Facial Response to Visual Stimuli: Using Pupil Response As an Indicator for Phenotype in ASD

Background:  Recent studies have indicated advances in the search for an autism phenotype (Bernier, et al., 2014).  fMRI data shed light on underlying neuroanatomical differences in the ASD brain, such as amygdala overgrowth (Amaral, Schumann, & Nordahl, 2008), interconnectivity of brain regions (Cassanova, 2007), and a three-phase brain growth model of neuroanatomical changes from early post-natal development, persisting to late adolescence/early adulthood (Courchesne, Campbell, & Solso, 2011). Although there is much to be gained from brain imaging data, the use of less invasive physiological measures from a clinical standpoint may be pursued to decrease age of diagnosis, confirm behavioral characteristics in the diagnostic process, and support better understanding of underlying neurologic function in terms of expression of phenotype. Preliminary research suggests baseline pupil dilation is markedly different in individuals with autism when compared to individuals without autism (Martineau, et al., 2011), and differences in performance on transient pupil reflex tests have been documented (Fan, Miles, Takahasi, & Yao, 2009).  Pupillometry is a viable measure of the autonomic nervous system (ANS) in a variety of neurologic disorders, including ASD (Daluwatte, et al., 2013). The pupil reflex test, a tool used to identify increased cerebrospinal fluid pressure, a characteristic observed on fMRI in ASD (Shen, et.al., 2013), holds promise for diagnosis.  Commonly observed characteristics of the visual system in ASD include visual acuity within normal limits, but difficulty with eye gaze and photosensitivity, indicative of possible cranial nerve damage and oculomotor palsy.

Objectives: a) confirm use of the pupil reflex test to identify adolescents with ASD; b) determine whether a potential phenotype for ASD, marked by pupil response differences, is present in late adolescence for a given ASD subtype; c) determine whether these differences can be observed on a basic neurological exam testing cranial nerves II and III.

Methods:  Utilizing eye-tracking software, this study examined differences in function of the sympathetic and parasympathetic nervous systems in 12 adolescents with ASD and 12 typically developing adolescents (TD) analyzing measures of pupil dilation/constriction, measures of cranial nerves underlying the pupillary reflex in response to pen light and swinging flashlight tests, and measures of ocular motility (optokinetic nystagmus).

Results:  The use of the pupil reflex test positively predicted participants' inclusion in the ASD group, demonstrating a decrease in latency of pupil constriction in response to light, as well as a decrease in latency of response and tracking, on tests of nystagmus, when compared to the TD group.

Conclusions: These findings hold promise for the use of pupil response as a potential biomarker for ASD, much like the use of PERRLA to describe neurologic function post-stroke, post-traumatic brain injury, or in the presence of a neurodegenerative disorder. Results further confirm this measure for use with a specific subtype of ASD later in development, confirming a persistence of ANS dysfunction later in life. Follow-up clinical testing may prove beneficial to further confirm these findings as a viable clinical tool for pediatricians, neurologists, and other health-care personnel diagnosing ASD, and to contribute to the existing body of knowledge related to eye-tracking and potential subtyping of ASD.