black, white , gray) and size (large, small). The number of relations between the elements 541 to 543 of cells 531 to 533, which must be integrated to obtain the correct answer, varies from 0 (when all the elements of cells 531 to 533 are identical), 1 when there is a relation (size, shape, color or number) that varies between boxes 531, 532 or between boxes 531, 533, 2 when there is a relationship (size, shape, color or number) that varies between boxes 531 and 532 and a relationship that varies between boxes 531 and 533. To suggest to the patient that an item is missing in box 534, box 534 includes a frame 544. To suggest to the patient to look for the missing item in box 534, the frames 521 and 522 advantageously have a shape identical or similar to that of the frame 544. The box 534 does not include any of the elements 541 to 543 present in the boxes 531 to 533.

Figures 3 to 7 illustrate different test visuals with different levels of difficulty to more accurately assess the cognitive abilities of a patient with a neurodevelopmental or neurodegenerative pathology. The matrices 51 in fact comprise three levels of complexity as a function of the number of logical links (0, 1 or 2) that must be integrated in order to obtain the correct answer.

On the other hand, we used two types of bad-response "inhibit", that is, element 523 in frame 521 is identical to elements 541 to 543 or wrong "neutral" responses. that is to say, the element 523 of the frame 521 is different from each of the elements 541 to 543. In FIG. 3, an example of a test visual whose level of difficulty is the simplest is illustrated. This is the "identical" condition. At this level of difficulty, the correct response proposed to the patient does not require the analysis of any relationship between the elements of the matrix 51. It is only expected of the patient that he determines the identity between the element 524 of the correct answer of the frame 522 and the elements 541 to 543, which are strictly identical (in this case a single black circle of the same size and likewise color). In Figures 4 and 5, there are illustrated test images whose level of difficulty is intermediate. In these test visuals, the patient must integrate a single relation (the shape) within the matrix 51 to obtain the correct answer, namely the geometric shape changes between the element 541 (single black circle) and the element. 543 (single black square) while the elements 541 and 542 are identical (single black circle). Thus, one and only one parameter differs between the elements 541 to 543: the shape. The patient must therefore integrate the variation of a single parameter to obtain the correct answer. In the examples of FIGS. 4 and 5, the correct answer is therefore the only black square 524 present in frame 522.

In the example of FIG. 4, the element 523 constituting the wrong response (a single black triangle) proposed in the frame 521 differs from the elements 541, 542 and 543. This test display comprises a bad answer 523 "neutral" , unambiguously with the elements of the matrix 51.

In the example of FIG. 5, the element 523 constituting the wrong response (a single black circle) proposed in the frame 521 is identical to one of the elements 541 and 542. The wrong response must therefore be "inhibited" by the patient. . This test display has a wrong "inhibit" response that the patient must not choose, even though it is identical to one of the elements of the matrix 51.

In Figures 6 and 7, there are illustrated test images whose level of difficulty is higher. In these test images, the patient must integrate the variation of two logical links between the three elements of the matrix 51 ("two-relationship matrices"), namely the size (the element 541 is larger than the element 542 ) and the geometric shape (the element 541 is a square, while the element 543 is a triangle). The patient must therefore integrate the variation of two parameters to obtain the correct answer. In the examples of FIGS. 6 and 7, the correct answer is therefore the only small black triangle 524 present in frame 522.

In the example of FIG. 6, the element 523 constituting the wrong response (single black circle) proposed in the frame 521 differs from all the elements 541 to 543. This test display comprises a bad "neutral" response, unambiguously with the elements of the matrix 51. In the test display of FIG. 6, the wrong answer 523 of the frame 521 differs from the correct answer only by a single parameter: this parameter is here the geometric form. With this level of difficulty, we can speak of a bad answer near or neutral.

In the example of Figure 7, the item 523 constituting the wrong answer (a single square full of small size) proposed in box 521 is identical to the 542 element. The wrong response must therefore be inhibited by the patient. This test display has a wrong "inhibit" response that the patient must not choose, even though it is identical to one of the elements of the matrix 51.

In the examples of the matrices shown in FIGS. 6 and 7, the two parameters that vary are the geometrical shape and the size of the elements 541 to 543. Throughout the test, the 4 parameters can be varied: the color (black, gray or white), the geometric shape (round, square, triangle), the number (1 or 2) and the size (large, small).

