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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    • "Brain regions in this loop become active when individuals maintain task relevant information, plan action sequences, and adapt behavior responses in order to achieve the goal. Breakdowns in the associative loop are affiliated with perseverative, inflexible behavior, and this limited behavioral repertoire has been conceptualized as contributing to " insistence on sameness " repetitive behaviors in ASD (Geurts, Corbett, & Solomon, 2009; South, Ozonoff, & McMahon, 2007). The associative loop includes a portion of the caudate from the striatum, which is noted to be active in the learning and planning of long action sequences (Middleton & Strick, 2000). "
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    ABSTRACT: Individuals with autism spectrum disorder (ASD) present with a variety of repetitive behaviors. These include stereotypies, compulsions and sameness behaviors, sensory disturbances, and intense preoccupations of topics. Animal models of repetitive behaviors led to hypotheses about the role of corticostriatal loops as the underlying neurobiology, including a recent tripartite model. I briefly review key components of corticostriatal loops of repetitive behaviors, and then synthesize the existing structural and functional magnetic resonance imaging (MRI) literature that examines these corticostriatal loops in ASD. The MRI literature provides partial support for the role of corticostriatal loops in repetitive behaviors, but not the tripartite model per se. This review highlights the need to consider alternate models and proposes two potential avenues of research for clarifying the pathophysiology of these complex and life-interfering behaviors.
    International Review of Research in Developmental Disabilities, Volume 49, Edited by Robert M Hodapp, Deborah J Fidler, 09/2015: pages 91-150; Elsevier.
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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 · 2.58 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 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.
    Clinical neuroimaging 03/2015; 110. DOI:10.1016/j.nicl.2015.02.024 · 2.53 Impact Factor
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