Pubmed du 27/07/15

Pubmed du jour

2015-07-27 12:03:50

1. {{Developmental Disabilities Program. Final rule}}. {Fed Regist};2015 (Jul 27);80(143):44795-44827.

This rule implements the Developmental Disabilities Assistance and Bill of Rights Act of 2000. The previous regulations were completed in 1997 before the current law was passed. The rule will align the regulations and current statute and will provide guidance to AIDD grantees.

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2. Balboni G, Tasso A, Muratori F, Cubelli R. {{The Vineland-II in Preschool Children with Autism Spectrum Disorders: An Item Content Category Analysis}}. {J Autism Dev Disord};2015 (Jul 26)
We investigated which item subsets of the Vineland-II can discriminate low-functioning preschoolers with ASD from matched peers with other neurodevelopmental disorders, using a regression analysis derived from a normative sample to account for cognitive and linguistic competencies. At variance with the typical profile, a pattern with Communication more impaired than Socialization was observed. The source of the frequently reported Socialization delay in ASD appears to be in Playing and Imitating skills only, not in other social adaptive behavior skills. The combination of item subsets Playing, Following instructions, Beginning to talk, and Speech skills provided the best discrimination between the two clinical groups. Evaluation of the Vineland-II score on item content categories is a useful procedure for a more efficient clinical description.

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3. Bavin EL, Prendergast LA, Kidd E, Baker E, Dissanayake C. {{Online processing of sentences containing noun modification in young children with high-functioning autism}}. {Int J Lang Commun Disord};2015 (Jul 27)
BACKGROUND: There is variability in the language of children with autism, even those who are high functioning. However, little is known about how they process language structures in real time, including how they handle potential ambiguity, and whether they follow referential constraints. Previous research with older autism spectrum disorder (ASD) participants has shown that these individuals can use context to access rapidly the meaning of ambiguous words. The severity of autism has also been shown to influence the speed in which children with ASD access lexical information. AIMS: To understand more about how children with ASD process language in real time (i.e., as it unfolds). The focus was the integration of information and use of referential constraints to identify a referent named in a sentence. METHODS & PROCEDURES: We used an eye-tracking task to compare performance between young, high-functioning children with autism (HFA) and children with typical development (TD). A large sample of 5-9-year-old children (mean age = 6;8 years), 48 with HFA and 56 with TD participated; all were attending mainstream schools. For each item participants were shown a display of four images that differed in two dimensions. Each sentence contained an adjective and noun that restricted the choice from four to two (the target and competitor), followed by a prepositional phrase (e.g., the blue square with dots); this added modifying information to provide a unique description of the target. We calculated looking time at the target, the competitor and the two distractors for each 200 ms time interval as children processed the sentence and looked at the display. Generalized estimating equations were used to carry out repeated-measures analyses on the proportion of looking time to target and competitor and time to fixate to target. OUTCOMES & RESULTS: Children in both groups (HFA and TD) looked at the target and competitor more than at the distractors following the adjective and noun and following the modifying information in the prepositional phrase more at the target. However, the HFA group was significantly slower in both phases and looked proportionally less at the target. Across the sample, IQ and language did not affect the results; however, age and attention had an impact. The older children showed an advantage in processing the information as did the children with higher attention scores. CONCLUSIONS & IMPLICATIONS: The HFA group took longer than the TD group to integrate the disambiguating information provided in the course of processing a sentence and integrate it with the visual information, indicating that for the ASD group incremental processing was not as advanced as for children with ASD, and they were less sensitive to referential conventions. Training for young children with ASD on the use of referential conventions and available contextual clues may be of benefit to them in understanding the language they hear.