The results of tests performed with the different test images are detailed later, for two aspects of the invention. The types of tests mentioned later will be designated F3, F4, F5, F6 and F7, with reference to the types of tests detailed above and illustrated respectively in FIGS. 3 to 7.

FIG. 8 schematically represents an example of a cognitive capacity evaluation device 1, according to an exemplary implementation of the invention. The device 1 comprises a processing device 2, typically a computer. This processing device 2 is, for example, configured to execute an evaluation application of the cognitive capacities. The processing device 2 includes (for example in its evaluation application) a database of test images. The processing device 2 is connected to a display device 3, typically a display monitor. The display device 3 is intended to display the test images selected by the processing device 2. Furthermore, the processing device 2 is connected to an acquisition interface 4 of a patient response. Depending on the desired functions, the acquisition interface 4 may comprise a validation button system 41 and 42, and / or an oculometer 43.

Advantageously, for the implementation of a first aspect of the invention, the interface 4 will include a simplified device for acquiring an answer, in the form of an interface with only two buttons, one 41 located on the left and the other 42 on the right. The patient can thus easily associate each button with one and only one respective response proposed to the left and right in a displayed test display. The patient is then expected to press the button corresponding to the side where the correct answer is located on the test display.

An evaluation application of the processing device 2 can typically use another application (for example the software marketed under the trade reference 'presentation' by the company Neurobehavioral Systems, Inc., known by the high temporal resolution of the display of visuals and the acquisition of answers) to implement the display of successive visuals and manage the acquisition of the parameters of the responses provided by the patient.

To facilitate the understanding of the patient, the processing device 2 can emit a signal representative of a good or a bad answer. The processing device 2 can thus control the display of a visual after each answer acquired. To facilitate the assimilation of the task, the test visual allows the patient to determine whether the answer he has just given is good or bad, for example by displaying a smiling face for a good answer and a sad face for a bad one. reply.

The processing device 2 allows the display of an intermediate image between two successive test images. This intermediate image is typically a eye-fixing cross located in the center of the screen, so as to induce the patient to focus for the next test visual and thereby make the test particularly reproducible.

For the execution of a cognitive capacity evaluation test with the evaluation device 1, a patient is placed facing the screen 3 and has the acquisition interface 4. The treatment device 2 is configured to automatically repeat the following operations:

- display a test visual;

- Acquire the patient's response to the test visual. The answer here is Boolean: the patient's answer is correct or the patient's answer is incorrect. One can assimilate the absence of answer after a given duration to an incorrect answer;

- measure the time between the display of the test display and the response provided by the patient.

Advantageously, the test is performed with a relatively large number of successive visuals, typically at least 20, in order to smooth the results. The number of successive visuals, however, must not be too high, to allow the patient to remain focused throughout the test. The evaluation application can calculate an average response time and an error rate for each level of difficulty for the test of a patient. The evaluation application may also display a graphical representation of the test result compared to other reference results, either of the patient or of a group of other patients.

The test was validated in 34 healthy adult subjects aged 27.71 years [18 years and 4 months to 43 years and 8 months]. We also established the developmental trajectory of the test on 62 children over 4 years old. If we group them by two years of age, we have included in this behavioral paradigm 12 children aged 4-5, 1 1 children aged 6-7, 1 1 children aged 8-9, 12 children aged 10-1 1, 9 children aged 1-2 years, and 7 adolescents aged 14 at 17 years old.

Three groups of patients also performed this test: 1 0 patients with an ARX gene mutation (mean age 1 8.70 years, [13 years 2 months-39 years 1 month]), 14 patients with trisomy 21 (mean age 25.26 years , [1 5 years and 7 months to 37 years and 5 months]) and 14 patients with fragile (syndrome (mean age 22.24 years, [14 years and 6 months to 31 years and 6 months]). The processing device 2 acquired the behavioral data by recording the response times and the error rates of the different patients. The test for one patient took place in four successive executions. At each execution, 45 visuals of test were successively displayed. Of the 45 visuals, nine visuals were displayed for each difficulty level shown in Figures 3 to 7.

