The neural substrates of cognitive control deficits in autism spectrum disorders

Department of Psychiatry & Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA.
Neuropsychologia (Impact Factor: 3.3). 06/2009; 47(12):2515-26. DOI: 10.1016/j.neuropsychologia.2009.04.019
Source: PubMed


Executive function deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive function deficits in ASDs, and only one in adolescents. The current study examined cognitive control - the ability to maintain task context online to support adaptive functioning in the face of response competition - in 22 adolescents aged 12-18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7 and BA 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms.

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    • "chi et al . , 2010 ; Pardini et al . , 2009 ; Thakkar et al . , 2008 ] have also been reported in ASD . Functional connectivity MRI studies in ASD have also uncovered significant alterations in connectivity involving ACC and PCC during cognitive tasks [ Agam , Joseph , Barton , & Manoach , 2010 ; Klein - hans et al . , 2008 ; Shih et al . , 2011 ; Solomon et al . , 2009 ] and during resting state [ Assaf et al . , 2010 ; Cher - kassky , Kana , Keller , & Just , 2006 ; Monk et al . , 2009 ; Weng et al . , 2010 ] . Thus , the cingulate cortex was cho - sen as the area of interest ( focusing on dACC and PCC ) due to its widespread alterations in function , anatomy , and connectivity reported in autism . T"
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    ABSTRACT: Neuroimaging studies have uncovered structural and functional alterations in the cingulate cortex in individuals with autism spectrum disorders (ASD). Such abnormalities may underlie neurochemical imbalance. In order to characterize the neurochemical profile, the current study examined the concentration of brain metabolites in dorsal ACC (dACC) and posterior cingulate cortex (PCC) in high-functioning adults with ASD. Twenty high-functioning adults with ASD and 20 age-and-IQ-matched typically developing (TD) peers participated in this Proton magnetic resonance spectroscopy (1H-MRS) study. LCModel was used in analyzing the spectra to measure the levels of N-Acetyl aspartate (NAA), choline (Cho), creatine (Cr), and glutamate/glutamine (Glx) in dACC and PCC. Groups were compared using means for the ratio of each metabolite to their respective Cr levels as well as on absolute internal-water-referenced measures of each metabolite. There was a significant increase in Cho in PCC for ASD adults, with a marginal increase in dACC. A reduction in NAA/Cr in dACC was found in ASD participants, compared to their TD peers. No significant differences in Glx/Cr or Cho/Cr were found in dACC. There were no statistically significant group differences in the absolute concentration of NAA, Cr, Glx, or NAA/Cr, Cho/Cr, and Glx/Cr in the PCC. Differences in the metabolic properties of dACC compared to PCC were also found. Results of this study provide evidence for possible cellular and metabolic differences in the dACC and PCC in adults with ASD. This may suggest neuronal dysfunction in these regions and may contribute to the neuropathology of ASD. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    No preview · Article · Nov 2015 · Autism Research
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    • "With the advances in neuroimaging tool, it is now well established that reduced brain connectivity is an underlying characteristic of ASD symptoms (Ruggeri et al., 2014; Solomon et al., 2009). In individuals with ASD, reduced fronto-parietal connectivity has been visualized in certain brain areas using fMRI, and is correlated to symptoms of attention deficit hyperactivity disorder (Solomon et al., 2009). Imaging studies can also be used to identify deficits in the activation of specific brain areas during cognitive tasks, such as the inferior and middle frontal gyri, the dorsal anterior cingulate cortex, and the basal ganglia (Dichter, 2012). "
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    ABSTRACT: Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders that is among the most severe in terms of prevalence, morbidity and impact to the society. It is characterized by complex behavioral phenotype and deficits in both social and cognitive functions. Although the exact cause of ASD is still not known, the main findings emphasize the role of genetic and environmental factors in the development of autistic behavior. Environmental factors are also likely to interact with the genetic profile and cause aberrant changes in brain growth, neuronal development, and functional connectivity. The past few years have seen an increase in the prevalence of ASD, as a result of enhanced clinical tests and diagnostic tools. Despite growing evidence for the involvement of endogenous biomarkers in the pathophysiology of ASD, early detection of this disorder remains a big challenge. This paper describes the main behavioral and cognitive features of ASD, as well as the symptoms that differentiate autism from other developmental disorders. An attempt will be made to integrate all the available evidence which point to reduced brain connectivity, mirror neurons deficits, and inhibition-excitation imbalance in individuals with ASD. Finally, this review discusses the main factors involved in the pathophysiology of ASD, and illustrates some of the most important markers used for the diagnosis of this debilitating disorder. