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Face processing has been reported to be atypical in Autism Spectrum Condition (ASC). The latency of the N170 event-related potential component in response to faces has been reported to be slower in children and adults with ASC compared to age-matched controls. To explore whether atypical face processing is evident earlier in development, we focused on the developmental precursor of the N170: the N290/P400 complex. We conducted a systematic review and metaanalysis of studies examining infants aged 6-24 months at elevated likelihood (EL) versus average likelihood (AL) for ASC. Using a random-effects multi-level model, we investigated differences in N290, P400 and Nc latency and amplitude in response to face stimuli between EL and AL infants, and whether these differences were associated with ASC outcomes at age 3. Fourteen studies (405 EL, 323 AL) met the inclusion criteria. EL infants showed no significant differences in N290, P400 and Nc latency or amplitude compared to AL infants. However, EL infants who later received an ASC diagnosis showed slightly longer N290 latency (g=0.13, 95% CI [0.00, 0.26]) and smaller P400 amplitudes (g=-0.23, 95% CI [-0.28,-0.19]). These findings show that subtle differences in face processing may already be present in EL infants who will develop ASC later in life, providing evidence of early atypical face processing in this group.

In a previously published study, we found atypical visual cortical laterality patterns during global motion perception in 5-month-old infants who showed high levels of autistic symptoms in toddlerhood. Here, using data from a separate experiment within the same recording session, we examined whether these results could reflect altered visual cortical functional connectivity in theta, alpha, and gamma rhythms. We assessed this in a sample of 5-month- old infants (n = 59; 39 elevated familial likelihood of autism) by means of electroencephalography (EEG) when they were watching videos showing social and non-social scenes. Gamma connectivity between midline and far-lateral visual cortex when viewing social scenes was linked to both later autism symptoms and global motion visual cortical laterality we reported in the previous study. This may indicate a shared integrative mechanism underlying social perception and global motion processing. Further, we found that higher midline-to-lateral theta connectivity in the visual cortex when perceiving non-social scenes in infancy was strongly associated with having more autistic symptoms at follow up, but uncorrelated with concurrent motion perception. Our study points to atypical functional connectivity in the visual cortex as a potential early marker of autistic symptoms and highlights a probable link between motion processing and social perception.

Missing data are common in social and clinical sciences and understanding the causes and patterns of missing data is important for selecting analysis approach and for the interpretation of the remaining data. Yet, knowledge about the factors influencing data loss is limited. Here, we assessed the contribution of genes and environments to data missingness across three experiments of infant brain and behavioural development. The sample consisted of 594 infant twins (330 monozygotic, 152 female, 178 male infants; 264 dizygotic, 132 female, 132 male infants) who were assessed with electroencephalography (EEG), pupillometry, and gaze tracking technologies at 5 months of age. Substantial familial factors (additive genetics and/or shared environment) for data missingness were found across all experiments. The amount of missing data showed only a low correlation across the experiments, suggesting a high degree of specificity in the factors contributing to missingness. The results underscore the need to adopt and improve procedural and analytical strategies that minimise data loss and its negative impacts on study conclusions.

1H-Magnetic resonance spectroscopy (1H-MRS) is a noninvasive technique for quantifying brain metabolites, including glutamate, glutathione (GSH), and γ-aminobutyric acid (GABA), which are essential for brain function and implicated in various neurodevelopmental conditions. As such, 1H-MRS methods that enable reliable and accurate measurement of these metabolites are of considerable clinical value. Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES; echo time [TE] = 80 ms) is a spectral editing technique that allows for the simultaneous quantification of GABA and GSH, using subtraction approaches to resolve these metabolites in a difference spectrum. Additionally, glutamate plus glutamine resonances (Glx) can be resolved either from the HERMES GABA-edited difference spectrum (GABA-DIFF) or from the sum of all HERMES transients (SUM spectrum). However, the reliability of 80-ms HERMES for quantification of Glx has not been systematically assessed. Here, we evaluate the agreement between Glx obtained from HERMES GABA-DIFF and SUM spectra with Glx derived from short-TE PRESS (TE = 35 ms), which is conventionally used for Glx estimation and has demonstrated reproducibility. Data were acquired from 139 participants across two brain regions (ACC and Thalamus voxels), three scanners, two diagnostic groups (autism and neurotypical development) and two age groups (adolescent/adult and preschooler). Comparisons were made using both creatine-scaled and tissue-corrected Glx estimates. Our findings demonstrate significant systematic and proportional bias between Glx estimates from HERMES (SUM and GABA-DIFF) and short-TE PRESS, consistent across scanners, voxels, age groups and diagnostic categories. These findings indicate that Glx estimates derived from HERMES are not directly comparable to those from short-TE PRESS, and this discrepancy is consistent across a multisite study setting. This underscores the importance of sequence selection and careful methodological consideration when integrating and interpreting data from 1H-MRS across different acquisition protocols.

