Visual processing in genetic conditions linked to autism: A behavioral study of binocular rivalry in individuals with 16p11.2 deletions and age-matched controls.

Close phenotypic characterization of individuals with genetic conditions linked to autism provides a promising approach to navigating the heterogeneity of autism spectrum conditions. The current study investigated sensory processing in individuals with a rare genetic event that is highly penetrant for autism, 16p11.2 deletions, using a well-characterized visual paradigm, binocular rivalry, which is thought to be a non-invasive index of excitatory/inhibitory balance in the visual cortex. We characterized rivalry dynamics in 45 adolescent and adult individuals (19 individuals with 16p11.2 deletions, 26 age-matched neurotypical controls). We found that binocular rivalry perceptual transition rates were significantly slower for individuals with 16p11.2 deletions, relative to controls. Importantly, these results could not be accounted for by differences in motor response latencies or perceptual decision criteria, which were matched between groups. Results should be interpreted with caution given the unmatched psychometric features between groups, such as IQ. Future studies should study visual processing in other genetic groups linked to autism beyond 16p to understand the specificity of these findings. These results highlight the importance of characterizing sensory functions in individuals with genetic alterations associated with autism.

Active visual search in naturalistic environments reflects individual differences in classic visual search performance.

Visual search is a ubiquitous activity in real-world environments. Yet, traditionally, visual search is investigated in tightly controlled paradigms, where head-restricted participants locate a minimalistic target in a cluttered array that is presented on a computer screen. Do traditional visual search tasks predict performance in naturalistic settings, where participants actively explore complex, real-world scenes? Here, we leverage advances in virtual reality technology to test the degree to which classic and naturalistic search are limited by a common factor, set size, and the degree to which individual differences in classic search behavior predict naturalistic search behavior in a large sample of individuals (N = 75). In a naturalistic search task, participants looked for an object within their environment via a combination of head-turns and eye-movements using a head-mounted display. Then, in a classic search task, participants searched for a target within a simple array of colored letters using only eye-movements. In each task, we found that participants' search performance was impacted by increases in set size-the number of items in the visual display. Critically, we observed that participants' efficiency in classic search tasks-the degree to which set size slowed performance-indeed predicted efficiency in real-world scenes. These results demonstrate that classic, computer-based visual search tasks are excellent models of active, real-world search behavior.

Brief Report: Differences in Naturalistic Attention to Real-World Scenes in Adolescents with 16p.11.2 Deletion.

Sensory differences are nearly universal in autism, but their genetic origins are poorly understood. Here, we tested how individuals with an autism-linked genotype, 16p.11.2 deletion ("16p"), attend to visual information in immersive, real-world photospheres. We monitored participants' (N = 44) gaze while they actively explored 360° scenes via headmounted virtual reality. We modeled the visually salient and semantically meaningful information in scenes and quantified the relative bottom-up vs. top-down influences on attentional deployment. We found, when compared to typically developed control (TD) participants, 16p participants' attention was less dominantly predicted by semantically meaningful scene regions, relative to visually salient regions. These results suggest that a reduction in top-down relative to bottom-up attention characterizes how individuals with 16p.11.2 deletions engage with naturalistic visual environments.

Atypical Mediofrontal Theta Oscillations Underlying Cognitive Control in Kindergarteners With Autism Spectrum Disorder.

BACKGROUND: Children with autism spectrum disorder (ASD) often exhibit deficits in cognitive control. Neuroimaging approaches have implicated disruptions to mediofrontal cortex structure and function. However, previous work is limited in testing whether young children with ASD exhibit disruptions to task-related theta oscillations thought to arise from the mediofrontal cortex. METHODS: Children with ASD (n = 43) and age- and sex-matched typically developing peers (n = 24) at kindergarten entry performed a child-friendly Go/NoGo task while 64-channel electroencephalography was recorded. Time-frequency approaches were employed to assess the magnitude of mediofrontal theta oscillations immediately after error (vs. correct) responses (early theta) as well as later emerging theta oscillations (late theta). We tested whether error-related mediofrontal theta oscillations differed as a function of diagnosis (ASD/typical) and timing (early/late theta). In addition, links to social and academic outcomes were tested. RESULTS: Overall, children showed increased theta power after error versus correct responses. Compared with typically developing children, children with ASD exhibited a selective reduction in error-related mediofrontal theta power during the late time window. There were no significant group differences for early theta power. Moreover, reduced error-related theta power during the late, but not early, time window significantly predicted poorer academic and social skills. CONCLUSIONS: Kindergarteners with ASD demonstrated a selective reduction in error-related mediofrontal theta power during a relatively late time window, which is consistent with impairments in specific cognitive processes that recruit top-down control. Targeting these particular cognitive control processes via intervention prior to school entry may promote more successful functional outcomes for children with ASD.

Brief Report: Examining Test-Retest Reliability of the Autism Diagnostic Observation Schedule (ADOS-2) Calibrated Severity Scores (CSS).

Describing the relative severity and change in autism symptoms is crucial for the appropriate characterization of clinical and research populations. The calibrated severity score (CSS) of the Autism Diagnostic Observation Schedule-2 (ADOS-2; Lord et al., 2012) was created to better describe autism symptom severity consistently across different ages and language levels. The CSS has been widely used to quantify and compare symptom severity on a 10-point scale across Modules; however, its test re-test reliability has not been studied. With 608 ADOS observations, we showed strong test re-test reliability of the CSS across all ADOS Modules. The results support the use of the ADOS CSS as a reliable tool to quantify autism symptom severity across development.

