1. Coskun MA, Loveland KA, Pearson DA, Papanicolaou AC, Sheth BR. {{Functional Assays of Local Connectivity in the Somatosensory Cortex of Individuals with Autism}}. {Autism Res};2013 (Feb 20)
Emerging evidence for differences between individuals with autism spectrum disorder (ASD) and neurotypical (NT) individuals in somatic processing and brain response to touch suggests somatosensory cortex as a promising substrate for elucidating differences in functional brain connectivity between individuals with and without autism. Signals from adjacent digits project to neighboring locations or representations in somatosensory cortex. When a digit is stimulated, i.e. touched, its representation in cortex is directly activated; local intracortical connections indirectly activate nonprimary cortical representations corresponding to adjacent digits. The response of the nonprimary cortical representations is thus a proxy for connection strength. Local overconnectivity in autism implies that the nonprimary/primary response ratios of the ASD group will be higher than those of the NT group. D1 and D2 of the dominant hand of the participant were individually stimulated while we recorded neural responses using magnetoencephalography. The cortical representations of D1 and D2 (somatosensory-evoked fields) were computed from the ensemble-averaged data using (a) dipole model fits and (b) singular value decomposition. Individual adjacent/primary response ratios were measured, and group response ratio data were fitted with straight lines. Local overconnectivity in autism implies steeper ASD vs. NT group slopes. Our findings did not support local overconnectivity. Slopes were found to be significantly shallower for the ASD group than the NT group. Our findings support the idea of local underconnectivity in the somatosensory cortex of the brains of individuals with ASD. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
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2. Grubb MA, Behrmann M, Egan R, Minshew NJ, Carrasco M, Heeger DJ. {{Endogenous Spatial Attention: Evidence for Intact Functioning in Adults With Autism}}. {Autism Res};2013 (Feb 20)
Rapid manipulation of the attention field (i.e. the location and spread of visual spatial attention) is a critical aspect of human cognition, and previous research on spatial attention in individuals with autism spectrum disorders (ASD) has produced inconsistent results. In a series of three psychophysical experiments, we evaluated claims in the literature that individuals with ASD exhibit a deficit in voluntarily controlling the deployment and size of the spatial attention field. We measured the spatial distribution of performance accuracies and reaction times to quantify the sizes and locations of the attention field, with and without spatial uncertainty (i.e. the lack of predictability concerning the spatial position of the upcoming stimulus). We found that high-functioning adults with autism exhibited slower reaction times overall with spatial uncertainty, but the effects of attention on performance accuracies and reaction times were indistinguishable between individuals with autism and typically developing individuals in all three experiments. These results provide evidence of intact endogenous spatial attention function in high-functioning adults with ASD, suggesting that atypical endogenous attention cannot be a latent characteristic of autism in general. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Lionel AC, Vaags AK, Sato D, Gazzellone MJ, Mitchell EB, Chen HY, Costain G, Walker S, Egger G, Thiruvahindrapuram B, Merico D, Prasad A, Anagnostou E, Fombonne E, Zwaigenbaum L, Roberts W, Szatmari P, Fernandez BA, Georgieva L, Brzustowicz LM, Roetzer K, Kaschnitz W, Vincent JB, Windpassinger C, Marshall CR, Trifiletti RR, Kirmani S, Kirov G, Petek E, Hodge JC, Bassett AS, Scherer SW. {{Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures}}. {Hum Mol Genet};2013 (Feb 20)
The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible for the clustering and localization of glycine and GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated in genetic risk for neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia and epilepsy including the neuroligins (NLGN2, NLGN4), the neurexins (NRXN1, NRXN2, NRXN3) and collybistin (ARHGEF9). Moreover, temporal lobe epilepsy has been linked to abnormally spliced GPHN mRNA lacking exons encoding the G-domain of the gephyrin protein, potentially arising due to cellular stress associated with epileptogenesis such as temperature and alkalosis. Here, we present clinical and genomic characterization of six unrelated subjects, with a range of neurodevelopmental diagnoses including ASD, schizophrenia or seizures, who possess rare de novo or inherited hemizygous microdeletions overlapping exons of GPHN at chromosome 14q23.3. The region of common overlap across the deletions encompasses exons 3-5, corresponding to the G-domain of the gephyrin protein. These findings, together with previous reports of homozygous GPHN mutations in connection with autosomal recessive molybdenum cofactor deficiency, will aid in clinical genetic interpretation of the GPHN mutation spectrum. Our data also add to the accumulating evidence implicating neuronal synaptic gene products as key molecular factors underlying the etiologies of a diverse range of neurodevelopmental conditions.
