1. Caplette L, Wicker B, Gosselin F. {{Atypical Time Course of Object Recognition in Autism Spectrum Disorder}}. {Sci Rep};2016 (Oct 18);6:35494.
In neurotypical observers, it is widely believed that the visual system samples the world in a coarse-to-fine fashion. Past studies on Autism Spectrum Disorder (ASD) have identified atypical responses to fine visual information but did not investigate the time course of the sampling of information at different levels of granularity (i.e. Spatial Frequencies, SF). Here, we examined this question during an object recognition task in ASD and neurotypical observers using a novel experimental paradigm. Our results confirm and characterize with unprecedented precision a coarse-to-fine sampling of SF information in neurotypical observers. In ASD observers, we discovered a different pattern of SF sampling across time: in the first 80 ms, high SFs lead ASD observers to a higher accuracy than neurotypical observers, and these SFs are sampled differently across time in the two subject groups. Our results might be related to the absence of a mandatory precedence of global information, and to top-down processing abnormalities in ASD.
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2. Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, Sailey A, Wynne R, Rose S, Melnyk S, Jill James S, Sequeira JM, Quadros EV. {{Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial}}. {Mol Psychiatry};2016 (Oct 18)
We sought to determine whether high-dose folinic acid improves verbal communication in children with non-syndromic autism spectrum disorder (ASD) and language impairment in a double-blind placebo control setting. Forty-eight children (mean age 7 years 4 months; 82% male) with ASD and language impairment were randomized to receive 12 weeks of high-dose folinic acid (2 mg kg-1 per day, maximum 50 mg per day; n=23) or placebo (n=25). Children were subtyped by glutathione and folate receptor-alpha autoantibody (FRAA) status. Improvement in verbal communication, as measured by a ability-appropriate standardized instrument, was significantly greater in participants receiving folinic acid as compared with those receiving placebo, resulting in an effect of 5.7 (1.0,10.4) standardized points with a medium-to-large effect size (Cohen’s d=0.70). FRAA status was predictive of response to treatment. For FRAA-positive participants, improvement in verbal communication was significantly greater in those receiving folinic acid as compared with those receiving placebo, resulting in an effect of 7.3 (1.4,13.2) standardized points with a large effect size (Cohen’s d=0.91), indicating that folinic acid treatment may be more efficacious in children with ASD who are FRAA positive. Improvements in subscales of the Vineland Adaptive Behavior Scale, the Aberrant Behavior Checklist, the Autism Symptom Questionnaire and the Behavioral Assessment System for Children were significantly greater in the folinic acid group as compared with the placebo group. There was no significant difference in adverse effects between treatment groups. Thus, in this small trial of children with non-syndromic ASD and language impairment, treatment with high-dose folinic acid for 12 weeks resulted in improvement in verbal communication as compared with placebo, particularly in those participants who were positive for FRAAs.Molecular Psychiatry advance online publication, 18 October 2016; doi:10.1038/mp.2016.168.
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3. Jamison TR, Schuttler JO. {{Overview and Preliminary Evidence for a Social Skills and Self-Care Curriculum for Adolescent Females with Autism: The Girls Night Out Model}}. {J Autism Dev Disord};2016 (Oct 18)
A majority of social skills research in autism spectrum disorder (ASD) and interventions target school age males and no published studies target adolescent females with ASD or related disabilities. Females with ASD are at risk for internalizing symptoms, and experience greater challenges in socialization and communication as social demands become increasingly complex in adolescence. This paper provides a thorough description of a social skills and self-care program designed to address the specific needs of adolescent females with ASD. The approach is peer mediated and occurs within natural or community settings to facilitate generalization. Findings from program evaluation data collected across 4 years illustrate significant improvements in perceived social competence, self-perception, and quality of life and suggests the approach is feasible and social valid.
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4. Katuwal GJ, Baum SA, Cahill ND, Dougherty CC, Evans E, Evans DW, Moore GJ, Michael AM. {{Inter-Method Discrepancies in Brain Volume Estimation May Drive Inconsistent Findings in Autism}}. {Front Neurosci};2016;10:439.
Previous studies applying automatic preprocessing methods on Structural Magnetic Resonance Imaging (sMRI) report inconsistent neuroanatomical abnormalities in Autism Spectrum Disorder (ASD). In this study we investigate inter-method differences as a possible cause behind these inconsistent findings. In particular, we focus on the estimation of the following brain volumes: gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and total intra cranial volume (TIV). T1-weighted sMRIs of 417 ASD subjects and 459 typically developing controls (TDC) from the ABIDE dataset were estimated using three popular preprocessing methods: SPM, FSL, and FreeSurfer (FS). Brain volumes estimated by the three methods were correlated but had significant inter-method differences; except TIVSPM vs. TIVFS, all inter-method differences were significant. ASD vs. TDC group differences in all brain volume estimates were dependent on the method used. SPM showed that TIV, GM, and CSF volumes of ASD were larger than TDC with statistical significance, whereas FS and FSL did not show significant differences in any of the volumes; in some cases, the direction of the differences were opposite to SPM. When methods were compared with each other, they showed differential biases for autism, and several biases were larger than ASD vs. TDC differences of the respective methods. After manual inspection, we found inter-method segmentation mismatches in the cerebellum, sub-cortical structures, and inter-sulcal CSF. In addition, to validate automated TIV estimates we performed manual segmentation on a subset of subjects. Results indicate that SPM estimates are closest to manual segmentation, followed by FS while FSL estimates were significantly lower. In summary, we show that ASD vs. TDC brain volume differences are method dependent and that these inter-method discrepancies can contribute to inconsistent neuroimaging findings in general. We suggest cross-validation across methods and emphasize the need to develop better methods to increase the robustness of neuroimaging findings.
