Eye-Tracking Biomarkers and Autism Diagnosis in Primary Care.

Importance: Finding effective and scalable solutions to address diagnostic delays and disparities in autism is a public health imperative. Approaches that integrate eye-tracking biomarkers into tiered community-based models of autism evaluation hold promise for addressing this problem. Objective: To determine whether a battery of eye-tracking biomarkers can reliably differentiate young children with and without autism in a community-referred sample collected during clinical evaluation in the primary care setting and to evaluate whether combining eye-tracking biomarkers with primary care practitioner (PCP) diagnosis and diagnostic certainty is associated with diagnostic outcome. Design, Setting, and Participants: Early Autism Evaluation (EAE) Hub system PCPs referred a consecutive sample of children to this prospective diagnostic study for blinded eye-tracking index test and follow-up expert evaluation from June 7, 2019, to September 23, 2022. Participants included 146 children (aged 14-48 months) consecutively referred by 7 EAE Hubs. Of 154 children enrolled, 146 provided usable data for at least 1 eye-tracking measure. Main Outcomes and Measures: The primary outcomes were sensitivity and specificity of a composite eye-tracking (ie, index) test, which was a consolidated measure based on significant eye-tracking indices, compared with reference standard expert clinical autism diagnosis. Secondary outcome measures were sensitivity and specificity of an integrated approach using an index test and PCP diagnosis and certainty. Results: Among 146 children (mean [SD] age, 2.6 [0.6] years; 104 [71%] male; 21 [14%] Hispanic or Latine and 96 [66%] non-Latine White; 102 [70%] with a reference standard autism diagnosis), 113 (77%) had concordant autism outcomes between the index (composite biomarker) and reference outcomes, with 77.5% sensitivity (95% CI, 68.4%-84.5%) and 77.3% specificity (95% CI, 63.0%-87.2%). When index diagnosis was based on the combination of a composite biomarker, PCP diagnosis, and diagnostic certainty, outcomes were concordant with reference standard for 114 of 127 cases (90%) with a sensitivity of 90.7% (95% CI, 83.3%-95.0%) and a specificity of 86.7% (95% CI, 70.3%-94.7%). Conclusions and Relevance: In this prospective diagnostic study, a composite eye-tracking biomarker was associated with a best-estimate clinical diagnosis of autism, and an integrated diagnostic model including PCP diagnosis and diagnostic certainty demonstrated improved sensitivity and specificity. These findings suggest that equipping PCPs with a multimethod diagnostic approach has the potential to substantially improve access to timely, accurate diagnosis in local communities.

Autistic Individuals Do Not Alter Visual Processing Strategy During Encoding Versus Recognition of Faces: A Hidden Markov Modeling Approach.

PURPOSE: Visual face recognition-the ability to encode, discriminate, and recognize the faces of others-is fundamentally supported by eye movements and is a common source of difficulty for autistic individuals. We aimed to evaluate how visual processing strategies (i.e., eye movement patterns) directly support encoding and recognition of faces in autistic and neurotypical (NT) individuals. METHODS: We used a hidden Markov modeling approach to evaluate the spatiotemporal dynamics of eye movements in autistic (n = 15) and neurotypical (NT) adolescents (n = 17) during a face identity recognition task. RESULTS: We discovered distinct eye movement patterns among all participants, which included a focused and exploratory strategy. When evaluating change in visual processing strategy across encoding and recognition phases, autistic individuals did not shift their eye movement patterns like their NT peers, who shifted to a more exploratory visual processing strategy during recognition. CONCLUSION: These findings suggest that autistic individuals do not modulate their visual processing strategy across encoding and recognition of faces, which may be an indicator of less efficient face processing.

Resting-state EEG power differences in autism spectrum disorder: a systematic review and meta-analysis.

