Genetic and environmental contributions to individual differences in visual attention and oculomotor control in early infancy.

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 5-6 months) 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.

Hemispheric functional segregation facilitates target detection during sustained visuospatial attention.

Visuospatial attention is strongly lateralized, with the right hemisphere commonly exhibiting stronger activation and connectivity patterns than the left hemisphere during attentive processes. However, whether such asymmetry influences inter-hemispheric information transfer and behavioral performance is not known. Here we used a region of interest (ROI) and network-based approach to determine steady-state fMRI functional connectivity (FC) in the whole cerebral cortex during a leftward/rightward covert visuospatial attention task. We found that the global FC topology between either ROIs or networks was independent on the attended side. The side of attention significantly modulated FC strength between brain networks, with leftward attention primarily involving the connections of the right visual network with dorsal and ventral attention networks in both the left and right hemisphere. High hemispheric functional segregation significantly correlated with faster target detection response times (i.e., better performance). Our findings suggest that the dominance of the right hemisphere in visuospatial attention is associated with an hemispheric functional segregation that is beneficial for behavioral performance.

Uncovering neurodevelopmental paths to autism spectrum disorder through an integrated analysis of developmental measures and neural sensitivity to faces.

BACKGROUND: Autism spectrum disorder (ASD) is highly heterogeneous in its etiology and manifestation. The neurobiological processes underlying ASD development are reflected in multiple features, from behaviour and cognition to brain functioning. An integrated analysis of these features may optimize the identification of these processes. METHODS: We examined cognitive and adaptive functioning and ASD symptoms between 8 and 36 months in 161 infants at familial high risk for ASD and 71 low-risk controls; we also examined neural sensitivity to eye gaze at 8 months in a subsample of 140 high-risk and 61 low-risk infants. We used linked independent component analysis to extract patterns of variation across domains and development, and we selected the patterns significantly associated with clinical classification at 36 months. RESULTS: An early process at 8 months, indicating high levels of functioning and low levels of symptoms linked to higher attention to gaze shifts, was reduced in infants who developed ASD. A longitudinal process of increasing functioning and low levels of symptoms was reduced in infants who developed ASD, and another process suggesting a stagnation in cognitive functioning at 24 months was increased in infants who developed ASD. LIMITATIONS: Although the results showed a clear significant trend relating to clinical classification, we found substantial overlap between groups. CONCLUSION: We uncovered underlying processes that acted together early in development and were associated with clinical outcomes. Our results highlighted the complexity of emerging ASD, which goes beyond the borders of clinical categories. Future work should integrate genetic data to investigate the specific genetic risks linked to these processes.

Infant responses to direct gaze and associations to autism: A live eye-tracking study.

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.

Manipulation of phasic arousal by auditory cues is associated with subsequent changes in visual orienting to faces in infancy.

This eye-tracking study investigated the effect of sound-induced arousal on social orienting under different auditory cue conditions in 5-month-old (n = 25; n = 13 males) and 10-month-old infants (n = 21; n = 14 males) participating in a spontaneous visual search task. Results showed: (1) larger pupil dilation discriminating between high and low volume (b = 0.02, p = 0.007), but not between social and non-social sounds (b = 0.004, p = 0.64); (2) faster visual orienting (b = - 0.09, p < 0.001) and better social orienting at older age (b = 0.94, p < 0.001); (3) a fast habituation effect on social orienting after high-volume sounds (χ2(2) = 7.39, p = 0.025); (4) a quadratic association between baseline pupil size and target selection (b = - 1.0, SE = 0.5, χ2(1) = 4.04, p = 0.045); (5) a positive linear association between pupil dilation and social orienting (b = 0.09, p = 0.039). Findings support adaptive gain theories of arousal, extending the link between phasic pupil dilation and task performance to spontaneous social orienting in infancy.

Understanding the nature of face processing in early autism: A prospective study.

Dimensional approaches to psychopathology interrogate the core neurocognitive domains interacting at the individual level to shape diagnostic symptoms. Embedding this approach in prospective longitudinal studies could transform our understanding of the mechanisms underlying neurodevelopmental disorders. Such designs require us to move beyond traditional group comparisons and determine which domain-specific alterations apply at the level of the individual, and whether they vary across distinct phenotypic subgroups. As a proof of principle, this study examines how the domain of face processing contributes to the emergence of autism spectrum disorder (ASD). We used an event-related potentials (ERPs) task in a cohort of 8-month-old infants with (n = 148) and without (n = 68) an older sibling with ASD, and combined traditional case-control comparisons with machine-learning techniques for prediction of social traits and ASD diagnosis at 36 months, and Bayesian hierarchical clustering for stratification into subgroups. A broad profile of alterations in the time-course of neural processing of faces in infancy was predictive of later ASD, with a strong convergence in ERP features predicting social traits and diagnosis. We identified two main subgroups in ASD, defined by distinct patterns of neural responses to faces, which differed on later sensory sensitivity. Taken together, our findings suggest that individual differences between infants contribute to the diffuse pattern of alterations predictive of ASD in the first year of life. Moving from group-level comparisons to pattern recognition and stratification can help to understand and reduce heterogeneity in clinical cohorts, and improve our understanding of the mechanisms that lead to later neurodevelopmental outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Attentive brain states in infants with and without later autism.

