1. Aasen G, Naerland T. {{Enhancing activity by means of tactile symbols: A study of a heterogeneous group of pupils with congenital blindness, intellectual disability and autism spectrum disorder}}. {J Intellect Disabil};2014 (Mar);18(1):61-75.
This study investigates responses to verbal versus tactile requests in children with congenital blindness, intellectual disability and autism spectrum disorder (ASD). Observation was conducted on two occasions. At T1, requests were given verbally, and at T2, tactile requests were given. All pupils perceived tactile symbols to be explicit requests to perform the act referred to by the symbols. The children seldom or never followed verbal requests. All children followed more tactile than verbal requests. Individual differences in verbal skills, motivations and the complexity of the activity are discussed. The availability of tactile symbols for individuals with congenital blindness, intellectual disability and ASD seems to increase their level of activity and their participation in school.
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2. Filipe MG, Frota S, Castro SL, Vicente SG. {{Atypical Prosody in Asperger Syndrome: Perceptual and Acoustic Measurements}}. {J Autism Dev Disord};2014 (Mar 4)
It is known that individuals with Asperger syndrome (AS) may show no problems with regard to what is said (e.g., lexical content) but tend to have difficulties in how utterances are produced, i.e., they may show prosodic impairments. In the present study, we focus on the use of prosodic features to express grammatical meaning. Specifically, we explored the sentence type difference between statements and questions that is conveyed by intonation, using perceptual and acoustic measurements. Children aged 8 and 9 years with AS (n = 12) were matched according to age and nonverbal intelligence with typically developing peers (n = 17). Although children with AS could produce categorically accurate prosodic patterns, their prosodic contours were perceived as odd by adult listeners, and acoustic measurements showed alterations in duration and pitch. Additionally, children with AS had greater variability in fundamental frequency contours compared to typically developing peers.
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3. Gandhi RM, Kogan CS, Messier C, Macleod LS. {{Visual-spatial learning impairments are associated with hippocampal PSD-95 protein dysregulation in a mouse model of fragile X syndrome}}. {Neuroreport};2014 (Mar 5);25(4):255-261.
Fragile X syndrome is the most common cause of inherited intellectual disability and is caused by the lack of fragile X mental retardation protein (FMRP) expression. In-vitro findings in mice and post-mortem autopsies in humans are characterized by dendritic spine abnormalities in the absence of Fmrp/FMRP. Biochemical and electrophysiological studies have identified postsynaptic density protein (PSD)-95 as having an established role in dendritic morphology as well as a molecular target of Fmrp. How Fmrp affects the expression of PSD-95 following behavioral learning is unknown. In the current study, wild type controls and Fmr1 knockout mice were trained in a subset of the Hebb-Williams (H-W) mazes. Dorsal hippocampal PSD-95 protein levels relative to a stable cytoskeleton protein (beta-tubulin) were measured. We report a significant upregulation of PSD-95 protein levels in wild type mice, whereas training-related protein increases were blunted in Fmr1 knockout mice. In addition, there was a significant negative correlation between mean total errors on the mazes and PSD-95 protein levels. The coefficient of determination indicated that the mean total errors on the H-W mazes accounted for 35% of the variance in PSD-95 protein levels. These novel findings suggest that reduced PSD-95-associated postsynaptic plasticity may contribute to the learning and memory deficits observed in human fragile X syndrome patients.
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4. Gomez C, Lizier JT, Schaum M, Wollstadt P, Grutzner C, Uhlhaas P, Freitag CM, Schlitt S, Bolte S, Hornero R, Wibral M. {{Reduced predictable information in brain signals in autism spectrum disorder}}. {Front Neuroinform};2014;8:9.
