Doctoral Thesis - Paula García

Introduction

The evaluation of the patient's visual system comprises a wide range of tests, ranging from structural measures to measures of visual function. The latter allow determining if a pathology affects the ability to extract visual information about the environment and can serve as a method for early detection and monitoring the evolution of an anomaly, provided that the number of mechanisms involved in the measurement is reduced¹.

Reducing the number of mechanisms involved is only possible if their properties are differentiated enough, either by the characteristics of the objects they respond to, their response to adaptation, or the tasks they can mediate. The three main types of retinal ganglion cells M, P, and K (magnocellular, parvocellular, and koniocellular cells)², whose fundamental task is to convey information from the retinal image to the cortex (Figure 1), show this differentiation, which has already been exploited to design different psychophysical tests^3-5.

The M, P, and K cells differ in size, response speed, selectivity to spatial and temporal frequency, and color². Both M and P process achromatic information, although M is the most sensitive mechanism when spatial frequency is low and temporal frequency is high⁶. P and K support red-green and blue-yellow chromatic mechanisms, respectively, and are more sensitive to low temporal frequencies². Despite these differences, the tuning regions of M, P, and K overlap, and isolating a mechanism entirely is difficult. However, it has been shown that it is possible to maximize the response probability of a particular pathway by using the spatiotemporal and chromatic characteristics of the stimulus^13-15, adaptation⁷, or task⁸.
These functional tests have allowed assessing the effect on visual function of various systemic and visual pathologies and neurological and psychological disorders. For example, the detrimental effect of glaucoma on all three pathways⁹, the defect in the magnocellular pathway linked to Alzheimer's¹⁰, or functional alterations in dyslexics¹¹. For other disorders, such as ADHD (Attention Deficit Hyperactivity Disorder) or Williams syndrome, information about the potential affected visual mechanisms is incomplete.
Studies on ADHD do not agree on whether there are affected visual pathways and which ones they might be. For example, an effect on the perception of the color blue has been described¹², not confirmed by other studies¹³, although these results could be influenced by the medication taken by the patients. In the study by Kim, S. et al¹², the anomaly in the perception of the color blue was detected using an arrangement test (Farnsworth Munsell 100 Hue Test), while the state of the achromatic mechanism is evaluated by other procedures, such as contrast sensitivity. It is common to use tests in which not only the stimulus but also the task and the variable to measure change depending on the mechanism being evaluated. If the objective is to determine which mechanism has suffered the greatest functional loss, this strategy entails the difficulty of establishing a common metric¹⁴.

On the other hand, although psychophysical tests have the advantage of being non-invasive and allowing the study of visual function, the measurements are often lengthy and require the patient to verbalize a description of the stimulus, which usually involves describing orientations or positions that can be challenging for patients with disorders such as dyslexia or ADHD. The proposed project aims to minimize these problems by attempting to unify and simplify the proposed psychophysical task for the patient and provide them with response procedures, considering populations with special difficulties. As for the procedure followed to favor the response of each visual pathway, the intention is to extend a strategy developed for the achromatic mechanism¹⁵ to desensitize the undesired mechanisms.

Objectives

The main objective of the project is to design, create, and validate a psychophysical measurement test capable of selectively favoring different visual pathways while maintaining a similar task and basic structure. The task proposed to the patient will be simple to facilitate understanding and completion of the test, taking into account the conditions of patients with special needs such as ADHD, for whom losses in different visual pathways have been described^12,13.

The aim is to develop a non-invasive, portable, moderately priced device that allows adaptations in the response registration method for patients with attention or verbal communication difficulties. We will start with a laptop computer, the screen of which will be characterized colorimetrically. After a literature review, the spatial-temporal and color characteristics of the stimuli will be chosen. A "probe" stimulus will be used to favor the visual pathway of interest, adding frequency and chromaticity-tuned noise to desensitize unwanted mechanisms. We will design a task accessible to as many patients as possible, implementing an adaptive psychophysical method to reduce measurement time. The usability and repeatability of the pilot device will be evaluated with a small population, and the software will be improved before expanding the sample to analyze agreement with reference devices. If the results are favorable, a database of normality of young subjects will be built, with which the pathological population of interest, initially young patients with ADHD, will be compared. With the developed device and the initiation of the intellectual property protection process, we will apply for available transfer and valorization calls.

