Eye Gaze and Pupillary Response in Angelman Syndrome

Background:

Angelman syndrome (AS) is a rare neurological disorder characterized by severe developmental disability, communication impairment, elevated seizure risk, and motor system abnormalities caused by disruption of maternally inherited E3 ubiquitin protein ligase gene (UBE3A) located in chromosome region 15 (15q11-q13) (Kishino, Lalande et al. 1997, Clayton-Smith and Laan 2003). Eye tracking measures, such as the evaluation of gaze points and pupil size, provide promising strategies to quantify the severity of symptoms and resolve subgroup heterogeneity across developmental disabilities (Sweeney, Takarae et al. 2004, Boraston and Blakemore 2007). Several eye tracking studies have reported that individual preference for geometric patterns over social scenes can predict diagnosis of ASD (Pierce, Conant et al. 2011, Gaietto 2014).

Objectives:

The aims of this study were to both determine the feasibility of social scene eye tracking and pupillometry measures in individuals with AS and to compare the performance of AS participants to individuals with idiopathic Autism Spectrum Disorder (ASD) and typically developing controls (TDC).

Methods:

Individuals with AS and age- and gender- matched controls completed a social eye tracking paradigm. Neurobehavioral characterization of AS participants was completed via a battery of psychological testing and caregiver behavioral evaluations such as the Bayley Scales of Infant and Toddler Development (BSID-III) (Bayley and Reuner 2006), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Vineland Adaptive Behavior Scales (VABS-II) (Sparrow, Balla et al. 1984).

Results:

Forty-seven percent of recruited AS participants completed the eye tracking paradigm.

Compared to TDC, AS subjects demonstrated significantly less preference for social scenes than geometric shapes. Additionally, AS subjects did not show increased pupil dilation, compared to TDC, when viewing social scenes versus geometric shapes. There was no significant difference found between AS and ASD subjects in either social eye tracking or pupillometry.

Conclusions:

This study is the first to demonstrate the feasibility of successful eye tracking in AS. Individuals with AS demonstrated both a lower preference for social stimuli than TDC. The use of eye tracking and pupillometry may represent an innovative measure for quantifying AS-associated impairments in social salience.

References

 Bayley, N. and G. Reuner (2006). Bayley scales of infant and toddler development: Bayley-III, Harcourt Assessment, Psych. Corporation San Antonio, Tex, USA.

Boraston, Z. and S. J. Blakemore (2007). "The application of eye‐tracking technology in the study of autism." The Journal of physiology 581(3): 893-898.

Clayton-Smith, J. and L. Laan (2003). "Angelman syndrome: a review of the clinical and genetic aspects." Journal of medical genetics 40(2): 87-95.

Gaietto, K., Shaffer, R., Warner, K., Mathieu-Frasier, L., Wink, L.K., & Erickson, C. (2014). Eye tracking utilizing age matched social scenes and geometric shapes. International Meeting for Autism Research (IMFAR) Atlanta, Georgia.

Kishino, T., et al. (1997). "UBE3A/E6-AP mutations cause Angelman syndrome." Nature genetics 15(1): 70-73.

Pierce, K., et al. (2011). "Preference for geometric patterns early in life as a risk factor for autism." Archives of general psychiatry 68(1): 101-109.

Sparrow, S. S., et al. (1984). "Vineland adaptive behavior scales."

Sweeney, J. A., et al. (2004). "Eye movements in neurodevelopmental disorders." Current opinion in neurology 17(1): 37-42.