1. Abdala AP, Toward MA, Dutschmann M, Bissonnette JM, Paton JF. {{Deficiency of GABAergic synaptic inhibition in the Kolliker-Fuse area underlies respiratory dysrhythmia in a mouse model of Rett syndrome}}. {J Physiol}. 2015.
Central apnoeas and respiratory irregularity are a common feature in Rett syndrome (RTT), a neurodevelopmental disorder most often caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2). We used a MECP2 deficient mouse model of RTT as a strategy to obtain insights into the neurobiology of the disease and into mechanisms essential for respiratory rhythmicity during normal breathing. Previously, we showed that, systemic administration of a GABA reuptake blocker in MECP2 deficient mice markedly reduced the occurrence of central apnoeas. Further, we found that, during central apnoeas, post-inspiratory drive (adductor motor) to the upper airways was enhanced in amplitude and duration in Mecp2 heterozygous female mice. Since pontine Kolliker-Fuse (KF) region drives post-inspiration, suppresses inspiration, and can reset the respiratory oscillator phase, we hypothesized that synaptic inhibition in this area is essential for respiratory rhythm regularity. In this study, we found that: (i) Mecp2 heterozygous mice show deficiency of GABA perisomatic bouton-like puncta and processes in the KF; (ii) blockade of GABA reuptake in the KF of RTT mice reduced breathing irregularity; (iii) conversely, blockade of GABAA receptors in the KF of healthy rats mimicked the RTT respiratory phenotype of recurrent central apnoeas and prolonged post-inspiratory activity. Our results show that reductions in synaptic inhibition within the KF induce rhythm irregularity whereas boosting GABA transmission reduces respiratory arrhythmia in a murine model of RTT. Our data suggest that manipulation of synaptic inhibition in KF may be a clinically important strategy for alleviating the life threatening respiratory disorders in RTT. This article is protected by copyright. All rights reserved.
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3. Decoteau CL, Underman K. {{Adjudicating non-knowledge in the Omnibus Autism Proceedings}}. {Soc Stud Sci}. 2015; 45(4): 471-500.
After 5600 families of children diagnosed with autism filed claims with the National Vaccine Injury Compensation Program in the United States, the court selected ‘test’ cases consolidated into the Omnibus Autism Proceedings, held from 2007 to 2008, to examine claims that vaccines caused the development of autism. The court found all of the causation theories presented to be untenable and did not award damages to any parents. We analyze the Omnibus Autism Proceedings as a struggle within the scientific field between the scientific orthodoxy of the respondents and the heterodox position taken by the plaintiffs, suggesting that the ruling in these cases helped to shore up hegemony on autism causation. Drawing on the literature on non-knowledge, we suggest that only the respondents had enough scientific capital to strategically direct non-knowledge toward genetic research, thereby foreclosing the possibility of environmental causation of autism. The plaintiffs, who promote a non-standard ontology of autism, suggest that the science on autism remains undone and should not be circumscribed. In analyzing the Omnibus Autism Proceedings with field theory, we highlight the way in which scientific consensus-building and the setting of research agendas are the result of struggle, and we show that the strategic deployment of non-knowledge becomes a major stake in battles for scientific legitimacy and the settling of scientific controversies.
4. Fletcher-Watson S, Petrou A, Scott-Barrett J, Dicks P, Graham C, O’Hare A, Pain H, McConachie H. {{A trial of an iPad intervention targeting social communication skills in children with autism}}. {Autism}. 2015.
This study evaluated a technology-based early intervention for social communication skills in pre-schoolers in a randomised controlled trial. Participants were 54 children aged under 6 years with a diagnosis of autism, assigned to either intervention or control conditions. The app engaged children, who played consistently, regardless of developmental level, and was rated highly by parents. There were no significant group differences in parent-report measures post-intervention, nor in a measure of parent-child play at follow-up. Therefore, this intervention did not have an observable impact on real-world social communication skills and caution is recommended about the potential usefulness of iPad apps for amelioration of difficulties in interaction. However, positive attitudes among participants, lack of harms and the potential of apps to deliver therapeutic content at low economic cost suggest this approach is worth pursuing further, perhaps targeting other skill domains.
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16. Solomon M, Ragland JD, Niendam TA, Lesh TA, Beck JS, Matter JC, Frank MJ, Carter CS. {{Atypical Learning in Autism Spectrum Disorders: A Functional Magnetic Resonance Imaging Study of Transitive Inference}}. {J Am Acad Child Adolesc Psychiatry}. 2015; 54(11): 947-55.
OBJECTIVE: To investigate the neural mechanisms underlying impairments in generalizing learning shown by adolescents with autism spectrum disorder (ASD). METHOD: A total of 21 high-functioning individuals with ASD aged 12 to 18 years, and 23 gender-, IQ-, and age-matched adolescents with typical development (TYP), completed a transitive inference (TI) task implemented using rapid event-related functional magnetic resonance imaging (fMRI). Participants were trained on overlapping pairs in a stimulus hierarchy of colored ovals where A>B>C>D>E>F and then tested on generalizing this training to new stimulus pairings (AF, BD, BE) in a « Big Game. » Whole-brain univariate, region of interest, and functional connectivity analyses were used. RESULTS: During training, the TYP group exhibited increased recruitment of the prefrontal cortex (PFC), whereas the group with ASD showed greater functional connectivity between the PFC and the anterior cingulate cortex (ACC). Both groups recruited the hippocampus and caudate comparably; however, functional connectivity between these regions was positively associated with TI performance for only the group with ASD. During the Big Game, the TYP group showed greater recruitment of the PFC, parietal cortex, and the ACC. Recruitment of these regions increased with age in the group with ASD. CONCLUSION: During TI, TYP individuals recruited cognitive control-related brain regions implicated in mature problem solving/reasoning including the PFC, parietal cortex, and ACC, whereas the group with ASD showed functional connectivity of the hippocampus and the caudate that was associated with task performance. Failure to reliably engage cognitive control-related brain regions may produce less integrated flexible learning in individuals with ASD unless they are provided with task support that, in essence, provides them with cognitive control; however, this pattern may normalize with age.
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19. Veenstra-VanderWeele J, McGuire K, Shui AM. {{Clinical Correlates of Early Generalized Overgrowth in Autism Spectrum Disorder}}. {J Am Acad Child Adolesc Psychiatry}. 2015; 54(11): 957-8.
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