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    531—Neural Mechanisms Associated with Autistic Behaviors in Animals

    Tuesday, November 12, 2013, 8:00 am - 12:00 noon

    531.20: Visual preference for images of humans in non-human primates; relevance to primate models of autism

    Location: Halls B-H

    ">D. DZIOBEK1, S. ZHANG2, J. ASHE1, *X. LU3;
    1Neurosci., Univ. of Minnesota, Minneapolis, MN; 2Univ. of Minnesota, Biomedical Engineering, MN; 3Brain Sci. Ctr., VA Med. Center, Minneapolis, Minneapolis, MN

    Abstract Body: Autism is a devastating neurological disorder of unknown cause, unclear pathogenesis and without an effective treatment that appears to be increasing in prevalence. Although there are many animal models of this disorder particularly in rodents, the relevance of these models to a human disease that is defined by abnormal social interaction is debatable. In an effort to characterize natural social behaviors in the non-human primate that might be targeted in developing a primate model of the disorder, we studied preferences for different classes of visual images: (i) neutral non-animate objects, (ii) images of familiar foods, and (iii) images of human faces. We trained non-human primates on a task in which they were presented two visual images simultaneously, and are asked to choose between them. First they were required to hold their gaze on a central fixation point for 500-700 ms after which were presented two images located at either 0 degree (right) and 90 degree (up) positions, or at 180 degree (left) and 270 degree (down) positions but maintained fixation on the center point for another 500-700 ms (delay). After this delay time, the center fixation point disappeared (Go signal) and the subject made a saccade to one of the images and to hold on the image target for 300 ms to receive the reward. The eye movements were monitored continuously and the subjects were rewarded regardless of which image they chose. We found that, when presented with two neutral inanimate images (e.g. two different chairs), the monkey showed no preference (51% vs. 49%). When images of a human face was paired with either a neutral object (e.g. palm tree or chair) and a familiar food (e.g. banana or peanuts), the monkey preferred the face in more than 90% of trials. There were no clear differences in preferences for familiar (experimenters) or unfamiliar (George W. Bush) faces relative to the other classes. Furthermore, in addition to choice preference, the animals had shorter reaction time and eye movement time to human faces. Our data suggest that the preference of non-human primates for human faces, even when the competing object was a familiar food, is driven by considerations of social cognition that are so prominent in humans. We believe that this natural tendency of non-human primates to prefer images of other primates could be used to probe autistic behavior in monkey models of autism.

    Lay Language Summary: The main finding of our study is that the performance of healthy monkeys on our experimental task is highly similar to the performance of non-autistic humans on a similar diagnostic task. Specifically, when given a choice of two pictures to look at, where one is a picture of a human face and the other is a picture of an inanimate object, a monkey will prefer to look at the picture of the human face more than 90% of the time. This occurs regardless of whether the human face is familiar or unfamiliar or if the competing image is of something with high value to the monkey, such as food.
    Autism spectrum disorder (ASD) is neurodevelopmental disorder that last an entire lifetime and has no known cure. Approximately 1 in 88 American children are diagnosed with ASD, and diagnosis rates have grown 10-17% annually. Unfortunately, the origin of the disease and the underlying changes occurring in the brain are largely unknown. It is defined by three clinical signs: Repetitive behaviors/aversion to change, poor language skills/reduced ability to learn or develop language skills, and diminished social cognition. The majority of current ASD studies use rodent-based animal models, but the relevance of rodents to a human disease that is characterized by abnormal social interaction is debatable. As an alternative, non-human primates (NHPs) exhibit a rich suite of behaviors, have well-defined social structures and interpersonal interactions, can be taught a variety of complex tasks, and have brains that are highly similar to those of humans.
    The results of this study provide first step toward building a realistic NHP model of autism by establishing how normal, healthy NHPs behave in a social cognition task, a task that we based on a diagnostic tool used to identify children that are at risk of developing ASD. The task we used is simple: the subject is asked to choose between two pictures to look at, and is identically rewarded for looking at either picture. Similarly to the diagnostic tool used on humans, we paired pictures of human faces with inanimate objects. Much like the children who have low risk of developing an ASD, the subjects in our study chose to look at the pictures of human faces at a substantially higher rate than the competing pictures. We believe that this natural tendency of non-human primates to prefer images of other primates could be used to probe autistic behavior in monkey models of autism.
    Future directions for research would be to study which brain regions are active during this task, and to see how modulation of them changes the behavioral output. Eliciting changes in the subjects’ behavioral output by inactivating or over-activating relevant brain regions via pharmacological or electrical stimulation would provide much needed insights into which neural circuits and processes could be perturbed in human cases of autism.
    The details of the experiment are as follows: A monkey faces a computer monitor and fixates at a central point on the screen. After maintaining fixation for a brief period of time, the subject is simultaneously presented with two images, generally a picture of a human face and a picture of another object, such as a piece of fruit or a chair. The subject continues to maintain fixation on the central point, after which the subject is given a signal instructing it to direct its gaze onto either of the two images. As a control, the subjects repeated the above task, but were presented pairs of non-face images, such as a toy and a flower. The subjects showed no preference when looking at the pairs of non-face images.