Beforehand, the task to be performed for each patient was explained using a paper support. Each patient performed a brief training to verify that the instruction was understood and to allow the patient to become familiar with the acquisition interface 4. The acquisition interface 4 used for the tests was two response boxes, placed one in the right hand; the other in the patient's left hand.

An analysis of error rates and response times for the correct responses was performed. In addition, subjects were excluded from the analysis for which the error rate for "identical" conditions and "a relationship with a bad neutral response" was much higher than that obtained on average over all conditions by the group to which the subject belonged. Indeed, these two conditions being the easiest of the paradigm, one can consider that these subjects did not really manage to understand the instruction. A preliminary study of 34 healthy subjects determined that there is a statistically significant effect of the number of relationships on response time to a test visual. For a single-relationship test, the response time is substantially the same in the presence of a wrong "inhibit" response and in the presence of a "neutral" type response. For a two-way test, the response time for a wrong response test "to be inhibited" is significantly greater than the response time for a neutral bad response. It can be noted that the effect of the number of relations has a preponderant effect on the response time compared to that of the type of bad response proposed (neutral or "to be inhibited"). Figures 9 and 10 respectively illustrate response times and average error rates obtained for healthy subjects for the five test variants previously detailed.

Figures 1 and 12 respectively illustrate the developmental trajectories for response times and error rates obtained as a function of the age of healthy subjects, as well as their mathematical modeling.

When studying the interaction between number of relationships and inhibition, we observe that up to the age of 6, the effect of inhibition is much greater than the effect of the number of relationships. Indeed, the error rates are much greater for a relationship with a response to be inhibited than for two relations without inhibition, whereas in the second, the level of reasoning is greater since it is necessary to combine two relations to obtain the answer. . For the group of 4-5 years, if we look at their response times, they are faster for conditions with response "to inhibit" than without. They are "attracted" by resemblance. It seems that it is then necessary to wait until the age of 10 for the effect of the inhibition to be no longer statistically significant for the "relationship" conditions. Finally, even in older adolescents, the profile obtained is not yet quite that of adults.

Figures 13 and 14 respectively illustrate response times and average error rates for healthy subjects (solid line), subjects with trisomy 21 (dotted line), subjects suffering from the mutation of the ARX gene (discontinuous line) and subjects with Fragile X syndrome (alternating line).

The comparison of the groups of patients for the three pathologies shows that there is no significant difference in terms of response time. All are slower than healthy subjects of the same chronological age. On the other hand, the groups of patients differ greatly in their error rates and the factors inducing these error rates. In fact, overall, trisomy 21 patients make significantly fewer errors than ARXs, which make them significantly less than patients with Fragile X syndrome. Specifically, patients with Fragile X syndrome stand out clearly from the other two groups in the presence of an "inhibit" response, which causes them great difficulty in selecting the right answer.

It can therefore be noted that the tests performed are highly discriminating for each of the pathologies studied. Tests can be performed at regular intervals for the same patient to precisely identify the evolution of his cognitive abilities. In addition, a population of patients undergoing treatment can be compared to a reference population suffering from the same pathology. The implementation of this first aspect of the invention for the evaluation of cognitive abilities thus facilitates the implementation of clinical studies or the analysis of the effectiveness of a possible treatment or rehabilitation.

The test images, the difficulty levels of which have been detailed with reference to FIGS. 3 to 7, are also used to implement a second aspect of the invention based on ocular tracking or oculometry (eye tracking in English). . The study of ocular monitoring makes it possible to deduce the cognitive strategy implemented by the patients to solve the test visuals. This technique of "capture of the gaze" thanks to a remote system (reflection of an infrared beam on the cornea of the subject's eye) is, by its non-invasiveness, particularly valuable for studying people with intellectual disabilities. Especially since it has the added advantage of not making noise (unlike MRI). Thus, as for the first aspect of the invention, successively displays different test visuals with different levels of difficulty.

The more rules needed to solve a matrix, the more the person must implement working memory. Bethell-Fox has introduced the idea that individuals differ qualitatively in the way to the choice of the answer. Indeed, there seem to be two different strategies for solving a problem: a strategy by constructive matching, based on the study of the matrix (preferably used by high-potential subjects), and a strategy by elimination, based on responses (preferably used by subjects with neurodevelopmental pathology). The first strategy is characterized by the elaboration of an ideal response which is then compared to the answers and corresponds globally to the mode of functioning of the healthy subjects. The second strategy uses a comparison of the features between the elements of the problem and the elements of the alternative responses.

