Functional brain imaging of facial emotion processing in individuals with intellectual impairments

From the relatively early descriptions of fragile X syndrome, it was recognised that there were differences in social communication, which overlapped or mirrored those seen in idiopathic autism. And in parallel, genetic screening of individuals with autism revealed fragile X syndrome as a leading inherited cause of autism. Reviewing the literature of both of these conditions; it is obvious that although as clinical entities they include individuals with varying degrees of cooccurring intellectual disabilities or impairments, the existing literature has largely included those who are more, or most, intellectually able. This is particularly so in brain imaging research, largely by reason of the significant challenges of the imaging environment, with many of the challenges of having a scan corresponding with particular difficulties for the individuals; e.g. the noise of the scanner being of particular difficulty for those with sensory hypersensitivities (common in fragile X syndrome and autism). In the current study, functional brain imaging was used to investigate the role of autism in the processing of facial emotions in two cohorts – one with special educational needs and one with fragile X syndrome. Particular consideration was given to whether the emerging patterns of activations in any way mirrored those seen in the extant literature and whether to any degree it could be considered that autism in the context of lower cognitive ability (be that by virtue of idiopathic intellectual impairment or a known single-gene disorder) has the same underlying neural correlates as in individuals of average or above average intellect. In a group of individuals with special educational needs, it was found that those with high autistic traits had a region of hyperactivation to neutral faces in the right rolandic operculum; replicating a finding previously described in a metaanalysis of prior functional imaging studies in individuals with autism and of average or enhanced cognitive ability. In parallel, the sub-group with low autistic traits had a cluster of significantly greater activation in the left supramarginal gyrus / angular gyrus in response to fearful facial stimuli compared to the autistic sub-group. This pattern of relative hypo-activation in individuals with autism to emotional stimuli is typical of the existing literature in autism and adds further weight to the idea that, at least in part, individuals with autism of lower cognitive ability show similar changes in neural function. In a group of individuals with fragile X syndrome, those with high autistic traits had a cluster of significantly lower brain activation in the left superior temporal gyrus / left supramarginal gyrus in response to fearful faces when compared to those with low autistic traits. This cluster overlapped previous findings in both the fragile X literature, but also prior work in the broader autism literature, suggesting that autism in the context of a monogenic form of ID may have similar neurobiological correlates as seen in idiopathic autism. The results from this study show firstly that imaging individuals with significant cognitive impairments is feasible. Secondly, the results suggest that autistic individuals who have concurrent intellectual impairments share some of the same patterns of brain function as seen in autistic individuals of average or enhanced cognitive ability, who are most commonly recruited for brain imaging studies. Finally, the results suggest that autistic traits in the context of fragile X syndrome are associated with brain activation differences, which overlap those previously described in idiopathic autism. Further research is necessary to quantify the nature and degree of this overlap more fully

Visual social attention in SYNGAP1-related intellectual disability

SYNGAP1-ID is a neurodevelopmental disorder caused by a mutation of the SYNGAP1 gene. Characterized by moderate to severe developmental delay, it is associated with several physical and behavioral issues as well as additional diagnoses, including autism. However, it is not known whether social cognitive differences seen in SYNGAP1-ID are similar to those previously identified in idiopathic or other forms of autism. This study therefore investigated visual social attention in SYNGAP1-ID. Eye movements were recorded across three passive viewing tasks (face scanning, pop-out, and social preference) of differing social complexity in 24 individuals with SYNGAP1-ID and 12 typically developing controls. We found that SYNGAP1-ID participants looked at faces less than the controls, and when they did look at faces, they had less time looking at and fewer fixations to the eyes. For the pop-out task, where social and nonsocial objects (Phone, car, face, bird, and face-noise) were presented in an array, those with SYNGAP1-ID spent significantly less time looking at the phone stimulus as well as fewer fixations to the face compared with the typically developing controls. When looking at two naturalistic scenes side by side, one social in nature (e.g., with children present) and the other not, there were no differences between the SYNGAP1-ID group and typically developing controls on any of the examined eye tracking measures. This study provides novel findings on the social attention of those with SYNGAP1-ID and helps to provide further evidence for using eye tracking as an objective measure of the social phenotype in this population in future clinical trials.</p

Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description

BACKGROUND: SYNGAP1-related intellectual disability (ID) is a recently described neurodevelopmental disorder that is caused by pathogenic variation in the SYNGAP1 gene. To date, the behavioural characteristics of this disorder have mainly been highlighted via the prevalence of existing diagnoses in case series. We set out to detail the behavioural features of this disorder by undertaking interviews with those who have a child with SYNGAP1-related ID to allow them to describe their child’s behaviour. METHODS: We conducted 27 semi-structured interviews with parents and caregivers which covered basic information (e.g., age, gender), family history, perinatal history, past medical history, developmental history, epilepsy, behavioural history, and a general description of their child’s behaviour. RESULTS: Using a mixed quantitative and qualitative approach, the responses from the parents indicated that those with SYNGAP1-related ID showed high rates of autism spectrum disorder (52%), difficulties with fine and gross motor skills, delays in language development, and a high prevalence of epilepsy (70%). A qualitative analysis highlighted their general behaviour affected the themes of daily living skills, distress-related behaviours, emotional regulation, difficulties with change, a lack of danger awareness, and sensory differences. Sensory features described involved auditory, visual, tactile, gustatory, and proprioceptive themes. CONCLUSIONS: Our findings and behavioural descriptions provide important insights as well as implications for the diagnosis and care of those with SYNGAP1-related ID. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-022-09437-x

Profiling Autism and Attention Deficit Hyperactivity Disorder Traits in Children with SYNGAP1-Related Intellectual Disability

SYNGAP1-related ID is a genetic condition characterised by global developmental delay and epilepsy. Individuals with SYNGAP1-related ID also commonly show differences in attention and social communication/interaction and frequently receive additional diagnoses of Autism Spectrum Disorder (ASD) or Attention Deficit Hyperactivity Disorder (ADHD). We thus set out to quantify ASD and ADHD symptoms in children with this syndrome. To assess ASD and ADHD, parents and caregivers of a child with SYNGAP1-related ID (N = 34) or a typically developing control (N = 21) completed the Social Responsiveness Scale-2, the Social Communication Questionnaire with a subset of these also completing the Conners-3. We found that those with SYNGAP1-related ID demonstrated higher levels of autistic traits on both the SRS and SCQ than typically developing controls. On the SRS, those with SYNGAP1-related ID scored highest for restricted repetitive behaviours, and were least impaired in social awareness. On the Conners-3, those with SYNGAP1-related ID also showed a high prevalence of ADHD traits, with scores demonstrating difficulties with peer relations but relatively low occurrence of symptoms for DSM-5 conduct disorder and DSM-5 oppositional defiant disorder. Hierarchical clustering analysis highlighted distinct SYNGAP1-related ID subgroups for both ASD and ADHD traits. These findings provide further characterisation of the SYNGAP1-related ID behavioural phenotype, guiding diagnosis, assessment and potential interventions.</p