De novo SCN2A splice site mutation in a boy with Autism spectrum disorder.

BACKGROUND: SCN2A is a gene that codes for the alpha subunit of voltage-gated, type II sodium channels, and is highly expressed in the brain. Sodium channel disruptions, such as mutations in SCN2A, may play an important role in psychiatric disorders. Recently, de novo SCN2A mutations in autism spectrum disorder (ASD) have been identified. The current study characterizes a de novo splice site mutation in SCN2A that alters mRNA and protein products. CASE PRESENTATION: We describe results from clinical and genetic characterizations of a seven-year-old boy with ASD. Psychiatric interview and gold standard autism diagnostic instruments (ADOS and ADI-R) were used to confirm ASD diagnosis, in addition to performing standardized cognitive and adaptive functioning assessments (Leiter-R and Vineland Adaptive Behavior Scale), and sensory reactivity assessments (Sensory Profile and Sensory Processing Scales). Genetic testing by whole exome sequencing revealed four de novo events, including a splice site mutation c.476 + 1G > A in SCN2A, a missense mutation (c.2263G > A) causing a p.V755I change in the TLE1 gene, and two synonymous mutations (c.2943A > G in the BUB1 gene, and c.1254 T > A in C10orf68 gene). The de novo SCN2A splice site mutation produced a stop codon 10 amino acids downstream, possibly resulting in a truncated protein and/or a nonsense-mediated mRNA decay. The participant met new DSM-5 criteria for ASD, presenting with social and communication impairment, repetitive behaviors, and sensory reactivity issues. The participant's adaptive and cognitive skills fell in the low range of functioning. CONCLUSION: This report indicates that a splice site mutation in SCN2A might be contributing to the risk of ASD. Describing the specific phenotype associated with SCN2A mutations might help to reduce heterogeneity seen in ASD.

Altered cingulum bundle microstructure in autism spectrum disorder.

OBJECTIVE: Here, we examined the cingulum bundle, a long-range white matter tract mediating dorsal limbic connectivity, using diffusion tensor imaging (DTI) tractography, in children and adolescents with autism spectrum disorder (ASD) versus controls. We hypothesised that cingulum bundle microstructure would be altered in ASD, based on evidence implicating abnormal white matter connectivity in this disorder. METHODS: DTI data were acquired for 19 ASD participants (IQ ⩾ 70; 7-18 years; mean = 12.4 ± 3.1) and 16 age-matched controls (7-18 years; mean = 12.3 ± 3.6) on a 3 T magnetic resonance imaging system. Deterministic tractography was used to isolate the cingulum bundle. Left and right cingulum bundles were examined for differences in several DTI metrics in ASD children/adolescents versus controls, including: fractional anisotropy (FA), mean, axial, and radial diffusivity. RESULTS: Significant age × group interaction effects were found for all DTI metrics (mean diffusivity: F 1,28 = 9.5, p = 0.005, radial diffusivity: F 1,28 = 7.8, p = 0.009, axial diffusivity: F 1,28 = 5.2, p = 0.03, FA: F 1,28 = 4.4, p = 0.04). Interaction effects were driven by increases in cingulum bundle diffusivity (mean, radial, and axial diffusivity), and decreased FA, in younger ASD participants within our sample versus controls. CONCLUSION: Our results point to immature microstructural organisation of the cingulum bundle in ASD, particularly during the early years of life, with implications for limbic network synchronisation and complex socio-emotional performance.

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.

Social visual attentional engagement and memory in Phelan-McDermid syndrome and autism spectrum disorder: a pilot eye tracking study.