Frequency drift in MR spectroscopy at 3T.

PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

Quantifying Caregiver Change Across Early Autism Interventions Using the Measure of NDBI Strategy Implementation: Caregiver Change (MONSI-CC).

This study aimed to provide initial validity and reliability of the Measure of NDBI Strategy Implementation-Caregiver Change (MONSI-CC), a novel measure that captures changes in caregivers' implementation of NDBI strategies during early intervention. The MONSI-CC was applied to 119 observations of 43 caregiver-child dyads of preschoolers with autism spectrum disorders (ASD). The MONSI-CC showed high inter-rater and test-retest reliability and captured significant improvements in caregivers' implementation of NDBI strategies. Significant associations between improvements in caregiver NDBI implementation and improvements in the child's ASD symptoms also emerged. Our work shows promising evidence for the utility of the MONSI-CC to evaluate implementation of NDBI strategies by caregivers as a mediating and moderating factor for treatment effects on children with ASD.

Neural correlates of infant action processing relate to theory of mind in early childhood.

The mechanisms that support infant action processing are thought to be involved in the development of later social cognition. While a growing body of research demonstrates longitudinal links between action processing and explicit theory of mind (TOM), it remains unclear why this link emerges in some measures of action encoding and not others. In this paper, we recruit neural measures as a unique lens into which aspects of human infant action processing (i.e., action encoding and action execution; age 7 months) are related to preschool TOM (age 3 years; n = 31). We test whether individual differences in recruiting the sensorimotor system or attention processes during action encoding predict individual differences in TOM. Results indicate that reduced occipital alpha during action encoding predicts TOM at age 3. This finding converges with behavioral work and suggests that attentional processes involved in action encoding may support TOM. We also test whether neural processing during action execution draws on the proto-substrates of effortful control (EC). Results indicate that frontal alpha oscillatory activity during action execution predicted EC at age 3-providing strong novel evidence that infant brain activity is longitudinally linked to EC. Further, we demonstrate that EC mediates the link between the frontal alpha response and TOM. This indirect effect is specific in terms of direction, neural response, and behavior. Together, these findings converge with behavioral research and demonstrate that domain general processes show strong links to early infant action processing and TOM.

Neural dynamics of executive function in cognitively able kindergarteners with autism spectrum disorders as predictors of concurrent academic achievement.

Although electrophysiological (electroencephalography) measures of executive functions (e.g. error monitoring) have been used to predict academic achievement in typically developing children, work investigating a link between error monitoring and academic skills in children with autism spectrum disorder is limited. In this study, we employed traditional electrophysiological and advanced time-frequency methods, combined with principal component analyses, to extract neural activity related to error monitoring and tested their relations to academic achievement in cognitively able kindergarteners with autism spectrum disorder. In total, 35 cognitively able kindergarteners with autism spectrum disorder completed academic assessments and the child-friendly "Zoo Game" Go/No-go task at school entry. The Go/No-go task successfully elicited an error-related negativity and error positivity in children with autism spectrum disorder as young as 5 years at fronto-central and posterior electrode sites, respectively. We also observed increased response-related theta power during errors relative to correct trials at fronto-central sites. Both larger error positivity and theta power significantly predicted concurrent academic achievement after controlling for behavioral performance on the Zoo Game and intelligence quotient. These results suggest that the use of time-frequency electroencephalography analyses, combined with traditional event-related potential measures, may provide new opportunities to investigate neurobiological mechanisms of executive function and academic achievement in young children with autism spectrum disorder.

Variability in Autism Symptom Trajectories Using Repeated Observations From 14 to 36 Months of Age.

OBJECTIVE: This study examined variability in autism symptom trajectories in toddlers referred for possible autism spectrum disorder (ASD) who had frequent observations from 14 to 36 months of age. METHOD: In total, 912 observations of the Autism Diagnostic Observation Schedule (ADOS) were obtained from 149 children (103 with ASD) followed from 14 to 36 months of age. As a follow-up to a previous analysis of ADOS algorithm scores, a different analytic approach (Proc Traj) was implemented to identify several courses of symptom trajectories using ADOS Calibrated Severity Scores in a larger sample. Proc Traj is a statistical method that clusters individuals into separate groups based on different growth trajectories. Changes in symptom severity based on individual ADOS items also were examined. RESULTS: Trajectory analysis of overall symptom severity identified 4 clusters (non-spectrum ∼25%; worsening ∼27%; moderately-improving ∼25%; severe-persistent ∼23%). Trajectory clusters varied significantly in the proportions of confirmatory ASD diagnosis, level of baseline and final verbal and nonverbal abilities, and symptom severity. For the moderately-improving group, social communication improved, whereas restricted and repetitive behaviors were stable over time. Language and verbal and nonverbal communication improved for many children, but several social affect and restricted and repetitive behavior symptoms remained stable or worsened. CONCLUSION: Significant variability in symptom trajectories was observed among toddlers referred for possible ASD. Changes in social and restricted and repetitive behavior domain scores did not always co-occur. Similarly, item-level trajectories did not always align with trajectories of overall severity scores. These findings highlight the importance of monitoring individual symptoms within broader symptom domains when conducting repeated assessments for young children with suspected ASD.