Autism spectrum disorder (ASD) is a common developmental disorder characterized by communication difficulties and impaired social interaction. Recent results suggest altered brain dynamics as a potential cause of symptoms in ASD. Here, we aim to describe potential information-processing consequences of these alterations by measuring active information storage (AIS)-a key quantity in the theory of distributed computation in biological networks. AIS is defined as the mutual information between the past state of a process and its next measurement. It measures the amount of stored information that is used for computation of the next time step of a process. AIS is high for rich but predictable dynamics. We recorded magnetoencephalography (MEG) signals in 10 ASD patients and 14 matched control subjects in a visual task. After a beamformer source analysis, 12 task-relevant sources were obtained. For these sources, stationary baseline activity was analyzed using AIS. Our results showed a decrease of AIS values in the hippocampus of ASD patients in comparison with controls, meaning that brain signals in ASD were either less predictable, reduced in their dynamic richness or both. Our study suggests the usefulness of AIS to detect an abnormal type of dynamics in ASD. The observed changes in AIS are compatible with Bayesian theories of reduced use or precision of priors in ASD.
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5. Grandgeorge M, Bourreau Y, Alavi Z, Lemonnier E, Tordjman S, Deleau M, Hausberger M. {{Interest towards human, animal and object in children with autism spectrum disorders: an ethological approach at home}}. {Eur Child Adolesc Psychiatry};2014 (Mar 4)
Autistic spectrum disorders (ASD) are characterised by attention deficits in communication and social interactions and a lack of interest in people. Data are mostly based on clinical situations. However, recent studies have shown a more mixed situation where children with ASD (ASD children) displayed interest towards humans, in both experimental and natural settings. The aim of this study was to assess the interest of ASD children in a natural standardised home setting. Here, we hypothesised that ASD children would display more interest towards animate stimuli-human and pet-when in the child’s home than in the lab experimental setting. We used an ethological approach involving observations, a methodological alternative to lab static techniques, to investigate the behaviour of ninety 6- to 12-year-old ASD and typical development (TD) children. Our results were consistent with those of the literature revealing that the ASD children displayed interest towards animate stimuli as did children with TD children. Interestingly, while the ASD children showed higher interest towards humans, e.g. their parent, than the TD children did, they showed less interest towards pet compared to the TD children. Our results suggested that animals are not inherently easy to decode for ASD children, in contrast with previous experiences where a pet was regarded as a more attractive partner, easier to be understood. At last, the ASD children changed more frequently their focus point than the TD children did. These differences may be explained by the reduced attention skills in ASD or the study’s context. To conclude, larger exploratory studies in natural settings conducted beyond ordinary human to human interactions are crucial for better understanding of the underlying mechanisms involved in social interactions in ASD.
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6. Hus V, Lord C. {{The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores}}. {J Autism Dev Disord};2014 (Mar 4)
The recently published Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) includes revised diagnostic algorithms and standardized severity scores for modules used to assess younger children. A revised algorithm and severity scores are not yet available for Module 4, used with verbally fluent adults. The current study revises the Module 4 algorithm and calibrates raw overall and domain totals to provide metrics of autism spectrum disorder (ASD) symptom severity. Sensitivity and specificity of the revised Module 4 algorithm exceeded 80 % in the overall sample. Module 4 calibrated severity scores provide quantitative estimates of ASD symptom severity that are relatively independent of participant characteristics. These efforts increase comparability of ADOS scores across modules and should facilitate efforts to examine symptom trajectories from toddler to adulthood.
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7. Jeong JW, Tiwari VN, Behen ME, Chugani HT, Chugani DC. {{In vivo detection of reduced Purkinje cell fibers with diffusion MRI tractography in children with autistic spectrum disorders}}. {Front Hum Neurosci};2014;8:110.