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4. Borgi M, Loliva D, Cerino S, Chiarotti F, Venerosi A, Bramini M, Nonnis E, Marcelli M, Vinti C, De Santis C, Bisacco F, Fagerlie M, Frascarelli M, Cirulli F. {{Effectiveness of a Standardized Equine-Assisted Therapy Program for Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Jul 26)
In this study the effectiveness of an equine-assisted therapy (EAT) in improving adaptive and executive functioning in children with autism spectrum disorder (ASD) was examined (children attending EAT, n = 15, control group n = 13; inclusion criteria: IQ > 70). Therapeutic sessions consisted in structured activities involving horses and included both work on the ground and riding. Results indicate an improvement in social functioning in the group attending EAT (compared to the control group) and a milder effect on motor abilities. Improved executive functioning was also observed (i.e. reduced planning time in a problem-solving task) at the end of the EAT program. Our findings provide further support for the use of animal-assisted intervention programs as complementary intervention strategies for children with ASD.

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5. Bos DJ, Merchan-Naranjo J, Martinez K, Pina-Camacho L, Balsa I, Boada L, Schnack H, Oranje B, Desco M, Arango C, Parellada M, Durston S, Janssen J. {{Reduced Gyrification Is Related to Reduced Interhemispheric Connectivity in Autism Spectrum Disorders}}. {J Am Acad Child Adolesc Psychiatry};2015 (Aug);54(8):668-676.

OBJECTIVE: Autism spectrum disorders (ASD) have been associated with atypical cortical gray and subcortical white matter development. Neurodevelopmental theories postulate that a relation between cortical maturation and structural brain connectivity may exist. We therefore investigated the development of gyrification and white matter connectivity and their relationship in individuals with ASD and their typically developing peers. METHOD: T1- and diffusion-weighted images were acquired from a representative sample of 30 children and adolescents with ASD (aged 8-18 years), and 29 typically developing children matched for age, sex, hand preference, and socioeconomic status. The FreeSurfer suite was used to calculate cortical volume, surface area, and gyrification index. Measures of structural connectivity were estimated using probabilistic tractography and tract-based spatial statistics (TBSS). RESULTS: Left prefrontal and parietal cortex showed a relative, age-dependent decrease in gyrification index in children and adolescents with ASD compared to typically developing controls. This result was replicated in an age-and IQ-matched sample provided by the Autism Brain Imaging Data Exchange (ABIDE) initiative. Furthermore, tractography and TBSS showed a complementary pattern in which left prefrontal gyrification was negatively related to radial diffusivity in the forceps minor in participants with ASD. CONCLUSION: The present study builds on earlier findings of abnormal gyrification and structural connectivity in the prefrontal cortex in ASD. It provides a more comprehensive neurodevelopmental characterization of ASD, involving interdependent changes in microstructural white and cortical gray matter. The findings of related abnormal patterns of gyrification and white matter connectivity support the notion of the intertwined development of 2 major morphometric domains in ASD.

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6. Carmo JC, Duarte E, Pinho S, Filipe CN, Marques JF. {{Preserved Proactive Interference in Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Jul 26)
In this study, we aimed to evaluate further the functioning and structuring of the semantic system in autism spectrum disorders (ASD). We analyzed the performance of 19 high-functioning young adults with ASD and a group of 20 age-, verbal IQ- and education-matched individuals with the Proactive Interference (PI) Paradigm to evaluate semantic functioning in ASD (Experiment 1). In Experiment 2, we analyzed the performances of both groups in a PI paradigm with manipulation of the level of typicality. In both experiments, we observed significant effects of trial and group but no trial by group interactions, which we interpreted as robust evidence of preserved PI (build up effect) that indicated the preservation of semantic mechanisms of encoding and retrieval.

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7. Choueiri R, Wagner S. {{A New Interactive Screening Test for Autism Spectrum Disorders in Toddlers}}. {J Pediatr};2015 (Aug);167(2):460-466.

