FNIRS AS A NEW BIOMARKER FOR RARE NEURODEVELOPMENTAL DISORDERS

Angelman syndrome (AS) and Creatine Transporter Deficiency (CTD) are rare neurodevelopmental disorders characterized by severe cognitive, motor, linguistic and behavioral impairments. AS is primarily caused by a mutation or deletion of the maternal UBE3A gene in chromosome 15, while CTD results from mutations in the SLC6A8 gene on the X chromosome, which impairs creatine transport into neurons.
A major challenge in neurodevelopmental disorder research is the lack of validated, objective measures capable of reliably quantifying brain function and tracking therapeutic effects over time. This limitation hampers accurate assessment of treatment efficacy and represents an obstacle to the design and success of clinical trials. In the absence of developmentally appropriate, real-time indicators of neural function, therapeutic development remains constrained, contributing to the limited effectiveness and slow progress of available interventions.
With the goal of integrating hemodynamic response metrics into clinical trial frameworks to improve diagnostic monitoring, patient stratification, and evaluation of treatment outcomes, this study investigates functional Near-Infrared Spectroscopy (fNIRS) as a feasible and sensitive biomarker in Angelman Syndrome (AS) and cortical visual dysfunction (CTD), using visually evoked cortical responses.
Our results demonstrate robust cerebral activation, with visual stimulation consistently eliciting reliable hemodynamic responses in neurotypical controls as well as in AS and CTD patients, with larger response amplitudes observed in the patient groups. Importantly, this repeatable activation was evident even in individuals with limited behavioral engagement, underscoring the high sensitivity, tolerability, and clinical viability of fNIRS as a non-invasive tool for objectively assessing sensory processing in behaviorally complex populations.