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Kennedy DP, Courchesne E. Functional abnormalities of the default network during self- and other-reflection in autism

Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0662, USA.
Social Cognitive and Affective Neuroscience (Impact Factor: 5.88). 07/2008; 3(2):177-90. DOI: 10.1093/scan/nsn011
Source: PubMed

ABSTRACT Recent studies of autism have identified functional abnormalities of the default network during a passive resting state. Since the default network is also typically engaged during social, emotional and introspective processing, dysfunction of this network may underlie some of the difficulties individuals with autism exhibit in these broad domains. In the present experiment, we attempted to further delineate the nature of default network abnormality in autism using experimentally constrained social and introspective tasks. Thirteen autism and 12 control participants were scanned while making true/false judgments for various statements about themselves (SELF condition) or a close other person (OTHER), and pertaining to either psychological personality traits (INTERNAL) or observable characteristics and behaviors (EXTERNAL). In the ventral medial prefrontal cortex/ventral anterior cingulate cortex, activity was reduced in the autism group across all judgment conditions and also during a resting condition, suggestive of task-independent dysfunction of this region. In other default network regions, overall levels of activity were not different between groups. Furthermore, in several of these regions, we found group by condition interactions only for INTERNAL/EXTERNAL judgments, and not SELF/OTHER judgments, suggestive of task-specific dysfunction. Overall, these results provide a more detailed view of default network functionality and abnormality in autism.