OBJECTIVE: To develop a clinically valid interactive level 2 screening assessment for autism spectrum disorders (ASD) in toddlers that is brief, easily administered, and scored by clinicians. STUDY DESIGN: We describe the development, training, standardization, and validation of the Rapid Interactive Screening Test for Autism in Toddlers (RITA-T) with ASD-specific diagnostic instruments. The RITA-T can be administered and scored in 10 minutes. We studied the validity of the RITA-T to distinguish between toddlers with ASD from toddlers with developmental delay (DD)/non-ASD in an early childhood clinic. We also evaluated the test’s performance in toddlers with no developmental concerns. We identified a cutoff score based on sensitivity, specificity, and positive predictive value of the RITA-T that best differentiates between ASD and DD/non-ASD. RESULTS: A total of 61 toddlers were enrolled. RITA-T scores were correlated with ASD-specific diagnostic tools (r = 0.79; P < .01) and ASD clinical diagnoses (r = 0.77; P < .01). Mean scores were significantly different in subjects with ASD, those with DD/non-ASD, and those with no developmental concerns (20.8 vs 13 vs 10.6, respectively; P < .0001). At a cutoff score of >14 , the RITA-T had a sensitivity of 1.00, specificity of 0.84, and positive predictive value of 0.88 for identifying ASD risk in a high-risk group. CONCLUSION: The RITA-T is a promising new level 2 interactive screening tool for improving the early identification of ASD in toddlers in general pediatric and early intervention settings and allowing access to treatment.

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8. Eversole M, Collins DM, Karmarkar A, Colton L, Quinn JP, Karsbaek R, Johnson JR, Callier NP, Hilton CL. {{Leisure Activity Enjoyment of Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2015 (Jul 26)
Enjoyment is a fundamental component of activity participation. This study compared leisure activity enjoyment experienced by typically developing children (TD; n = 64) and those with autism spectrum disorders (ASD; n = 67) from age 6 to 13. The TD children enjoyed formal and physical activities significantly more than the children with ASD. Symptom severity was negatively related to enjoyment of overall, formal, physical and social activities. Older children with ASD enjoyed overall, informal, recreational, and self-improvement activities significantly less than younger children, but no differences were seen across TD age groups. Children with ASD enjoyed swimming significantly more than TD children. Understanding patterns of activity enjoyment is useful for being better able to address a child’s motivation to participate in various life activities.

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9. Friedrich EV, Sivanathan A, Lim T, Suttie N, Louchart S, Pillen S, Pineda JA. {{An Effective Neurofeedback Intervention to Improve Social Interactions in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Jul 26)
Neurofeedback training (NFT) approaches were investigated to improve behavior, cognition and emotion regulation in children with autism spectrum disorder (ASD). Thirteen children with ASD completed pre-/post-assessments and 16 NFT-sessions. The NFT was based on a game that encouraged social interactions and provided feedback based on imitation and emotional responsiveness. Bidirectional training of EEG mu suppression and enhancement (8-12 Hz over somatosensory cortex) was compared to the standard method of enhancing mu. Children learned to control mu rhythm with both methods and showed improvements in (1) electrophysiology: increased mu suppression, (2) emotional responsiveness: improved emotion recognition and spontaneous imitation, and (3) behavior: significantly better behavior in every-day life. Thus, these NFT paradigms improve aspects of behavior necessary for successful social interactions.

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10. Gillberg IC, Helles A, Billstedt E, Gillberg C. {{Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years After Initial Diagnosis}}. {J Autism Dev Disord};2015 (Jul 26)
We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had never met criteria for an additional psychiatric/neurodevelopmental diagnosis and more than half had ongoing comorbidity (most commonly either ADHD or depression or both). Any psychiatric comorbidity increased the risk of poorer outcome. The minority of the AS group who no longer met criteria for a full diagnosis of an autism spectrum disorder were usually free of current psychiatric comorbidity. The high rate of psychiatric/neurodevelopmental comorbidities underscores the need for a full psychiatric/neurodevelopmental assessment at follow-up of males with AS.