Narrative reviews have described various resting-state EEG power differences in autism across all five canonical frequency bands, with increased power for low and high frequencies and reduced power for middle frequencies. However, these differences have yet to be quantified using effect sizes and probed robustly for consistency, which are critical next steps for clinical translation. Following PRISMA guidelines, we conducted a systematic review of published and gray literature on resting-state EEG power in autism. We performed 10 meta-analyses to synthesize and quantify differences in absolute and relative resting-state delta, theta, alpha, beta, and gamma EEG power in autism. We also conducted moderator analyses to determine whether demographic characteristics, methodological details, and risk-of-bias indicators might account for heterogeneous study effect sizes. Our literature search and study selection processes yielded 41 studies involving 1,246 autistic and 1,455 neurotypical individuals. Meta-analytic models of 135 effect sizes demonstrated that autistic individuals exhibited reduced relative alpha (g = -0.35) and increased gamma (absolute: g = 0.37, relative: g = 1.06) power, but similar delta (absolute: g = 0.06, relative: g = 0.10), theta (absolute: g = -0.03, relative: g = -0.15), absolute alpha (g = -0.17), and beta (absolute: g = 0.01, relative: g = 0.08) power. Substantial heterogeneity in effect sizes was observed across all absolute (I2: 36.1-81.9%) and relative (I2: 64.6-84.4%) frequency bands. Moderator analyses revealed that age, biological sex, IQ, referencing scheme, epoch duration, and use of gold-standard autism diagnostic instruments did not moderate study effect sizes. In contrast, resting-state paradigm type (eyes-closed versus eyes-open) moderated absolute beta, relative delta, and relative alpha power effect sizes, and resting-state recording duration moderated relative alpha power effect sizes. These findings support further investigation of resting-state alpha and gamma power as potential biomarkers for autism.

Elevated and accelerated: Locus coeruleus activity and visual search abilities in autistic children.

BACKGROUND: Autistic individuals excel at visual search, however, the neural mechanism(s) underlying this advantage remain unclear. The locus coeruleus-norepinephrine (LC-NE) system, which plays a critical role in sensory perception and selective attention, has been shown to function in a persistently elevated state in individuals on the spectrum. However, the relationship between elevated tonic LC-NE activity and accelerated search in autism has not been explored. OBJECTIVE: To examine the relationship between visual search abilities and resting pupil diameter (an indirect measure of tonic LC-NE activation) in autistic and neurotypical children. METHODS: Participants were 24 school-aged autistic children and 24 age- and IQ-matched neurotypical children aged 8-15 years. Children completed two tasks: a resting eye-tracking task and a visual search paradigm. For the resting eye-tracking task, pupil diameter was monitored while participants fixated a central crosshair. For the visual search paradigm, participants were instructed to find the target (vertical line) embedded within an array of tilted (10°) distractor lines. The target was present on 50% of trials, and displayed within set sizes of 18, 24, and 36 items. RESULTS: Consistent with previous studies, autistic children had significantly larger resting pupil size and searched faster and more efficiently compared to their neurotypical peers. Eye-tracking findings revealed that accelerated search was associated with fewer, not shorter, fixations in the autism group. Autistic children also showed reduced leftward search bias. Larger resting pupil size, indicative of increased tonic activation of the LC-NE system, was associated with greater search efficiency, longer fixation durations, and reduced leftward bias. Finally, within both groups reduced leftward bias was associated with increased autism symptomatology. DISCUSSION: Together, these findings add to the existing body of research highlighting superior search in autism, suggest that elevated tonic LC-NE activity may contribute to more efficient search, and link non-social visual-spatial processing strengths to autism symptoms.

Diagnostic Accuracy of Primary Care Clinicians Across a Statewide System of Autism Evaluation.

OBJECTIVES: To evaluate the diagnostic accuracy of the Early Autism Evaluation (EAE) Hub system, a statewide network that provides specialized training and collaborative support to community primary care providers in the diagnosis of young children at risk for autism spectrum disorder (ASD). METHODS: EAE Hub clinicians referred children, aged 14 to 48 months, to this prospective diagnostic study for blinded follow-up expert evaluation including assessment of developmental level, adaptive behavior, and ASD symptom severity. The primary outcome was agreement on categorical ASD diagnosis between EAE Hub clinician (index diagnosis) and ASD expert (reference standard). RESULTS: Among 126 children (mean age: 2.6 years; 77% male; 14% Latinx; 66% non-Latinx white), 82% (n = 103) had consistent ASD outcomes between the index and reference evaluation. Sensitivity was 81.5%, specificity was 82.4%, positive predictive value was 92.6%, and negative predictive value was 62.2%. There was no difference in accuracy by EAE Hub clinician or site. Across measures of development, there were significant differences between true positive and false negative (FN) cases (all Ps < .001; Cohen's d = 1.1-1.4), with true positive cases evidencing greater impairment. CONCLUSIONS: Community-based primary care clinicians who receive specialty training can make accurate ASD diagnoses in most cases. Diagnostic disagreements were predominately FN cases in which EAE Hub clinicians had difficulty differentiating ASD and global developmental delay. FN cases were associated with a differential diagnostic and phenotypic profile. This research has significant implications for the development of future population health solutions that address ASD diagnostic delays.

