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1.
Cell Rep ; 5(3): 738-47, 2013 Nov 14.
Article in English | MEDLINE | ID: mdl-24210821

ABSTRACT

Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism.


Subject(s)
Brain Mapping/methods , Brain/physiopathology , Child Development Disorders, Pervasive/physiopathology , Adolescent , Brain/pathology , Child , Child Development Disorders, Pervasive/diagnosis , Child Development Disorders, Pervasive/pathology , Cohort Studies , Female , Humans , Magnetic Resonance Imaging , Male
2.
Autism ; 13(5): 523-38, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19759065

ABSTRACT

Research examining set-shifting has revealed significant difficulties for adults with autism spectrum disorders (ASDs). However, research with high-functioning children with ASDs has yielded mixed results. The current study tested 6- to 13-year-old high-functioning children with ASD and typically developing controls matched on age, gender, and IQ using the Intradimensional/Extradimensional (ID/ED) Shift Test from the Cambridge Neuropsychological Test Automated Battery. Children with ASDs completed as many ED shifts and reversal ED shifts as controls; however, they made significantly more errors than controls while completing the ED reversal shifts. Analyses on a subset of cases revealed a significant positive correlation between ED reversal errors and the number of repetitive behavior symptoms in the ASD group. These findings suggest that high-functioning children with ASDs require additional feedback to shift successfully. In addition, the relationship between set-shifting and non-social symptoms suggests its utility as a potentially informative intermediate phenotype in ASDs.


Subject(s)
Child Development Disorders, Pervasive/psychology , Neuropsychological Tests , Set, Psychology , Stereotypic Movement Disorder/psychology , Adolescent , Child , Female , Humans , Male , Wechsler Scales
3.
J Autism Dev Disord ; 39(12): 1735-9, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19565331

ABSTRACT

Recent research indicates that individuals with autism do not effectively use inner speech during the completion of cognitive tasks. We used Articulatory Suppression (AS) to interfere with inner speech during completion of alternate items from the Tower of London (TOL). AS detrimentally affected TOL performance among typically developing (TD) adolescents (n = 25), but did not significantly diminish performance among adolescents with high functioning (IQ > 80) autism spectrum disorders (n = 28). Moreover, the TD group's TOL performance under AS was indistinguishable from the autism group's impaired baseline TOL performance. These findings suggest that diminished inner speech usage among individuals with high functioning autism spectrum disorders (relative to TD controls) may contribute to executive dysfunction associated with these disorders.


Subject(s)
Child Development Disorders, Pervasive/psychology , Cognition Disorders/psychology , Cognition , Language , Thinking , Adolescent , Child , Child Development Disorders, Pervasive/complications , Cognition Disorders/complications , Executive Function , Female , Humans , Male , Neuropsychological Tests , Young Adult
4.
Cereb Cortex ; 19(8): 1787-94, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19068486

ABSTRACT

Unmasking the neural basis of neurodevelopmental disorders, such as autism spectrum disorders (ASD), requires studying functional connectivity during childhood when cognitive skills develop. A functional connectivity magnetic resonance imaging (fcMRI) analysis was performed on data collected during Go/NoGo task performance from 24 children ages 8-12 years (12 with ASD; 12 controls matched on age and intellectual functioning). We investigated the connectivity of the left and right inferior frontal cortex (IFC; BA 47), key regions for response inhibition, with other active regions in frontal, striatal, and parietal cortex. Groups did not differ on behavioral measures or functional connectivity of either IFC region. A trend for reduced connectivity in the right IFC for the ASD group was revealed when controlling for age. In the ASD group, there was a significant negative correlation between age and 2 right IFC correlation pairs: right IFC-bilateral presupplementary motor area (BA 6) and right IFC-right caudate. Compared with typical controls, children with ASD may not have gross differences in IFC functional connectivity during response inhibition, which contrasts with an adult study of ASD that reported reduced functional connectivity. This discrepancy suggests an atypical developmental trajectory in ASD for right IFC connectivity with other neural regions supporting response inhibition.


Subject(s)
Autistic Disorder/pathology , Frontal Lobe/growth & development , Age Factors , Analysis of Variance , Autistic Disorder/physiopathology , Cerebral Cortex/growth & development , Cerebral Cortex/physiopathology , Child , Cognition Disorders/physiopathology , Female , Frontal Lobe/pathology , Frontal Lobe/physiopathology , Humans , Image Processing, Computer-Assisted , Language Tests , Magnetic Resonance Imaging , Male , Nerve Net/pathology , Nerve Net/physiopathology , Neuropsychological Tests
5.
Neuroimage ; 38(1): 184-93, 2007 Oct 15.
Article in English | MEDLINE | ID: mdl-17707658

ABSTRACT

Superior performance on the Embedded Figures Task (EFT) has been attributed to weak central coherence in perceptual processing in Autism Spectrum Disorder (ASD). The present study used functional magnetic resonance imaging to examine the neural basis of EFT performance in 7- to 12-year-old ASD children and age- and IQ-matched controls. ASD children activated only a subset of the distributed network of regions activated in controls. In frontal cortex, control children activated left dorsolateral, medial and dorsal premotor regions whereas ASD children only activated the dorsal premotor region. In parietal and occipital cortices, activation was bilateral in control children but unilateral (left superior parietal and right occipital) in ASD children. Further, extensive bilateral ventral temporal activation was observed in control, but not ASD children. ASD children performed the EFT at the same level as controls but with reduced cortical involvement, suggesting that disembedded visual processing is accomplished parsimoniously by ASD relative to typically developing brains.


Subject(s)
Autistic Disorder/physiopathology , Brain/physiopathology , Cognition Disorders/physiopathology , Evoked Potentials , Pattern Recognition, Visual , Task Performance and Analysis , Autistic Disorder/complications , Brain Mapping/methods , Child , Cognition Disorders/complications , Humans , In Vitro Techniques , Magnetic Resonance Imaging/methods , Male
6.
Dev Neuropsychol ; 28(3): 809-27, 2005.
Article in English | MEDLINE | ID: mdl-16266250

ABSTRACT

Executive function (EF) abilities were investigated in 72 children with high-functioning autism (HFA) spectrum disorders through the collection of parent ratings and performance on laboratory measures of EF. In addition, discrepancy analysis was used to isolate executive functioning on tasks that carry multiple demands. Comparison of HFA and Asperger Disorder (AD) groups did not reveal consistent differences in EF. Results did indicate global EF deficits in the combined group of children with HFA and AD. Within the EF domain, specific deficits in flexibility and organization were most prominent.


Subject(s)
Autistic Disorder/epidemiology , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Adolescent , Asperger Syndrome/diagnosis , Asperger Syndrome/epidemiology , Autistic Disorder/diagnosis , Child , Child, Preschool , Female , Humans , Male , Neuropsychological Tests , Observer Variation , Severity of Illness Index
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