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: 3.45). 06/2009; 47(12):2515-26. DOI: 10.1016/j.neuropsychologia.2009.04.019
Source: PubMed

ABSTRACT 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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Available from: Susan M Ravizza, Aug 16, 2015
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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.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 04/2015; 43. DOI:10.1016/j.ijdevneu.2015.04.003 · 2.92 Impact Factor
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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: 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 et al., 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.
    03/2015; 110. DOI:10.1016/j.nicl.2015.02.024
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    • "Brain imaging studies in the normative population point to the importance of activation in executive function circuitry for all set-shifting levels, such as lateral prefrontal and superior medial prefrontal, cingulate, striatum, parietal, and cerebellum regions [Buchsbaum, Greer, Chang, & Berman, 2005; Crone, Donohue, et al., 2006; Ezekiel, Bosma, & Morton, 2012; Monchi, Petrides , Petre, Worsley, & Dagher, 2001; Morton, Bosma, & Ansari, 2009; Rubia et al., 2006; Schmitz, Rubia, Daly, Smith, Williams, & Murphy, 2006; Shafritz, Kartheiser , & Belger, 2005; Shafritz, Dichter, Baranek, & Belger, 2008; Smith, Taylor, Brammer, & Rubia, 2004; Solomon et al., 2009; Wager, Jonides, & Reading, 2004; Wendelken, Munakata, Baym, Souza, & Bunge, 2012]. Developmental studies demonstrate that younger school age children show greater prefrontal cortex activation (lateral prefrontal, cingulate), and decreased parietal and striatal activation in comparison to older children and young adults [Crone, Donohue, et al., 2006; Morton et al., 2009; Wendelken et al., 2012; but see Rubia et al., 2006]. "
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    ABSTRACT: Autism spectrum disorder (ASD) is often associated with high levels of inflexible thinking and rigid behavior. The neural correlates of these behaviors have been investigated in adults and older adolescents, but not children. Prior studies utilized set-shifting tasks that engaged multiple levels of shifting, and depended on learning abstract rules and establishing a strong prepotent bias. These additional demands complicate simple interpretations of the results. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of set-shifting in 20 children (ages 7–14) with ASD and 19 typically developing, matched, control children. Participants completed a set-shifting task that minimized nonshifting task demands through the use of concrete instructions that provide spatial mapping of stimuli-responses. The shift/stay sets were given an equal number of trials to limit the prepotent bias. Both groups showed an equivalent “switch cost,” responding less accurately and slower to Switch stimuli than Stay stimuli, although the ASD group was less accurate overall. Both groups showed activation in prefrontal, striatal, parietal, and cerebellum regions known to govern effective set-shifts. Compared to controls, children with ASD demonstrated decreased activation of the right middle temporal gyrus across all trials, but increased activation in the mid-dorsal cingulate cortex/superior frontal gyrus, left middle frontal, and right inferior frontal gyri during the Switch vs. Stay contrast. The successful behavioral switching performance of children with ASD comes at the cost of requiring greater engagement of frontal regions, suggesting less efficiency at this lowest level of shifting.
    Autism Research 01/2015; DOI:10.1002/aur.1454 · 4.53 Impact Factor
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