Reduced Local and Increased Long-Range Functional Connectivity of the Thalamus in Autism Spectrum Disorder.
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ABSTRACT:
SUBMITTER: Tomasi D
PROVIDER: S-EPMC6319176 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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Project description:Autism spectrum disorder (ASD) is often described as a disorder of aberrant neural connectivity. Although it is important to study the pathophysiology of ASD in the developing cortex, the functional connectivity in the brains of young children with ASD has not been well studied. In this study, brain activity was measured non-invasively during consciousness in 50 young human children with ASD and 50 age- and gender-matched typically developing human (TD) children. We employed a custom child-sized magnetoencephalography (MEG) system in which sensors were located as close to the brain as possible for optimal recording in young children. We focused on theta band oscillations because they are thought to be involved in long-range networks associated with higher cognitive processes. The ASD group showed significantly reduced connectivity between the left-anterior and the right-posterior areas, exhibiting a decrease in the coherence of theta band (6 Hz) oscillations compared with the TD group. This reduction in coherence was significantly correlated with clinical severity in right-handed children with ASD. This is the first study to demonstrate reduced long-range functional connectivity in conscious young children with ASD using a novel MEG approach.
| S-EPMC4321624 | biostudies-literature
Project description:Long-range cortical functional connectivity is often reduced in autism spectrum disorders (ASD), but the nature of local cortical functional connectivity in ASD has remained elusive. We used magnetoencephalography to measure task-related local functional connectivity, as manifested by coupling between the phase of alpha oscillations and the amplitude of gamma oscillations, in the fusiform face area (FFA) of individuals diagnosed with ASD and typically developing individuals while they viewed neutral faces, emotional faces, and houses. We also measured task-related long-range functional connectivity between the FFA and the rest of the cortex during the same paradigm. In agreement with earlier studies, long-range functional connectivity between the FFA and three distant cortical regions was reduced in the ASD group. However, contrary to the prevailing hypothesis in the field, we found that local functional connectivity within the FFA was also reduced in individuals with ASD when viewing faces. Furthermore, the strength of long-range functional connectivity was directly correlated to the strength of local functional connectivity in both groups; thus, long-range and local connectivity were reduced proportionally in the ASD group. Finally, the magnitude of local functional connectivity correlated with ASD severity, and statistical classification using local and long-range functional connectivity data identified ASD diagnosis with 90% accuracy. These results suggest that failure to entrain neuronal assemblies fully both within and across cortical regions may be characteristic of ASD.
| S-EPMC3581984 | biostudies-literature
Project description:There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with the disorder. Here, we investigated how regional homogeneity (ReHo), a measure of similarity of a voxel's timeseries to its nearest neighbors, varies across age in individuals with ASD and typically developing (TD) individuals using a cross-sectional design. Resting-state fMRI data obtained from a publicly available database were analyzed to determine group differences in ReHo between three age cohorts: children, adolescents, and adults. In typical development, ReHo across the entire brain was higher in children than in adolescents and adults. In contrast, children with ASD exhibited marginally lower ReHo than TD children, while adolescents and adults with ASD exhibited similar levels of local connectivity as age-matched neurotypical individuals. During all developmental stages, individuals with ASD exhibited lower local connectivity in sensory processing brain regions and higher local connectivity in complex information processing regions. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. These results demonstrate that local connectivity is disrupted in ASD across development, with the most pronounced differences occurring in childhood. Developmental changes in ReHo do not mirror findings from fMRI studies of long-range connectivity in ASD, pointing to a need for more nuanced accounts of brain connectivity alterations in the disorder.
| S-EPMC4673031 | biostudies-literature
Project description:Individuals with autism spectrum disorder (ASD) demonstrate poor social functioning, which may be related to atypical emotional face processing. Altered functional connectivity among brain regions, particularly involving limbic structures may be implicated. The current magnetoencephalography (MEG) study investigated whole-brain functional connectivity of eight a priori identified brain regions during the implicit presentation of happy and angry faces in 20 7 to 10-year-old children with ASD and 22 typically developing controls. Findings revealed a network of increased alpha-band phase synchronization during the first 400 ms of happy face processing in children with ASD compared to controls. This network of increased alpha-band phase synchronization involved the left fusiform gyrus, right insula, and frontal regions critical for emotional face processing. In addition, greater connectivity strength of the left fusiform gyrus (maximal 85 to 208 ms) and right insula (maximal 73 to 270 ms) following happy face presentation in children with ASD compared to typically developing controls was found. These findings reflect altered neuronal communication in children with ASD only to happy faces during implicit emotional face processing.
