1. Bhatara A, Quintin EM, Levy B, Bellugi U, Fombonne E, Levitin DJ. {{Perception of emotion in musical performance in adolescents with autism spectrum disorders}}. {Autism Res} (Aug 17)
Individuals with autism spectrum disorders (ASD) are impaired in understanding the emotional undertones of speech, many of which are communicated through prosody. Musical performance also employs a form of prosody to communicate emotion, and the goal of this study was to examine the ability of adolescents with ASD to understand musical emotion. We designed an experiment in which each musical stimulus served as its own control while we varied the emotional expressivity by manipulating timing and amplitude variation. We asked children and adolescents with ASD and matched controls as well as individuals with Williams syndrome (WS) to rate how emotional these excerpts sounded. Results show that children and adolescents with ASD are impaired relative to matched controls and individuals with WS at judging the difference in emotionality among the expressivity levels. Implications for theories of emotion in autism are discussed in light of these findings.
2. Dingfelder HE, Mandell DS. {{Bridging the Research-to-Practice Gap in Autism Intervention: An Application of Diffusion of Innovation Theory}}. {J Autism Dev Disord} (Aug 18)
There is growing evidence that efficacious interventions for autism are rarely adopted or successfully implemented in public mental health and education systems. We propose applying diffusion of innovation theory to further our understanding of why this is the case. We pose a practical set of questions that administrators face as they decide about the use of interventions. Using literature from autism intervention and dissemination science, we describe reasons why efficacious interventions for autism are rarely adopted, implemented, and maintained in community settings, all revolving around the perceived fit between the intervention and the needs and capacities of the setting. Finally, we suggest strategies for intervention development that may increase the probability that these interventions will be used in real-world settings.
3. Leveille C, Barbeau EB, Bolduc C, Limoges E, Berthiaume C, Chevrier E, Mottron L, Godbout R. {{Enhanced connectivity between visual cortex and other regions of the brain in autism: a REM sleep EEG coherence study}}. {Autism Res} (Aug 17)
Functional interregional neural coupling was measured as EEG coherence during REM sleep, a state of endogenous cortical activation, in 9 adult autistic individuals (21.1+/-4.0 years) and 13 typically developed controls (21.5+/-4.3 years) monitored for two consecutive nights in a sleep laboratory. Spectral analysis was performed on 60 s of artefact-free EEG samples distributed equally throughout the first four REM sleep periods of the second night. EEG coherence was calculated for six frequency bands (delta, theta, alpha, sigma, beta, and total spectrum) using a 22-electrode montage. The magnitude of coherence function was computed for intra- and interhemispheric pairs of recording sites. Results were compared by Multivariate Analysis of Variance (MANOVA). Each time the autistic group showed a greater EEG coherence than the controls; it involved intrahemispheric communication among the left visual cortex (O1) and other regions either close to or distant from the occipital cortex. In contrast, lower coherence values involved frontal electrodes in the right hemisphere. No significant differences between groups were found for interhemispheric EEG coherence. These results show that the analysis of EEG coherence during REM sleep can disclose patterns of cortical connectivity that can be reduced or increased in adults with autism compared to typically developed individuals, depending of the cortical areas studied. Superior coherence involving visual perceptual areas in autism is consistent with an enhanced role of perception in autistic brain organization.