Associations between attentional biases to fearful faces and social-emotional development in infants with and without an older sibling with autism.

During the first year of life, infants become increasingly attuned to facial emotion, with heightened sensitivity to faces conveying threat observed by age seven months as illustrated through attentional biases (e.g., slower shifting away from fearful faces). Individual differences in these cognitive attentional biases have been discussed in relation to broader social-emotional functioning, and the current study examines these associations in infants with an older sibling with autism spectrum disorder (ASD), a group with an elevated likelihood of a subsequent ASD diagnosis (ELA; n = 33), and a group of infants with no family history of ASD who are at low likelihood of ASD (LLA; n = 24). All infants completed a task measuring disengagement of attention from faces at 12 months (fearful, happy, neutral), and caregivers completed the Infant-Toddler Social and Emotional Assessment at 12, 18, and/or 24 months. For the full sample, greater fear bias in attention disengagement at 12 months related to more internalizing behaviors at 18 months, and this was driven by the LLA infants. When examining groups separately, findings revealed that LLA with a greater fear bias had more difficult behaviors at 12, 18, and 24 months; in contrast, ELA showed the opposite pattern, and this was most pronounced for ELA who later received an ASD diagnosis. These preliminary group-level findings suggest that heightened sensitivity to fearful faces might serve an adaptive function in children who later receive an ASD diagnosis, but in infants with no family history of ASD, increased biases might reflect a marker of social-emotional difficulties.

Exploring Subtypes of Repetitive Behavior in Children with Autism Through Functional Analysis and Wearable Technology: a Pilot Biobehavioral Assessment.

Objectives: Prior research has established assessment methodologies, such as functional analysis to identify specific contexts in which restricted and repetitive behavior (RRB) occurs, and measures of heart rate variability (HRV) to index the level of autonomic arousal in individuals with autism spectrum disorder (ASD). Yet, a gap remains in integrating multiple assessment methodologies to examine the complex underlying mechanisms of RRB. This study piloted a multi-disciplinary approach to assess both the functional behavioral and neurophysiological factors that may underlie occurrences of RRB. The study (a) evaluated the effect of a modified functional analysis protocol on delineating functional subtypes of RRB and (b) explored the effect of using a wearable technology within a functional analysis on identifying the relationship between RRB and HRV. Method: A single-case alternating treatment design was used to randomly alternate noncontingent low-stimulation and high-stimulation conditions in a modified functional analysis protocol. Simultaneous measurement of RRB and HRV was obtained through direct behavioral observations and a wristband that collects blood volume pulse, respectively. Visual analysis of time series data was used to determine the functional subtypes of RRB, and nonparametric correlational analyses were conducted to determine the association between HRV and RRB. Results: Findings from a sample of six participants suggest preliminary effectiveness of the assessment protocol in identifying subtypes of RRB and a significant correlation between HRV and RRB. Conclusions: This study demonstrates the potential effect and usability of a wearable technology-aided biobehavioral approach to assess RRB and HRV in individuals with ASD.

Measures of tonic and phasic activity of the locus coeruleus-norepinephrine system in children with autism spectrum disorder: An event-related potential and pupillometry study.

A growing body of research suggests that locus coeruleus-norepinephrine (LC-NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics of both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] and event-related potential [ERP]) indices may provide meaningful insights about the nature of LC-NE function in ASD. Twenty-four children with ASD and 27 age- and nonverbal-IQ matched typically developing (TD) children completed two experiments: (1) a resting eye-tracking task to measure tonic pupil diameter, and (2) a three-stimulus oddball paradigm to measure phasic responsivity using PDR and ERP. Consistent with prior reports, our results indicate that children with ASD exhibit increased tonic (resting pupil diameter) and reduced phasic (PDR and ERP) activity of the LC-NE system compared to their TD peers. For both groups, decreased phasic responsivity was associated with increased resting pupil diameter. Lastly, tonic and phasic LC-NE indices were primarily related to measures of attention-deficit/hyperactivity disorder (ADHD), and not ASD, symptomatology. These findings expand our understanding of neurophysiological differences present in ASD and demonstrate that aberrant LC-NE activation may be associated with atypical arousal and decreased responsivity to behaviorally-relevant information in ASD.

