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ABSTRACT: Autism spectrum disorders (ASD) are heterogeneous, neurodevelopmental disorders with early onset, characterized by a triad of impairments in reciprocal interaction and communication as well as repetitive and restricted interests and activities. Though underlying causes still remain largely unknown, there is now evidence for abnormal growth trajectories in the early brain development in ASD during vulnerable periods and subsequent impairment of neuronal organization and differentiation of neuronal networks. A growing number of studies over the last 10 years support the efficacy of behaviorally based interventions in ASD for the improvement of social communication and behavioral functioning. In contrast, research on neurobiologically based therapies for ASD is still at its beginnings. In this article, we will provide a selective overview of novel interventions and trainings based on neurobiological principles. Directions and options for future research on treatment aiming at restoration of normal plasticity in disrupted brain circuits in ASD are discussed.
Restorative neurology and neuroscience. 04/2013;
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ABSTRACT: This study broadly examines executive (EF) and visuo-motor function in 30 adolescent and adult individuals with high-functioning autism spectrum disorder (ASD) in comparison to 28 controls matched for age, gender, and IQ. ASD individuals showed impaired spatial working memory, whereas planning, cognitive flexibility, and inhibition were spared. Pure movement execution during visuo-motor information processing also was intact. In contrast, execution time of reading, naming, and of visuo-motor information processing tasks including a choice component was increased in the ASD group. Results of this study are in line with previous studies reporting only minimal EF difficulties in older individuals with ASD when assessed by computerized tasks. The finding of impaired visuo-motor information processing should be accounted for in further neuropsychological studies in ASD.
Journal of Autism and Childhood Schizophrenia 09/2012; · 3.06 Impact Factor
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Richard Anney,
Lambertus Klei,
Dalila Pinto,
Joana Almeida,
Elena Bacchelli,
Gillian Baird,
Nadia Bolshakova, Sven Bölte,
Patrick F Bolton,
Thomas Bourgeron, [......],
Edwin H Cook,
Louise Gallagher,
Michael Gill,
Joachim Hallmayer,
Andrew D Paterson,
James S Sutcliffe,
Peter Szatmari,
Veronica J Vieland,
Hakon Hakonarson,
Bernie Devlin
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ABSTRACT: While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Human Molecular Genetics 07/2012; 21(21):4781-92. · 7.64 Impact Factor
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ABSTRACT: Current theories of the pathophysiology of autism spectrum disorders (ASD) have focused on abnormal temporal coordination of neural activity in cortical circuits as a core impairment of the disorder. In the current study, we examined the possibility that gamma-band activity may be crucially involved in aberrant brain functioning in ASD. Magneto-encephalographic (MEG) data were recorded from 13 adult human participants with ASD and 16 controls during the presentation of Mooney faces. MEG data were analyzed in the 25-150 Hz frequency range and a beamforming approach was used to identify the sources of spectral power. Participants with ASD showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces, while responses to inverted stimuli were in the normal range. Impaired perceptual organization in the ASD group was accompanied by a reduction in both the amplitude and phase locking of gamma-band activity. A beamforming approach identified distinct networks during perceptual organization in controls and participants with ASD. In controls, perceptual organization of Mooney faces involved increased 60-120 Hz activity in a frontoparietal network, while in the ASD group stronger activation was found in visual regions. These findings highlight the contribution of impaired gamma-band activity toward complex visual processing in ASD, suggesting atypical modulation of high-frequency power in frontoposterior networks.
Journal of Neuroscience 07/2012; 32(28):9563-73. · 7.11 Impact Factor
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Sven Bölte
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ABSTRACT: The Social Responsiveness Scale (SRS) is a tool for quantitative autism assessment in children and adolescents. The SRS-A addresses social responsiveness in adulthood. Reliability and validity using the German adaptation of the SRS-A was examined in 20 adults with Autism Spectrum Disorder (ASD), 62 with other mental disorders (CLIN) and 163 typically developing (TD) participants. Cronbach's alpha ranged from .71 (TD) to .89 (ASD). A SRS-A total score of 67 had a sensitivity of .85, and a specificity of .83 for ASD versus CLIN/TD. Correlations with established autism scales (ADOS, AQ, SCQ) were moderate to high (r = .25-.83). Results provide adequate preliminary support for the application of the SRS-A.
