Gilbert SJ, Bird G, Brindley R, et al. Atypical recruitment of medial prefrontal cortex in autism spectrum disorders: an fMRI study of two executive function tasks

Institute of Cognitive Neuroscience and Department of Psychology, University College London, London, UK.
Neuropsychologia (Impact Factor: 3.3). 02/2008; 46(9):2281-91. DOI: 10.1016/j.neuropsychologia.2008.03.025
Source: PubMed


Recent studies have suggested an uneven profile of executive dysfunction in autism spectrum disorders (ASD). For example, some authors have reported deficits on newly developed tests of executive function sensitive to rostral prefrontal function, despite spared, or even superior, performance on other tests. We investigated the performance of a group of high-functioning participants with ASD (N=15) and an age- and IQ-matched control group (N=18) on two executive function tests, whilst undergoing functional magnetic resonance imaging (fMRI). Behaviourally, there were no significant differences between the two groups. In a classical test of executive function (random response generation), BOLD signal differed between the groups in the cerebellum but not in the frontal lobes. However, on a new test of executive function (selection between stimulus-oriented and stimulus-independent thought), the ASD group exhibited significantly greater signal-change in medial rostral prefrontal cortex (especially Brodmann Area 10) in the comparison of stimulus-oriented versus stimulus-independent attention. In addition, the new test (but not the classical test) provided evidence for abnormal functional organisation of medial prefrontal cortex in ASD. These results underline the heterogeneity of different tests of executive function, and suggest that executive functioning in ASD is associated with task-specific functional change.

Download full-text


Available from: Paul W Burgess,
29 Reads
  • Source
    • "It is also important to note that the paradigm used in this study was not designed to elicit global differences in executive function, as both the primary and control conditions (i.e., attend-face and attend-house) necessitated some working memory (i.e., a one-back task). Recent research on frontal lobe function in ASD shows variable results, with some executive function tasks eliciting normal or increased activation patterns (Dichter et al. 2009; Gilbert et al. 2008). Findings for DLPFC in fact parallel those of Dichter and colleagues (Dichter et al. 2009), who reported increased activation of dorsal anterior cingulate and medial prefrontal cortices in ASD during a target detection task. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study examines whether deficits in visual information processing in autism-spectrum disorder (ASD) can be offset by the recruitment of brain structures involved in selective attention. During functional MRI, 12 children with ASD and 19 control participants completed a selective attention one-back task in which images of faces and houses were superimposed. When attending to faces, the ASD group showed increased activation relative to control participants within multiple prefrontal cortex areas, including dorsolateral prefrontal cortex (DLPFC). DLPFC activation in ASD was associated with increased response times for faces. These data suggest that prefrontal cortex activation may represent a compensatory mechanism for diminished visual information processing abilities in ASD.
    Journal of Autism and Developmental Disorders 09/2014; 45(4). DOI:10.1007/s10803-014-2233-4 · 3.34 Impact Factor
  • Source
    • "This might indicate that the behavioral effects reported in Karvat and Kimchi (2013) arise by restoring medial prefrontal acetylcholine availability ; i.e., restoring precision dynamics at higher cortical levels such that sensory precision is no longer (relatively) high. However, while there are many reports of abnormal medial prefrontal cortex function in autism (Gilbert et al., 2008; Watanabe et al., 2012), there is, at present, little neurochemical evidence for low brain acetylcholine levels in human autism. Furthermore, acetylcholine is not only involved in " attentionlike " (Feldman and Friston, 2010) modulation of perception, but is also implicated in widespread facilitation of many cognitive processes, including novelty processing (Pepeu and Giovannini, 2004), conscious awareness and sleep states (Perry et al., 1999) and interacts with other monoaminergic neurotransmitter systems . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Autism is a neurodevelopmental disorder characterized by problems with social-communication, restricted interests and repetitive behavior. A recent and thought-provoking article presented a normative explanation for the perceptual symptoms of autism in terms of a failure of Bayesian inference (Pellicano and Burr, 2012). In response, we suggested that when Bayesian inference is grounded in its neural instantiation-namely, predictive coding-many features of autistic perception can be attributed to aberrant precision (or beliefs about precision) within the context of hierarchical message passing in the brain (Friston et al., 2013). Here, we unpack the aberrant precision account of autism. Specifically, we consider how empirical findings-that speak directly or indirectly to neurobiological mechanisms-are consistent with the aberrant encoding of precision in autism; in particular, an imbalance of the precision ascribed to sensory evidence relative to prior beliefs.
    Frontiers in Human Neuroscience 05/2014; 8:302. DOI:10.3389/fnhum.2014.00302 · 3.63 Impact Factor
  • Source
    • "Interestingly, in a 1994 study, Hughes et al. (1994) failed to see a deficit on the reversal stage of the CANTAB attentional set shifting task, although clear impairments were seen in the extra-dimensional shift stage, shown to be dependent upon the mPFC. An fMRI study found different patterns of activations of the mPFC between ASD participants and a control group whilst performing a task of executive function (Gilbert et al. 2008). Furthermore, the mPFC has shown to be crucial for effective completion of extra-dimensional shifting suggesting that abnormal functioning within this region may contribute to the behavioural differences seen in ASD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The establishment of robust and replicable behavioural testing paradigms with translational value for psychiatric diseases is a major step forward in developing and testing etiology-directed treatment for these complex disorders. Based on the existing literature, we have generated an inventory of applied rodent behavioural testing paradigms relevant to autism spectrum disorders (ASD). This inventory focused on previously used paradigms that assess behavioural domains that are affected in ASD, such as social interaction, social communication, repetitive behaviours and behavioural inflexibility, cognition as well as anxiety behaviour. A wide range of behavioural testing paradigms for rodents were identified. However, the level of face and construct validity is highly variable. The predictive validity of these paradigms is unknown, as etiology-directed treatments for ASD are currently not on the market. To optimise these studies, future efforts should address aspects of reproducibility and take into account data about the neurodevelopmental underpinnings and trajectory of ASD. In addition, with the increasing knowledge of processes underlying ASD, such as sensory information processes and synaptic plasticity, phenotyping efforts should include multi-level automated analysis of, for example, representative task-related behavioural and electrophysiological read-outs.
    Psychopharmacology 03/2014; 231:1125-1146. DOI:10.1007/s00213-013-3268-5 · 3.88 Impact Factor
Show more