Postmortem neuropathology studies report reduced number and size of Purkinje cells (PC) in a majority of cerebellar specimens from persons diagnosed with autism spectrum disorders (ASD). We used diffusion weighted MRI tractography to investigate whether structural changes associated with reduced number and size of PC, could be detected in vivo by measuring streamlines connecting the posterior-lateral region of the cerebellar cortex to the dentate nucleus using an independent component analysis with a ball and stick model. Seed regions were identified in the cerebellar cortex, and streamlines were identified to two sorting regions, the dorsal dentate nucleus (DDN) and the ventral dentate nucleus (VDN), and probability of connection and measures of directional coherence for these streamlines were calculated. Tractography was performed in 14 typically developing children (TD) and 15 children with diagnoses of ASD. Decreased numbers of streamlines were found in the children with ASD in the pathway connecting cerebellar cortex to the right VDN (p-value = 0.015). Reduced fractional anisotropy (FA) values were observed in pathways connecting the cerebellar cortex to the right DDN (p-value = 0.008), the right VDN (p-value = 0.010) and left VDN (p-value = 0.020) in children with ASD compared to the TD group. In an analysis of single subjects, reduced FA in the pathway connecting cerebellar cortex to the right VDN was found in 73% of the children in the ASD group using a threshold of 3 standard errors of the TD group. The detection of diffusion changes in cerebellum may provide an in vivo biomarker of Purkinje cell pathology in children with ASD.
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8. Pasco G, Clark B, Dragan I, Kalambayi F, Slonims V, Tarpan AK, Wittemeyer K. {{A training and development project to improve services and opportunities for social inclusion for children and young people with autism in Romania}}. {Autism};2014 (Mar 3)
In 2010, the Romanian Angel Appeal Foundation launched a 3-year national training and development programme to develop and deliver a model of diagnostic and therapeutic services aimed at promoting social inclusion for children and young people with autism spectrum disorders. The project adopted a number of strategies aimed at developing knowledge and skills among professionals and increasing awareness in political and public spheres: (a) a three-stage training programme designed to increase knowledge of autism spectrum disorders and promote best practice among professionals working in services providing for children with autism spectrum disorders and their families, on a nationwide basis; (b) two online courses for general practitioners and psychiatrists, with content relating to the identification, diagnosis and treatment of autism spectrum disorders; (c) a total of 40 counselling and assistance centres for people with autism spectrum disorders were launched in partnership with local authorities; (d) a national strategy for social and professional integration of people with autism spectrum disorders developed through consultation with political, statutory and voluntary sector partners; and (d) a nationwide media campaign to raise awareness of the needs of children and young people with autism spectrum disorders that reached over eight million people. The project provides a transferable model to achieve important improvements in the quantity and quality of services on a national level within a brief time frame.
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9. Radell ML, Mercado E, 3rd. {{Modeling possible effects of atypical cerebellar processing on eyeblink conditioning in autism}}. {Cogn Affect Behav Neurosci};2014 (Mar 4)
Autism is unique among other disorders in that acquisition of conditioned eyeblink responses is enhanced in children, occurring in a fraction of the trials required for control participants. The timing of learned responses is, however, atypical. Two animal models of autism display a similar phenotype. Researchers have hypothesized that these differences in conditioning reflect cerebellar abnormalities. The present study used computer simulations of the cerebellar cortex, including inhibition by the molecular layer interneurons, to more closely examine whether atypical cerebellar processing can account for faster conditioning in individuals with autism. In particular, the effects of inhibitory levels on delay eyeblink conditioning were simulated, as were the effects of learning-related synaptic changes at either parallel fibers or ascending branch synapses from granule cells to Purkinje cells. Results from these simulations predict that whether molecular layer inhibition results in an enhancement or an impairment of acquisition, or changes in timing, may depend on (1) the sources of inhibition, (2) the levels of inhibition, and (3) the locations of learning-related changes (parallel vs. ascending branch synapses). Overall, the simulations predict that a disruption in the balance or an overall increase of inhibition within the cerebellar cortex may contribute to atypical eyeblink conditioning in children with autism and in animal models of autism.
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10. Rhodes C. {{Do Social Stories help to decrease disruptive behaviour in children with autistic spectrum disorders? A review of the published literature}}. {J Intellect Disabil};2014 (Mar);18(1):35-50.
