Background The current study used eye tracking to investigate attention and recognition memory in Phelan-McDermid syndrome (PMS), a rare genetic disorder characterized by intellectual disability, motor delays, and a high likelihood of comorbid autism spectrum disorder (ASD). Social deficits represent a core feature of ASD, including decreased propensity to orient to or show preference for social stimuli. Methods We used a visual paired-comparison task with both social and non-social images, assessing looking behavior to a novel image versus a previously viewed familiar image to characterize social attention and recognition memory in PMS (n = 22), idiopathic ASD (iASD, n = 38), and typically developing (TD) controls (n = 26). The idiopathic ASD cohort was divided into subgroups with intellectual disabilities (ID; developmental quotient < 70) and without (developmental quotient > 70) and the PMS group into those with and without a co-morbid ASD diagnosis. Results On measures of attention, the PMS group with a comorbid ASD diagnosis spent less time viewing the social images compared to non-social images; the rate of looking back and forth between images was lowest in the iASD with ID group. Furthermore, while all groups demonstrated intact recognition memory when novel non-social stimuli were initially presented (pre-switch), participants with PMS showed no preference during the post-switch memory presentation. In iASD, the group without ID, but not the group with ID, showed a novelty preference for social stimuli. Across indices, individuals with PMS and ASD performed more similarly to PMS without ASD and less similarly to the iASD group. Conclusion These findings demonstrate further evidence of differences in attention and memory for social stimuli in ASD and provide contrasts between iASD and PMS.

Phelan-McDermid Syndrome (PMS) is a rare genetic disorder caused by deletion or sequence variation in the SHANK3 gene at terminal chromosome 22 that confers high likelihood of comorbid autism spectrum disorder (ASD). Whereas individuals with idiopathic ASD (iASD) can demonstrate diverse patterns of sensory differences, PMS is mainly characterized by sensory hyporesponsiveness. This study used electrophysiology and a passive auditory habituation paradigm to test for neural markers of hyporesponsiveness. EEG was recorded from 15 individuals with PMS, 15 with iASD, and 16 with neurotypical development (NT) while a series of four consecutive 1,000 Hz tones was repeatedly presented. We found intact N1, P2, and N2 event-related potentials (ERPs) and habituation to simple auditory stimuli, both in individuals with iASD and in those with PMS. Both iASD and PMS groups showed robust responses to the initial tone and decaying responses to each subsequent tone, at levels comparable to the NT control group. However, in PMS greater initial N1 amplitude and habituation were associated with auditory hypersensitivity, and P2 habituation correlated with ASD symptomatology. Additionally, further classification of the PMS cohort into genetic groupings revealed dissociation of initial P2 amplitude and habituation of N1 based on whether the deletions included additional genes beyond solely SHANK3 and those not thought to contribute to phenotype. These results provide preliminary insight into early auditory processing in PMS and suggest that while neural response and habituation is generally preserved in PMS, genotypic and phenotypic characteristics may drive some variability. These initial findings provide early evidence that the robust pattern of behavioral hyporesponsiveness in PMS may be due, at least in audition, to higher order factors.

Corollary discharge (CD) signals are “copies” of motor signals sent to sensory regions that allow animals to adjust sensory consequences of self-generated actions. Autism spectrum disorder (ASD) is characterized by sensory and motor deficits, which may be underpinned by altered CD signaling. We evaluated oculomotor CD using the blanking task, which measures the influence of saccades on visual perception, in 30 children with ASD and 35 typically developing (TD) children. Participants were instructed to make a saccade to a visual target. Upon saccade initiation, the presaccadic target disappeared and reappeared to the left or right of the original position. Participants indicated the direction of the jump. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of the presaccadic target and use it to inform perception. We used multilevel modeling to examine the influence of saccade landing site on trans-saccadic perceptual judgements. We found that, compared with TD participants, children with ASD were more sensitive to target displacement and less reliant on saccade landing site when spatial uncertainty of the post-saccadic target was high. This pattern was driven by ASD participants with less severe restricted and repetitive behaviors. These results suggest a relationship between altered CD signaling and core ASD symptoms.

A common example of social differences in autism spectrum disorder is poor modulation of reciprocal gaze, including reduced duration of eye contact and difficulty detecting the aim of another’s gaze. It remains unclear, however, whether such differences are specific to the social domain, or are instead indicative of broader alterations in processes of visual engagement and disengagement in autism spectrum disorder. To assess whether children with autism spectrum disorder experience altered engagement of visual attention, and whether such processes are specific to social stimuli, we implemented a gap-overlap eye-tracking paradigm consisting of both social and nonsocial images with children with autism spectrum disorder ( n = 35) and typical development ( n = 32). Children with autism spectrum disorder demonstrated a significantly reduced overall gap effect (i.e. difference in saccade latency to peripheral stimuli between overlap and gap trials) compared with the controls. This reduction spanned both social and nonsocial conditions. Our findings suggest that children with autism spectrum disorder experience alterations in general processes of engagement of visual attention, and that these alterations are not specific to the social domain, but do associate with cognitive functioning. Affected processes of visual engagement in autism spectrum disorder may contribute to features like poor reciprocal gaze, but social-specific symptoms of autism spectrum disorder likely originate from other subcortical processes or higher order cognition. Lay abstract Limited eye contact and difficulty tracking where others are looking are common in people with autism spectrum disorder. It is unclear, however, whether these are specifically social differences; it is possible that they are a result of broader alterations in engaging and disengaging visual attention. We used eye-tracking technology with children with autism spectrum disorder ( n = 35) and typical development ( n = 32), showing them both social and nonsocial imaging to test their visual attention. Children with autism spectrum disorder had a significant difference in how long it took them to look from an image in the middle to one on the side, depending on whether the middle image stayed on the screen or flashed off before the one on the side appeared. This difference was present for both social and nonsocial images, and was related to cognitive ability for only the children with autism spectrum disorder. Our findings suggest that children with autism spectrum disorder have differences in general processes of engaging visual attention that are not specifically social in nature, and that these processes may relate to cognitive ability in autism spectrum disorder. Affected processes of visual engagement in autism spectrum disorder may contribute to symptoms like reduced eye contact, but social-specific symptoms of autism spectrum disorder likely do not stem from reduced visual engagement alone.