BACKGROUND: The current study used eye tracking to investigate attention and recognition memory in Phelan-McDermid syndrome (PMS), a rare genetic disorder characterized by intellectual disability, motor delays, and a high likelihood of comorbid autism spectrum disorder (ASD). Social deficits represent a core feature of ASD, including decreased propensity to orient to or show preference for social stimuli. METHODS: We used a visual paired-comparison task with both social and non-social images, assessing looking behavior to a novel image versus a previously viewed familiar image to characterize social attention and recognition memory in PMS (n = 22), idiopathic ASD (iASD, n = 38), and typically developing (TD) controls (n = 26). The idiopathic ASD cohort was divided into subgroups with intellectual disabilities (ID; developmental quotient < 70) and without (developmental quotient > 70) and the PMS group into those with and without a co-morbid ASD diagnosis. RESULTS: On measures of attention, the PMS group with a comorbid ASD diagnosis spent less time viewing the social images compared to non-social images; the rate of looking back and forth between images was lowest in the iASD with ID group. Furthermore, while all groups demonstrated intact recognition memory when novel non-social stimuli were initially presented (pre-switch), participants with PMS showed no preference during the post-switch memory presentation. In iASD, the group without ID, but not the group with ID, showed a novelty preference for social stimuli. Across indices, individuals with PMS and ASD performed more similarly to PMS without ASD and less similarly to the iASD group. CONCLUSION: These findings demonstrate further evidence of differences in attention and memory for social stimuli in ASD and provide contrasts between iASD and PMS.

Reduced engagement of visual attention in children with autism spectrum disorder.

LAY ABSTRACT: Limited eye contact and difficulty tracking where others are looking are common in people with autism spectrum disorder. It is unclear, however, whether these are specifically social differences; it is possible that they are a result of broader alterations in engaging and disengaging visual attention. We used eye-tracking technology with children with autism spectrum disorder (n = 35) and typical development (n = 32), showing them both social and nonsocial imaging to test their visual attention. Children with autism spectrum disorder had a significant difference in how long it took them to look from an image in the middle to one on the side, depending on whether the middle image stayed on the screen or flashed off before the one on the side appeared. This difference was present for both social and nonsocial images, and was related to cognitive ability for only the children with autism spectrum disorder. Our findings suggest that children with autism spectrum disorder have differences in general processes of engaging visual attention that are not specifically social in nature, and that these processes may relate to cognitive ability in autism spectrum disorder. Affected processes of visual engagement in autism spectrum disorder may contribute to symptoms like reduced eye contact, but social-specific symptoms of autism spectrum disorder likely do not stem from reduced visual engagement alone.

Brief Report: A Job-Based Social Skills Program (JOBSS) for Adults with Autism Spectrum Disorder: A Pilot Randomized Controlled Trial.

Adults with autism spectrum disorder (ASD) have low employment rates; even those who are employed have low wages and limited hours. This study evaluated the effectiveness of the Job-Based Social Skills (JOBSS) curriculum, a manualized, 15-week, group-delivered intervention for adults with ASD. The intervention aimed to increase social-pragmatic skills necessary to obtain and maintain employment. Twenty-two adults were randomly assigned to either JOBSS intervention or wait-list control groups. Results showed significant improvement in social cognition, as reported by caregivers, among JOBSS group participants compared to wait-list control participants. Forty-five percent of intervention participants gained employment in the six months following participation. This curriculum has potential to improve social skills of adults with ASD, thereby increasing successful employment.

Neurological considerations: autism and Parkinson's disease.

Within the spectrum of disorders that manifest obsessive-compulsive (OC) features lies a sub-cluster of neurological conditions. Autism and Parkinson's disease (PD) are examples of two such neurological disorders that seem quite dissimilar on the surface. Yet, both conditions can include repetitive behaviors of a compulsive-impulsive nature. Furthermore, while autism and PD differ in other associated symptom domains that shape the course of each disorder, both disorders share some phenomenology in the core domain of repetitive behaviors and involve basal ganglia and frontal lobe dysfunction, similar to OC disorder (OCD). Accordingly, examination of the similarities and differences between autism and PD may provide insight into the pathophysiology and treatment of OC spectrum disorders. The current review focuses on the phenomenology, comorbidity, course of illness, family history, brain circuitry, and treatment of autism and PD, as they relate to OCD and OC spectrum disturbances.