EEG microstates suggest atypical resting-state network activity in high-functioning children and adolescents with autism spectrum development.

EEG microstates represent transient electrocortical events that reflect synchronized activities of large-scale networks, which allows investigations of brain dynamics with sub-second resolution. We recorded resting EEG from 38 children and adolescents with Autism Spectrum Development (ASD) and 48 age, IQ, sex, and handedness-matched typically developing (TD) participants. The EEG was segmented into a time series of microstates using modified k-means clustering of scalp voltage topographies. The frequency and global explained variance (GEV) of a specific microstate (type C) were significantly lower in the ASD group compared to the TD group while the duration of the same microstate was correlated with the presence of ASD-related behaviors. The duration of this microstate was also positively correlated with participant age in the TD group, but not in the ASD group. Further, the frequency and duration of the microstate were significantly correlated with the overall alpha power only in the TD group. The signal strength and GEV for another microstate (type G) was greater in the ASD group than the TD group, and the associated topographical pattern differed between groups with greater variations in the ASD group. While more work is needed to clarify the underlying neural sources, the existing literature supports associations between the two microstates and the default mode and salience networks. The current study suggests specific alterations of temporal dynamics of the resting cortical network activities as well as their developmental trajectories and relationships to alpha power, which has been proposed to reflect reduced neural inhibition in ASD.

Implications of Sensory Processing and Attentional Differences Associated With Autism in Academic Settings: An Integrative Review.

The impact of classroom environments on student engagement and academic performance is well-documented. Autism spectrum disorder (ASD) is associated with atypical sensory processing and attentional impairments, which may lead to challenges in successfully accessing educational material within these settings. These symptoms may help explain why students with ASD show discrepancies between intellectual ability and academic performance. Given the increasing number of students with ASD present in classrooms, understanding strengths and weaknesses in sensory processing and attention is necessary in order to design better classroom environments and develop more efficacious accommodations and interventions to support optimal student success. Therefore, the objectives of this review are to provide a brief review of the current literature on sensory processing and attention in ASD, survey how sensory and attentional functions affect academic outcomes in both neurotypical and ASD learners, and suggest potential accommodations/interventions for students with ASD based on these findings.

Attentional Disengagement and the Locus Coeruleus - Norepinephrine System in Children With Autism Spectrum Disorder.

BACKGROUND: Differences in non-social attentional functions have been identified as among the earliest features that distinguish infants later diagnosed with autism spectrum disorder (ASD), and may contribute to the emergence of core ASD symptoms. Specifically, slowed attentional disengagement and difficulty reorienting attention have been found across the lifespan in those at risk for, or diagnosed with, ASD. Additionally, the locus coeruleus-norepinephrine (LC-NE) system, which plays a critical role in arousal regulation and selective attention, has been shown to function atypically in ASD. While activity of the LC-NE system is associated with attentional disengagement and reorienting in typically developing (TD) individuals, it has not been determined whether atypical LC-NE activity relates to attentional disengagement impairments observed in ASD. OBJECTIVE: To examine the relationship between resting pupil diameter (an indirect measure of tonic LC-NE activation) and attentional disengagement in children with ASD. METHODS: Participants were 21 school-aged children with ASD and 20 age- and IQ-matched TD children. The study consisted of three separate experiments: a resting eye-tracking task and visual and auditory gap-overlap paradigms. For the resting eye-tracking task, pupil diameter was monitored while participants fixated a central crosshair. In the gap-overlap paradigms, participants were instructed to fixate on a central stimulus and then move their eyes to peripherally presented visual or auditory targets. Saccadic reaction times (SRT), percentage of no-shift trials, and disengagement efficiency were measured. RESULTS: Children with ASD had significantly larger resting pupil size compared to their TD peers. The groups did not differ for overall SRT, nor were there differences in SRT for overlap and gap conditions between groups. However, the ASD group did evidence impairments in disengagement (larger step/gap effects, higher percentage of no-shift trials, and reduced disengagement efficiency) compared to their TD peers. Correlational analyses showed that slower, less efficient disengagement was associated with increased pupil diameter. CONCLUSION: Consistent with prior reports, children with ASD show significantly larger resting pupil diameter, indicative of atypically elevated tonic LC-NE activity. Associations between pupil size and measures of attentional disengagement suggest that atypically increased tonic activation of the LC-NE system may be associated with poorer attentional disengagement in children with ASD.

