Development Of Eye-tracking Measures For Assessment Of Autism And Effects Of Oxytocin

Autism spectrum disorder(ASD)is a severe pervasive developmental disorder.The latest epidemiological survey in the United States showed that its incidence was as high as one in 54,while China and European countries had the same prevalence of approximately one percent.This disorder normally originates in early life,mostly during the first few years of life,and influences neurological development,causing varying degrees of mental retardation,and impairments in social responsivity and speech and expression of repetitive behaviors.Thus,ASD causes a huge economic burden to both families and society.The only proven intervention is high intensity and long-term behavioral training,however,there is a critical period for behavioral therapy with studies showing that the earlier behavioral intervention is conducted the better the prognosis,so early diagnosis is of key importance.At present,because different degrees of public awareness of the disorder,access to appropriate medical resources and the skill and experience of doctors,many subjects cannot get diagnosed effectively.Recently,noninvasive eye-tracking methods using a variety of simple paradigms have been considered as a potential approach to provide an effective and easy-to-obtain diagnostic index for early screening for autism,since it can sensitively detect changes in the visual attention preferences of children with ASD.However,these studies mainly focused on Caucasians.Excepting for diagnosis,the drug intervention for autism was also a difficult target.Studies also focused on establishing the effects of intranasal treatment of the neuropeptide oxytocin,which is known to enhance a number of different aspects of social behavior in both animal models and humans and is increasingly being considered as a potential treatment which could help improve social communication and responsivity deficits in ASD.The purpose of the studies reported in this thesis was to:(1)to establish Chinese version of objective eye tracking indices to distinguish ASD from healthy individuals;(2)first to use eye tracking paradigms to investigate the effects of intranasal oxytocin on social attention in different sample(healthy individuals with different autistic traits and low function children diagnosed with ASD).Study 1,we conducted four eye-tracking paradigms including social compared with non-social stimuli to determine differences in patterns of visual attention between young Chinese(2-7 years old)children with ASD(n = 35)and age-and sex-matched typically developing children(n = 34).In addition,compared the difference and effectiveness among four tasks with independent t test and ROC curve.The results indicated the dancing versus geometric pattern paradigm was the most effective with the children with ASD showing a significantly reduced interest in the social dancing stimuli(95%CI,0.697-0.906,p < 0.001).This reduced interest in the social stimulus in ASD children performed best in classification.The results were similar to previous Caucasian studies which subjects also avoided looking social stimuli.Based on the results of Study 1,in Study 2 four similar eye-tracking paradigms to those in the first study were used but modified into adult versions and a further two paradigms(emotional face processing and emotional empathy)added to investigate the effect of intranasal oxytocin on the gaze patterns of healthy male adults.We performed a randomized placebo-controlled within subject design experiment to investigate the effect of either intranasal oxytocin(24IU)or placebo spray on gaze patterns in 40 healthy men.Results showed that oxytocin increased attention of subjects to both static and dynamic social,relative to non-social cues in four different paradigms,and this was associated with trait autism scores.In another task results showed that oxytocin increased attention towards the eyes relative to other salient face regions in fearful faces(p = 0.001).In the final emotional empathy task subjects were presented with positive and negative valence emotional scenes and asked to rate their empathic feelings.Results reveled that oxytocin enhanced emotional empathy ratings to both negative and positive stimuli by increasing the proportion of time spent viewing the faces of humans in the picture stimuli and correspondingly decreasing attention towards other contextual parts of the pictures.Thus,overall intranasal oxytocin promoted increased attention towards social compared with non-social stimuli and the eyes and faces on individuals displaying emotion.Considered previous studies only tested oxytocin effect on function of autism kid through questionnaires,behavioral assessments and tasks,in Study 3 we firstly investigated the effect of a single dose of intranasal oxytocin(based on eye tracking index)compared with placebo spray on gaze patterns on children with ASD(n = 40)using a between subjects design.The two most effective paradigms found in Studies 1 and 2 were selected: dynamic dancing human compared with dynamic geometric patterns and emotional face processing.We collected eye tracking data both at baseline and 45 minutes after receiving the nasal spray(oxytocin vs.placebo).At baseline,ADOS-2,autism severity questionnaires and eye tracking data were used to assign subjects into two matched groups.Two weeks later,all children attended the test again and the groups received either oxytocin or placebo nasal spray(double blind)and 45 minutes later they completed their second eye tracking session.The results revealed that oxytocin compared to placebo increased attention to the social human dancing pictures while decreasing it for the non-social dynamic geometric patterns.Additionally,oxytocin enhanced the proportion of time of children spent viewing the eye region across all face emotions and the attention to eye region was negatively related to their social communication score.In summary,intranasal oxytocin may be a potential treatment for improving attention towards social stimuli in children with ASD.Overall,the studies carried out demonstrate firstly that differential attention to social versus non-social visual stimuli can reliably distinguish children with ASD from healthy controls,with dynamic dancing humans versus geometric patterns being the most sensitive and effective paradigm.Secondly,intranasal oxytocin in both healthy individuals and children with ASD,increased attention towards social relative to nonsocial cues and to the eyes or faces of individuals expressing emotions.Future studies involving larger clinical sample sizes are need to further confirm if these eye tracking paradigms can reliably assist in aiding early diagnosis of autism,and to explore whether a longer-term oxytocin treatment intervention can improve the social attention and responsivity of children with ASD.