Journal of Autism and Childhood Schizophrenia 12/2011; 42(9):1998-9. · 3.06 Impact Factor
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Henrik Anckarsäter,
Sebastian Lundström,
Linnea Kollberg,
Nora Kerekes,
Camilla Palm,
Eva Carlström,
Niklas Långström,
Patrik K E Magnusson,
Linda Halldner, Sven Bölte,
Christopher Gillberg,
Clara Gumpert,
Maria Råstam,
Paul Lichtenstein
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ABSTRACT: The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing longitudinal twin study targeting all twins born in Sweden since July 1, 1992. Since 2004, parents of twins are interviewed regarding the children's somatic and mental health and social environment in connection with their 9th or 12th birthdays (CATSS-9/12). By January 2010, 8,610 parental interviews concerning 17,220 twins had been completed, with an overall response rate of 80%. At age 15 (CATSS-15) and 18 (CATSS-18), twins and parents complete questionnaires that, in addition to assessments of somatic and mental health, include measures of personality development and psychosocial adaptation. Twin pairs in CATSS-9/12 with one or both twins screening positive for autism spectrum disorders, attention deficit/hyperactivity disorder, tic disorders, developmental coordination disorder, learning disorders, oppositional defiant disorder, conduct disorder, obsessive-compulsive disorder, and/or eating problems have been followed with in-depth questionnaires on family, social environment and personality, and subsequently by clinical assessments at age 15 together with randomly selected population controls, including 195 clinically assessed twin pairs from the first 2 year cohorts (CATSS-15/DOGSS). This article describes the cohorts and study groups, data collection, and measures used. Prevalences, distributions, heritability estimates, ages at onset, and sex differences of mental health problems in the CATSS-9/12, that were analyzed and found to be overall comparable to those of other clinical and epidemiological studies. The CATSS study has the potential of answering important questions on the etiology of childhood mental health problems and their role in the development of later adjustment problems.
Twin Research and Human Genetics 12/2011; 14(6):495-508. · 1.70 Impact Factor
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Henrik Anckarsäter,
Sebastian Lundström,
Linnea Kollberg,
Nora Kerekes,
Camilla Palm,
Eva Carlström,
Niklas Långström,
Patrik K. E. Magnusson,
Linda Halldner, Sven Bölte,
Christopher Gillberg,
Clara Gumpert,
Maria Råstam
[show abstract]
[hide abstract]
ABSTRACT: The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing longitudinal twin study targeting all twins born in Sweden since July 1, 1992. Since 2004, parents of twins are interviewed regarding the children's somatic and mental health and social environment in connection with their 9th or 12th birthdays (CATSS-9/12). By January 2010, 8,610 parental interviews concerning 17,220 twins had been completed, with an overall response rate of 80%. At age 15 (CATSS-15) and 18 (CATSS-18), twins and parents complete questionnaires that, in addition to assessments of somatic and mental health, include measures of personality development and psychosocial adaptation. Twin pairs in CATSS-9/12 with one or both twins screening positive for autism spectrum disorders, attention deficit/hyperactivity disorder, tic disorders, developmental coordination disorder, learning disorders, oppositional defiant disorder, conduct disorder, obsessive–compulsive disorder, and/or eating problems have been followed with in-depth questionnaires on family, social environment and personality, and subsequently by clinical assessments at age 15 together with randomly selected population controls, including 195 clinically assessed twin pairs from the first 2 year cohorts (CATSS-15/DOGSS). This article describes the cohorts and study groups, data collection, and measures used. Prevalences, distributions, heritability estimates, ages at onset, and sex differences of mental health problems in the CATSS-9/12, that were analyzed and found to be overall comparable to those of other clinical and epidemiological studies. The CATSS study has the potential of answering important questions on the etiology of childhood mental health problems and their role in the development of later adjustment problems.
Twin Research and Human Genetics. 11/2011; 14(06):495 - 508.
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ABSTRACT: Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli and enhanced activity of early visual areas. Ten autistic and ten matched control participants underwent 151-channel whole-head magnetoencephalography. Participants were presented with 400 embedded or isolated letters ('S' or 'H') and asked to indicate which of the two letters was shown. Performance was equal in both groups, but event-related magnetic fields differed between groups in an early (100-150 ms) and a later (350-400 ms) time window. In the early time window, autistic individuals differed from control participants in the embedded, but not in the isolated condition, reflecting reduced processing of the irrelevant context in autistic individuals. In the later time window, amplitude differences between the embedded and isolated conditions were measured in control participants only, suggesting that "disembedding" processes were not required in autistic individuals. Source localisation indicated that activity in individuals with ASD peaked in the primary visual cortex in both conditions and time windows indicating an effortless (automatic, bottom-up) local process, whereas activity in controls peaked outside the visual cortex.
