Non-invasive evaluation of brain activity with functional Near-Infrared Spectroscopy (fNIRS): from normative population to Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) are neurological conditions affecting brain maturation and causing difficulties in social, cognitive and emotional functioning. Most NDDs are still without an effective treatment, with the lack of clinical biomarkers for monitoring brain function significantly hindering the development of the therapeutic pipeline. Many methodological constraints (mostly, related to the invasiveness of procedures and the need of subjects’ compliance) prevent to shift neuroimaging protocols typically used in adults to NDDs populations, limiting functional neuroimaging research in this field. However, emerging evidence suggests that functional Near Infrared Spectroscopy (fNIRS) might be exploited to generate unbiased and reliable measures of developing brain in order to assist diagnosis and drug efficacy studies. Thus, this PhD project aimed to address the research gap in the field, evaluating feasibility, reliability and validity of fNIRS as a novel non-invasive biomarker to measure brain function in under investigated clinical populations of NDDs. To this purpose, a novel standardized fNIRS procedure to measure visual-evoked hemodynamic responses (vHDR) in the occipital cortex has been devised in normative adult population and optimized for children enriching it with high entertaining value. Moreover, test/retest reliability of vHDR metrics has been assessed in the adult population at three different timepoints, proving the robustness of this measure. This innovative experimental paradigm established a quick and easy strategy for measuring vHDR with fNIRS that maximizes the compliance of young subjects, setting the background for testing its feasibility in clinical samples. Thus, the potential application of vHDR measurement was assessed in two cross-sectional studies comparing fNIRS signal in NDDs groups and control cohorts. A first study was conducted in autistic female (fASD) preschoolers and age-matched typically-developed girls. The aim of this activity was to clarify whether fNIRS could provide a biomarker that might support early clinical assessment of fASD, in parallel advancing the knowledge about phenotype’s gender-specificity of this cohort. Then, starting from encouraging data on the preclinical mouse model, the sensitivity of technique was evaluated in a rare metabolic disease caused by genetic deficiency of creatine transporter (CTD), where the translational validation of the imaging biomarker might open the way to its use in drug efficacy trials. In both clinical samples the feasibility and validity of vHDR have been robustly assessed. These results might expand the frontiers of fNIRS technique, pointing to the analysis of vHDR as a valuable tool for assessing brain function in both observational studies and clinical trials including NDDs patients.