Etiologic Evaluation of Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is clinically and etiologically heterogeneous. A causal genetic variant can be identified in approximately 20% to 25% of affected individuals with current clinical genetic testing, and all patients with an ASD diagnosis should be offered genetic etiologic evaluation. We suggest that exome sequencing with copy number variant coverage should be the first-line etiologic evaluation for ASD. Neuroimaging, neurophysiologic, metabolic, and other biochemical evaluations can provide insight into the pathophysiology of ASD but should be recommended in the appropriate clinical circumstances.

Pearls & Oy-sters: CACNA1A-Related Paroxysmal Tonic Upgaze With Ataxia Responsive to Acetazolamide.

A 9-month-old male infant was evaluated for sudden onset of paroxysmal episodes of forced, conjugate upward eye deviation. Extensive in-hospital evaluation including electrophysiology and neuroimaging studies were reassuring against seizures or a structural abnormality. Given the clinical presentation of sudden onset intermittent upward eye deviations, downbeating saccades, associated ataxia, and typical development, a clinical diagnosis of paroxysmal tonic upgaze (PTU) with ataxia was made. Targeted genetic testing of CACNA1A was performed, which revealed a variant of undetermined significance, which was later classified as a de novo pathogenic variant after protein modeling and parental testing performed. Off-label use of oral acetazolamide was prescribed, which led to dose-responsive decrease in the frequency and intensity of eye movement episodes. After 6 months of episode freedom at 2 years of age, acetazolamide was discontinued without return of episodes. Neurodevelopmental assessments revealed continued typical development. This case is presented to describe the diagnostic formulation, etiologic evaluation, and symptomatic treatment of CACNA1A-related PTU with ataxia.

Social cognition and brain morphology: implications for developmental brain dysfunction.

The social-cognitive deficits associated with several neurodevelopmental and neuropsychiatric disorders have been linked to structural and functional brain anomalies. Given the recent appreciation for quantitative approaches to behavior, in this study we examined the brain-behavior links in social cognition in healthy young adults from a quantitative approach. Twenty-two participants were administered quantitative measures of social cognition, including the social responsiveness scale (SRS), the empathizing questionnaire (EQ) and the systemizing questionnaire (SQ). Participants underwent a structural, 3-T magnetic resonance imaging (MRI) procedure that yielded both volumetric (voxel count) and asymmetry indices. Model fitting with backward elimination revealed that a combination of cortical, limbic and striatal regions accounted for significant variance in social behavior and cognitive styles that are typically associated with neurodevelopmental and neuropsychiatric disorders. Specifically, as caudate and amygdala volumes deviate from the typical R > L asymmetry, and cortical gray matter becomes more R > L asymmetrical, overall SRS and Emotion Recognition scores increase. Social Avoidance was explained by a combination of cortical gray matter, pallidum (rightward asymmetry) and caudate (deviation from rightward asymmetry). Rightward asymmetry of the pallidum was the sole predictor of Interpersonal Relationships and Repetitive Mannerisms. Increased D-scores on the EQ-SQ, an indication of greater systemizing relative to empathizing, was also explained by deviation from the typical R > L asymmetry of the caudate.These findings extend the brain-behavior links observed in neurodevelopmental disorders to the normal distribution of traits in a healthy sample.

Social cognition and neural substrates of face perception: implications for neurodevelopmental and neuropsychiatric disorders.

BACKGROUND: Social cognition is an important aspect of social behavior in humans. Social cognitive deficits are associated with neurodevelopmental and neuropsychiatric disorders. In this study we examine the neural substrates of social cognition and face processing in a group of healthy young adults to examine the neural substrates of social cognition. METHODS: Fifty-seven undergraduates completed a battery of social cognition tasks and were assessed with electroencephalography (EEG) during a face-perception task. A subset (N=22) were administered a face-perception task during functional magnetic resonance imaging. RESULTS: Variance in the N170 EEG was predicted by social attribution performance and by a quantitative measure of empathy. Neurally, face processing was more bilateral in females than in males. Variance in fMRI voxel count in the face-sensitive fusiform gyrus was predicted by quantitative measures of social behavior, including the Social Responsiveness Scale (SRS) and the Empathizing Quotient. CONCLUSIONS: When measured as a quantitative trait, social behaviors in typical and pathological populations share common neural pathways. The results highlight the importance of viewing neurodevelopmental and neuropsychiatric disorders as spectrum phenomena that may be informed by studies of the normal distribution of relevant traits in the general population.

Human preferences for symmetry: subjective experience, cognitive conflict and cortical brain activity.

This study examines the links between human perceptions, cognitive biases and neural processing of symmetrical stimuli. While preferences for symmetry have largely been examined in the context of disorders such as obsessive-compulsive disorder and autism spectrum disorders, we examine various these phenomena in non-clinical subjects and suggest that such preferences are distributed throughout the typical population as part of our cognitive and neural architecture. In Experiment 1, 82 young adults reported on the frequency of their obsessive-compulsive spectrum behaviors. Subjects also performed an emotional Stroop or variant of an Implicit Association Task (the OC-CIT) developed to assess cognitive biases for symmetry. Data not only reveal that subjects evidence a cognitive conflict when asked to match images of positive affect with asymmetrical stimuli, and disgust with symmetry, but also that their slowed reaction times when asked to do so were predicted by reports of OC behavior, particularly checking behavior. In Experiment 2, 26 participants were administered an oddball Event-Related Potential task specifically designed to assess sensitivity to symmetry as well as the OC-CIT. These data revealed that reaction times on the OC-CIT were strongly predicted by frontal electrode sites indicating faster processing of an asymmetrical stimulus (unparallel lines) relative to a symmetrical stimulus (parallel lines). The results point to an overall cognitive bias linking disgust with asymmetry and suggest that such cognitive biases are reflected in neural responses to symmetrical/asymmetrical stimuli.