Background: Strong evidence from twin and family studies suggests that the genetic liability to autism may be expressed through personality and language characteristics qualitatively similar, but ...more subtly expressed than those defining the full syndrome. This study examined behavioral features of this ‘broad autism phenotype’ (BAP) in relation to performance on a measure of social‐cognition in an attempt to tease out this complex clinical picture and identify markers of underlying neuropsychological systems of genetic significance to autism. We hypothesized that mild social‐cognitive impairment would be associated with clinically defined social characteristics of the BAP (aloof personality style, lower quality social relationships, and impaired pragmatic language use).
Method: Forty‐eight parents of individuals with autism (13 of whom were identified as ‘aloof’), and 22 control parents, were administered the ‘Eyes Test’, a social‐cognitive measure that taps the ability to read complex psychological states from viewing only the eye region of faces.
Results: Whereas social‐cognitive ability was unimpaired among parents of autistic children in general, the subgroup of parents defined as ‘aloof’ displayed significant social‐cognitive deficits on the ‘Eyes Test’. Impaired social‐cognitive ability was associated with low quality of friendships and problems with pragmatic language use, associations which mirror those documented in autism. Conclusions: Findings suggest that social‐cognitive impairments co‐segregate with conceptually related personality, social, and language features that constitute the BAP, and point towards performance on the Eyes Test as a genetically meaningful endophenotype.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Active contour segmentation and its robust implementation using level set methods are well-established theoretical approaches that have been studied thoroughly in the image analysis literature. ...Despite the existence of these powerful segmentation methods, the needs of clinical research continue to be fulfilled, to a large extent, using slice-by-slice manual tracing. To bridge the gap between methodological advances and clinical routine, we developed an open source application called ITK-SNAP, which is intended to make level set segmentation easily accessible to a wide range of users, including those with little or no mathematical expertise. This paper describes the methods and software engineering philosophy behind this new tool and provides the results of validation experiments performed in the context of an ongoing child autism neuroimaging study. The validation establishes SNAP intrarater and interrater reliability and overlap error statistics for the caudate nucleus and finds that SNAP is a highly reliable and efficient alternative to manual tracing. Analogous results for lateral ventricle segmentation are provided.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors that typically emerge by 24 months of age. To develop effective early ...interventions that can potentially ameliorate the defining deficits of ASD and improve long-term outcomes, early detection is essential. Using prospective neuroimaging of 59 6-month-old infants with a high familial risk for ASD, we show that functional connectivity magnetic resonance imaging correctly identified which individual children would receive a research clinical best-estimate diagnosis of ASD at 24 months of age. Functional brain connections were defined in 6-month-old infants that correlated with 24-month scores on measures of social behavior, language, motor development, and repetitive behavior, which are all features common to the diagnosis of ASD. A fully cross-validated machine learning algorithm applied at age 6 months had a positive predictive value of 100% 95% confidence interval (CI), 62.9 to 100, correctly predicting 9 of 11 infants who received a diagnosis of ASD at 24 months (sensitivity, 81.8%; 95% CI, 47.8 to 96.8). All 48 6-month-old infants who were not diagnosed with ASD were correctly classified specificity, 100% (95% CI, 90.8 to 100); negative predictive value, 96.0% (95% CI, 85.1 to 99.3). These findings have clinical implications for early risk assessment and the feasibility of developing early preventative interventions for ASD.