4. Redfern RE, Daou MC, Li L, Munson M, Gericke A, Ross AH. {{A mutant form of PTEN linked to autism}}. {Protein Sci} (Aug 17)
The tumor suppressor, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), is a phosphoinositide (PI) phosphatase specific for the 3-position of the inositol ring. PTEN has been implicated in autism for a subset of patients with macrocephaly. Various studies identified patients in this subclass with one normal and one mutated PTEN gene. We characterize the binding, structural properties, activity and subcellular localization of one of these autism-related mutants, H93R PTEN. Even though this mutation is located at the phosphatase active site, we find that it affects the functions of neighboring domains. H93R PTEN binding to phosphatidylserine-bearing model membranes is 5.6 fold enhanced in comparison to wild type PTEN. In contrast, we find that binding to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) model membranes is 2.5 fold decreased for the mutant PTEN in comparison to wild type PTEN. The structural change previously found for wild type PTEN upon interaction with PI(4,5)P(2), is absent for H93R PTEN. Consistent with the increased binding to phosphatidylserine, we find enhanced plasma membrane association of PTEN-GFP in U87MG cells. However, this enhanced plasma membrane association does not translate into increased PI(3,4,5)P(3) turnover, since in vivo studies show a reduced activity of the H93R PTEN-GFP mutant. Because the interaction of PI(4,5)P(2) with PTEN’s N-terminal domain is diminished by this mutation, we hypothesize that the interaction of PTEN’s N-terminal domain with the phosphatase domain is impacted by the H93R mutation, preventing PI(4,5)P(2) from inducing the conformational change that activates phosphatase activity.
5. Urdinguio RG, Fernandez AF, Lopez-Nieva P, Rossi S, Huertas D, Kulis M, Liu CG, Croce C, Calin GA, Esteller M. {{Disrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome}}. {Epigenetics} (Oct 18);5(7)
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate post-transcriptional gene expression. They influence a wide range of physiological functions, including neuronal processes, and are regulated by various mechanisms, such as DNA methylation. This epigenetic mark is recognized by transcriptional regulators such as the methyl CpG binding protein Mecp2. Rett syndrome is a complex neurological disorder that has been associated with mutations in the gene coding for Mecp2. Thus, we examined the possible miRNA misregulation caused by Mecp2 absence in a mouse model of Rett syndrome. Using miRNA expression microarrays, we observed that the brain of Rett syndrome mice undergoes a disruption of the expression profiles of miRNAs. Among the significantly altered miRNAs (26%, 65 of 245), overall downregulation of these transcripts was the most common feature (71%), while the remaining 30% were upregulated. Further validation by quantitative RT-PCR demonstrated that the most commonly disrupted miRNAs were miR-146a, miR-146b, miR-130, miR-122a, miR-342 and miR-409 (downregulated) and miR-29b, miR329, miR-199b, miR-382, miR-296, miR-221 and miR-92 (upregulated). Most importantly, transfection of miR-146a in a neuroblastoma cell line caused the downregulation of IL-1 receptor-associated kinase 1 (Irak1) levels, suggesting that the identified defect of miR-146a in Rett syndrome mice brains might be responsible for the observed upregulation of Irak1 in this model of the human disease. Overall, we provide another level of molecular deregulation occurring in Rett syndrome that might be useful for understanding the disease and for designing targeted therapies.
6. Vladusich T, Olu-Lafe O, Kim DS, Tager-Flusberg H, Grossberg S. {{Prototypical category learning in high-functioning autism}}. {Autism Res} (Aug 17)
An ongoing debate in developmental cognitive neuroscience is whether individuals with autism are able to learn prototypical category representations from multiple exemplars. Prototype learning and memory were examined in a group of high-functioning autistic boys and young men, using a classic paradigm in which participants learned to classify novel dot patterns into one of two categories. Participants were trained on distorted versions of category prototypes until they reached a criterion level of performance. During transfer testing, participants were shown the training items together with three novel stimulus sets manifesting variable levels of physical distortion (low, medium, or high distortion) relative to the unseen prototypes. Two experiments were conducted, differing only in the manner in which the physical distortions were defined. In the first experiment, a subset of autistic individuals learned categories more slowly than controls, accompanied by an overall diminution in transfer-testing performance. The autism group did, however, manifest a typical pattern of performance across the testing conditions, relative to controls. In the second experiment, group means did not differ statistically in either the training or testing phases. Taken together, these data indicate that high-functioning autistic individuals do not manifest gross deficits in prototypical category learning. A theoretical discussion is given in terms of how perceptual grouping may interact with category learning.