Neuropsychologia 09/2011; 49(11):3011-7. · 3.64 Impact Factor
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Dalila Pinto,
Alistair Pagnamenta,
Lambertus Klei,
Richard Anney,
Daniele Merico,
Regina Regan,
Judith Conroy,
Tiago Magalhaes,
Catarina Correia,
Brett Abrahams, [......],
Andrew Paterson,
Margaret Pericak-Vance,
Gerard Schellenberg,
Peter Szatmari,
Astrid Vicente,
Veronica Vieland,
Ellen Wijsman,
Stephen Scherer,
James Sutcliffe,
Catalina Betancur
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[hide abstract]
ABSTRACT: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Nature 07/2011; 466:368-372. · 36.28 Impact Factor
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ABSTRACT: To review current studies on the effectiveness of neurofeedback as a method of treatment of the core symptoms of autism spectrum disorders (ASD).
Studies were selected based on searches in PubMed, Ovid MEDLINE, EMBASE, ERIC, and CINAHL using combinations of the following keywords: 'Neurofeedback' OR 'EEG Biofeedback' OR 'Neurotherapy' OR 'Mu-Rhythm' OR 'SMR' AND 'Autism' OR 'Autism Spectrum Disorder' OR 'Pervasive Developmental Disorder'.
The existing evidence does not support the use of neurofeedback in the treatment of ASD. Studies with outcomes in favour of neurofeedback might be showing an improvement in comorbid attention-deficit-hyperactivity disorder symptoms rather than a true improvement in core ASD symptoms.
Limitations of this review are those inherent in the studies available, including small sample size, short duration, variable diagnostic criteria, and insufficient control interventions, all causing a lack of generalizability.
Developmental Medicine & Child Neurology 07/2011; 53(11):986-93. · 2.92 Impact Factor
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ABSTRACT: Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD.
Journal of Autism and Childhood Schizophrenia 06/2011; 42(5):726-33. · 3.06 Impact Factor
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ABSTRACT: Despite the skewed sex ratio, few studies have addressed possible cognitive sex differences in autism spectrum disorders (ASDs). This study compared visual attention to detail (ATTD) and selected executive functions (EF) in 35 males and 21 females with higher-functioning ASD and unaffected sibling controls. Females with ASD outperformed males on EF as assessed by the Trail Making Test B-A. Males with ASD showed superior performance for ATTD as measured by the Block Design Test (BD) when compared with females. EF difficulties in males were correlated with more stereotypic behaviours and interests on the Autism Diagnostic Interview-Revised or the Autism Diagnostic Observation Schedule. The results indicated clinically meaningful cognitive sex differences in ASD, particularly an association between EF and stereotypic behaviours and interests. ATTD as a potential basis for specific cognitive strengths (e.g. scientific/savant skills) might be more pronounced in males with ASD.
Autism 03/2011; 15(4):497-511. · 2.27 Impact Factor
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ABSTRACT: Research indicates that autism is the extreme end of a continuously distributed trait. The Social Responsiveness Scale (SRS) and the Social and Communication Disorders Checklist (SCDC) aim to assess autistic traits. The objective of this study was to compare their clinical validity. The SRS showed sensitivities of .74 to .80 and specificities of .69 to 1.00 for autism. Sensitivities were .85 to .90 and specificities .28 to.82 for the SCDC. Correlations with the ADI-R, ADOS and SCQ were higher for the SRS than for the SCDC. The SCDC seems superior to the SRS to screen for unspecific social and communicative deficits including autism. The SRS appears more suitable than the SCDC in clinical settings and for specific autism screening.
Journal of Autism and Childhood Schizophrenia 01/2011; 41(1):66-72. · 3.06 Impact Factor
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ABSTRACT: To review neuropsychological models of theory of mind (ToM), executive functions (EF), and central coherence (CC) as framework for cognitive abnormalities in autism spectrum disorders (ASD).
Behavioral and functional imaging studies are described that assess social-cognitive, emotional, and executive functions as well as locally oriented perception in ASD.
Impairments in ToM and EF as well as alterations in CC are frequently replicated phenomena in ASD. Especially problems concerning social perception and ToM have high explanatory value for clinical symptomatology. Brain activation patterns differ between individuals with and without ASD for ToM, EF, und CC functions. An approach focussing on reduced cortical connectivity seems to be increasingly favored over explanations focussing on single affected brain sites.
A better understanding of the complexities of ASD in future research demands the integration of clinical, neuropsychological, functional imaging, and molecular genetics evidence. Weaknesses in ToM and EF as well as strengths in detail-focussed perception should be used for individual intervention planning.
