Dataset Information

Reduced Local and Increased Long-Range Functional Connectivity of the Thalamus in Autism Spectrum Disorder.

ABSTRACT: It is hypothesized that brain network abnormalities in autism spectrum disorder (ASD) reflect local overconnectivity and long-range underconnectivity. However, this is not a consistent finding in recent studies, which could reflect the developmental nature and the heterogeneity of ASD. Here, we tested 565 ASD and 602 neurotypical (NT) males, and 91 ASD and 233 NT females using local functional connectivity density (lFCD) mapping and seed-voxel correlation analyses to assess how local and long-range connectivities differ in ASD. Compared with NT males, ASD males had lower and weaker age-related increases in thalamic lFCD, which were associated with symptoms of autism. Post-hoc seed-voxel correlation analyses for the thalamus cluster revealed stronger connectivity with auditory, somatosensory, motoric, and interoceptive cortices for ASD than for NT, both in males and in females, which decreased with age in both ASD and NT. These results document the disruption of local thalamic connectivity and dysregulation of thalamo-cortical networks, which might contribute to perceptual, motoric, and interoceptive impairments, and are also consistent with a developmental delay in functional connectivity in ASD.

SUBMITTER: Tomasi D

PROVIDER: S-EPMC6319176 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Reduced Local and Increased Long-Range Functional Connectivity of the Thalamus in Autism Spectrum Disorder.

Tomasi Dardo D Volkow Nora D ND

Cerebral cortex (New York, N.Y. : 1991) 20190201 2

It is hypothesized that brain network abnormalities in autism spectrum disorder (ASD) reflect local overconnectivity and long-range underconnectivity. However, this is not a consistent finding in recent studies, which could reflect the developmental nature and the heterogeneity of ASD. Here, we tested 565 ASD and 602 neurotypical (NT) males, and 91 ASD and 233 NT females using local functional connectivity density (lFCD) mapping and seed-voxel correlation analyses to assess how local and long-ra ...[more]

PMID: 29300843

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Project description:IMPORTANCE:Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. OBJECTIVES:To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. DESIGN, SETTING, AND PARTICIPANTS:We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. MAIN OUTCOMES AND MEASURES:We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. RESULTS:Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t???3.13, P?<?.001 corrected). The strength of such connections was associated with the severity of autistic traits in the ASD group (all r???0.21, P?<?.0067 corrected). In addition, subcortico-cortical interaction decreased with age in the entire sample (all r???-0.09, P?<?.012 corrected), although this association was significant only in typically developing participants (all r???-0.13, P?<?.009 corrected). CONCLUSIONS AND RELEVANCE:Our results showing ASD-related impairment in the interaction between primary sensory cortices and subcortical regions suggest that the sensory processes they subserve abnormally influence brain information processing in individuals with ASD. This might contribute to the occurrence of hyposensitivity or hypersensitivity and of difficulties in top-down regulation of behavior.

Project description:BACKGROUND:Disruptive behaviors are prevalent in children with autism spectrum disorder (ASD) and often cause substantial impairments. However, the underlying neural mechanisms of disruptive behaviors remain poorly understood in ASD. In children without ASD, disruptive behavior is associated with amygdala hyperactivity and reduced connectivity with the ventrolateral prefrontal cortex (vlPFC). This study examined amygdala reactivity and connectivity in children with ASD with and without co-occurring disruptive behavior disorders. We also investigated differential contributions of externalizing behaviors and callous-unemotional traits to variance in amygdala connectivity and reactivity. METHODS:This cross-sectional study involved behavioral assessments and neuroimaging in three groups of children 8 to 16 years of age: 18 children had ASD and disruptive behavior, 20 children had ASD without disruptive behavior, and 19 children were typically developing control participants matched for age, gender, and IQ. During functional magnetic resonance imaging, participants completed an emotion perception task of fearful versus calm faces. Task-specific changes in amygdala reactivity and connectivity were examined using whole-brain, psychophysiological interaction, and multiple regression analyses. RESULTS:Children with ASD and disruptive behavior showed reduced amygdala-vlPFC connectivity compared with children with ASD without disruptive behavior. Externalizing behaviors and callous-unemotional traits were associated with amygdala reactivity to fearful faces in children with ASD after controlling for suppressor effects. CONCLUSIONS:Reduced amygdala-vlPFC connectivity during fear processing may differentiate children with ASD and disruptive behavior from children with ASD without disruptive behavior. The presence of callous-unemotional traits may have implications for identifying differential patterns of amygdala activity associated with increased risk of aggression in ASD. These findings suggest a neural mechanism of emotion dysregulation associated with disruptive behavior in children with ASD.

Dataset Information

Reduced Local and Increased Long-Range Functional Connectivity of the Thalamus in Autism Spectrum Disorder.

Publications

Reduced Local and Increased Long-Range Functional Connectivity of the Thalamus in Autism Spectrum Disorder.

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