Social cognitive skills groups increase medial prefrontal cortex activity in children with autism spectrum disorder.

Few studies have examined the neural mechanisms of change following social skills interventions for children with autism spectrum disorder (ASD). This study examined the neural effects of social cognitive skills groups during functional MRI (fMRI) tasks of irony comprehension and eye gaze processing in school-aged children with ASD. Verbally fluent children (ages 8-11) were randomized to social cognitive skills groups or facilitated play comparison groups. Behavioral assessments and fMRI scans were obtained at baseline and endpoint (12 weeks). During fMRI, children completed two separate tasks to engage social cognition circuitry: comprehension of potentially ironic scenarios (n = 34) and viewing emotionally expressive faces with direct or averted gaze (n = 24). Whole-brain analyses were conducted to examine neural changes following treatment. Regression analyses were also conducted to explore the relationship between neural and behavioral changes. When comparing the two groups directly, the social cognitive skills group showed greater increases in activity in the medial prefrontal cortex (mPFC), implicated in theory of mind, relative to the comparison group for both irony comprehension and gaze processing tasks. Increased mPFC activity during the irony task was associated with improvement in social functioning on the Social Responsiveness Scale across both groups. Findings indicate that social cognitive skills interventions may increase activity in regions associated with social cognition and mentalizing abilities. LAY SUMMARY: Social skills groups are a common intervention for school-aged children with ASD. However, few studies have examined the neural response to social skills groups in school-aged children with ASD. Here, we report on a study evaluating neural outcomes from an empirically supported social cognitive skills training curriculum using fMRI. This study seeks to understand the effects of targeting emotion recognition and theory of mind on the brain circuitry involved in social cognition in verbally fluent children ages 8-11. Results indicate increased neural activity in the mPFC, a region considered to be a central hub of the "social brain," in children randomized to social cognitive skills groups relative to a comparison group that received a high-quality, child-directed play approach. In addition, increased activation in the mPFC during an irony comprehension task was associated with gains in social functioning across both groups from pre- to post-treatment. This is the first fMRI study of social skills treatment outcomes following a randomized trial with an active treatment condition in school-aged children with ASD.

Erratum to: Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome.

[This corrects the article DOI: 10.1186/s11689-016-9138-9.].

Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder caused by deletion or mutation in the SHANK3 gene, is one of the more common single-locus causes of autism spectrum disorder (ASD). PMS is characterized by global developmental delay, hypotonia, delayed or absent speech, increased risk of seizures, and minor dysmorphic features. Impairments in language and communication are one of the most consistent characteristics of PMS. Although there is considerable overlap in the social communicative deficits associated with PMS and ASD, there is a dearth of data on underlying abnormalities at the level of neural systems in PMS. No controlled neuroimaging studies of PMS have been reported to date. The goal of this study was to examine the neural circuitry supporting the perception of auditory communicative signals in children with PMS as compared to idiopathic ASD (iASD). METHODS: Eleven children with PMS and nine comparison children with iASD were scanned using functional magnetic resonance imaging (fMRI) under light sedation. The fMRI paradigm was a previously validated passive auditory task, which presented communicative (e.g., speech, sounds of agreement, disgust) and non-communicative vocalizations (e.g., sneezing, coughing, yawning). RESULTS: Previous research has shown that the superior temporal gyrus (STG) responds selectively to communicative vocal signals in typically developing children and adults. Here, selective activity for communicative relative to non-communicative vocalizations was detected in the right STG in the PMS group, but not in the iASD group. The PMS group also showed preferential activity for communicative vocalizations in a range of other brain regions associated with social cognition, such as the medial prefrontal cortex (MPFC), insula, and inferior frontal gyrus. Interestingly, better orienting toward social sounds was positively correlated with selective activity in the STG and other "social brain" regions, including the MPFC, in the PMS group. Finally, selective MPFC activity for communicative sounds was associated with receptive language level in the PMS group and expressive language in the iASD group. CONCLUSIONS: Despite shared behavioral features, children with PMS differed from children with iASD in their neural response to communicative vocal sounds and showed relative strengths in this area. Furthermore, the relationship between clinical characteristics and neural selectivity also differed between the two groups, suggesting that shared ASD features may partially reflect different neurofunctional abnormalities due to differing etiologies.

Randomized comparative trial of a social cognitive skills group for children with autism spectrum disorder.

OBJECTIVE: This study evaluated the efficacy of a targeted social skills training group in school-aged children with autism spectrum disorder (ASD). The intervention, Seaver-NETT (Nonverbal communication, Emotion recognition, and Theory of mind Training), is a 12-session cognitive-behavioral intervention (CBI) for verbal, school-aged children targeting ASD-specific social behavioral impairments. METHOD: Sixty-nine children with ASD, 8 to 11 years of age, with verbal IQs greater than 70, participated in a randomized comparative trial to examine the efficacy of NETT relative to a facilitated play group. Treatment outcomes included caregiver reports of social behavior and neuropsychological assessments of social cognition conducted by blinded raters. Outcomes were collected at baseline, endpoint, and 3 months posttreatment. RESULTS: Significant improvements were found on social behavior outcomes such as nonverbal communication, empathic responding, and social relations in the NETT condition relative to the active control at endpoint. Verbal IQ moderated the interaction effect on social behavior, with higher verbal IQ associated with improvements in the CBI condition. No significant improvements were found on social cognitive outcomes. No significant group differences were found at 3-month follow-up conducted with approximately half the sample (n = 34). CONCLUSION: These data indicate that targeted CBI social skills groups such as NETT improve social communication deficits in verbal, school-aged children with ASD. The moderating effects of high verbal IQ suggest a need to consider participant and treatment characteristics associated with outcomes in future studies. Clinical trial registration information-Neural and Behavioral Outcomes of Social Skills Groups in Children With Autism Spectrum Disorder; https://clinicaltrials.gov; NCT01190917.