Reading affect in the face and voice: neural correlates of interpreting communicative intent in children and adolescents with autism spectrum disorders.

CONTEXT: Understanding a speaker's communicative intent in everyday interactions is likely to draw on cues such as facial expression and tone of voice. Prior research has shown that individuals with autism spectrum disorders (ASD) show reduced activity in brain regions that respond selectively to the face and voice. However, there is also evidence that activity in key regions can be increased if task demands allow for explicit processing of emotion. OBJECTIVES: To examine the neural circuitry underlying impairments in interpreting communicative intentions in ASD using irony comprehension as a test case, and to determine whether explicit instructions to attend to facial expression and tone of voice will elicit more normative patterns of brain activity. DESIGN, SETTING, AND PARTICIPANTS: Eighteen boys with ASD (aged 7-17 years, full-scale IQ >70) and 18 typically developing (TD) boys underwent functional magnetic resonance imaging at the Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles. MAIN OUTCOME MEASURES: Blood oxygenation level-dependent brain activity during the presentation of short scenarios involving irony. Behavioral performance (accuracy and response time) was also recorded. RESULTS: Reduced activity in the medial prefrontal cortex and right superior temporal gyrus was observed in children with ASD relative to TD children during the perception of potentially ironic vs control scenarios. Importantly, a significant group x condition interaction in the medial prefrontal cortex showed that activity was modulated by explicit instructions to attend to facial expression and tone of voice only in the ASD group. Finally, medial prefrontal cortex activity was inversely related to symptom severity in children with ASD such that children with greater social impairment showed less activity in this region. CONCLUSIONS: Explicit instructions to attend to facial expression and tone of voice can elicit increased activity in the medial prefrontal cortex, part of a network important for understanding the intentions of others, in children with ASD. These findings suggest a strategy for future intervention research.

Frontal contributions to face processing differences in autism: evidence from fMRI of inverted face processing.

Functional neuroimaging studies of face processing deficits in autism have typically focused on visual processing regions, such as the fusiform face area (FFA), which have shown reduced activity in autism spectrum disorders (ASD), though inconsistently. We recently reported reduced activity in the inferior frontal region in ASD, implicating impaired mirror-neuron systems during face processing. In the present study, we used fMRI during a face processing task in which subjects had to match faces presented in the upright versus inverted position. Typically developing (TD) children showed a classic behavioral inversion effect, increased reaction time for inverted faces, while this effect was significantly reduced in ASD subjects. The fMRI data showed similar responses in the fusiform face area for ASD and TD children, with both groups demonstrating increased activation for inverted faces. However, the groups did differ in several brain regions implicated in social cognition, particularly prefrontal cortex and amygdala. These data suggest that the behavioral differences in processing upright versus inverted faces for TD children are related not to visual information processing but to the social significance of the stimuli. Our results are consistent with other recent studies implicating frontal and limbic dysfunction during face processing in autism.

Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations.

Background: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by psychiatric and neurological features. Most reported cases are caused by 22q13.3 deletions, leading to SHANK3 haploinsufficiency, but also usually encompassing many other genes. While the number of point mutations identified in SHANK3 has increased in recent years due to large-scale sequencing studies, systematic studies describing the phenotype of individuals harboring such mutations are lacking. Methods: We provide detailed clinical and genetic data on 17 individuals carrying mutations in SHANK3. We also review 60 previously reported patients with pathogenic or likely pathogenic SHANK3 variants, often lacking detailed phenotypic information. Results: SHANK3 mutations in our cohort and in previously reported cases were distributed throughout the protein; the majority were truncating and all were compatible with de novo inheritance. Despite substantial allelic heterogeneity, four variants were recurrent (p.Leu1142Valfs*153, p.Ala1227Glyfs*69, p.Arg1255Leufs*25, and c.2265+1G>A), suggesting that these are hotspots for de novo mutations. All individuals studied had intellectual disability, and autism spectrum disorder was prevalent (73%). Severe speech deficits were common, but in contrast to individuals with 22q13.3 deletions, the majority developed single words, including 41% with at least phrase speech. Other common findings were consistent with reports among individuals with 22q13.3 deletions, including hypotonia, motor skill deficits, regression, seizures, brain abnormalities, mild dysmorphic features, and feeding and gastrointestinal problems. Conclusions: Haploinsufficiency of SHANK3 resulting from point mutations is sufficient to cause a broad range of features associated with PMS. Our findings expand the molecular and phenotypic spectrum of PMS caused by SHANK3 point mutations and suggest that, in general, speech impairment and motor deficits are more severe in the case of deletions. In contrast, renal abnormalities associated with 22q13.3 deletions do not appear to be related to the loss of SHANK3.