The use of eye tracking thus makes it possible to discriminate between the two strategies. In addition to monitoring the cognitive abilities of a patient, this aspect of the invention is intended to determine the effectiveness of treatments or re-educations by detecting a change of logical approach in a patient.

The study of the proposed eye tracking aims in particular to determine the proportion of fixation time of the matrix 51 and the number of transitions between the matrix 51 and the response zone 52. Other interesting parameters can be extrapolated from the eye tracking: index of distribution of the matrix fixation time (proportion of time spent on the cells 531 to 534 of the matrix 51), and / or the latency of the first look transition of the matrix 51 towards the response zone 52. For this purpose, the acquisition interface 4 advantageously includes an oculometer 43 associated with an application executed on the processing device 2. The oculometer 43 typically comprises an infra-red transmitter and an infra-red camera arranged near the device 3. The oculometer allows non-invasively determining the position of the eyes in the space and the direction of the gaze. Such a non-invasive method is particularly advantageous for application to patients with pathologies of neurodevelopment or neurodegenerative diseases. The position of the eyes in the space and the direction of the gaze is calculated from the reflection of the infrared beam on the cornea of the subject's eye by means of the camera. The application can therefore determine the position on the display device 3 fixed by the eye.

Eye movements, fixations of the gaze and pupillary diameter of patients can be recorded by means of a device marketed under the trade name Eyetracker Tobii X120. This device is a remote, binocular system with a sampling frequency of 60 Hz, a precision of 0.5 degrees of visual angle and a tolerance of head movements of 20 cm in all directions (via in-application compensation) so that there is no physical constraint on the patients' heads.

Before implementing the assessment of cognitive abilities based on ocular monitoring, a preliminary calibration step is advantageously performed. The calibration step allows the eye tracking device to adjust to each patient. In practice, the calibration successively displays five circles of colors, which appear successively at different locations of the display device 3. The display of the rounds is accompanied by sound stimuli to attract the attention of the patient. The calibration makes it possible to assign known fixing positions (display position of the rounds) to a position of the patient's eye.

For each sample measured by the camera of the eye tracker 43, the application executed on the treatment device 2 determines the location fixed by the patient on the display device 3. For each sample, the application determines whether it is a fixation, an ocular saccade or a missing data.

The application advantageously interpolates certain missing samples: for example during an eye blink, the application may have a certain number of samples for which the position fixed by the patient is undetermined.

When several successive samples of missing data cover a duration of less than 400 ms, these missing data can be likened to a physiological blink. A sample i is considered a saccade, when the distance between the position Pmi measured by this sample and the position measured in a previous sample exceeds a certain threshold h.

To limit the incidence of noise in the samples measured, a position value Pi is advantageously associated with each sample i, by calculating a moving average (filter) between the measured positions for a predefined number r of the last measured positions (average over one sliding window). Missing data can be obtained during the mobile filtering by the nearest neighbors interpolation method, so as to preserve the saccades, which would not allow a linear interpolation. A distance Di is advantageously calculated between the position value Pi calculated for a sample i and the position value P _ir calculated for the sample ir.

Comparing the distance Di to the threshold h:

the sample i is classified as a saccade if Di> h;

the sample i is classified as a fixation if Dkh.

For each sample, Boolean values are assigned for the presence or absence of the gaze in the following zones:

matrix 51;

- box 531;

- box 532;

- box 533;

- box 534;

response zone 52;

- box 521;

- frame 522.