Background

Infants vary significantly in the way they process and respond to sensory stimuli, and altered sensory processing has been reported among infants later diagnosed with autism. Previous work with adolescents and adults suggests that variability in sensory processing may have a strong genetic basis. Yet, little is known about the etiological factors influencing sensory differences in infancy, when brain circuits supporting social and non-social cognition are sculpted and learning about the world via sensory input largely occurs in interaction with caregivers.

Methods

We analysed data from a community sample of monozygotic (MZ) and dizygotic (DZ) 5-month-old same-sex twins (n = 285 pairs, n = 158 MZ pairs, n = 150 male pairs) from the BabyTwins Study in Sweden (BATSS) using exploratory factor analysis, generalised estimating equations and multivariate twin models to delineate the phenotypic and etiological structure of individual variability across different sensory processing dimensions, as measured by the Infant/Toddler Sensory Profile. Developmental links to later autistic traits were also assessed, as measured by total scores from the Quantitative Checklist for Autism in Toddlers at 36 months.

Results

Results suggested separability between sensory processing dimensions (i.e. sensation seeking, sensation avoiding, sensory sensitivity and low registration) at a phenotypic and etiological level, with significant contributions from additive genetics and family environment that were unique to each sensory dimension and significant but smaller contributions from shared influences. Sensory domains also showed etiological separability, with unique genetic influences to each domain, while contributions from shared environment were in part shared across domains. A higher incidence of tactile-related behaviours and behaviours associated with sensory sensitivity, sensation avoiding, and low registration were significantly associated with higher levels of autistic traits in toddlerhood.

Conclusions

This study provides a map of the phenotypic and etiological structure of sensory processing in infancy, which will be informative for studies of both typical and atypical development.

Infants differ in their level of eye movement control, which at the extreme could be linked to autism. We assessed eye movements in 450 twins (225 pairs, 57% monozygotic, 46% female, aged 5–6months) using the gap-overlap eye-tracking task. Shorter latency in the gap condition was associated with having more parent-rated autistic traits at 2 years. Latency across the task's three conditions was primarily explained by one highly heritable latent factor likely representing individual differences in basic oculomotor efficiency and/or in visual information processing. Additionally, disengagement of attention was linked to unique genetic factors, suggesting that genetic factors involved in visual attention are different from those involved in basic visual information processing and oculomotor efficiency.

Adaptive behaviour refers to the everyday skills that individuals are expected to have to function independently, based on their age and societal norms. Currently, we know little about the role of genetic and environmental factors in parent-rated adaptive behaviours in early infancy. The aim of this study was to investigate the aetiological factors that influence individual variability in different adaptive behaviour domains at 5 months, and the degree of genetic and environmental influences that are unique and shared across these domains. We analysed data from the Vineland Adaptive Behaviour Scale (VABS-II) motor domain and combined domain of socialization and communication (social-communication) using a multivariate twin modelling approach. Participants were a community sample of monozygotic and dizygotic twins assessed at 5 months of age (n = 594). The results show high shared environmental influence on both motor (0.67) and social-communication (0.78) domains with 45% shared variance. Both had low, but significant heritability estimates (0.21 and 0.12, respectively) but did not share genetic variance. No statistically significant associations were found between polygenic scores for autism, ADHD, schizophrenia, depression, and bipolar disorder, and either of the adaptive behaviours measured here. Our results highlight the importance of shared environmental factors in the development of social-communication and motor skills in infancy, whether it is through social interaction with caregivers, or the stimuli and opportunities presented at home. Summary During development structural arm length representation is underestimated, while the functional arm length representation is overestimated. Underestimation of structural arm length is driven by an underestimation of hand length, as forearm length is accurate. Structural hand length is underestimated, supporting that underestimation of hand length is a characteristic of human body representation. The opposite pattern of results between structural and functional arm representation suggests the existence of multiple independent representations of the body.

