Task Performance Modulates Functional Connectivity Involving the Dorsolateral Prefrontal Cortex in Patients with Schizophrenia

Abstract

Previous studies have suggested that patients with schizophrenia and healthy controls exhibit differential activation of and connectivity involving the dorsolateral prefrontal cortex (DLPFC) during working memory tasks, though their findings remain inconsistent. The functional integration perspective further suggests that working memory performance also modulates differences in functional interactions of the DLPFC between patients and controls. To explore this possibility, 45 healthy controls and 45 patients with schizophrenia were recruited to perform a 2-back task during functional magnetic resonance imaging (fMRI). Each group was further divided into two subgroups based on task performance to examine the modulatory effect of performance on functional interactions of the DLPFC, as measured via psychophysiological interaction (PPI) analyses. We observed that, in patients with schizophrenia who exhibited impaired working memory capacity and decreased brain activation/deactivation, functional interactions between the right/left DLPFC and angular cortex were decreased relative to those of healthy controls. Furthermore, we observed an interaction effect of working memory performance and diagnosis on functional connectivity between the right/left DLPFC seed region and posterior regions such as the angular cortex, fusiform gyrus, and middle occipital gyrus. This interaction effect was mainly driven by the negative correlation between functional connectivity and performance in healthy controls, and by the positive correlation in patients with schizophrenia. These results demonstrate the effects of inter-individual differences in working memory performance on functional interactions between the DLPFC and posterior regions in patients with schizophrenia as well as healthy controls, which may shed new light on the neural basis of working memory.

Altered intrinsic and extrinsic connectivity in schizophrenia

“…The WM paradigm used a blocked design, numeric n-back task, with numbers 0–9 as stimuli, which has been used in previous studies ( Deserno et al, 2012 , Salomon et al, 2011 , Wu et al, 2017 ). The paradigm alternated between rest and task.…”

“…In order to ensure compliance during the subsequent acquisition, a training session was conducted prior to scanning. The training procedure was the same as that used in our previous study ( Wu et al, 2017 ). In brief, the training task was similar to the formal task, though only one 0-back and one 2-back trial were included.…”

Altered functional connectivity strength and its correlations with cognitive function in subjects with ultra‐high risk for psychosis at rest

“…Working memory and executive function impairments are regarded as core cognitive deficits in schizophrenia . Functional imaging studies consistently identify abnormal neural activation and connectivity that involve the dorsolateral prefrontal cortex (DLPFC), such as decreased functional interactions between the bilateral DLPFC and angular gyrus and dysfunction of the left frontoparietotemporal cortex during a working memory task . Moreover, Eryilmaz et al found that patients with schizophrenia showed reduced connectivity in the frontoparietal control network at rest but normal connectivity during a task.…”

Biologically relevant subgroups within the schizophrenia syndrome

“…Based on patient's performance on a working memory task, a report showed that the group with better performance exhibited increased functional connectivity involving DLPFC and other areas in comparison to the remaining patients and controls 449 In terms of graph parameters, and in agreement with our results, other studies supported abnormal SW properties in schizophrenia, such as lower CLC and higher PL in beta band resulting in lower SW values 115 . In the same vein, decreased SW network properties in beta, alpha and gamma frequency bands were described in a wellfunctioning group of patients 126 .…”

“…. Indeed, controls with better and worse cognitive performance did not differ in functional connectivity449 . Therefore, it seems that patients appear to compensate for their disruptions in functional connectivity by increasing some connections.…”