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.

The Behavioral Profile of SYNGAP1-Related Intellectual Disability.

This study aimed to describe the behavioral profile of individuals with SYNGAP1-ID. Parents/carers of 30 individuals aged 3-18 years old with a diagnosis of SYNGAP1-ID and 21 typically developing individuals completed the Vineland-3 Adaptive Behavior Scale and the Child Behavior Checklist. We found that those with SYNGAP1-ID showed fewer adaptive behaviors and higher levels of internalizing and externalizing behaviors across almost all domains compared to typically developing controls. There was some evidence that these differences were greatest in older children, and more apparent in those with co-occuring epilepsy. This characterization of the phenotype of SYNGAP1-ID significantly aids our understanding of the behavioral profile of this population and is a step towards the development of tailored interventions.

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.

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.

Lessons from a catalogue of 6674 brain recordings.

It is now possible for scientists to publicly catalogue all the data they have ever collected on one phenomenon. For a decade, we have been measuring a brain response to visual symmetry called the sustained posterior negativity (SPN). Here we report how we have made a total of 6674 individual SPNs from 2215 participants publicly available, along with data extraction and visualization tools (https://osf.io/2sncj/). We also report how re-analysis of the SPN catalogue has shed light on aspects of the scientific process, such as statistical power and publication bias, and revealed new scientific insights.

EEG as a translational biomarker and outcome measure in fragile X syndrome.

Targeted treatments for fragile X syndrome (FXS) have frequently failed to show efficacy in clinical testing, despite success at the preclinical stages. This has highlighted the need for more effective translational outcome measures. EEG differences observed in FXS, including exaggerated N1 ERP amplitudes, increased resting gamma power and reduced gamma phase-locking in the sensory cortices, have been suggested as potential biomarkers of the syndrome. These abnormalities are thought to reflect cortical hyper excitability resulting from an excitatory (glutamate) and inhibitory (GABAergic) imbalance in FXS, which has been the target of several pharmaceutical remediation studies. EEG differences observed in humans also show similarities to those seen in laboratory models of FXS, which may allow for greater translational equivalence and better predict clinical success of putative therapeutics. There is some evidence from clinical trials showing that treatment related changes in EEG may be associated with clinical improvements, but these require replication and extension to other medications. Although the use of EEG characteristics as biomarkers is still in the early phases, and further research is needed to establish its utility in clinical trials, the current research is promising and signals the emergence of an effective translational biomarker.

Sleep Abnormalities in the Synaptopathies-SYNGAP1-Related Intellectual Disability and Phelan-McDermid Syndrome.

Neurodevelopmental disorders are frequently associated with sleep disturbances. One class of neurodevelopmental disorders, the genetic synaptopathies, is caused by mutations in genes encoding proteins found at the synapse. Mutations in these genes cause derangement of synapse development and function. We utilized a validated sleep instrument, Children's Sleep Habits Questionnaire (CSHQ) to examine the nature of sleep abnormalities occurring in individuals with two synaptopathies-Phelan-McDermid syndrome (PMD) (N = 47, male = 23, female = 24, age 1-46 years) and SYNGAP1-related intellectual disability (SYNGAP1-ID) (N = 64, male = 31, female = 33, age 1-64 years), when compared with unaffected siblings (N = 61, male = 25, female = 36, age 1-17 years). We found that both PMD and SYNGAP1-ID have significant sleep abnormalities with SYNGAP1-ID having greater severity of sleep disturbance than PMD. In addition, sleep disturbances were more severe for PMD in individuals 11 years and older compared with those less than 11 years old. Individuals with either disorder were more likely to use sleep aids than unaffected siblings. In conclusion, sleep disturbances are a significant phenotype in the synaptopathies PMD and SYNGAP1-ID. Improved sleep is a viable endpoint for future clinical trials for these neurodevelopmental disorders.

Neural responses to dynamic adaptation reveal the dissociation between the processing of the shape of contours and textures.

Shape-adaptation studies show that surround textures can inhibit the processing of contours. Using event-related potentials (ERP), we examined the time-course of neural processes involved in contour-shape and texture-shape processing following adaptation to contours and textures. Contours were made of Gabor strings whose orientations were either tangential or orthogonal to the contour path, while textures were made of a series of contours arranged in parallel. We focused on two ERP components -P1, related to low-level visual processes and N1, broadly indicative of mid-level vision- and, on ERP difference waves (no-adaptor minus with-adaptor) to isolate the effects of adaptation, which are fundamentally distinct from individual processes driving P1 and N1 components. We found that in the absence of adaptation, the N1 component for contour-tests peaked later and increased in amplitude compared to the N1 for texture-tests. Following adaptation, the ERP difference wave for contour-tests revealed an early and a late component that were differentially affected by the presence of surround texture, but critically not by its orientation. For texture-tests, the early component was of opposite polarity for contours compared to texture adaptors. From the temporal sequence of ERP modulations, we conclude that texture processing begins before contour processing and encompasses the stages of perceptual processing reflected in both the low-level P1 and the mid-level N1 vision-related components. Our study provides novel evidence on the nature of separable and temporally distinct texture and contour processing mechanisms, shown in two difference wave components, that highlights the multi-faceted nature of dynamic adaptation to shape when presented in isolation and in context.