Neural basis of irony comprehension in children with autism: the role of prosody and context.

While individuals with autism spectrum disorders (ASD) are typically impaired in interpreting the communicative intent of others, little is known about the neural bases of higher-level pragmatic impairments. Here, we used functional MRI (fMRI) to examine the neural circuitry underlying deficits in understanding irony in high-functioning children with ASD. Participants listened to short scenarios and decided whether the speaker was sincere or ironic. Three types of scenarios were used in which we varied the information available to guide this decision. Scenarios included (i) both knowledge of the event outcome and strong prosodic cues (sincere or sarcastic intonation), (ii) prosodic cues only or (iii) knowledge of the event outcome only. Although children with ASD performed well above chance, they were less accurate than typically developing (TD) children at interpreting the communicative intent behind a potentially ironic remark, particularly with regard to taking advantage of available contextual information. In contrast to prior research showing hypoactivation of regions involved in understanding the mental states of others, children with ASD showed significantly greater activity than TD children in the right inferior frontal gyrus (IFG) as well as in bilateral temporal regions. Increased activity in the ASD group fell within the network recruited in the TD group and may reflect more effortful processing needed to interpret the intended meaning of an utterance. These results confirm that children with ASD have difficulty interpreting the communicative intent of others and suggest that these individuals can recruit regions activated as part of the normative neural circuitry when task demands require explicit attention to socially relevant cues.

A clinician-administered observation and corresponding caregiver interview capturing DSM-5 sensory reactivity symptoms in children with ASD.

BACKGROUND: Sensory reactivity is a new criterion for autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). However, there is no consensus on how to reliably measure sensory reactivity, particularly in minimally verbal individuals. The current study is an initial validation of the Sensory Assessment for Neurodevelopmental Disorders (SAND), a novel clinician-administered observation and corresponding caregiver interview that captures sensory symptoms based on DSM-5 criteria for ASD. METHODS: Eighty children between the ages of 2 and 12 participated in this study; 44 children with ASD and 36 typically developing (TD) children. Sensory reactivity symptoms were measured using the SAND and the already validated Short Sensory Profile (SSP). Initial psychometric properties of the SAND were examined including reliability, validity, sensitivity and specificity. RESULTS: Children with ASD showed significantly more sensory reactivity symptoms compared to TD children across sensory domains (visual, tactile, and auditory) and within sensory subtypes (hyperreactivity, hyporeactivity and seeking). The SAND showed strong internal consistency, inter-rater reliability and test-retest reliability, high sensitivity (95.5%) and specificity (91.7%), and strong convergent validity with the SSP. SIGNIFICANCE: The SAND provides a novel method to characterize sensory reactivity symptoms based on DSM-5 criteria for ASD. This is the first known sensory assessment that combines a clinician-administered observation and caregiver interview to optimally capture sensory phenotypes characteristic of individuals with neurodevelopmental disorders. The SAND offers a beneficial new tool for both research and clinical purposes and has the potential to meaningfully enhance gold-standard assessment of ASD. Autism Res 2017, 10: 1133-1140. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder.