The fixation of a given zone by the gaze extending over several samples, it is possible to determine for each zone its fixing time. From collected data, the following parameters are advantageously determined for each test display:

the number of transitions between the matrix 51 and the zone 52;

the number of transitions between the disjoint zones, the disjoint zones being each cells 531 to 534 and each of the frames 521 and 522;

the fixing time for each of the disjoint zones, for the matrix 51 and for the zone 52;

the proportion of respective fixing times of each of the cells 531 to 534 with respect to the time taken to answer;

the latency of the first transition between the matrix 51 and the zone 52 of the responses;

the duration between the beginning of the visual test display and the first fixation of a given zone. The principle of eye tracking analyzes is to obtain indices of the cognitive strategies used by the subjects according to the regions of the screen observed by them. As a result, we eliminated subjects using their peripheral vision from a central fixation point to solve the task, assuming that their eye tracking data does not reflect the way they solve the task. Thus, one can eliminate a test when the fixing time on box 534 (empty box materializing the expected response) is abnormally high compared to the time spent on this box, on average by the entire group.

Advantageously, it is also possible to determine the response time and the error rate according to this second aspect of the invention. One can also know the time spent on the right and the wrong answer. The eye tracking may also be combined with a button interface 41 and 42, as detailed for the first aspect of the invention, to determine the response time and the accuracy of the response.

During the eye tracking task, patients are seated in a comfortable, height-adjustable chair (the height of the seat has been adapted according to the size of the persons to obtain good quality measurements), which is stable. This chair had a footrest that was especially useful for children. The patients were positioned facing the display device 3 at a distance of approximately 70 cm from the oculometer 43 (transmitter / infrared camera focused on the patient's eyes). The oculometer 43 was inclined by 1 ° relative to the horizontal.

Throughout the duration of the measurements, an experimenter controlled in real time the quality of the data acquired, on a second display device.

In order to favor the quality of the measurements, the number of test visuals displayed to the patient has been smaller than for the first aspect of the invention. Each patient performed four successive series of tests, each series comprising the display of 15 test visuals, divided into three visuals for each of the five levels of difficulty mentioned above. The number of right answers on the left and right answers on the right side of the display 3 were balanced, and the test images did not have a detectable sequence.

Advantageously, an intermediate image has been displayed between the successive test visuals. This intermediate image is typically a test pattern formed by a fixing cross of the eye placed in the center of the screen or in the center of the matrix 51 of the test visual displayed next, so as to induce the patient to focus for the next test visual and thus make the test particularly reproducible.

The ocular monitoring task was validated in 21 healthy adult subjects aged 27.59 on average (18 years and 4 months to 41 years and 10 months). We have also established the development trajectory for these visuals on 38 children over 4 years old. If grouped by four-year-olds, were included: 1 1 children aged 4-7, 15 children aged 8-1 1, 12 children aged 12-16.

Two groups of patients also performed this task: 13 patients with trisomy 21 (mean age of 24.05 years (14 years and 2 months to 38 years and 8 months)) and 14 patients with fragile syndrome (mean age 23.82 years old (13 years and 5 months to 31 years and 7 months)). FIGS. 15 and 16 respectively illustrate the number of transitions between the matrix 51 and the response zone 52, and the duration of the latency of the first transition between the matrix 51 and the response zone 52, for the healthy subjects for the subjects. five test variants detailed previously. FIG. 17 shows the respective fixing times of the following zones of the test visuals: matrix 51, element 541; element 542; item 543 and answers for healthy subjects.

There is a statistically significant effect of the number of relationships to be integrated on the number of transitions in healthy subjects. On the other hand, there is no statistically significant effect of inhibition.

A statistically significant effect of the number of relationships to be integrated over the duration of the latency of the first transition between the matrix 51 and the response zone 52 can be seen. Overall, the higher the level of difficulty of the test visual, the more the subject healthy devotes time to the observation of the matrix 51 before consulting the response zone 52.

It can also be seen that a healthy subject spends most of his fixation time on the matrix 51. By analyzing the eye follow-up of healthy subjects, we find that they first fix box 531, then box 532, then box 533 before setting the response zone 52.

FIGS. 18, 19 and 20 respectively illustrate the number of transitions between the matrix 51 and the response zone 52, the latencies of first fixation of the regions: element 541, element 542, element 543, and responses 523, 524, and respective fixation times of the same regions, for healthy subjects (solid line) and for subjects with trisomy 21 (dotted line).

Subjects with trisomy 21 achieve a number of transitions between matrix 51 and zone 52 significantly greater than that of healthy subjects. The number of relationships to be integrated has a statistically significant effect on the number of transitions between the matrix 51 and the response zone 52 for subjects with trisomy 21. The first transition latency between the matrix and the responses is approximately 600 ms regardless of the difficulty level of the test visual. There is no effect of the number of relationships on this parameter.