Equivalent Behavioral Facilitation to Tactile Cues in Children with Autism Spectrum Disorder.

The alerting network, a subcomponent of attention, enables humans to respond to novel information. Children with ASD have shown equivalent alerting in response to visual and/or auditory stimuli compared to typically developing (TD) children. However, it is unclear whether children with ASD and TD show equivalent alerting to tactile stimuli. We examined (1) whether tactile cues affect accuracy and reaction times in children with ASD and TD, (2) whether the duration between touch-cues and auditory targets impacts performance, and (3) whether behavioral responses in the tactile cueing task are associated with ASD symptomatology. Six- to 12-year-olds with ASD and TD participated in a tactile-cueing task and were instructed to respond with a button press to a target sound /a/. Tactile cues were presented at 200, 400, and 800 ms (25% each) prior to the auditory target. The remaining trials (25%) were presented without tactile cues. Findings suggested that both groups showed equivalent alerting responses to tactile cues. Additionally, all children were faster to respond to auditory targets at longer cue-target intervals. Finally, there was an association between rate of facilitation and RRB scores in all children, suggesting that patterns of responding to transient phasic cues may be related to ASD symptomatology.

Associations between sensory processing and electrophysiological and neurochemical measures in children with ASD: an EEG-MRS study.

BACKGROUND: Autism spectrum disorder (ASD) is associated with hyper- and/or hypo-sensitivity to sensory input. Spontaneous alpha power, which plays an important role in shaping responsivity to sensory information, is reduced across the lifespan in individuals with ASD. Furthermore, an excitatory/inhibitory imbalance has also been linked to sensory dysfunction in ASD and has been hypothesized to underlie atypical patterns of spontaneous brain activity. The present study examined whether resting-state alpha power differed in children with ASD as compared to TD children, and investigated the relationships between alpha levels, concentrations of excitatory and inhibitory neurotransmitters, and atypical sensory processing in ASD. METHODS: Participants included thirty-one children and adolescents with ASD and thirty-one age- and IQ-matched typically developing (TD) participants. Resting-state electroencephalography (EEG) was used to obtain measures of alpha power. A subset of participants (ASD = 16; TD = 16) also completed a magnetic resonance spectroscopy (MRS) protocol in order to measure concentrations of excitatory (glutamate + glutamine; Glx) and inhibitory (GABA) neurotransmitters. RESULTS: Children with ASD evidenced significantly decreased resting alpha power compared to their TD peers. MRS estimates of GABA and Glx did not differ between groups with the exception of Glx in the temporal-parietal junction. Inter-individual differences in alpha power within the ASD group were not associated with region-specific concentrations of GABA or Glx, nor were they associated with sensory processing differences. However, atypically decreased Glx was associated with increased sensory impairment in children with ASD. CONCLUSIONS: Although we replicated prior reports of decreased alpha power in ASD, atypically reduced alpha was not related to neurochemical differences or sensory symptoms in ASD. Instead, reduced Glx in the temporal-parietal cortex was associated with greater hyper-sensitivity in ASD. Together, these findings may provide insight into the neural underpinnings of sensory processing differences present in ASD.

Electrophysiological Measures of Tactile and Auditory Processing in Children With Autism Spectrum Disorder.