Phelan-McDermid syndrome (PMS) is a single-locus cause of developmental delay, autism spectrum disorder, and minimal verbal abilities. There is an urgent need to identify objective outcome measures of expressive language for use in this and other minimally verbal populations. One potential tool is an automated language processor called Language ENvironment Analysis (LENA). LENA was used to obtain over 542 h of audio in 18 children with PMS. LENA performance was adequate in a subset of children with PMS, specifically younger children and those with fewer stereotypic vocalizations. One LENA-derived language measure, Vocalization Ratio, had improved accuracy in this sample and may represent a novel expressive language measure for use in severely affected populations.

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

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

Rapid and Objective Assessment of Neural Function in Autism Spectrum Disorder Using Transient Visual Evoked Potentials.

OBJECTIVE: There is a critical need to identify biomarkers and objective outcome measures that can be used to understand underlying neural mechanisms in autism spectrum disorder (ASD). Visual evoked potentials (VEPs) offer a noninvasive technique to evaluate the functional integrity of neural mechanisms, specifically visual pathways, while probing for disease pathophysiology. METHODS: Transient VEPs (tVEPs) were obtained from 96 unmedicated children, including 37 children with ASD, 36 typically developing (TD) children, and 23 unaffected siblings (SIBS). A conventional contrast-reversing checkerboard condition was compared to a novel short-duration condition, which was developed to enable objective data collection from severely affected populations who are often excluded from electroencephalographic (EEG) studies. RESULTS: Children with ASD showed significantly smaller amplitudes compared to TD children at two of the earliest critical VEP components, P60-N75 and N75-P100. SIBS showed intermediate responses relative to ASD and TD groups. There were no group differences in response latency. Frequency band analyses indicated significantly weaker responses for the ASD group in bands encompassing gamma-wave activity. Ninety-two percent of children with ASD were able to complete the short-duration condition compared to 68% for the standard condition. CONCLUSIONS: The current study establishes the utility of a short-duration tVEP test for use in children at varying levels of functioning and describes neural abnormalities in children with idiopathic ASD. Implications for excitatory/inhibitory balance as well as the potential application of VEP for use in clinical trials are discussed.

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.

Measuring Sensory Reactivity in Autism Spectrum Disorder: Application and Simplification of a Clinician-Administered Sensory Observation Scale.

Sensory reactivity is a new DSM-5 criterion for autism spectrum disorder (ASD). The current study aims to validate a clinician-administered sensory observation in ASD, the Sensory Processing Scale Assessment (SPS). The SPS and the Short Sensory Profile (SSP) parent-report were used to measure sensory reactivity in children with ASD (n = 35) and typically developing children (n = 27). Sixty-five percent of children with ASD displayed sensory reactivity symptoms on the SPS and 81.1 % on the SSP. SPS scores significantly predicted SSP scores. We next identified the five SPS tasks that best differentiated groups. Our results indicate that a combination of parent-report and at least the five most differentiating observational tasks may be most sensitive in identifying the presence of sensory reactivity issues.

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.

Erratum: A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome.

[This corrects the article DOI: 10.1186/2040-2392-5-54.].

Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder.

OBJECTIVE: To examine the neural basis of impairments in interpreting facial emotions in children and adolescents with autism spectrum disorders (ASD). METHOD: Twelve children and adolescents with ASD and 12 typically developing (TD) controls matched faces by emotion and assigned a label to facial expressions while undergoing functional magnetic resonance imaging. RESULTS: Both groups engaged similar neural networks during facial emotion processing, including activity in the fusiform gyrus (FG) and prefrontal cortex. However, between-group analyses in regions of interest revealed that when matching facial expressions, the ASD group showed significantly less activity than the TD group in the FG, but reliably greater activity in the precuneus. During the labeling of facial emotions, no between-group differences were observed at the behavioral or neural level. Furthermore, activity in the amygdala was moderated by task demands in the TD group but not in the ASD group. CONCLUSIONS: These findings suggest that children and adolescents with ASD in part recruit different neural networks and rely on different strategies when processing facial emotions. High-functioning individuals with ASD may be relatively unimpaired in the cognitive assessment of basic emotions, yet still show differences in the automatic processing of facial expressions.