It is found that subjects with trisomy 21 generally fix box 533 first for a very short time before setting zone 52, then set boxes 531 and 532 at a later stage, despite the need to consult them to solve the test.

Subjects with trisomy 21 fix the matrix 51 for a significantly shorter time than the healthy subjects and fix the response zone 52 for a significantly longer time than the healthy subjects. Patients with trisomy 21 thus spend a much smaller proportion of fixation time on the matrix 51.

FIGS. 21, 22 and 23 respectively illustrate the number of transitions between the matrix 51 and the response zone 52, the latencies of first fixation on the regions: element 541, element 542, element 543 and responses 523 and 524, and the durations respective fixation of the same regions of the test visuals, for healthy subjects (solid line) and for subjects with age-matched fragility syndrome (dotted line).

People with Fragile X Syndrome perform a number of transitions between matrix 51 and zone 52 significantly greater than that of healthy subjects. The number of relationships to be integrated has an insignificant effect on the number of transitions between matrix 51 and zone 52 for subjects with Fragile X syndrome. The latency of the first transition between the matrix 51 and the responses is approximately 400 ms regardless of the number of relations of the test display. There is therefore no effect of the number of relationships on this parameter.

It is found that people with Fragile-Fragile Disorder usually set zone 52 first before setting box 533. These subjects only fix boxes 531 and 532 at a very late stage, despite the need to consult these boxes. to solve the test.

Subjects with Fragile X syndrome fix matrix 51 for a significantly shorter time than healthy subjects and fix response zone 52 for a significantly longer time than healthy subjects. Patients with Fragile X syndrome therefore spend a much smaller proportion of the fixation time on the matrix 51. It can also be noted that the tests performed in ocular monitoring make it possible to deduce the logical strategy used, based on the number of transitions between the matrix 51 and the response zone 52, the proportion of fixation time passed on the matrix 51 and on the element 541 reflecting a complete analysis of the matrix 51, and the latency of first fixation of the matrix 51 towards the answers 523, 524. For example, it can be deduced that the person uses a strategy by constructive matching, based on the study of the matrix 51 if it passes a significant proportion of time on this matrix 51, on the element 541, present a latency of first attachment of the matrix 51 to the long responses and a reduced number of alternations between the matrix 51 and the responses. On the contrary, the person uses an elimination strategy based on the comparison of the responses 523, 524 if the proportion of time spent on the matrix 51 and the element 541 is small, whereas this proportion is strong for the responses, and the number alternations (transitions) between the matrix 51 and the responses is high. In this case, the first fixation time of the matrix 51 is substantially constant regardless of the number of relationships in the test images presented.

Some measured parameters have a very discriminating character for each of the pathologies that have been the subject of a study, in particular: the duration of first fixation of the matrix 51 and the fixing time of the different zones. Moreover, this device makes it possible to obtain quantitative quantified values reflecting the cognitive strategy of the patients.

Therefore, tests can be performed at regular intervals for the same patient to identify precisely the evolution of his cognitive abilities, including his ability to change logic of problem solving. In addition, a population of patients undergoing treatment can be compared to a reference population with the same pathology. The implementation of this second aspect of the invention for the evaluation of cognitive abilities thus facilitates the implementation of clinical studies.

Claims

Device (1) for assessing the cognitive capacities of a patient suffering from a neurodevelopmental or neurodegenerative pathology, characterized in that it comprises:

- a display device (3);

a test device (2) configured to:

- locate the location of the display device fixed by an eye of the patient;

- automatically perform the following sequence:

the display (3) of a test display including:

a matrix of dimension two by two, first, second and third boxes of the matrix respectively including first, second and third graphic elements, a fourth box suggesting that a graphic element is missing;

- two and only two response proposals, including a good response proposal and a bad response proposal, each response proposal including a graphical element;

- determine the number of glance transitions between the matrix and the response propositions;

- repeat the sequence for several test visuals including at least:

a first type of test display in which the first, second and third graphic elements are identical and in which the good response proposition is a graphic element identical to the first graphic element;

a second type of test display in which the first and second graphic elements are identical, the third graphic element having one and only one different parameter with respect to the first and second graphic elements, the good response proposition being a graphic element identical to the third graphic element;

a third type of test display in which the first to third graphic elements are different, the first and second graphic elements differing only from a single parameter, the first and third graphic elements differing only from a single parameter; good response proposition being a graphic element different from the first to third graphic elements and different from the second and third graphic elements respectively by a single parameter; said parameters being chosen from the group including the geometric shape of the graphic element, the number of geometric shapes present in the graphic element, the color of the graphic element, and the size of the graphic element.

