Monitoring of Cognitive Function in Multiple Sclerosis: An Innovative Approach through Pupillometry and Gaze Metrics

This thesis explores the use of pupillometry and gaze metrics as innovative tools to assess neural plasticity in patients with multiple sclerosis (MS). For this purpose, an advanced eye tracker, the Tobii Pro Glasses 3, was used to monitor changes in pupillary diameter and gaze direction while performing four different cognitive tests: Stroop Test, Symbol Digit Modalities Test, Trail Making Test, and Attentional Matrices. These tests were chosen for their ability to stimulate various cognitive functions, including attention, visual and working memory, and cognitive flexibility. Pupillometry was employed to provide insights into neural activity dynamics that may indirectly reflect cognitive capacity and brain adaptation processes, particularly in neurodegenerative conditions like MS. By analysing pupil size changes during cognitive tasks, we aimed to understand how neural circuits respond to cognitive demands. In addition to pupillometry, gaze metrics were extracted by analysing where subjects focused their gaze and how they processed visual information, allowing an assessment of their ability to integrate and recall information. Algorithms developed to analyse these metrics made it possible to extract useful data on response time, visual attention, and cognitive dynamics. This approach offers more detailed and informative metrics than the simple final score of cognitive tests. Although cognitive tests are designed to measure specific functions, they often involve several functions that can be difficult to separate. Pupillometric and gaze metrics, however, allow better discrimination between the functions involved, providing a more detailed picture of cognitive functioning. An essential aspect of the project is the development of an interactive screen that allows clinicians to view all pupillometric and gaze metrics in an intuitive and integrated manner. This screen provides an immediate overview of relevant measurements, facilitating clinical interpretation and practical application of the data to improve therapeutic management of MS patients. In the current phase of the project, data were collected exclusively on healthy subjects, providing a baseline. Initial results show pupillometric differences in response to stimuli of varying complexity, even in healthy subjects, suggesting a correlation between cognitive activation and pupillometric measurements. These preliminary results are an important starting point for future analyses in MS patients. In future phases, the tests will be applied to MS patients, allowing comparison between the neural dynamics of patients and healthy subjects. This comparison will be crucial for identifying differences in synaptic plasticity and post-relapse resilience, offering new perspectives for MS therapy. Although not directly explored in this study, pupillometric analysis could provide an indirect measure of locus coeruleus activity and norepinephrine release, both crucial for synaptic plasticity. Future studies may investigate this, as improved plasticity may aid recovery from neurological damage, potentially enabling a full return to normal function in relapsing-remitting MS (RRMS). This project is carried out within the framework of the “RAISE - Robotics and AI for Socio-economic Empowerment” project (ECS00000035), funded by the European Union - NextGenerationEU and by the Ministry of University and Research (MUR), under the National Recovery and Resilience Plan (NRRP), Mission 4, Component 2, Investment 1.5.