ATYPICAL PUPILLARY LIGHT REFLEX IN INDIVIDUALS WITH AUTISM

Background: Pupillary light reflex (PLR) refers to the involuntary response whereby the pupil size changes in response to a short flash light. Our recent preliminary study revealed that individuals with autism showed significantly longer constriction latencies and smaller constriction amplitudes as compared to unaffected individuals. PLR may represent a promising biomarker in that PLR latencies served as an effective discriminator (89.6%) between affected and unaffected individuals within our pilot sample (24 children with autism and 44 controls). We proposed to further investigate such atypical PLR-associated brain activities in children with autism by using functional MRI (fMRI) with integrated PLR test.Objective/Hypothesis: Previous animal studies had shown that cerebellum dysfunctions may lead to a prolonged PLR latency. We hypothesize that prolonged PLR latencies observed in our preliminary study are associated with cerebellum dysfunctions in children with autism.Specific Aims:(1) Develop an integrated PLR-fMRI protocol for imaging PLR-associated brain activities with a focus on cerebellum.(2) Test the hypothesis that the observed atypical PLR latency in individuals with autism is associated with abnormal cerebellum functions.Study Design: An integrated PLR test unit will be developed for a 3T Siemens Trio scanner with a standard 8-channel head coil. PLR will be induced using light stimulus delivered binocularly via optical fiber bundles. Pupillary response will be monitored and recorded using a MRI-compatible long range optical imaging unit. A group of 25 individuals with high functioning autism and an equal number of demographically matched controls will be tested in this integrated PLR-fMRI study.Impact: Biomarker research is one of research priorities in autism as recognized in the Strategic Plan for ASD Research by U.S. Department of Health & Human Services. Unfortunately, no consistent biomarkers have been identified thus far. The PLR testing procedure is low-cost, non-invasive, objective, and has the potential to be implemented for very young children. The quantifiable PLR responses can be experimentally traced to study the influence from various components involved in PLR pathway. Thus, PLR provides an effective avenue for honing in on specific neuropsychological mechanisms of biological significance to autism. This project will generate unique results that can help us better understand our novel preliminary observations. It is anticipated that as functional biomarkers, the PLR measurements will advance our understanding of neurodevelopmental differences in the autism brain.