Biomarker of the colour perception of a mammal subject based on pupil frequency tagging

Patent metadata

Field	Value
Publication number	US-11229356-B2
Application number	US-201816499386-A
Country	US
Kind code	B2
Filing date	Mar 29, 2018
Priority date	Mar 31, 2017
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

Abstract

Evaluation of the perception of colors by mammals with a view to obtaining a characteristic biomarker of each tested subject takes advantage of the slow pupillary oscillatory response to generate an objective neurological signature of this perception of colors. A method based on pupil frequency tagging is used at a tagging frequency Ftag adapted to the pupil response speed. A dynamic two-color stimulus is displayed, this stimulus comprising a two-color pattern the colors of which are inverted at the frequency Ftag, one of the colors gradually varying in a range of possible values. From the pupillary response, a signal representative of the oscillation power of the pupil is generated. The minimum of this signal corresponds to the relative iso-luminance of the tested pair of colors.

First claim

The invention claimed is:

1. Method for generating an indicator or biomarker (SIG power , APPROX power ) of the perception of colors by a mammal subject, comprising the following steps:
subjecting the mammal subject to at least one dynamic multi-color stimulus comprising displaying, on a display peripheral, a multi-color pattern at least two colors of which are periodically inverted at a frequency called the tagging frequency (F tag ),
controlling a modification over time of at least one (C 2 ) of the two colors of the multi-color pattern during the display of the dynamic multi-color stimulus, in order to make the displayed luminance of this color vary,
acquiring, with an image-acquiring device, an oscillatory response (SIG resp ) of at least one pupil of the mammal subject, during the display of the dynamic multi-color stimulus, and
generating, from the acquired response, a signal (SIG power , APPROX power ) representative of the power of the oscillatory response (SIG resp ) of power, the pupil as a function of the modification over time of at least one of the two colors during the display of the dynamic multi-color stimulus.

2. The method according to claim 1 , further comprising a step of determining the iso-luminance two-color configuration of the two colors of the dynamic multi-color stimulus corresponding to a minimum (MIN) of the generated signal (SIG power , APPROX power ).

3. The method according to claim 1 , wherein the other color (C 1 ) of the multi-color pattern is kept fixed during the display of the dynamic multi-color stimulus.

4. The method according to claim 1 , wherein the tagging frequency (F tag ) is dependent on the subject.

5. The method according to claim 4 , further comprising a prior step of determining the tagging frequency (F tag ), by subjecting the subject to at least one calibration light flash, measuring an average response time of the pupil of the mammal subject to the calibration light flash, and setting the tagging frequency depending on the measured average response time.

6. The method according to claim 1 , wherein the mammal subject is subjected to two successive dynamic multi-color stimuli based on two different pairs of colors.

7. The method of claim 6 , wherein multi-color stimuli are two-color stimuli.

8. The method according to claim 1 , wherein the generated signal is a signal representative of the oscillation power of the pupil at the tagging frequency and/or at one or more of its harmonics, representative of the variation in the frequency component, at said tagging frequency and/or at one or more of its harmonics, of the oscillatory response of the pupil.

9. The method according to claim 8 , wherein the generation of the signal representative of the oscillation power (SIG power , APPROX power ) of the pupil at the tagging frequency (F tag ) and/or at one or more of its harmonics comprises applying, to the acquired response (SIG resp ), a discrete fast Fourier transform in a moving time window (W i ) and storing in memory, for each time window, the value (P i,tag ) of the frequency component at the tagging frequency and/or at one or more of its harmonics of the obtained frequency spectrum.

10. The method according to claim 1 , wherein the generation of the signal representative of the power of the oscillatory response comprises determining an amplitude of variation in the diameter of the pupil in response to each inversion of the colors of the multi-color pattern, said signal (SIG power , APPROX power ) being formed from the amplitudes thus determined.

11. Method for determining an indicator or biomarker characteristic of a pathology of a mammal subject, comprising the following steps:
generating at least two indicators or biomarkers (SIG power , APPROX power ) of f the perception of colors by the mammal subject at two separate respective times (t 1 , t 2 ), by performing the method according to claim 1 , and
determining an indicator characteristic of a pathology by the modification between the two separate respective times thus generated power signals (SIG power , APPROX power ) of the pupil.

12. The method according to claim 11 , wherein the step of generating at least two indicators or biomarkers comprises determining, for each of the two times (t 1 , t 2 ), the iso-luminance two-color configuration of the two colors of the dynamic multi-color stimulus corresponding to a minimum (MIN) of the generated signal (SIG power , APPROX power ), and the modification indicator comprises a difference between the color values (c 2 (t 1 ), c 2 (t 2 )) of the two determined two-color configurations.

13. Method to diagnose a pathology or to track the progress of a pathology of a mammal subject, comprising a step of providing a modification indicator obtained for the mammal subject by performing the method according to claim 11 , and diagnosing the pathology or tracking the progress of the pathology based on the modification indicator.

14. The method according to claim 13 , wherein the pathology is selected from the group consisting of: multiple sclerosis, hepatitis, diabetes, neurodegenerative diseases, neurodevelopmental diseases, neurovascular diseases, intoxications, age-related macular degeneration, glaucoma and retinal diseases.

15. The method according to claim 14 , wherein the neurodegenerative disease is selected from the group consisting of: Alzheimer's and Parkinson's disease.

16. The method according to claim 14 , wherein the neurodevelopmental disease is selected from the group consisting of: schizophrenia and autism.

17. The method according to claim 14 , wherein the neurovascular disease is stroke.

18. The method of claim 1 , wherein the multi-color stimulus is a two-color stimulus and the multi-color pattern is a two-color pattern.

19. System for generating an indicator or biomarker (SIG power , APPROX power ) of the perception of colors by a mammal subject, comprising:
a display peripheral,
a computational system for stimulating the mammal subject with a dynamic multi-color, stimulus, the computational system controlling the display, on the display periphery, of a multi-color pattern at least two colors of which are periodically inverted at a frequency called the tagging frequency (F tag ),
a color controller configured to modify over time at least one (C 2 ) of the two colors of the multi-color pattern during the display of the dynamic multi-color stimulus, in order to make the displayed luminance of this color vary,
an image-acquiring device for acquiring an oscillatory response (SIG resp ) of at least one pupil of the mammal subject, during the display of the dynamic multi-color stimulus, and
an indicator or biomarker generator configured to generate, from the acquired response, a signal (SIG power , APPROX power ) representative of the power of the oscillatory response (SIG resp ) of the pupil as a function of the modification over time of at least one of the two colors during the display of the dynamic multi-color stimulus.

20. System for determining an indicator or biomarker characteristic of a pathology of a mammal subject, comprising:
a system for generating an indicator or biomarker of the perception of colors by a mammal subject according to claim 19 , and
a processing module configured to determine an indicator of modification between two power signals (SIG power , APPROX power ) generated, by the system for generating an indicator or biomarker of the perception of colors, at two separate times (t 1 , t 2 ) for the same subject using the same dynamic multi-c

Assignees

• Inst Du Cerveau Et De La Moelle Epiniere Icm
• Centre Nat Rech Scient
• Inst Nat Sante Rech Med
• Assist Publique Hopitaux De Paris Ap Hp
• Univ Sorbonne
• Centre National De La Racherche Scient Cnrs

Inventors

• Pouget Pierre
• Daye Pierre
• Lorenceau Jean

Classifications

• A61B3/145

  by video means · CPC title

• A61B3/112 Primary

  for measuring diameter of pupils · CPC title

• A61B3/066

  for testing colour vision · CPC title