Abstract Schizophrenia and autism both feature significant impairments in social cognition and social functioning, but the specificity and mechanisms of these deficits remain unknown. Recent research ...suggests that social cognitive deficits in both disorders may arise from dysfunctions in the neural systems that underlie social cognition. We explored the neural activation of discrete brain regions implicated in social cognitive and face processing in schizophrenia subgroups and autism spectrum disorders during complex social judgments of faces. Twelve individuals with autism spectrum disorders (ASD), 12 paranoid individuals with schizophrenia (P-SCZ), 12 non-paranoid individuals with schizophrenia (NP-SCZ), and 12 non-clinical healthy controls participated in this cross sectional study. Neural activation, as indexed by blood oxygenation level dependent (BOLD) contrast, was measured in a priori regions of interest while individuals rated faces for trustworthiness. All groups showed significant activation of a social cognitive network including the amygdala, fusiform face area (FFA), superior temporal sulcus (STS), and ventrolateral prefrontal cortex (VLPFC) while completing a task of complex social cognition (i.e. trustworthiness judgments). ASD and P-SCZ individuals showed significantly reduced neural activation in the right amygdala, FFA, and left VLPFC as compared to controls and in the left VLPFC as compared to NP-SCZ individuals during this task. These findings lend support to models hypothesizing well-defined neural substrates of social cognition and suggest a specific neural mechanism that may underlie social cognitive impairments in both autism and paranoid schizophrenia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective: To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared with a comparison group (controls) and a group with idiopathic autism. Method: The study ...included 53 boys 18 to 42 months of age with FXS, 68 boys with idiopathic autism (autism spectrum disorder), and a comparison group of 50 typically developing and developmentally delayed controls. Structural brain volumes were examined using magnetic resonance imaging across two time points, at 2 to 3 and again at 4 to 5 years of age, and total brain volumes and regional (lobar) tissue volumes were examined. In addition, a selected group of subcortical structures implicated in the behavioral features of FXS (e.g., basal ganglia, hippocampus, amygdala) was studied. Results: Children with FXS had larger global brain volumes compared with controls but were not different than children with idiopathic autism, and the rate of brain growth from 2 to 5 years of age paralleled that seen in controls. In contrast to children with idiopathic autism who had generalized cortical lobe enlargement, children with FXS showed specific enlargement in the temporal lobe white matter, cerebellar gray matter, and caudate nucleus, but a significantly smaller amygdala. Conclusions: This structural longitudinal magnetic resonance imaging study of preschoolers with FXS observed generalized brain overgrowth in children with FXS compared with controls, evident at age 2 and maintained across ages 4 to 5. In addition, different patterns of brain growth that distinguished boys with FXS from boys with idiopathic autism were found. (Contains 3 figures and 7 tables.)
Specific differences in visual orienting, critical in social-cognitive development, are associated with differences in white matter microstructure of the splenium.
ObjectiveThe authors sought to ...determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors.MethodData were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low-risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal pathways and the splenium and genu of the corpus callosum.ResultsVisual orienting latencies were longer in 7-month-old infants who expressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD.ConclusionsFlexibly and efficiently orienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis.
Background
Atypical sensory responsivity and sensory interests are now included in the DSM 5 diagnostic criteria for autism spectrum disorder (ASD) under the broad domain of restricted and repetitive ...behavior (RRB). However, relatively little is known about the emergence of sensory‐related features and their relation to conventionally defined RRB in the first years of life.
Methods
Prospective, longitudinal parent‐report data using the Sensory Experiences Questionnaire (SEQ) were collected for 331 high‐risk toddlers (74 of whom met diagnostic criteria for ASD at age 2) and 135 low‐risk controls. Longitudinal profiles for SEQ scores were compared between groups across ages 12–24 months. Associations between SEQ measures and measures of RRB subtypes (based on the Repetitive Behavior Scale, Revised) were also examined.
Results
Longitudinal profiles for all SEQ scores significantly differed between groups. SEQ scores were elevated for the ASD group from age 12 months, with differences becoming more pronounced across the 12–24 month interval. At both 12 and 24 months, most measures derived from the SEQ were significantly associated with all subtypes of RRB.
Conclusions
These findings suggest that differences in sensory responsivity may be evident in high‐risk infants later diagnosed with ASD in early toddlerhood, and that the magnitude of these differences increases over the second year of life. The high degree of association between SEQ scores and RRB supports the conceptual alignment of these features but also raises questions as to explanatory mechanisms.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract Background Autism Spectrum Disorder (ASD) is a developmental disorder defined by behavioural features that emerge during the first years of life. Research indicates that abnormalities in ...brain connectivity are associated with these behavioural features. However, inclusion of individuals past the age of onset of the defining behaviours complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioural abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified as ASD. The current study maps the emergence of these inefficiencies in the first year of life. Methods The study utilizes data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions in order to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Results Inefficiencies in high-risk infants later classified as ASD were detected from 6 months onward in regions involved in low-level sensory processing. Additionally, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. Conclusion These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization, and eventually higher-level cognitive processes and social behaviour.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Autism has been thought to be characterized, in part, by dysfunction in emotional and social cognition, but the pathology of the underlying processes and their neural substrates remain poorly ...understood. Several studies have hypothesized that abnormal amygdala function may account for some of the impairments seen in autism, specifically, impaired recognition of socially relevant information from faces. We explored this issue in eight high-functioning subjects with autism in four experiments that assessed recognition of emotional and social information, primarily from faces. All tasks used were identical to those previously used in studies of subjects with bilateral amygdala damage, permitting direct comparisons. All subjects with autism made abnormal social judgments regarding the trustworthiness of faces; however, all were able to make normal social judgments from lexical stimuli, and all had a normal ability to perceptually discriminate the stimuli. Overall, these data from subjects with autism show some parallels to those from neurological subjects with focal amygdala damage. We suggest that amygdala dysfunction in autism might contribute to an impaired ability to link visual perception of socially relevant stimuli with retrieval of social knowledge and with elicitation of social behavior.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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