| S-EPMC6191493 | biostudies-literature
Project description:Autism spectrum disorder (ASD) is characterized neurophysiologically by, among other things, functional connectivity abnormalities in the brain. Recent evidence suggests that the nature of these functional connectivity abnormalities might not be uniform throughout maturation. Comparing between adolescents and young adults (ages 14-21) with ASD and age- and IQ-matched typically developing (TD) individuals, we previously documented, using magnetoencephalography (MEG) data, that local functional connectivity in the fusiform face areas (FFA) and long-range functional connectivity between FFA and three higher order cortical areas were all reduced in ASD. Given the findings on abnormal maturation trajectories in ASD, we tested whether these results extend to preadolescent children (ages 7-13). We found that both local and long-range functional connectivity were in fact normal in this younger age group in ASD. Combining the two age groups, we found that local and long-range functional connectivity measures were positively correlated with age in TD, but negatively correlated with age in ASD. Last, we showed that local functional connectivity was the primary feature in predicting age in ASD group, but not in the TD group. Furthermore, local functional connectivity was only correlated with ASD severity in the older group. These results suggest that the direction of maturation of functional connectivity for processing of faces from childhood to young adulthood is itself abnormal in ASD, and that during the processing of faces, these trajectory abnormalities are more pronounced for local functional connectivity measures than they are for long-range functional connectivity measures.
| S-EPMC6292522 | biostudies-literature
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.
| S-EPMC5008437 | biostudies-literature
Project description:Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with cognitive, motor, and emotional symptoms. The thalamus and basal ganglia form circuits with the cortex supporting all three of these behavioral domains. Abnormalities in the structure of subcortical regions may suggest atypical development of these networks, with implications for understanding the neural basis of ASD symptoms. Findings from previous volumetric studies have been inconsistent. Here, using advanced surface-based methodology, we investigated localized differences in shape and surface area in the basal ganglia and thalamus in ASD, using T1-weighted anatomical images from the Autism Brain Imaging Data Exchange (373 male participants aged 7-35 years with ASD and 384 typically developing). We modeled effects of diagnosis, age, and their interaction on volume, shape, and surface area. In participants with ASD, we found expanded surface area in the right posterior thalamus corresponding to the pulvinar nucleus, and a more concave shape in the left mediodorsal nucleus. The shape of both caudal putamen and pallidum showed a relatively steeper increase in concavity with age in ASD. Within ASD participants, restricted, repetitive behaviors were positively associated with surface area in bilateral globus pallidus. We found no differences in overall volume, suggesting that surface-based approaches have greater sensitivity to detect localized differences in subcortical structure. This work adds to a growing body of literature implicating corticobasal ganglia-thalamic circuits in the pathophysiology of ASD. These circuits subserve a range of cognitive, emotional, and motor functions, and may have a broad role in the complex symptom profile in ASD.
| S-EPMC5026732 | biostudies-literature
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.
| S-EPMC7173634 | biostudies-literature
Project description:Adaptation is a fundamental property of cortical neurons and has been suggested to be altered in individuals with autism spectrum disorder (ASD). We used fMRI to measure adaptation induced by repeated audio-visual stimulation in early sensory cortical areas in individuals with ASD and neurotypical (NT) controls. The initial transient responses were equivalent between groups in both visual and auditory cortices and when stimulation occurred with fixed-interval and randomized-interval timing. However, in auditory but not visual cortex, the post-transient sustained response was greater in individuals with ASD than NT controls in the fixed-interval timing condition, reflecting reduced adaptation. Further, individual differences in the sustained response in auditory cortex correlated with ASD symptom severity. These findings are consistent with hypotheses that ASD is associated with increased neural responsiveness but that responsiveness differences only manifest after repeated stimulation, are specific to the temporal pattern of stimulation, and are confined to specific cortical regions.
| S-EPMC6203433 | biostudies-literature
Project description:Autism is known to be associated with major perceptual atypicalities. We have recently proposed a general model to account for these atypicalities in Bayesian terms, suggesting that autistic individuals underuse predictive information or priors. We tested this idea by measuring adaptation to numerosity stimuli in children diagnosed with autism spectrum disorder (ASD). After exposure to large numbers of items, stimuli with fewer items appear to be less numerous (and vice versa). We found that children with ASD adapted much less to numerosity than typically developing children, although their precision for numerosity discrimination was similar to that of the typical group. This result reinforces recent findings showing reduced adaptation to facial identity in ASD and goes on to show that reduced adaptation is not unique to faces (social stimuli with special significance in autism), but occurs more generally, for both parietal and temporal functions, probably reflecting inefficiencies in the adaptive interpretation of sensory signals. These results provide strong support for the Bayesian theories of autism.
| S-EPMC4485114 | biostudies-other