Jennifer B. Wagner

Eye-Tracking, Autonomic, and Electrophysiological Correlates of Emotional Face Processing in Adolescents with Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) often have difficulty with social-emotional cues. This study examined the neural, behavioral, and autonomic correlates of emotional face processing in adolescents with ASD and typical development (TD) using eye-tracking and event-related potentials (ERPs) across two different paradigms. Scanning of faces was similar across groups in the first task, but the second task found that face-sensitive ERPs varied with emotional expressions only in TD. Further, ASD showed enhanced neural responding to non-social stimuli. In TD only, attention to eyes during eye-tracking related to faster face-sensitive ERPs in a separate task; in ASD, a significant positive association was found between autonomic activity and attention to mouths. Overall, ASD showed an atypical pattern of emotional face processing, with reduced neural differentiation between emotions and a reduced relationship between gaze behavior and neural processing of faces.

Functional connectivity in the first year of life in infants at-risk for autism: a preliminary near-infrared spectroscopy study

Background: Autism spectrum disorder (ASD) has been called a “developmental disconnection syndrome,” however the majority of the research examining connectivity in ASD has been conducted exclusively with older children and adults. Yet, prior ASD research suggests that perturbations in neurodevelopmental trajectories begin as early as the first year of life. Prospective longitudinal studies of infants at risk for ASD may provide a window into the emergence of these aberrant patterns of connectivity. The current study employed functional connectivity near-infrared spectroscopy (NIRS) in order to examine the development of intra- and inter-hemispheric functional connectivity in high- and low-risk infants across the first year of life. Methods: NIRS data were collected from 27 infants at high risk for autism (HRA) and 37 low-risk comparison (LRC) infants who contributed a total of 116 data sets at 3-, 6-, 9-, and 12-months. At each time point, HRA and LRC groups were matched on age, sex, head circumference, and Mullen Scales of Early Learning scores. Regions of interest (ROI) were selected from anterior and posterior locations of each hemisphere. The average time course for each ROI was calculated and correlations for each ROI pair were computed. Differences in functional connectivity were examined in a cross-sectional manner. Results: At 3-months, HRA infants showed increased overall functional connectivity compared to LRC infants. This was the result of increased connectivity for intra- and inter-hemispheric ROI pairs. No significant differences were found between HRA and LRC infants at 6- and 9-months. However, by 12-months, HRA infants showed decreased connectivity relative to LRC infants. Conclusions: Our preliminary results suggest that atypical functional connectivity may exist within the first year of life in HRA infants, providing support to the growing body of evidence that aberrant patterns of connectivity may be a potential endophenotype for ASD.

Neural correlates of familiar and unfamiliar face processing in infants at risk for autism spectrum disorders.

Examining the neural correlates associated with processing social stimuli offers a viable option to the challenge of studying early social processing in infants at risk for autism spectrum disorders (ASDs). The present investigation included 32 12-month olds at high risk for ASD and 24 low-risk control infants, defined on the basis of family history. Infants were presented with familiar and unfamiliar faces, and three components of interest were explored for amplitude and latency differences. The anticipated developmental effects of emerging hemispheric asymmetry for face-sensitive components (the N290 and P400) were observed, as were familiarity effects for a component related to attention (the Nc). Although there were no striking group differences in the neural response to faces, there was some evidence for a developmental lag in an attentional component for the high-risk group. The infant ASD endophenotype, though elusive, may be better defined through expanding the age of study and addressing change over time in response to varied stimuli.

The Role of Early Visual Attention in Social Development.

Faces convey important information about the social environment, and even very young infants are preferentially attentive to face-like over non-face stimuli. Eye-tracking studies have allowed researchers to examine which features of faces infants find most salient across development, and the present study examined scanning of familiar (i.e., mother) and unfamiliar (i.e., stranger) static faces at 6, 9, and 12 months of age. Infants showed a preference for scanning their mother’s face as compared to a stranger’s face, and displayed increased attention to the eye region as compared to the mouth region. Infants also showed patterns of decreased attention to eyes and increased attention to mouths between 6 and 12 months. Associations between visual attention at 6, 9, and 12 months and the Communication and Symbolic Behavior Scales DP (CSBS-DP) at 18 months were also examined, and a significant positive relation between attention to eyes at 6 months and the social subscale of the CSBS-DP at 18 months was found. This effect was driven by infants’ attention to their mother’s eyes. No relations between face scanning in 9- and 12-month-olds and social outcome at 18 months were found. The potential for using individual differences in early infant face processing to predict later social outcome is discussed.

Neural processing of facial identity and emotion in infants at high-risk for autism spectrum disorders.

Deficits in face processing and social impairment are core characteristics of autism spectrum disorder. The present work examined 7-month-old infants at high-risk for developing autism and typically developing controls at low-risk, using a face perception task designed to differentiate between the effects of face identity and facial emotions on neural response using functional Near-Infrared Spectroscopy. In addition, we employed independent component analysis, as well as a novel method of condition-related component selection and classification to identify group differences in hemodynamic waveforms and response distributions associated with face and emotion processing. The results indicate similarities of waveforms, but differences in the magnitude, spatial distribution, and timing of responses between groups. These early differences in local cortical regions and the hemodynamic response may, in turn, contribute to differences in patterns of functional connectivity.