Metabolic mapping of deep brain structures and associations with symptomatology in autism spectrum disorders.

Structural neuroimaging studies in autism report atypical volume in deep brain structures which are related to symptomatology. Little is known about metabolic changes in these regions, and how they vary with age and sex, and/or relate to clinical behaviors. Using magnetic resonance spectroscopy we measured N-acetylaspartate, choline, creatine, myoinositol and glutamate in the caudate, putamen, and thalamus of 20 children with autism and 16 typically developing controls (7-18 years). Relative to controls, individuals with autism had elevated glutamate/creatine in the putamen. In addition, both groups showed age-related increases in glutamate in this region. Boys, relative to girls had increased choline/creatine in the thalamus. Lastly, there were correlations between glutamate, choline, and myoinositol in all three regions, and behavioral scores in the ASD group. These findings suggest changes in deep gray matter neurochemistry, which are sensitive to diagnosis, age and sex, and are associated with behavioral differences.

Neural correlates of inhibition of socially relevant stimuli in adults with autism spectrum disorder.

Adults with autism spectrum disorder (ASD) can demonstrate difficulties with inhibiting inappropriate social responses. Presently, little research has utilized socially relevant stimuli to explore the modulatory effects of emotion on cognitive control in this population. To assess neural mechanisms of inhibiting social stimuli, we presented images of happy or sad facial expressions in a Go/NoGo task to unmedicated adults with ASD and to controls during functional magnetic resonance imaging (fMRI). Groups did not differ on behavioral measures. Brain activation in response to NoGo vs. Go trials revealed differing regional patterns of activation within groups. Controls recruited brain regions involved in inhibition (dorsal- [DLPFC] and ventro-lateral prefrontal cortices [VLPFC], anterior cingulate cortex [ACC]), response suppression (parietal lobe), interoceptive awareness (insula), and also the fusiform and middle temporal gyri. Adults with ASD only recruited the VLPFC and right fusiform gyrus, and weakly activated the ACC and insula. Between-group comparisons indicated that controls activated the DLPFC, while adults with ASD relied on the VLPFC and the fusiform gyrus to inhibit responses. Adults with ASD may have relied more on visual association cortex, possibly as a means of recruiting additional neural processes that could act as a compensatory mechanism.

Effects of age and symptomatology on cortical thickness in autism spectrum disorders.

Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours.

The effect of diagnosis, age, and symptom severity on cortical surface area in the cingulate cortex and insula in autism spectrum disorders.

Functional activity in the anterior cingulate cortex and insula has been reported to be abnormal during social tasks in autism spectrum disorders. However, few studies have examined surface morphometry in these regions and how this may be related to autism spectrum disorder symptomatology. In this study, 27 individuals with autism spectrum disorders and 25 controls between the ages of 7 to 39 years underwent structural magnetic resonance imaging. Our primary analysis examined differences in surface area in the cingulate and insula, between individuals with and without autism spectrum disorders, as well as age-related changes and associations with social impairments. Surface area in the right cingulate was significantly different between groups and decreased more rapidly with age in autism spectrum disorder participants. In addition, greater surface area in the insula and isthmus was associated with poorer social behaviors. Results suggest atypical surface morphometry in brain regions involved in social function, which appeared to be related to poorer social ability scores.

Advancing paternal age and simplex autism.

De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling for maternal age, results support a significant interaction of linear paternal age and sex of the child on simplex family type. Female ASD cases were significantly more likely to be simplex as paternal age increased, but the increase for males was not significant. Findings suggest that ASD arising from non-familial, de novo events may be far less prominent in males than in females, even if more prevalent in males, due to the substantially larger number of male cases attributable to other, more strongly male-biased risk factors.

Endocrine disruptors and childhood social impairment.

Prenatal exposure to endocrine disruptors has the potential to impact early brain development. Neurodevelopmental toxicity in utero may manifest as psychosocial deficits later in childhood. This study investigates prenatal exposure to two ubiquitous endocrine disruptors, the phthalate esters and bisphenol A (BPA), and social behavior in a sample of adolescent inner-city children. Third trimester urines of women enrolled in the Mount Sinai Children's Environmental Health Study between 1998 and 2002 (n=404) were analyzed for phthalate metabolites and BPA. Mother-child pairs were asked to return for a follow-up assessment when the child was between the ages of 7 and 9 years. At this visit, mothers completed the Social Responsiveness Scale (SRS) (n=137), a quantitative scale for measuring the severity of social impairment related to Autistic Spectrum Disorders (ASD) in the general population. In adjusted general linear models increasing log-transformed low molecular weight (LMW) phthalate metabolite concentrations were associated with greater social deficits (ß=1.53, 95% CI 0.25-2.8). Among the subscales, LMWP were also associated with poorer Social Cognition (ß=1.40, 95% CI 0.1-2.7); Social Communication (ß=1.86, 95% CI 0.5-3.2); and Social Awareness (ß=1.25, 95% CI 0.1-2.4), but not for Autistic Mannerisms or Social Motivation. No significant association with BPA was found (ß=1.18, 95% CI -0.75, 3.11). Prenatal phthalate exposure was associated with childhood social impairment in a multiethnic urban population. Even mild degrees of impaired social functioning in otherwise healthy individuals can have very important adverse effects over a child's lifetime. These results extend our previous finding of atypical neonatal and early childhood behaviors in relation to prenatal phthalate exposure.