Application of Functional Near Infrared Spectroscopy in Neurodevelopmental Disorders

To understand the development of brain function there is a crucial need to quantitatively assess brain activation from early childhood. This would be particularly important in early intervention of neurodevelopmental disorders such as Autism Spectrum Disorders (ASD). Early intervention and therapies have a significant effect on the outcome of ASD in later life. Diagnosis of ASD and its differentiation from other developmental delays however can be difficult in toddler population. Moreover, the neurobiological impairments behind the cognitive function in ASD and other developmental delays in early childhood are unknown.;The choice of technique in neuroimaging depends on the type of information that one seeks, but more importantly the pool of subjects under the study. Assessment of brain function in children and toddlers can be a challenging matter both for typical groups and populations with ASD. Therefore the need for a patient friendly system that could be used for monitoring the brain function for toddler population has become essential. The current brain imaging modalities (such as fMRI or PET), however, make it challenging to study the brain function at a young age, mostly due to patient movement or invasive nature of the study. Functional near infrared spectroscopy (fNIRS) is an emerging brain imaging technology for noninvasive measurements of the local changes in cerebral hemodynamic levels, associated with brain activity. fNIRS uses light in near infrared region that can probe the cortical regions of the brain. The NIR absorption spectrum of the tissue is sensitive to changes in the concentration of oxy- and deoxy-hemoglobin, the two main biomarkers of brain function. Most importantly for pediatric applications, NIRS instruments are much smaller and less restraining compared to fMRI or PET and can tolerate subject motion to a larger extent than fMRI. These features make this patient-friendly technique well suited to study children with neurodevelopmental disorders such as ASD, when keeping the subjects still for long periods of time becomes extremely challenging.;Temporal variations in cerebral hemodynamics, as measured by fNIRS can provide key information on brain function. For the brain, as an organ with high metabolic demand, cerebral autoregulation (CA) keeps the cerebral blood flow (CBF) constant, which is a vital mechanism to optimize oxygen delivery. In this research a new parameter, Oxygenation Variability Index (OV index), directly obtained from fNIRS data is introduced. This index measures the changes in oxygen saturation in the prefrontal cortex in frequencies related to cerebral autoregulation (<0.1 Hz). Two clinical studies to compare the functional development of the brain were conducted. First in typical children from ages of 4-8 performing a Go/No-Go task where the result indicated that OV index increased significantly with age between 4 and 6 years and decreased afterward, reaching a plateau. Therefore the index could be a correlate of brain development in children and can elucidate the developmental abnormalities. This research then focused on a group of 24-36 months old typical and language delay (LD) toddlers at risk of ASD watching a video. The measure of OV index showed significant difference between LD and typical toddlers, with the latter showing a higher level of OV Index. Moreover, the data analyses for the above subjects were extended to explore the relation between other features of NIRS signal between subjects and with other behavioral measures.;In summary, this research is devising an imaging platform as a fast, non-invasive, portable, and user-friendly method to assess the status of brain function. The application of this work can be utilized in real time situations and over a wide range of developmental stages to follow changes in cerebral hemodynamics with age (brain development) and, potentially, link hemodynamic characteristics to the cognitive status of the children. The establishment of such biomarkers will open new possibilities for diagnostics of neurodevelopmental disorders and, ultimately, for therapeutic intervention.