Behavioral differences in responding to tactile and auditory stimuli are widely reported in individuals with autism spectrum disorder (ASD). However, the neural mechanisms underlying distinct tactile and auditory reactivity patterns in ASD remain unclear with theories implicating differences in both perceptual and attentional processes. The current study sought to investigate (1) the neural indices of early perceptual and later attentional factors underlying tactile and auditory processing in children with and without ASD, and (2) the relationship between neural indices of tactile and auditory processing and ASD symptomatology. Participants included 14, 6-12-year-olds with ASD and 14 age- and non-verbal IQ matched typically developing (TD) children. Children participated in an event-related potential (ERP) oddball paradigm during which they watched a silent video while being presented with tactile and auditory stimuli (i.e., 80% standard speech sound/a/; 10% oddball speech sound/i/; 10% novel vibrotactile stimuli on the fingertip with standard speech sound/a/). Children's early and later ERP responses to tactile (P1 and N2) and auditory stimuli (P1, P3a, and P3b) were examined. Non-parametric analyses showed that children with ASD displayed differences in early perceptual processing of auditory (i.e., lower amplitudes at central region of interest), but not tactile, stimuli. Analysis of later attentional components did not show differences in response to tactile and auditory stimuli in the ASD and TD groups. Together, these results suggest that differences in auditory responsivity patterns could be related to perceptual factors in children with ASD. However, despite differences in caregiver-reported sensory measures, children with ASD did not differ in their neural reactivity to infrequent touch-speech stimuli compared to TD children. Nevertheless, correlational analyses confirmed that inter-individual differences in neural responsivity to tactile and auditory stimuli were related to social skills in all children. Finally, we discuss how the paradigm and stimulus type used in the current study may have impacted our results. These findings have implications for everyday life, where individual differences in responding to tactile and auditory stimuli may impact social functioning.

Brief Report: Reduced Heart Rate Variability in Children with Autism Spectrum Disorder.

Dysregulation of the autonomic nervous system (ANS), which can be indexed by heart rate variability (HRV), has been posited to contribute to core features of autism spectrum disorder (ASD). However, the relationship between ASD and HRV remains uncertain. We assessed tonic and phasic HRV of 21 children with ASD and 21 age- and IQ-matched typically developing (TD) children and examined (1) group differences in HRV and (2) associations between HRV and ASD symptomatology. Children with ASD showed significantly lower tonic HRV, but similar phasic HRV compared to TD children. Additionally, reduced tonic HRV was associated with atypical attentional responsivity in ASD. Our findings suggest ANS dysregulation is present in ASD and may contribute to atypical attentional responses to sensory stimulation.

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder.

Although diagnosed on the basis of deficits in social communication and interaction, autism spectrum disorder (ASD) is also characterized by superior performance on a variety of visuospatial tasks, including visual search. In neurotypical individuals, region-specific concentrations of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) are associated with individual differences in attention and perception. While it has been hypothesized that ASD may be associated with an excitatory-inhibitory imbalance, it remains unclear how this may contribute to accelerated visual search performance in individuals with ASD. To investigate this, 21 children with ASD and 20 typically developing children participated in a visual search task and a magnetic resonance spectroscopy study to detect neurochemical concentrations, including GABA. Region-specific neurochemicals were examined in the right frontal eye fields, right temporal-parietal junction (rTPJ), and bilateral visual cortex (VIS). GABA concentrations did not differ between groups; however, in children with ASD, greater GABA concentration in the VIS was related to more efficient search. Additionally, lower VIS GABA levels were also associated with increased social impairment. Finally, we found reduced N-acetyl aspartate, total creatine, glutamate and glutamine (Glx), GABA/Glx in the rTPJ, suggestive of neuronal dysfunction in a critical network hub. Our results show that GABA concentrations in the VIS are related to efficient search in ASD, thus providing further evidence of enhanced discrimination in ASD. Autism Res 2020, 13: 550-562. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children with autism spectrum disorder (ASD) often perform better than their non-ASD peers on visual search tasks; however, it is unclear how they achieve this superior performance. Using magnetic resonance spectroscopy to measure neurochemicals in the brain, we found that the level of one, gamma-aminobutyric acid, in the visual cortex was directly related to search abilities in children with ASD. These results suggest that faster search may relate to enhanced perceptual functioning in children with ASD.