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Apr 2015 · International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience
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    • "Previous task-based functional magnetic resonance imaging (fMRI) studies primarily using region-of-interest (ROI) analyses found support for the hypo-connectivity theory (Just et al., 2012; Minshew and Williams, 2007). These experiments found hypo-connectivity within the temporal–parietal junction in a theory of mind task (Kana et al., 2009), the limbic system in a face perception task (Kleinhans et al., 2008), between the frontal and parietal regions in a working memory task (Koshino et al., 2005), and between the frontal, parietal and occipital regions in a cognitive control task (Solomon et al., 2009). However, later task-based fMRI studies found hyper-connectivity in connections involving the posterior superior temporal sulcus in visual search tasks (Shih et al., 2011), the medial temporal lobe in face perception tasks (Welchew et al., 2005), within the left hemisphere in a source recognition task (Noonan et al., 2009), between the inferior frontal gyrus, and between the inferior parietal lobule and the superior temporal sulcus in exploring whole-brain connectivity have included subjects with a wide range of ages, allowing for the possibility that a certain age group was driving the functional connectivity findings in the results (Assaf et al., 2010; Gotts et al., 2012). "
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    ABSTRACT: Background Disrupted cortical connectivity is thought to underlie the complex cognitive and behavior profile observed in individuals with autism spectrum disorder (ASD). Previous neuroimaging research has identified patterns of both functional hypo- and hyper-connectivity in individuals with ASD. A recent theory attempting to reconcile conflicting results in the literature proposes that hyper-connectivity of brain networks may be more characteristic of young children with ASD, while hypo-connectivity may be more prevalent in adolescents and adults with the disorder when compared to typical development (TD) (Uddin etal., 2013). Previous work has examined only young children, mixed groups of children and adolescents, or adult cohorts in separate studies, leaving open the question of developmental influences on functional brain connectivity in ASD. Methods The current study tests this developmental hypothesis by examining within- and between-network resting state functional connectivity in a large sample of 26 children, 28 adolescents, and 18 adults with ASD and age- and IQ-matchedTD individuals for the first time using an entirely data-driven approach. Independent component analyses (ICA) and dual regression was applied to data from three age cohorts to examine the effects of participant age on patterns of within-networkwhole-brain functional connectivity in individuals with ASD compared with TD individuals. Between-network connectivity differences were examined for each age cohort by comparing correlations between ICA components across groups. Results We find that in the youngest cohort (age 11 and under), children with ASD exhibit hyper-connectivity within large-scale brain networks as well as decreased between-network connectivity compared with age-matchedTD children. In contrast, adolescents with ASD (age 11–18) do not differ from TD adolescents in within-network connectivity, yet show decreased between-network connectivity compared with TD adolescents. Adults with ASD show no within- or between-network differences in functional network connectivity compared with neurotypical age-matched individuals. Conclusions Characterizing within- and between-network functional connectivity in age-stratified cohorts of individuals with ASD and TD individuals demonstrates that functional connectivity atypicalities in the disorder are not uniform across the lifespan. These results demonstrate how explicitly characterizing participant age and adopting a developmental perspective can lead to a more nuanced understanding of atypicalities of functional brain connectivity in autism.
    Full-text · Article · Mar 2015 · Clinical neuroimaging
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