Meta-analysis of 41 Functional Neuroimaging Studies of Executive Function in Schizophrenia

Department of Psychiatry, University of California-Davis School of Medicine, Sacramento, CA 95817, USA.
Archives of general psychiatry (Impact Factor: 14.48). 09/2009; 66(8):811-22. DOI: 10.1001/archgenpsychiatry.2009.91
Source: PubMed


Prefrontal cortical dysfunction is frequently reported in schizophrenia. It remains unclear whether this represents the coincidence of several prefrontal region- and process-specific impairments or a more unitary dysfunction in a superordinate cognitive control network. Whether these impairments are properly considered reflective of hypofrontality vs hyperfrontality remains unresolved.
To test whether common nodes of the cognitive control network exhibit altered activity across functional neuroimaging studies of executive cognition in schizophrenia and to evaluate the direction of these effects.
PubMed database.
Forty-one English-language, peer-reviewed articles published prior to February 2007 were included. All reports used functional neuroimaging during executive function performance by adult patients with schizophrenia and reported whole-brain analyses in standard stereotactic space. Tasks primarily included the delayed match-to-sample, N-back, AX-CPT, and Stroop tasks.
Activation likelihood estimation modeling reported activation maxima as the center of a 3-dimensional gaussian function in the meta-analysis, with statistical thresholding and correction for multiple comparisons.
In within-group analyses, healthy controls and patients activated a similarly distributed cortical-subcortical network, prominently including the dorsolateral prefrontal cortex (PFC), ventrolateral PFC, anterior cingulate cortex (ACC), and thalamus. In between-group analyses, patients showed reduced activation in the left dorsolateral PFC, rostral/dorsal ACC, left thalamus (with significant co-occurrence of these areas), and inferior/posterior cortical areas. Increased activation was observed in several midline cortical areas. Activation within groups varied modestly by task.
Healthy adults and schizophrenic patients activate a qualitatively similar neural network during executive task performance, consistent with the engagement of a general-purpose cognitive control network, with critical nodes in the dorsolateral PFC and ACC. Nevertheless, patients with schizophrenia show altered activity with deficits in the dorsolateral PFC, ACC, and mediodorsal nucleus of the thalamus. Increases in activity are evident in other PFC areas, which could be compensatory in nature.

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    • "Previous studies using n-back tasks, which require working memory and executive function , have indicated that patients with schizophrenia have impaired activation of the DLPFC (Callicott et al., 2000, 2003; Jansma et al., 2004; Perlstein et al., 2001; Schneider et al., 2007). On the other hand, previous studies have also shown that patients with schizophrenia have greater activation compared to healthy controls in the PFC, suggesting a shift of inverted U-curve shape activity (Callicott et al., 2003; Jansma et al., 2004; Potkin et al., 2009) or a compensatory response using preserved functions (Callicott et al., 2003; Minzenberg et al., 2009; Potkin et al., 2009; Schneider et al., 2007; Takizawa et al., 2008). Recent studies using n-back tasks also revealed that task-related reduced activity, deactivation, was absent during greater cognitive load condition compared to smaller load, suggesting disruption of resting brain activity in schizophrenia (Guerrero-Pedraza et al., 2012; Sambataro et al., 2010). "

    Full-text · Dataset · Dec 2015
    • "Behavioral studies have, in fact, revealed abnormalities in RL in both first episode (Murray et al., 2008) and chronic (Waltz et al., 2007, 2011) schizophrenia. Furthermore, functional imaging studies have produced evidence of altered neural activity in dopamine-rich subcortical structures, such as the basal ganglia (Deserno et al., 2013; Gradin et al., 2011; Koch et al., 2010), as well as dopamine targets in the frontal cortex (anterior cingulate cortex and prefrontal cortex; Goghari et al., 2011; Minzenberg et al., 2009), known to figure critically in cognitive control. Interestingly, across studies in patient samples, RL impairments have shown correlations with the severity of both positive and negative "
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    ABSTRACT: Early identification efforts for psychosis have thus far yielded many more individuals "at risk" than actually develop psychotic illness. Here, we test whether measures of reinforcement learning (RL), known to be impaired in chronic schizophrenia, are related to the severity of clinical risk symptoms. Because of the reliance of RL on dopamine-rich frontostriatal systems and evidence of dopamine system dysfunction in the psychosis prodrome, RL measures are of specific interest in this clinical population. The current study examines relationships between psychosis risk symptoms and RL task performance in a sample of adolescents and young adults (n = 70) receiving mental health services. We observed significant correlations between multiple measures of RL performance and measures of both positive and negative symptoms. These results suggest that RL measures may provide a psychosis risk signal in treatment-seeking youth. Further research is necessary to understand the potential predictive role of RL measures for conversion to psychosis.
    No preview · Article · Nov 2015 · Journal of Nervous & Mental Disease
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    • "ALE meta-analysis is a quantitative coordinate-based voxel-wise meta-analysis method that takes into account the exact location of brain activity in individual studies and provides a likelihood estimation of the overlapping activation between the results of different studies. ALE meta-analyses have already been largely used to reveal neural correlates of neuropsychiatric diseases, such as dementia syndromes (e.g., Schroeter et al., 2007, 2009, 2014; Schroeter and Neumann, 2011) and neural correlates of cognitive processes , for example, motor inhibition and reflexive reorienting (Levy and Wagner, 2011), task switching (Derrfuss et al., 2005), or executive functions (Goghari, 2011; Minzenberg et al., 2009). Recently, the ALE meta-analysis method has been used to investigate neural correlates of subliminal processing of arousing stimuli in general and to detect whether these neural correlates differ according to the stimulus modality (physiological stimuli, faces, lexical and auditory stimuli) (Brooks et al., 2012). "
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