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5. Kuzmanovic B, Rigoux L, Vogeley K. {{Brief Report: Reduced Optimism Bias in Self-Referential Belief Updating in High-Functioning Autism}}. {J Autism Dev Disord};2016 (Oct 18)
Previous research has demonstrated irrational asymmetry in belief updating: people tend to take into account good news and neglect bad news. Contradicting formal learning principles, belief updates were on average larger after better-than-expected information than after worse-than-expected information. In the present study, typically developing subjects demonstrated this optimism bias in self-referential judgments. In contrast, adults with high-functioning autism spectrum disorder (ASD) were significantly less biased when updating self-referential beliefs (each group n = 21, matched for age, gender and IQ). These findings indicate a weaker influence of self-enhancing motives on prospective judgments in ASD. Reduced susceptibility to emotional and motivational biases in reasoning in ASD could elucidate impairments of social cognition, but may also confer important cognitive benefits.
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6. Lombardo MV, Lai MC, Auyeung B, Holt RJ, Allison C, Smith P, Chakrabarti B, Ruigrok AN, Suckling J, Bullmore ET, Ecker C, Craig MC, Murphy DG, Happe F, Baron-Cohen S. {{Unsupervised data-driven stratification of mentalizing heterogeneity in autism}}. {Sci Rep};2016 (Oct 18);6:35333.
Individuals affected by autism spectrum conditions (ASC) are considerably heterogeneous. Novel approaches are needed to parse this heterogeneity to enhance precision in clinical and translational research. Applying a clustering approach taken from genomics and systems biology on two large independent cognitive datasets of adults with and without ASC (n = 694; n = 249), we find replicable evidence for 5 discrete ASC subgroups that are highly differentiated in item-level performance on an explicit mentalizing task tapping ability to read complex emotion and mental states from the eye region of the face (Reading the Mind in the Eyes Test; RMET). Three subgroups comprising 45-62% of ASC adults show evidence for large impairments (Cohen’s d = -1.03 to -11.21), while other subgroups are effectively unimpaired. These findings delineate robust natural subdivisions within the ASC population that may allow for more individualized inferences and accelerate research towards precision medicine goals.
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7. Lynn AC, Padmanabhan A, Simmonds D, Foran W, Hallquist MN, Luna B, O’Hearn K. {{Functional connectivity differences in autism during face and car recognition: underconnectivity and atypical age-related changes}}. {Dev Sci};2016 (Oct 16)
Face recognition abilities improve between adolescence and adulthood over typical development (TD), but plateau in autism, leading to increasing face recognition deficits in autism later in life. Developmental differences between autism and TD may reflect changes between neural systems involved in the development of face encoding and recognition. Here, we focused on whole-brain connectivity with the fusiform face area (FFA), a well-established face-preferential brain region. Older children, adolescents, and adults with and without autism completed the Cambridge Face Memory Test, and a matched car memory test, during fMRI scanning. We then examined task-based functional connectivity between the FFA and the rest of the brain, comparing autism and TD groups during encoding and recognition of face and car stimuli. The autism group exhibited underconnectivity, relative to the TD group, between the FFA and frontal and primary visual cortices, independent of age. Underconnectivity with the medial and rostral lateral prefrontal cortex was face-specific during encoding and recognition, respectively. Conversely, underconnectivity with the L orbitofrontal cortex was evident for both face and car encoding. Atypical age-related changes in connectivity emerged between the FFA and the R temporoparietal junction, and R dorsal striatum for face stimuli only. Similar differences in age-related changes in autism emerged for FFA connectivity with the amygdala across both face and car recognition. Thus, underconnectivity and atypical development of functional connectivity may lead to a less optimal face-processing network in the context of increasing general and social cognitive deficits in autism.
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8. Oien RA, Hart L, Schjolberg S, Wall CA, Kim ES, Nordahl-Hansen A, Eisemann MR, Chawarska K, Volkmar FR, Shic F. {{Parent-Endorsed Sex Differences in Toddlers with and Without ASD: Utilizing the M-CHAT}}. {J Autism Dev Disord};2016 (Oct 18)
Sex differences in typical development can provide context for understanding ASD. Baron-Cohen (Trends Cogn Sci 6(6):248-254, 2002) suggested ASD could be considered an extreme expression of normal male, compared to female, phenotypic profiles. In this paper, sex-specific M-CHAT scores from N = 53,728 18-month-old toddlers, including n = 185 (32 females) with ASD, were examined. Results suggest a nuanced view of the « extreme male brain theory of autism ». At an item level, almost every male versus female disadvantage in the broader population was consistent with M-CHAT vulnerabilities in ASD. However, controlling for total M-CHAT failures, this male disadvantage was more equivocal and many classically ASD-associated features were found more common in non-ASD. Within ASD, females showed relative strengths in joint attention, but impairments in imitation.
