Machine Learning and AI Applied to fNIRS Data Reveals Novel Brain Activity Biomarkers in Stable Subclinical Multiple Sclerosis (2509.21770v1)

Abstract: People with Multiple Sclerosis (MS) complain of problems with hand dexterity and cognitive fatigue. However, in many cases, impairments are subtle and difficult to detect. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique that measures brain hemodynamic responses during cognitive or motor tasks. We aimed to detect brain activity biomarkers that could explain subjective reports of cognitive fatigue while completing dexterous tasks and provide targets for future brain stimulation treatments. We recruited 15 people with MS who did not have a hand (Nine Hole Peg Test [NHPT]), mobility, or cognitive impairment, and 12 age- and sex-matched controls. Participants completed two types of hand dexterity tasks with their dominant hand, single task and dual task (NHPT while holding a ball between the fifth finger and hypothenar eminence of the same hand). We analyzed fNIRS data (oxygenated and deoxygenated hemoglobin levels) using a machine learning framework to classify MS patients from controls based on their brain activation patterns in bilateral prefrontal and sensorimotor cortices. The K-Nearest Neighbor classifier achieved an accuracy of 75.0% for single manual dexterity tasks and 66.7% for the more complex dual manual dexterity tasks. Using XAI, we found that the most important brain regions contributing to the machine learning model were the supramarginal/angular gyri and the precentral gyrus (sensory integration and motor regions) of the ipsilateral hemisphere, with suppressed activity and slower neurovascular response in the MS group. During both tasks, deoxygenated hemoglobin levels were better predictors than the conventional measure of oxygenated hemoglobin. This nonconventional method of fNIRS data analysis revealed novel brain activity biomarkers that can help develop personalized brain stimulation targets.