Luminance-polarity distribution across the symmetry axis affects the electrophysiological response to symmetry.

Electrophysiological studies of symmetry have found a difference wave termed the Sustained Posterior Negativity (SPN) related to the presence of symmetry. Yet the extent to which the SPN is modulated by luminance-polarity and colour content is unknown. Here we examine how luminance-polarity distribution across the symmetry axis, grouping by luminance polarity, and the number of colours in the stimuli, modulate the SPN. Stimuli were dot patterns arranged either symmetrically or quasi-randomly. There were several arrangements: 'segregated'-symmetric dots were of one polarity and randomly-positioned dots were of the other; 'unsegregated'-symmetric dots were of both polarities in equal proportions; 'anti-symmetric'-dots were of opposite polarity across the symmetry axis; 'polarity-grouped anti-symmetric'-this is the same as anti-symmetric but with half the pattern of one polarity and the other half of opposite polarity; multi-colour symmetric patterns made of two, three to four colours. We found that the SPN is: (i) reduced by the amount of position-symmetry, (ii) sensitive to luminance-polarity mismatch across the symmetry axis, and (iii) not modulated by the number of colours in the stimuli. Our results show that the sustained nature of the SPN coincides with the late onset of a topographic microstate sensitive to symmetry. These findings emphasise the importance of not only position symmetry, but also luminance polarity matching across the symmetry axis.

Electrophysiological responses to symmetry presented in the left or in the right visual hemifield.

Symmetry is a highly salient feature in the visual world, abundant in both man-made and natural objects. In particular, humans find reflectional symmetry most salient. Electrophysiological work on symmetry perception has identified a difference wave known as the Sustained Posterior Negativity (SPN) originating from extrastriate areas. Amplitude is more negative for symmetrical than random patterns, from around 200 msec after stimulus onset. For the first time, we report responses to patterns presented exclusively in one hemifield. Participants were presented with reflection or random dot patterns to the left and right of fixation (3.2°). They judged whether the patterns were light red or dark red in colour. In Experiment 1, the pair always included one symmetrical and one random pattern. In Experiments 2 and 3 we varied the information presented contralaterally. The SPN was generated separately in each hemisphere in response to what was presented in the contralateral visual hemifield (a lateralised SPN). We conclude that a symmetry-sensitive network of extrastriate areas can be activated independently in each cerebral hemisphere.

An Electrophysiological Index of Perceptual Goodness.

A traditional line of work starting with the Gestalt school has shown that patterns vary in strength and salience; a difference in "Perceptual goodness." The Holographic weight of evidence model quantifies goodness of visual regularities. The key formula states that W = E/N, where E is number of holographic identities in a pattern and N is number of elements. We tested whether W predicts the amplitude of the neural response to regularity in an extrastriate symmetry-sensitive network. We recorded an Event Related Potential (ERP) generated by symmetry called the Sustained Posterior Negativity (SPN). First, we reanalyzed the published work and found that W explained most variance in SPN amplitude. Then in four new studies, we confirmed specific predictions of the holographic model regarding 1) the differential effects of numerosity on reflection and repetition, 2) the similarity between reflection and Glass patterns, 3) multiple symmetries, and 4) symmetry and anti-symmetry. In all cases, the holographic approach predicted SPN amplitude remarkably well; particularly in an early window around 300-400 ms post stimulus onset. Although the holographic model was not conceived as a model of neural processing, it captures many details of the brain response to symmetry.

When your decisions are not (quite) your own: action observation influences free choices.

A growing number of studies have begun to assess how the actions of one individual are represented in an observer. Using a variant of an action observation paradigm, four experiments examined whether one person's behaviour can influence the subjective decisions and judgements of another. In Experiment 1, two observers sat adjacent to each other and took turns to freely select and reach to one of two locations. Results showed that participants were less likely to make a response to the same location as their partner. In three further experiments observers were asked to decide which of two familiar products they preferred or which of two faces were most attractive. Results showed that participants were less likely to choose the product or face occupying the location of their partner's previous reaching response. These findings suggest that action observation can influence a range of free choice preferences and decisions. Possible mechanisms through which this influence occurs are discussed.

Right-lateralized alpha desynchronization during regularity discrimination: hemispheric specialization or directed spatial attention?

When actively classifying abstract patterns according to their regularity, alpha desynchronization (ERD) becomes right lateralized over posterior brain areas. This could reflect temporary enhancement of contralateral visual inputs and specifically a shift of attention to the left, or right hemisphere specialization for regularity discrimination. This study tested these competing hypotheses. Twenty-four participants discriminated between dot patterns containing a reflection or a translation. The direction of the transformation, which matched one half onto the other half, was either vertical or horizontal. The strategy of shifting attention to one side of the patterns would not produce lateralized ERD in the horizontal condition. However, right-lateralized ERD was found in all conditions, regardless of orientation. We conclude that right hemisphere networks that incorporate the early posterior regions are specialized for regularity discrimination.