An evaluation device according to claim 1, wherein the test device (2) is configured to determine that the patient uses an elimination resolution strategy if the determined number of transitions is greater than a threshold.

3. Evaluation device (1) according to claim 1 or 2, wherein:

in the second type of test display, the bad response proposal includes a graphic element different from the first to third graphic elements, this graphic element differing from the graphic element of the correct answer by a single parameter;

in the third type of test visual, the poor response proposition includes a graphic element different from the first to third graphic elements, this graphic element differing from the graphical element of the correct response by a single parameter;

said sequence is repeated for several test visuals including at least:

a fourth type of test display in which the first and second graphic elements are identical, the third graphic element having one and only one parameter different from the first and second graphic elements, the good response proposition being a graphic element identical to the third graphical element, the bad response proposal includes a graphic element identical to one of the first to third graphic elements;

a fifth type of test display in which the first to third graphic elements are different, the first and second graphic elements differing only from a single parameter, the first and third graphic elements differing only from a single parameter, the good response proposal being a graphic element different from the first to third graphic elements and different from the second and third graphic elements respectively by a single parameter, the bad response proposal includes a graphic element identical to one of the first to third elements graphics.

An evaluation device (1) according to any one of the preceding claims, wherein said test device (2) is configured to repeat said sequence multiple times for each of said types of visuals.

. Evaluation device (1) according to any one of the preceding claims, wherein said test device (2) is configured to display, prior to the display of each test display, an image including a pattern, the matrix ( 51) of the displayed test display being centered on this pattern.

. An evaluation device (1) according to any one of the preceding claims, wherein said test device (2) is configured to display an empty frame (544) in the fourth box (534) of the matrix (51) of each visual test and to display the geometric shapes of good and bad response proposals in frames (521, 522) identical to that of the fourth box.

. An evaluation device (1) according to any one of the preceding claims, wherein said test device (2) is configured to determine the time between the first fixation of the matrix (51) of a test display and the fixation one of the response proposals (521, 522) for each of the sequences, and configured to determine that the patient uses an elimination resolution strategy if the determined duration exceeds a threshold.

. Evaluation device (1) according to any one of the preceding claims, wherein the test device (2) is configured to determine the respective fixing times of the matrix (51) and the response proposals of a visual display. test for each of the sequences.

. An evaluation device (1) according to any one of the preceding claims, comprising an acquisition interface (4) of a patient response, wherein the test device (2) is configured to automatically perform each of said sequences :

acquisition of the user's response provided to said interface for the displayed test display;

- the measurement of the time separating the display of the test display from the answer acquired.

0. Device (1) for assessing the cognitive capacities of a patient suffering from a neurodevelopmental or neurodegenerative pathology, characterized in that it comprises:

an interface (41) for acquiring a response from the patient;

a device (2) configured to:

- automatically perform the following sequence:

the display (3) of a test display including: a matrix (51) of dimension two by two, first, second and third boxes of the matrix respectively including first, second and third graphic elements, a fourth box suggesting that a graphic element is missing;

acquisition of the user response provided to said interface (41) for the displayed test display;

the measurement of the time separating the display of the test display from the acquired response;

- repeat the sequence for several test visuals including at least:

a third type of test display in which the first to third graphic elements are different, the first and second graphic elements differing only from a single parameter, the first and third graphic elements differing only from a single parameter; good response proposition being a graphic element different from the first to third graphic elements and different from the second and third graphic elements respectively by a single parameter;

said parameters being chosen from the group including the geometric shape of the graphic element, the number of geometric shapes present in the graphic element, the color of the graphic element, and the size of the graphic element.