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4. Sasson NJ, Lam KS, Childress D, Parlier M, Daniels JL, Piven J. {{The Broad Autism Phenotype Questionnaire: Prevalence and Diagnostic Classification}}. {Autism Res};2013 (Feb 20)
The Broad Autism Phenotype Questionnaire (BAPQ) was administered to a large community-based sample of biological parents of children with autism (PCAs) and comparison parents (CPs) (n = 1,692). Exploratory factor analysis and internal consistency parameters confirmed a robust three-factor structure of the BAPQ, corresponding to the proposed aloof, pragmatic language and rigidity subscales. Based upon the distribution of Broad Autism Phenotype (BAP) features in the general population, new normative cutoff values for BAPQ subscales were established that provide increased specificity relative to those previously reported, and thus enhance the utility of the BAPQ for diagnostically classifying the BAP. These cutoffs were also used to estimate prevalence of the BAP and its three components, with rates ranging between 14-23% for PCAs and between 5-9% for CPs. Analysis of patterns of BAP characteristics within family members revealed that BAP features were more likely to co-occur in PCAs relative to CPs. Collectively, these findings extend the utility of the BAPQ and provide additional evidence that it is an efficient and reliable tool for disaggregating the heterogeneity of autism through the identification of meaningful subgroups of parents. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
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5. Tallantyre E, Robertson NP. {{Autism and intellectual disability}}. {J Neurol};2013 (Feb 20)
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6. Tyszka JM, Kennedy DP, Paul LK, Adolphs R. {{Largely Typical Patterns of Resting-State Functional Connectivity in High-Functioning Adults with Autism}}. {Cereb Cortex};2013 (Feb 20)
A leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, yet the majority of studies report effects that are either very weak, inconsistent across studies, or explain results incompletely. Here we apply multiple analytical approaches to resting-state BOLD-fMRI data at the whole-brain level. Neurotypical and high-functioning adults with autism displayed very similar patterns and strengths of resting-state connectivity. We found only limited evidence in autism for abnormal resting-state connectivity at the regional level and no evidence for altered connectivity at the whole-brain level. Regional abnormalities in functional connectivity in autism spectrum disorder were primarily in the frontal and temporal cortices. Within these regions, functional connectivity with other brain regions was almost exclusively lower in the autism group. Further examination showed that even small amounts of head motion during scanning have large effects on functional connectivity measures and must be controlled carefully. Consequently, we suggest caution in the interpretation of apparent positive findings until all possible confounding effects can be ruled out. Additionally, we do not rule out the possibility that abnormal connectivity in autism is evident at the microstructural synaptic level, which may not be reflected sensitively in hemodynamic changes measured with BOLD-fMRI.
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7. Zalla T, Labruyere N, Georgieff N. {{Perceiving Goals and Actions in Individuals with Autism Spectrum Disorders}}. {J Autism Dev Disord};2013 (Feb 19)
In the present study, we investigated the ability to parse familiar sequences of action into meaningful events in young individuals with autism spectrum disorders (ASDs), as compared to young individuals with typical development (TD) and young individuals with moderate mental retardation or learning disabilities (MLDs). While viewing two videotaped movies, participants were requested to detect the boundary transitions between component events at both fine and coarse levels of the action hierarchical structure. Overall, reduced accuracy for event detection was found in participants with ASDs, relative to participants with TD, at both levels of action segmentation. The performance was, however, equally diminished in participants with ASDs and MLDs under the course-grained segmentation suggesting that difficulties to detect fine-grained events in ASDs cannot be explained by a general intellectual dysfunction. Reduced accuracy for event detection was related to diminished event recall, memory for event sequence and Theory of Mind abilities. We hypothesized that difficulties with event detection result from a deficit disrupting the on-line processing of kinematic features and physical changes of dynamic human actions. An impairment at the earlier stages of the event encoding process might contribute to deficits in episodic memory and social functioning in individuals with ASDs.