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11. Gori I, Giuliano A, Muratori F, Saviozzi I, Oliva P, Tancredi R, Cosenza A, Tosetti M, Calderoni S, Retico A. {{Gray Matter Alterations in Young Children with Autism Spectrum Disorders: Comparing Morphometry at the Voxel and Regional Level}}. {J Neuroimaging};2015 (Jul 27)
BACKGROUND AND PURPOSE: Sophisticated algorithms to infer disease diagnosis, pathology progression and patient outcome are increasingly being developed to analyze brain MRI data. They have been successfully implemented in a variety of diseases and are currently investigated in the field of neuropsychiatric disorders, including autism spectrum disorder (ASD). We aim to test the ability to predict ASD from subtle morphological changes in structural magnetic resonance imaging (sMRI). METHODS: The analysis of sMRI of a cohort of male ASD children and controls matched for age and nonverbal intelligence quotient (NVIQ) has been carried out with two widely used preprocessing software packages (SPM and Freesurfer) to extract brain morphometric information at different spatial scales. Then, support vector machines have been implemented to classify the brain features and to localize which brain regions contribute most to the ASD-control separation. RESULTS: The features extracted from the gray matter subregions provide the best classification performance, reaching an area under the receiver operating characteristic curve (AUC) of 74%. This value is enhanced to 80% when considering only subjects with NVIQ over 70. CONCLUSIONS: Despite the subtle impact of ASD on brain morphology and a limited cohort size, results from sMRI-based classifiers suggest a consistent network of altered brain regions.

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12. Haebig E, Kaushanskaya M, Ellis Weismer S. {{Lexical Processing in School-Age Children with Autism Spectrum Disorder and Children with Specific Language Impairment: The Role of Semantics}}. {J Autism Dev Disord};2015 (Jul 26)
Children with autism spectrum disorder (ASD) and specific language impairment (SLI) often have immature lexical-semantic knowledge; however, the organization of lexical-semantic knowledge is poorly understood. This study examined lexical processing in school-age children with ASD, SLI, and typical development, who were matched on receptive vocabulary. Children completed a lexical decision task, involving words with high and low semantic network sizes and nonwords. Children also completed nonverbal updating and shifting tasks. Children responded more accurately to words from high than from low semantic networks; however, follow-up analyses identified weaker semantic network effects in the SLI group. Additionally, updating and shifting abilities predicted lexical processing, demonstrating similarity in the mechanisms which underlie semantic processing in children with ASD, SLI, and typical development.

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13. Kestemont J, Vandekerckhove M, Bulnes LC, Matthys F, Overwalle FV. {{Causal Attribution in Individuals with Subclinical and Clinical Autism Spectrum Disorder: an fMRI Study}}. {Soc Neurosci};2015 (Jul 27)
This neuroimaging study compares brain activation during causal attribution to three different attribution loci (i.e. self, another person and situation) across a typical population without (N = 20) or with subclinical Autism Spectrum symptoms (N = 18) and a clinical population with Autism Spectrum Disorder (ASD; N = 11). While they underwent fMRI, all participants read short sentences describing positive and negative behaviors and thoughts of another person directed towards the participant (i.e., « you »). Participants were then asked to attribute these behaviors to themselves, the other person or the situation. Behavioral measures revealed self-serving attributions (i.e. attributing positive events to the self, while attributing negative events externally from the self) in all three participant groups. Neural measures revealed a great deal of shared activation across the three attribution loci and across the three participant groups in the temporo-parietal junction, the posterior superior sulcus and the precuneus. Comparison between groups revealed more widespread activation in both subclinical and clinical ASD participants, which may be indicative of the extra neural resources these participants invest to compensate their impairments.

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14. Krishnan N, Krishnan K, Connors CR, Choy MS, Page R, Peti W, Van Aelst L, Shea SD, Tonks NK. {{PTP1B inhibition suggests a therapeutic strategy for Rett syndrome}}. {J Clin Invest};2015 (Jul 27)
The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.

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15. Tautz L. {{PTP1B: a new therapeutic target for Rett syndrome}}. {J Clin Invest};2015 (Jul 27):1-4.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that is characterized by successive loss of acquired cognitive, social, and motor skills and development of autistic behavior. RTT affects approximately 1 in 10,000 live female births and is the second most common cause of severe mental retardation in females after Down syndrome. Currently, there is no cure or effective therapy for RTT. Approved treatment regimens are presently limited to supportive management of specific physical and mental disabilities. In this issue, Krishnan and colleagues reveal that the protein tyrosine phosphatase PTP1B is upregulated in patients with RTT and in murine models and provide strong evidence that targeting PTP1B has potential as a viable therapeutic strategy for the treatment of RTT.

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