Fractionation of social brain circuits in autism spectrum disorders

Section on Cognitive Neuropsychology, Laboratory of Brain and Cognition, National Institute of Mental Health (NIMH), National Institutes of Health, Bethesda, MD 20892, USA. .
Brain (Impact Factor: 9.2). 07/2012; 135(Pt 9):2711-25. DOI: 10.1093/brain/aws160
Source: PubMed


Autism spectrum disorders are developmental disorders characterized by impairments in social and communication abilities and repetitive behaviours. Converging neuroscientific evidence has suggested that the neuropathology of autism spectrum disorders is widely distributed, involving impaired connectivity throughout the brain. Here, we evaluate the hypothesis that decreased connectivity in high-functioning adolescents with an autism spectrum disorder relative to typically developing adolescents is concentrated within domain-specific circuits that are specialized for social processing. Using a novel whole-brain connectivity approach in functional magnetic resonance imaging, we found that not only are decreases in connectivity most pronounced between regions of the social brain but also they are selective to connections between limbic-related brain regions involved in affective aspects of social processing from other parts of the social brain that support language and sensorimotor processes. This selective pattern was independently obtained for correlations with measures of social symptom severity, implying a fractionation of the social brain in autism spectrum disorders at the level of whole circuits.

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Available from: Stephen J. Gotts
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    • "In an fMRI study we conducted, atypical processing of emotional expressions in adults with ASD was found to be subtended by a weaker functional connectivity between the AMG and PM (Grèzes et al., 2009). Similarly, Gotts et al. (2012) showed, using a whole-brain functional connectivity approach in fMRI, a decoupling between brain regions in the evaluation of socially relevant signals from motor-related circuits in ASDs. The results suggest the possibility that weak limbic–motor pathways might contribute to difficulties in perceiving social signals as action opportunities that trigger immediate but flexible behavioral response in the observer. "
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    ABSTRACT: Emotional signals influence others' behavior. They trigger a host of responses in the observer. Perception of emotional signals incorporates not only the appraisal of the emotional content of the signal but also the preparation of an adaptive reaction to it. This interplay between two processes is reflected in the limbic–motor interactions in the human brain. Data showing impaired connectivity between the limbic and motor brain regions in pathologies associated with diminished social skills also support this claim.
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    • "However, an important additional factor that has recently been highlighted is that the developmental stage of participants examined has not been carefully considered in much of the autism neuroimaging literature (Uddin, Supekar & Menon, 2013b). Most of the previous studies that have found hypo-connectivity in ASD have examined heterogeneous samples consisting of participants across wide age ranges (J.S. Anderson, Druzgal, Froehlich, DuBray, Lange et al., 2011; Gotts, Simmons, Milbury, Wallace, Cox et al., 2012; Kennedy & Courchesne, 2008). However, the majority of studies that have focused on child populations have found evidence for hyper-connectivity in ASD (Di Martino, Kelly, Grzadzinski, Zuo, Mennes et al., 2011; Lynch, Uddin, Supekar, Khouzam, Phillips et al., 2013; Uddin, Supekar, Lynch, Khouzam, Phillips et al., 2013a; Washington , Gordon, Brar, Warburton, Sawyer et al., 2014). "
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    ABSTRACT: Individuals with autism spectrum disorders (ASD) exhibit early and lifelong impairments in attention across multiple domains. While the disorder is known to affect attention processes, very little is currently known about the brain networks underlying attention in ASD, and even less is known about whether these atypicalities persist across the lifespan. We used functional connectivity analysis applied to resting state functional magnetic resonance imaging (fMRI) data to explore the dorsal (DAN) and ventral (VAN) attention networks in two separate age cohorts of children and adults with and without ASD. We find significant developmental differences in functional connectivity of brain regions that are critical for attention in children and adults with ASD. Specifically, children with ASD show hyper-connectivity of regions-of-interest (ROIs) in both attention networks compared with both typically developing (TD) children and adults with ASD. In contrast, adults with ASD show hypo-connectivity of these networks compared with neurotypical adults. These findings are consistent with the notion that consideration of developmental stage is critical in studies of functional connectivity in ASD. This study further illustrates diverging developmental patterns for top-down and bottom-up attention systems in autism.
    No preview · Article · Nov 2015 · Developmental Science
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    • "To avoid a priori selection of specific regions of interest (ROIs), we used a data-driven approach to map the wFCS at the voxel level and identified the regions that showed aberrant FCS in the TS patients. Similar approaches have been applied to study mental dysfunction (Gotts et al. 2012; Wang et al. 2014) and to search for connectivity hubs within the brain (Buckner et al. 2009; Tomasi and Volkow 2010). A set of regions including the bilateral IPS, ANG, cuneus, and cerebellum showed reduced wFCS in the TS patients compared with the HCs. "
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    ABSTRACT: Turner syndrome (TS), a disorder caused by the congenital absence of one of the 2 X chromosomes in female humans, provides a valuable human “knockout model” for studying the functions of the X chromosome. At present, it remains unknown whether and how the loss of the X chromosome influences intrinsic functional connectivity (FC), a fundamental phenotype of the human brain. To address this, we performed resting-state functional magnetic resonance imaging and specific cognitive assessments on 22 TS patients and 17 age-matched control girls. A novel data-driven approach was applied to identify the disrupted patterns of intrinsic FC in TS. The TS girls exhibited significantly reduced whole-brain FC strength within the bilateral postcentral gyrus/intraparietal sulcus, angular gyrus, and cuneus and the right cerebellum. Furthermore, a specific functional subnetwork was identified in which the intrinsic FC between nodes was mostly reduced in TS patients. Particularly, this subnetwork is composed of 3 functional modules, and the disruption of intrinsic FC within one of these modules was associated with the deficits of TS patients in math-related cognition. Taken together, these findings provide novel insight into how the X chromosome affects the human brain and cognition, and emphasize an important role of X-linked genes in intrinsic neural coupling.
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