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie 01/2011; 39(2):79-90. · 0.99 Impact Factor
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ABSTRACT: This study addresses the question whether personality dimensions differ between children with autism spectrum disorders (ASD) and attention deficit/hyperactivity disorder (ADHD), and whether these personality characteristics influence social problems in these groups of children.
68 children with ADHD (n = 32) and ASD (n = 36) were assessed with the Junior Temperament and Character Inventory (JTCI 7-11 R) and the Social Responsiveness Scale (SRS), as rated by the parents. Diagnosis of ASD was confirmed with standardized diagnostic instruments (ADOS und ADI-R).
Both children with ASD and ADHD displayed significantly decreased scores in persistence, self-directedness and cooperativeness compared to normative values. Additionally, children with ASD showed extremely low reward dependence and differed significantly from children with ADHD in the temperament dimensions harm avoidance and reward dependence as well as in the character dimensions self-directedness and cooperativeness. In both groups, personality dimensions, especially reward dependence, were predictive of social responsiveness, as assessed by the SRS.
The results suggest that specific personality characteristics are present already in young children with ASD and ADHD and may have an impact on their social competence.
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie 01/2011; 39(2):133-41. · 0.99 Impact Factor
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ABSTRACT: About 10% of autistic individuals exhibit some form of islets of abilities in the face of serious intellectual or mental disability ("savant syndrome"). The aim of this study was to investigate brain mechanisms in a sample of autistic subjects with outstanding memory. We investigated seven mnemonist savants with high-functioning autism spectrum disorder and seven matched controls with 151-channel whole-head magnetencephalography in a continuous old-new paradigm. They were presented with 300 pseudowords and 300 shapes and had to indicate by button press, whether the presented stimulus had been shown before. Unexpectedly, mnemonist savants did not perform better than controls, but were outperformed in the recognition of pseudowords. Accordingly, event-related magnetic fields elicited by pseudowords showed widespread old-new effects in controls, but not in savants. A source analysis of its early components revealed right occipital activation in savants, but left parietal activation in controls. This might be related to a visual processing style in mnemonist savants that proved to be inefficient in this task. During the possibly familiarity-based recognition of shapes, there were earlier and more widespread bilateral old-new effects in mnemonist savants, what might reflect their experience with figural material. In a neuropsychological test battery, mnemonist savants performed comparably to autistic people without special memory skills. However, a different factor structure of these tests pointed to a different organization of memory in mnemonist savants compared to controls that is characterized by its relative independence of general intelligence.
Behavioural brain research 12/2010; 215(1):114-21. · 3.22 Impact Factor
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Richard Anney,
Lambertus Klei,
Dalila Pinto,
Regina Regan,
Judith Conroy,
Tiago R Magalhaes,
Catarina Correia,
Brett S Abrahams,
Nuala Sykes,
Alistair T Pagnamenta, [......],
Gerard D Schellenberg,
Stephen W Scherer,
James S Sutcliffe,
Peter Szatmari,
Astrid M Vicente,
Veronica J Vieland,
Ellen M Wijsman,
Bernie Devlin,
Sean Ennis,
Joachim Hallmayer
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ABSTRACT: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Human Molecular Genetics 10/2010; 19(20):4072-82. · 7.64 Impact Factor
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Richard Anney,
Lambertus Klei,
Dalila Pinto,
Regina Regan,
Judith Conroy,
Tiago Magalhaes,
Catarina Correia,
Brett Abrahams,
Nuala Sykes,
Alistair Pagnamenta, [......],
Gerard Schellenberg,
Stephen Scherer,
James Sutcliffe,
Peter Szatmari,
Astrid Vicente,
Veronica Vieland,
Ellen Wijsman,
Bernie Devlin,
Sean Ennis,
Joachim Hallmayer
[show abstract]
[hide abstract]
ABSTRACT: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 x 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 x 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Human Molecular Genetics 10/2010; 19(20):4072-4082. · 7.64 Impact Factor
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Dalila Pinto,
Alistair T Pagnamenta,
Lambertus Klei,
Richard Anney,
Daniele Merico,
Regina Regan,
Judith Conroy,
Tiago R Magalhaes,
Catarina Correia,
Brett S Abrahams, [......],
Andrew D Paterson,
Margaret A Pericak-Vance,
Gerard D Schellenberg,
Peter Szatmari,
Astrid M Vicente,
Veronica J Vieland,
Ellen M Wijsman,
Stephen W Scherer,
James S Sutcliffe,
Catalina Betancur
[show abstract]
[hide abstract]
ABSTRACT: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Nature 07/2010; 466(7304):368-72. · 36.28 Impact Factor
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Autism 05/2010; 14(3):155-9. · 2.27 Impact Factor