A structured search and identification of themes within the literature regarding the use of Social Stories to decrease disruptive behaviour in children with autistic spectrum disorders is presented. The examination of seven studies showed that the Social Story intervention was successful for the majority of the participants, although the level of success was variable. Overall, Social Stories appear to be an acceptable intervention for use in the classroom, however unplanned verbal prompting by teachers, in some studies, reduced confidence in the effectiveness of Social Stories when used in isolation. An increasing body of literature has indicated that Social Stories are an effective intervention for children diagnosed with autistic spectrum disorders, however very few studies have addressed the efficacy of Social Stories when used with children with other disabilities.
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11. Roy A, Roy M, Deb S, Unwin G. {{Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review}}. {J Intellect Disabil Res};2014 (Mar 4)
BACKGROUND: ASC (autism spectrum conditions) may result from a failure of striatal beta endorphins to diminish with maturation. Many symptoms of ASC resemble behaviours induced in animals or humans by opiate administration, including decreased socialisation, diminished crying, repetitive stereotypies, insensitivity to pain and motor hyperactivity. Naltrexone, an opioid antagonist, has been used in the management of children with ASC and can produce a clinically significant reduction in the serious and life-threatening behaviour of self-injury for individuals who have not been responsive to any other type of treatment and is important for this reason. It was therefore appropriate to reconsider the available evidence and a systematic review was undertaken. METHODS: Four electronic databases were searched for relevant journal articles. In addition, cross-referencing of pertinent reviews and a hand search for articles in major international intellectual disability (ID) journals between the years 2010 and 2012 was carried out to ensure that all relevant articles were identified. We also searched databases for unpublished clinical trials to overcome publication bias. Each database was searched up to present (February 2013) with no restrictions on the date of publication. The search terms consisted of broad expressions used to describe ID and autistic spectrum disorder as well as terms relating to opioid antagonists and specific drugs. All studies identified by the electronic database search and hand search were examined on the basis of title alone for relevance and duplication. The abstracts of the remaining papers were then scrutinised against the inclusion criteria. Where abstracts failed to provide adequate information, the full texts for these papers were obtained. All the full texts were then evaluated against the inclusion proforma. Two reviewers carried out all the stages of the process independently. The reviewers met to discuss their selections and where disagreements arose, these were settled by discussion with a member of the study group. Data from each study meeting the inclusion criteria were extracted on a pre-piloted data extraction form. The quality of each study was further assessed using the Jadad scale, a tool developed to assess the quality of randomised controlled trials. RESULTS: 155 children participated in 10 studies; 27 received placebo. Of the 128 that received naltrexone 98 (77%) showed statistically significant improvement in symptoms of irritability and hyperactivity. Side effects were mild and the drug was generally well tolerated. CONCLUSIONS: Naltrexone may improve hyperactivity and restlessness in children with autism but there was not sufficient evidence that it had an impact on core features of autism in majority of the participants. It is likely that a subgroup of children with autism and abnormal endorphin levels may respond to naltrexone and identifying the characteristics of these children must become a priority.
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12. Sung M, Chin CH, Lim CG, Liew HS, Lim CS, Kashala E, Weng SJ. {{What’s in the pipeline? Drugs in development for autism spectrum disorder}}. {Neuropsychiatr Dis Treat};2014;10:371-381.
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with both core symptoms and associated symptoms (eg, irritability, aggression, and comorbidities) that affect both the individual and the family/systems around them. There have been recent advances in the understanding of the underlying pathophysiology of ASD pertaining to genetics, epigenetics, neurological, hormonal, and environmental factors that contribute to the difficulties found in individuals with ASD. With this improved understanding, there has been a shift in the application of psychopharmacology in ASD and its related disorders. A literature review was conducted to examine research published in the last 5 years between different classes of psychotropic medications and ASD. The broad scope of the existing literature for the use of conventional medications is summarized and novel medications are discussed.