Functional brain organization for number processing in pre‐verbal infants

Humans are born with the ability to mentally represent the approximate numerosity of a set of objects, but little is known about the brain systems that sub-serve this ability early in life and their relation to the brain systems underlying symbolic number and mathematics later in development. Here we investigate processing of numerical magnitudes before the acquisition of a symbolic numerical system or even spoken language, by measuring the brain response to numerosity changes in pre-verbal infants using functional near-infrared spectroscopy (fNIRS). To do this, we presented infants with two types of numerical stimulus blocks: number change blocks that presented dot arrays alternating in numerosity and no change blocks that presented dot arrays all with the same number. Images were carefully constructed to rule out the possibility that responses to number changes could be due to non-numerical stimulus properties that tend to co-vary with number. Interleaved with the two types of numerical blocks were audio-visual animations designed to increase attention. We observed that number change blocks evoked an increase in oxygenated hemoglobin over a focal right parietal region that was greater than that observed during no change blocks and during audio-visual attention blocks. The location of this effect was consistent with intra-parietal activity seen in older children and adults for both symbolic and non-symbolic numerical tasks. A distinct set of bilateral occipital and middle parietal channels responded more to the attention-grabbing animations than to either of the types of numerical stimuli, further dissociating the specific right parietal response to number from a more general bilateral visual or attentional response. These results provide the strongest evidence to date that the right parietal cortex is specialized for numerical processing in infancy, as the response to number is dissociated from visual change processing and general attentional processing.

Neural processing of repetition and non-repetition grammars in 7- and 9-month-old infants.

An essential aspect of infant language development involves the extraction of meaningful information from a continuous stream of auditory input. Studies have identified early abilities to differentiate auditory input along various dimensions, including the presence or absence of structural regularities. In newborn infants, frontal and temporal regions were found to respond differentially to these regularities (Gervain et al., 2008), and in order to examine the development of this abstract rule learning we presented 7- and 9-month-old infants with syllables containing an ABB pattern (e.g., “balolo”) or an ABC pattern (e.g., “baloti”) and measured activity in left and right lateral brain regions using near-infrared spectroscopy (NIRS). While prior newborn work found increases in oxyhemoglobin (oxyHb) activity in response to ABB blocks as compared to ABC blocks in anterior regions, 7- and 9-month-olds showed no differentiation between grammars in oxyHb. However, changes in deoxyhemoglobin (deoxyHb) pointed to a developmental shift, whereby 7-month-olds showed deoxyHb responding significantly different from zero for ABB blocks, but not ABC blocks, and 9-month-olds showed the opposite pattern, with deoxyHb responding significantly different from zero for the ABC blocks but not the ABB blocks. DeoxyHb responses were more pronounced over anterior regions. A grammar by time interaction also illustrated that during the early blocks, deoxyHb was significantly greater to ABC than in later blocks, but there was no change in ABB activation over time. The shift from stronger activation to ABB in newborns (Gervain et al., 2008) and 7-month-olds in the present study to stronger activation to ABC by 9-month-olds here is discussed in terms of changes in stimulus salience and novelty preference over the first year of life. The present discussion also highlights the importance of future work exploring the coupling between oxyHb and deoxyHb activation in infant NIRS studies.

Differences in Neural Correlates of Speech Perception in 3 Month Olds at High and Low Risk for Autism Spectrum Disorder

In this study, we investigated neural precursors of language acquisition as potential endophenotypes of autism spectrum disorder (ASD) in 3-month-old infants at high and low familial ASD risk. Infants were imaged using functional near-infrared spectroscopy while they listened to auditory stimuli containing syllable repetitions; their neural responses were analyzed over left and right temporal regions. While female low risk infants showed initial neural activation that decreased over exposure to repetition-based stimuli, potentially indicating a habituation response to repetition in speech, female high risk infants showed no changes in neural activity over exposure. This finding may indicate a potential neural endophenotype of language development or ASD specific to females at risk for the disorder.

Differential Attention to Faces in Infant Siblings of Children with Autism Spectrum Disorder and Associations with Later Social and Language Ability.

A growing body of literature has begun to explore social attention in infant siblings of children with autism spectrum disorder (ASD) with hopes of identifying early differences that are associated with later ASD or other aspects of development. The present study used eye-tracking to familiar (mother) and unfamiliar (stranger) faces in two groups of 6-month-old infants: infants with no family history of ASD (low-risk controls; LRC), and infants at high risk for ASD (HRA), by virtue of having an older sibling with ASD. HRA infants were further characterized based on autism classification at 24 months or older as HRA- (HRA without an ASD outcome) or HRA+ (HRA with an ASD outcome). For time scanning faces overall, HRA+ and LRC showed similar patterns of attention, and this was significantly greater than in HRA-. When examining duration of time spent on eyes and mouth, all infants spent more time on eyes than mouth, but HRA+ showed the greatest amount of time looking at these regions, followed by LRC, then HRA-. LRC showed a positive association between 6-month attention to eyes and 18-month social-communicative behavior, while HRA- showed a negative association between attention to eyes at 6 months and expressive language at 18 months (all correlations controlled for non-verbal IQ; HRA- correlations held with and without the inclusion of the small sample of HRA+). Differences found in face scanning at 6 months, as well as associations with social communication at 18 months, point to potential variation in the developmental significance of early social attention in children at low and high risk for ASD.