Background

Individuals with autism spectrum disorder (ASD) experience a wide array of neurological, psychiatric and medical comorbidities, yet little attention has been given to the potential link between ASD and migraine, one of the most prevalent neurological disorders worldwide. This study aimed to investigate whether a genetic predisposition for ASD is linked to migraine and its major subtypes, with and without aura. Additionally, potential moderator and mediators of the association between ASD and migraine were explored.

Methods

Polygenic scores (PGS) for ASD were constructed based on the genome-wide association study by the Psychiatric Genomics Consortium, on the UK Biobank cohort dataset comprising 337,386 participants using PRSice-2. Regression analyses were performed to investigate the association of ASD PGS with migraine and its major subtypes, with and without aura. Sex was explored as a potential moderating factor. The mediation analyses took into consideration variables such as education, personality trait neuroticism, body mass index (BMI) and four categories of comorbidities (psychiatric, vascular, neurologic and others).

Results

ASD PGS were significantly and positively associated with migraine (odds ratio (OR) = 1.04, 95% confidence interval (CI) = 1.02–1.05, p < 0.002), migraine without aura (OR = 1.05, 95% CI = 1.02–1.07, p < 0.002) and migraine with aura (OR = 1.05, 95% CI = 1.02–1.07, p < 0.002). No moderating effect of sex on the association between ASD PGS and migraine was observed. As for potential mediators, only the personality trait neuroticism significantly mediated the association between ASD PGS and migraine, with the proportion of effect mediated 8.75% (95% CI = 4–18%).

Conclusions

Our study suggests that individuals genetically predisposed to autism are at higher risk of experiencing migraine, including the two major subtypes, with and without aura. While emphasizing the complex shared genetic and pathophysiological interactions of these conditions, the role of personality trait neuroticism as a mediator of this relationship is highlighted.

Being looked at is an important communicative signal, and attenuated responses to such direct gaze have been suggested as an early sign of autism. Using live eye tracking, we examined whether direct gaze elicits different gaze responses in infants at ages 10, 14 and 18 months with and without later autism in real-life interaction. The sample consisted of 169 infants: 35 with elevated likelihood of autism and subsequent diagnosis, 94 without subsequent diagnosis and 40 with typical likelihood of autism. Infants in all groups tended to look more towards the adult’s face shortly after the direct gaze occurred. Neither how much nor how quickly the infants responded to the direct gaze differentiated the without elevated likelihood of autism and subsequent diagnosis and with elevated likelihood of autism and subsequent diagnosis groups. Infants in the typical likelihood group looked more at the face after the direct-gaze event than infants in the two elevated likelihood groups, but this result is tentative. In an exploratory analysis, infants in the elevated likelihood of autism and subsequent diagnosis group looked away quicker from faces with direct gaze than infants in the typical likelihood group, but this measure did not correlate with dimensional autism or differentiate between the two elevated likelihood groups. The current results suggest that attenuated behavioural responses to direct gaze in infancy are neither strong nor specific early markers of autism.

Lay abstract

When other people look directly towards us, we often respond by looking back at them, and such direct-gaze responses are important for establishing eye contact. Atypical eye contact is common in autism, but how and when this aspect of autism develops is not well understood. Here, we studied whether how much and how quickly infants respond to others’ direct gaze is associated with autism in toddlerhood. We did this by measuring direct-gaze responses in a playful social interaction using live eye tracking. The study included 169 infants, of whom 129 had an elevated likelihood of developing autism due to having a first-degree family member with the condition, and 40 with typical likelihood of autism. In the elevated likelihood group, 35 were diagnosed with autism spectrum disorder at 3 years of age, and 94 were not. The results showed that infants in all three groups tended to increase their looking towards the adult’s face after the adult looked directly at them. However, neither how much nor how quickly the infants responded to direct gaze by looking back at the adult reliably differentiated the infants with or without subsequent autism. While infants in the elevated likelihood of autism and subsequent diagnosis group tended to look away quicker from faces with direct gaze than infants in the typical likelihood group, this measure did not differentiate between the two elevated likelihood groups. We interpret the results as supporting the view that atypical direct-gaze responses are not early markers of autism.