References

1. Anderson RS. The psychophysics of glaucoma: improving the structure/function relationship. Prog Retin Eye Res. 2006 Jan;25(1):79-97. doi: 10.1016/j.preteyeres.2005.06.001.
2. Solomon S (2021). Retinal ganglion cells and the magnocellullar, parvocellular, and koniocellular subcortical visual pathways from the eye to the brain. En Barton JJs y Leff A, eds. Handbook of Clinical Neurology. 178. 31-50. Elsevier.
3. Jampel HD, Singh K, Lin SC, Chen TC, Francis BA, Hodapp E, Samples JR, Smith SD (2011). Assessment of Visual Function in Glaucoma: A Report by the American Academy of Ophthalmology, Ophthalmology, 118, 5, 986-1002, https://doi.org/10.1016/j.ophtha.2011.03.019
4. Edwards M, Goodhew SC, & Badcock DR (2021). Using perceptual tasks to selectively measure magnocellular and parvocellular performance: Rationale and a user’s guide. Psychonomic Bulletin & Review, 28(4), 1029–1050. https://doi.org/10.3758/s13423-020-01874-w
5. Preto S, Gomes CC. Glaucoma and short-wavelength light sensitivity (blue light). En: Advances in Intelligent Systems and Computing. Cham: Springer International Publishing; 2019. p. 56–67.
6. Merigan WH, Maunsell JH. Macaque vision after magnocellular lateral geniculate lesions. Vis Neurosci [Internet]. 1990;5(4):347–52. Disponible en: http://dx.doi.org/10.1017/s0952523800000432
7. Pokorny J (2011). Review: steady and pulsed pedestals, the how and why of post-receptoral pathway separation. J Vis. 11(5):1-23. doi: https://doi.org/10.1167/11.5.7.
8. Goodbourn PT, Bosten JM, Hogg RE, Bargary G, Lawrance-Owen AJ, Mollon JD. Do different “magnocellular tasks” probe the same neural substrate? Proc Biol Sci [Internet]. 2012;279(1745):4263–71. Disponible en: http://dx.doi.org/10.1098/rspb.2012.1430
9. Sample PA, Medeiros FA, Racette L, Pascual JP, Boden C, Zangwill LM, Bowd C, Weinreb RN (2006). Identifying glaucomatous vision loss with visual-function-specific perimetry in the diagnostic innovations in glaucoma study. Invest Ophthalmol Vis Sci. 47(8):3381-9. doi: 10.1167/iovs.05-1546. PMID: 16877406.
10. Valenti DA (2010). Alzheimer's disease: Visual system review, Optometry - Journal of the American Optometric Association. 81, 12-21, https://doi.org/10.1016/j.optm.2009.04.101.
11. Ahmadi K, Pouretemad HR, Esfandiari J, Yoonessi A, & Yoonessi A. (2015). Psychophysical evidence for impaired Magno, parvo, and konio-cellular pathways in dyslexic children. Journal of Ophthalmic & Vision Research, 10(4), 433–440. https://doi.org/10.4103/2008-322X.176911
12. Kim S, Chen S & Tannock R. (2014). Visual function and color vision in adults with Attention-Deficit/Hyperactivity Disorder. Journal of Optometry, 7(1), 22–36. https://doi.org/10.1016/j.optom.2013.07.001
13. Brown AC, Peters JL, Parsons C, Crewther DP, & Crewther SG. (2020). Efficiency in Magnocellular processing: A common deficit in neurodevelopmental disorders. Frontiers in Human Neuroscience, 14, 49. https://doi.org/10.3389/fnhum.2020.00049
14. Antón A, Capilla P, Morilla-Grasa A, Luque MJ, Artigas JM, Felipe A (2012). Multichannel Functional Testing in Normal Subjects, Glaucoma Suspects, and Glaucoma Patients. Invest. Ophthalmol. Vis. Sci. 53(13):8386-8395. doi: https://doi.org/10.1167/iovs.12-9944.
15. Barbur JL, Harlow AJ and Pant GT (1994). Insights into the different exploits of colour in the visual cortex. Proc Biol Sci, 258, 327–34. https://doi.org/10.1098/rspb.1994.0181

ADHD, psychophysics, vision, optometry, visual perception, visual pathways

Campus Burjassot/Paterna

C/ Doctor Moliner, 50. 46100 Burjassot (València)

963 544 094 / (9635) 43909

The present research project is part of the University Teaching Staff Training Program (FPU22), in which the principal investigator, Paula García Balaguer, has been selected as a beneficiary after a rigorous selection process in the competitive call of the Ministry of Science, Innovation and Universities. The grants awarded in this call are aligned with the State Plan for Scientific, Technical and Innovation Research (State Plan for R&D&I) 2021-2023, within the framework of the State Program to Develop, Attract and Retain Talent.