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    • "In simpler words, the precuneus may have to work harder and gather more information through its widespread connections , when the meaning of the social interaction is not easily interpretable. This conclusion is supported by studies indicating how abnormalities in precuneus/posterior cingulate and their functional connectivity are present in a variety of attentional and cognitive deficits [Bonnelle et al., 2011; Castellanos et al., 2008; Sharp et al., 2011] as well as psychiatric and neurodevelopmental disorders that result in social impairments [Bluhm et al., 2007; Bluhm et al., 2009; Kennedy and Courchesne, 2008]. MFG/IFG is known to process the meaning of human actions (i.e. in terms of intentions and goals), and to activate in conjunction with the precuneus when behaviorally relevant though unattended stimuli are presented [Corbetta et al., 2008]. "
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    ABSTRACT: Human beings often observe other people's social interactions without being a part of them. Whereas the implications of some brain regions (e.g. amygdala) have been extensively examined, the implication of the precuneus remains yet to be determined. Here we examined the implication of the precuneus in third-person perspective of social interaction using functional magnetic resonance imaging (fMRI). Participants performed a socially irrelevant task while watching the biological motion of two agents acting in either typical (congruent to social conventions) or atypical (incongruent to social conventions) ways. When compared to typical displays, the atypical displays elicited greater activation in the central and posterior bilateral precuneus, and in frontoparietal and occipital regions. Whereas the right precuneus responded with greater activation also to upside down than upright displays, the left precuneus did not. Correlations and effective connectivity analysis added consistent evidence of an interhemispheric asymmetry between the right and left precuneus. These findings suggest that the precuneus reacts to violations of social expectations, and plays a crucial role in third-person perspective of others' interaction even when the social context is unattended. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 10/2014; 35(10). DOI:10.1002/hbm.22543 · 6.92 Impact Factor
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    • "Neuropathological studies have found atypicalities in cortical organization in ASD, particularly decreased pruning of prefrontal neurons (Courchesne et al., 2011), abnormal structure and organization of cortical mini-columns (Casanova, Buxhoeveden, Switala, & Roy, 2002), attenuated differentiation of temporal and frontal cortical cells (Voineagu et al., 2011), and atypical axonal development (Zikopoulos & Barbas, 2010). Functional neuroimaging studies have revealed decreased neural specialization for social information processing (e.g., processing of faces, biological motion, and theory of mind tasks; McPartland, Coffman, & Pelphrey, 2011; Pelphrey, Shultz, Hudac, & Vander Wyk, 2011), atypical prefrontal activation during executive function tasks (Philip et al., 2012), aberrant processing of auditory and language stimuli (Gomot, Belmonte, Bullmore, Bernard, & Baron-Cohen, 2008; Redcay & Courchesne, 2008) including reduced left-lateralization for the processing of language (Kleinhans, Mü ller, Cohen, & Courchesne, 2008; Knaus, Silver, Lindgren, Hadjikhani, & Tager-Flusberg, 2008; Redcay & Courchesne, 2008) and atypical functional connectivity among brain systems both at rest and across a range of functional tasks (Kennedy & Courchesne, 2008; Minshew & Williams, 2007). More generally, functional neuroimaging studies have revealed a pattern of enhanced activation in lower order motor and sensory brain regions and attenuated activation of higher order regions related to social cognition and executive function during complex tasks (Di Martino et al., 2009) and more unreliable or variable cortical responses (Dinstein et al., 2012; Mü ller, Kleinhans, Kemmotsu, Pierce, & Courchesne, 2003). "
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    ABSTRACT: This article suggests future directions for research aimed at improving our understanding of the etiology and pathophysiology of autism spectrum disorder (ASD) as well as pharmacologic and psychosocial interventions for ASD across the lifespan. The past few years have witnessed unprecedented transformations in the understanding of ASD neurobiology, genetics, early identification, and early intervention. However, recent increases in ASD prevalence estimates highlight the urgent need for continued efforts to translate novel ASD discoveries into effective interventions for all individuals with ASD. In this article we highlight promising areas for ongoing and new research expected to quicken the pace of scientific discovery and ultimately the translation of research findings into accessible and empirically supported interventions for those with ASD. We highlight emerging research in the following domains as particularly promising and pressing: (a) preclinical models, (b) experimental therapeutics, (c) early identification and intervention, (d) psychiatric comorbidities and the Research Domain Criteria initiative, (e) ecological momentary assessment, (f) neurotechnologies, and (g) the needs of adults with ASD. Increased research emphasis in these areas has the potential to hasten the translation of knowledge on the etiological mechanisms of ASD to psychosocial and biological interventions to reduce the burden of ASD on affected individuals and their families.
    Journal of Clinical Child & Adolescent Psychology 09/2014; 43(5):828-843. DOI:10.1080/15374416.2014.945214 · 1.92 Impact Factor
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    • "The study of Autism Spectrum Disorders (ASD), in particular , has benefited from these methods, with a growing number of studies evaluating the hypothesis that the behavioral impairments in ASD result from abnormal brain connectivity (e.g., Castelli et al., 2002; Belmonte et al., 2004; Just et al., 2004; see Müller et al., 2011,for review). To date, most resting-state (as well as task-based) fMRI studies of ASD have found evidence of decreased correlations throughout a variety of brain regions involved in social processing (e.g., Kennedy and Courchesne, 2008; Monk et al., 2009; Assaf et al., 2010; Weng et al., 2010; Anderson et al., 2011b; Ebisch et al., 2011; Gotts et al., 2012; von dem Hagen et al., 2012). However, not all studies have found this pattern. "
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    ABSTRACT: We have previously argued from a theoretical basis that the standard practice of regression of the Global Signal from the FMRI time series in functional connectivity studies is ill advised, particularly when comparing groups of participants. Here, we demonstrate in resting-state data from participants with an Autism Spectrum Disorder and matched controls that these concerns are also well founded in real data. Using the prior theoretical work to formulate predictions, we show: 1) rather than simply altering the mean or range of correlation values amongst pairs of brain regions, Global Signal Regression systematically alters the rank ordering of values in addition to introducing negative values, 2) it leads to a reversal in the direction of group correlation differences relative to other preprocessing approaches, with a higher incidence of both long-range and local correlation differences that favor the Autism Spectrum Disorder group, 3) the strongest group differences under other preprocessing approaches are the ones most altered by Global Signal Regression, and 4) locations showing group differences no longer agree with those showing correlations with behavioral symptoms within the Autism Spectrum Disorder group. The correlation matrices of both participant groups under Global Signal Regression were well predicted by our previous mathematical analyses, demonstrating that there is nothing mysterious about these results. Finally, when independent physiological nuisance measures are lacking, we provide a simple alternative approach for assessing and lessening the influence of global correlations on group comparisons that replicates our previous findings. While this alternative performs less well for symptom correlations than our favored preprocessing approach that includes removal of independent physiological measures, it is preferable to the use of Global Signal Regression, which prevents unequivocal conclusions about the direction or location of group differences.
    Frontiers in Human Neuroscience 06/2013; 7:356. DOI:10.3389/fnhum.2013.00356 · 2.90 Impact Factor
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