Eye-Tracking As a Translational Tool to Study Social Development in Preclinical Nonhuman Primate Models of ASD

Background: Deficits in social behavior are prominent features of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and schizophrenia (SZ). Eye tracking studies provide insight into how individuals with ASD and SZ process social information and have consistently documented atypical gaze patterns to social stimuli in these patient populations. Similar eye-tracking methods can be applied to preclinical animal model systems to explore social impairments relevant to symptoms observed in people with NDDs. Like humans, rhesus macaques (Macaca mulatta) use vision as their primary sensory modality and display complex social signals such as facial expressions, gestures, and vocalizations. Given the complexity behind potential causes and behaviors affected by NDDs, the use of eye-tracking paradigms in concordance with other measures in rhesus macaques may serve to bridge the gap between translational research efforts in rodent animal models and patient populations.

Objectives: In order to apply eye-tracking technology to animal models for human disease, it is first essential to understand the typical development of visual attention and social cognition in rhesus macaques. Using longitudinal social development data, we investigated the relationship between how young rhesus macaques view social stimuli in an eye-tracking paradigm and how they interact with their mother and similar-aged peers.

Methods: We studied 14 male rhesus macaques that serve as a control group for a nonhuman primate maternal immune activation study. Monkeys were mother-reared, received access to social groups, and participated in assessments throughout development such as eye-tracking and behavioral observations using a standard ethogram of social and nonsocial behavior. Eye-tracking data were collected using a modified incubator box that allowed for opportunistic sampling from unrestrained monkeys. We presented the monkeys with the same naturalistic monkey social stimuli across multiple time points from 1 month through 6 months old with additional preliminary data at 2 years old. The social development data presented here span from approximately 1 month of age through 2 years old.

Results: In our eye-tracking paradigm, monkeys viewed the social stimuli for a significantly longer time when they were 6 months old than in their first three months (p<0.05). Furthermore, preliminary analyses suggest that there is a significant positive correlation between monkeys’ looking time duration for social stimuli in the eye-tracking paradigm and the number of initiated social interactions with their peers (p<0.05).

Conclusions: Our results suggest that rather than habituation to stimuli presented during the eye-tracking paradigm, monkeys may develop an increased interest in social stimuli during this early critical period of social development. Furthermore, this propensity to view social stimuli may be related to similar propensities to interact with their peers. Continued analyses of how other measures of social behavior and cognition relate to visual attention can help to both understand the development of social cognition in rhesus macaques as well as how eye-tracking in monkeys can maximize the translational utility of preclinical models of NDDs.