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9. Pogue AI, Lukiw WJ. {{Natural and Synthetic Neurotoxins in Our Environment: From Alzheimer’s Disease (AD) to Autism Spectrum Disorder (ASD)}}. {J Alzheimers Dis Parkinsonism};2016 (Aug);6(4)
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10. Stavropoulos KK, Viktorinova M, Naples A, Foss-Feig J, McPartland JC. {{Autistic traits modulate conscious and nonconscious face perception}}. {Soc Neurosci};2016 (Oct 18)
BACKGROUND: Difficulty with emotion perception is a core feature of autism spectrum disorder (ASD) that is also associated with the broader autism phenotype. OBJECTIVES: The current study explored the neural underpinnings of conscious and non-conscious perceptions of affect in typically developing individuals with varying levels of autistic-like traits, as measured by the Autism Quotient (AQ). We investigated the relationship between autistic traits and face processing efficiency using event-related potentials (ERPs). METHODS: In 20 typically developing adults, we utilized ERPs (the P100, N170, and P300) to measure differences in face processing for emotional faces that were presented either (a) too quickly to reach conscious awareness (16 ms) or (b) slowly enough to be consciously observed (200 ms). RESULTS: All individuals evidenced increased P100 and P300 amplitude and and shorter N170 latencies for nonconscious versus consciously presented faces. Individuals with high AQ scores evidenced delayed ERP components. CONCLUSIONS: Nonconsciously perceived emotional faces elicited enhanced neural responses regardless of AQ score. Higher levels of autistic traits were associated with inefficient face perception (i.e., longer latency of ERP components). This delay parallels processing delays observed in ASD. These data suggest that inefficient social perception is present in individuals with subclinical levels of social impairment.
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11. Veenstra-VanderWeele J, Cook EH, King BH, Zarevics P, Cherubini M, Walton-Bowen K, Bear MF, Wang PP, Carpenter RL. {{Arbaclofen in Children and Adolescents with Autism Spectrum Disorder: A Randomized, Controlled, Phase 2 Trial}}. {Neuropsychopharmacology};2016 (Oct 17)
Several lines of emerging data point to an imbalance between neuronal excitation and inhibition in at least a subgroup of individuals with autism spectrum disorder (ASD), including in those with fragile X syndrome (FXS), one of the most common genetic syndromes within ASD. In animal models of FXS and of ASD, GABA-B agonists have improved both brain and behavioral phenotypes, including social behavior. A phase 2 randomized, placebo-controlled, crossover trial found that the GABA-B agonist arbaclofen improved social avoidance symptoms in FXS. A pilot open label trial of arbaclofen suggested similar benefits in ASD. We therefore evaluated arbaclofen in a randomized, placebo-controlled, phase 2 study of 150 participants, ages 5-21 years old, with ASD. No difference from placebo was detected on the primary outcome measure, the parent-rated Aberrant Behavior Checklist Social Withdrawal/Lethargy subscale. However, a specified secondary analysis found improvement on the clinician-rated Clinical Global Impression of Severity. An exploratory post-hoc analysis of participants with a consistent rater across the trial revealed greater improvement in the Vineland Adaptive Behavior Scales II Socialization domain in participants receiving arbaclofen. Affect lability (11%) and sedation (9%) were the most common adverse events. In this exploratory study, secondary analyses suggest that arbaclofen may have the potential to improve symptoms in some children with ASD, but further study will be needed to replicate and extend these initial findings.Neuropsychopharmacology accepted article preview online, 17 October 2016. doi:10.1038/npp.2016.237.
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12. Wright SD, Wright CA, D’Astous V, Wadsworth AM. {{Autism Aging}}. {Gerontol Geriatr Educ};2016 (Oct 17)
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13. Yaylaci F, Miral S. {{A Comparison of DSM-IV-TR and DSM-5 Diagnostic Classifications in the Clinical Diagnosis of Autistic Spectrum Disorder}}. {J Autism Dev Disord};2016 (Oct 17)
Aim of this study was to compare children diagnosed with Pervasive Developmental Disorder (PDD) according to DSM-IV-TR and DSM-5 diagnostic systems. One hundred fifty children aged between 3 and 15 years diagnosed with PDD by DSM-IV-TR were included. PDD symptoms were reviewed through psychiatric assessment based on DSM-IV-TR and DSM-5 criteria. Clinical severity was determined using Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC). A statistically significant decrease (19.3 %) was detected in the diagnostic ratio with DSM-5. Age and symptom severity differed significantly between those who were and were not diagnosed with PDD using DSM-5. B4 criteria in DSM-5 was most common criterion. Results indicate that individuals diagnosed with PDD by DSM-IV-TR criteria may not be diagnosed using DSM-5 criteria.