Attentional bias to fearful faces in infants at high risk for autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) and their first-degree relatives show differences from neurotypical individuals in emotional face processing. Prospective studies of infant siblings of children with ASD, a group at high risk for autism (HRA), allow researchers to examine the early emergence of these differences. This study used eye tracking to examine disengagement of attention from emotional faces (fearful, happy, neutral) at 6, 9, and 12 months in low-risk control infants (LRC) and HRA infants who received a subsequent clinical judgment of ASD (HRA+) or non-ASD (HRA-). Infants saw centrally presented faces followed by a peripheral distractor (with face remaining present). For each emotion, latency to shift to the distractor and percentage of trials with no shift were calculated. Results showed increased saccadic latency and a greater percentage of no-shift trials for fearful faces. No between-group differences were present for emotion; however, there was an interaction between age and group for disengagement latency, with HRA+ infants slower to shift at 12 months compared with the other 2 groups. Exploratory correlational analyses looking at shift biases to fearful faces alongside measures of social behavior at 12 and 18 months (from the Communication and Symbolic Behavior Scales) revealed that for HRA+ infants, 9- and 12-month fear biases were significantly related to 12- and 18-month social abilities, respectively. This work suggests that both low- and high-risk infants show biases to threat-relevant faces, and that for HRA+, differences in attention shifting emerge with age, and a stronger fear bias could potentially relate to less social difficulty. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Atypical Relationships Between Spontaneous EEG and fMRI Activity in Autism.

Autism spectrum disorders (ASDs) have been linked to atypical communication among distributed brain networks. However, despite decades of research, the exact nature of these differences between typically developing (TD) individuals and those with ASDs remains unclear. ASDs have been widely studied using resting-state neuroimaging methods, including both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). However, little is known about how fMRI and EEG measures of spontaneous brain activity are related in ASDs. In the present study, two cohorts of children and adolescents underwent resting-state EEG (n = 38 per group) or fMRI (n = 66 ASD, 57 TD), with a subset of individuals in both the EEG and fMRI cohorts (n = 17 per group). In the EEG cohort, parieto-occipital EEG alpha power was found to be reduced in ASDs. In the fMRI cohort, blood oxygen level-dependent (BOLD) power was regionally increased in right temporal regions and there was widespread overconnectivity between the thalamus and cortical regions in the ASD group relative to the TD group. Finally, multimodal analyses indicated that while TD children showed consistently positive relationships between EEG alpha power and regional BOLD power, these associations were weak or negative in ASDs. These findings suggest atypical links between alpha rhythms and regional BOLD activity in ASDs, possibly implicating neural substrates and processes that coordinate thalamocortical regulation of the alpha rhythm.

Caregiver Touch-Speech Communication and Infant Responses in 12-Month-Olds at High Risk for Autism Spectrum Disorder.

Multimodal communication may facilitate attention in infants. This study examined the presentation of caregiver touch-only and touch + speech input to 12-month-olds at high (HRA) and low risk for ASD. Findings indicated that, although both groups received a greater number of touch + speech bouts compared to touch-only bouts, the duration of overall touch that overlapped with speech was significantly greater in the HRA group. Additionally, HRA infants were less responsive to touch-only bouts compared to touch + speech bouts suggesting that their mothers may use more touch + speech communication to elicit infant responses. Nonetheless, the exact role of touch in multimodal communication directed towards infants at high risk for ASD warrants further exploration.

Dopaminergic hypo-activity and reduced theta-band power in autism spectrum disorder: A resting-state EEG study.

BACKGROUND: Prior studies using a variety of methodologies have reported inconsistent dopamine (DA) findings in individuals with autism spectrum disorder (ASD), ranging from dopaminergic hypo- to hyper-activity. Theta-band power derived from scalp-recorded electroencephalography (EEG), which may be associated with dopamine levels in frontal cortex, has also been shown to be atypical in ASD. The present study examined spontaneous eye-blink rate (EBR), an indirect, non-invasive measure of central dopaminergic activity, and theta power in children with ASD to determine: 1) whether ASD may be associated with atypical DA levels, and 2) whether dopaminergic dysfunction may be associated with aberrant theta-band activation. METHOD: Participants included thirty-two children with ASD and thirty-two age-, IQ-, and sex-matched typically developing (TD) children. Electroencephalography and eye-tracking data were acquired while participants completed an eyes-open resting-state session. Blinks were counted and EBR was determined by dividing blink frequency by session duration and theta power (4-7.5 Hz) was extracted from midline leads. RESULTS: Eye-blink rate and theta-band activity were significantly reduced in children with ASD as compared to their TD peers. For all participants, greater midline theta power was associated with increased EBR (related to higher DA levels). CONCLUSIONS: These results suggest that ASD may be associated with dopaminergic hypo-activity, and that this may contribute to atypical theta-band power. Lastly, EBR may be a useful tool to non-invasively index dopamine levels in ASD and could potentially have many clinical applications, including selecting treatment options and monitoring treatment response.