Early difficulties in engaging attentive brain states in social settings could affect learning and have cascading effects on social development. We investigated this possibility using multichannel electroencephalography during a face/non-face paradigm in 8-month-old infants with (FH, n = 91) and without (noFH, n = 40) a family history of autism spectrum disorder (ASD). An event-related potential component reflecting attention engagement, the Nc, was compared between FH infants who received a diagnosis of ASD at 3 years of age (FH-ASD; n = 19), FH infants who did not (FH-noASD; n = 72) and noFH infants (who also did not, hereafter noFH-noASD; n = 40). 'Prototypical' microstates during social attention were extracted from the noFH-noASD group and examined in relation to later categorical and dimensional outcome. Machine-learning was used to identify the microstate features that best predicted ASD and social adaptive skills at three years. Results suggested that whilst measures of brain state timing were related to categorical ASD outcome, brain state strength was related to dimensional measures of social functioning. Specifically, the FH-ASD group showed shorter Nc latency relative to other groups, and duration of the attentive microstate responses to faces was informative for categorical outcome prediction. Reduced Nc amplitude difference between faces with direct gaze and a non-social control stimulus and strength of the attentive microstate to faces contributed to the prediction of dimensional variation in social skills. Taken together, this provides consistent evidence that atypical attention engagement precedes the emergence of difficulties in socialization and indicates that using the spatio-temporal characteristics of whole-brain activation to define brain states in infancy provides an important new approach to understanding of the neurodevelopmental mechanisms that lead to ASD.

Latent trajectories of adaptive behaviour in infants at high and low familial risk for autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is characterised by persisting difficulties in everyday functioning. Adaptive behaviour is heterogeneous across individuals with ASD, and it is not clear to what extent early development of adaptive behaviour relates to ASD outcome in toddlerhood. This study aims to identify subgroups of infants based on early development of adaptive skills and investigate their association with later ASD outcome. Methods: Adaptive behaviour was assessed on infants at high (n = 166) and low (n = 74) familial risk for ASD between 8 and 36 months using the Vineland Adaptive Behavior Scales (VABS-II). The four domains of VABS-II were modelled in parallel using growth mixture modelling to identify distinct classes of infants based on adaptive behaviour. Then, we associated class membership with clinical outcome and ASD symptoms at 36 months and longitudinal measures of cognitive development. Results: We observed three classes characterised by decreasing trajectories below age-appropriate norms (8.3%), stable trajectories around age-appropriate norms (73.8%), and increasing trajectories reaching average scores by age 2 (17.9%). Infants with declining adaptive behaviour had a higher risk (odds ratio (OR) = 4.40; confidence interval (CI) 1.90; 12.98) for ASD and higher parent-reported symptoms in the social, communication, and repetitive behaviour domains at 36 months. Furthermore, there was a discrepancy between adaptive and cognitive functioning as the class with improving adaptive skills showed stable cognitive development around average scores. Conclusions: Findings confirm the heterogeneity of trajectories of adaptive functioning in infancy, with a higher risk for ASD in toddlerhood linked to a plateau in the development of adaptive functioning after the first year of life.

Brain Networks Underlying Eye's Pupil Dynamics.

Phasic changes in eye's pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness.

Temporal Information Entropy of the Blood-Oxygenation Level-Dependent Signals Increases in the Activated Human Primary Visual Cortex.

Time-domain analysis of blood-oxygenation level-dependent (BOLD) signals allows the identification of clusters of voxels responding to photic stimulation in primary visual cortex (V1). However, the characterization of information encoding into temporal properties of the BOLD signals of an activated cluster is poorly investigated. Here, we used Shannon entropy to determine spatial and temporal information encoding in the BOLD signal within the most strongly activated area of the human visual cortex during a hemifield photic stimulation. We determined the distribution profile of BOLD signals during epochs at rest and under stimulation within small (19-121 voxels) clusters designed to include only voxels driven by the stimulus as highly and uniformly as possible. We found consistent and significant increases (2-4% on average) in temporal information entropy during activation in contralateral but not ipsilateral V1, which was mirrored by an expected loss of spatial information entropy. These opposite changes coexisted with increases in both spatial and temporal mutual information (i.e., dependence) in contralateral V1. Thus, we showed that the first cortical stage of visual processing is characterized by a specific spatiotemporal rearrangement of intracluster BOLD responses. Our results indicate that while in the space domain BOLD maps may be incapable of capturing the functional specialization of small neuronal populations due to relatively low spatial resolution, some information encoding may still be revealed in the temporal domain by an increase of temporal information entropy.