Neural correlates of set-shifting: decomposing executive functions in schizophrenia

Abstract

321Background: Although there is considerable evidence that patients with schizophrenia have impaired executive functions, the neural mechanisms underlying these deficits are unclear. Generation and selection is one of the basic mechanisms of executive functioning. We investigated the neural correlates of this mechanism by means of functional magnetic resonance imaging (fMRI) in patients with schizophrenia and healthy controls. Methods: We used the Wisconsin Card Sorting Test (WCST) in an event-related fMRI study to analyze neural activation patterns during the distinct components of the WCST in 36 patients with schizophrenia and 28 controls. We focused our analyses on the process of set-shifting. After participants received negative feedback, they had to generate and decide on a new sorting rule. Results: A widespread activation pattern encompassing the inferior and middle frontal gyrus, parietal, temporal and occipital cortices, anterior cingulate cortex (ACC), supplementary motor area, insula, caudate, thalamus and brainstem was observed in patients with schizophrenia after negative versus positive feedback, whereas in healthy controls, significant activation clusters were more confined to the cortical areas. Significantly increased activation in the rostral ACC after negative feedback and in the dorsal ACC during matching after negative feedback were observed in schizophrenia patients compared with controls. Controls showed activation in the bilateral dorsolateral prefrontal cortex (Brodmann area 46), whereas schizophrenia patients showed activation in the right dorsolateral prefrontal cortex only. Limitations: All patients were taking neuroleptic medication, which has an impact on cognitive function as well as on dopaminergic and serotonergic prefrontal metabolism. Conclusion: Our data suggest that, in patients with schizophrenia, set-shifting is associated with increased activation in the rostral and dorsal ACC, reflecting higher emotional and cognitive demands, respectively.

What do we know about the relationship between source monitoring deficits and executive dysfunction?

“…Activation of the dorsolateral prefrontal cortex (BA46) has also been related to performance on the Stroop task (Aarts, Roelofs, & van Turennout, 2008;MacDonald, Cohen, Stenger, & Carter, 2000) and the N-back task (for a detailed review about cerebral regions activated during the N-back task, see Collette & Van der Linden, 2002). Furthermore, Wilmsmeier et al (2010) found activation of the dorsolateral prefrontal cortex (BA46) with healthy adults when investigating only the set-shifting component of the WCST. Consequently, when considering the common neural bases of source and specific executive processes, we postulate that a correlation between source and executive tasks should be observed when assessing specific executive processes.…”

Atlas-Based Diffusion Tensor Imaging Correlates of Executive Function

“…In as much as MCI reflects a lesser amount of pathological burden compared to AD, one might expect there to be less integrity loss and accordingly a more preserved network where both anterior and posterior regions are more preserved. Recent research using fMRI has elaborated the structure and function of this purported network where several regions of activity have been related to impaired tests of EF in different clinical populations [46–49]. Similarly, structural MRI has revealed both anterior and posterior (parietal) areas of cortical volume change consistent with performance on measures of EF in subjects with MCI and AD [1, 2].…”

Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction

“…Abnormalities in the functional activation of the insula and ACC have been reported across a variety of tasks ranging from working memory paradigms to complex social processing 95,96 (see Wylie and Tregellas 2 ). Studies investigating functional integration (during resting or task-related states) across multiple brain regions report a prominent reduction in connectivity involving both the insula 97,98 and ACC 99,100 with other brain regions.…”