An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia

PLOS ONE, Aug 2010

Background While much is known about the role of prefrontal cortex (PFC) in working memory (WM) deficits of schizophrenia, the nature of the relationship between cognitive components of WM and brain activation patterns remains unclear. We aimed to elucidate the neural correlates of the maintenance component of verbal WM by examining correct and error trials with event-related fMRI. Methodology/Findings Twelve schizophrenia patients (SZ) and thirteen healthy control participants (CO) performed a phonological delayed-matching-to-sample-task in which a memory set of three nonsense words was presented, followed by a 6-seconds delay after which a probe nonsense word appeared. Participants decided whether the probe matched one of the targets, and rated the confidence of their decision. Blood-oxygen-level-dependent (BOLD) activity during WM maintenance was analyzed in relation to performance (correct/error) and confidence ratings. Frontal and parietal regions exhibited increased activation on correct trials for both groups. Correct and error trials were further segregated into true memory, false memory, guess, and true error trials. True memory trials were associated with increased bilateral activation of frontal and parietal regions in both groups but only CO showed deactivation in PFC. There was very little maintenance-related cortical activity during guess trials. False memory was associated with increased left frontal and parietal activation in both groups. Conclusion These findings suggest that a wider network of frontal and parietal regions support WM maintenance in correct trials compared with error trials in both groups. Furthermore, a more extensive and dynamic pattern of recruitment of the frontal and parietal networks for true memory was observed in healthy controls compared with schizophrenia patients. These results underscore the value of parsing the sources of memory errors in fMRI studies because of the non-linear nature of the brain-behavior relationship, and suggest that group comparisons need to be interpreted in more specific behavioral contexts.

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An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia

Citation: Kim J, Matthews NL, Park S ( An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia Jejoong Kim 0 Natasha L. Matthews 0 Sohee Park 0 Andre Aleman, University of Groningen, Netherlands 0 1 Department of Psychology and the Center for Integrative and Cognitive Neuroscience, Vanderbilt University , Nashville , Tennessee, United States of America, 2 Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 3 Department of Brain and Cognitive Sciences, Seoul National University , Seoul , Korea , 4 The Queensland Brain Institute, The University of Queensland , St Lucia, Queensland , Australia Background: While much is known about the role of prefrontal cortex (PFC) in working memory (WM) deficits of schizophrenia, the nature of the relationship between cognitive components of WM and brain activation patterns remains unclear. We aimed to elucidate the neural correlates of the maintenance component of verbal WM by examining correct and error trials with event-related fMRI. Methodology/Findings: Twelve schizophrenia patients (SZ) and thirteen healthy control participants (CO) performed a phonological delayed-matching-to-sample-task in which a memory set of three nonsense words was presented, followed by a 6-seconds delay after which a probe nonsense word appeared. Participants decided whether the probe matched one of the targets, and rated the confidence of their decision. Blood-oxygen-level-dependent (BOLD) activity during WM maintenance was analyzed in relation to performance (correct/error) and confidence ratings. Frontal and parietal regions exhibited increased activation on correct trials for both groups. Correct and error trials were further segregated into true memory, false memory, guess, and true error trials. True memory trials were associated with increased bilateral activation of frontal and parietal regions in both groups but only CO showed deactivation in PFC. There was very little maintenancerelated cortical activity during guess trials. False memory was associated with increased left frontal and parietal activation in both groups. Conclusion: These findings suggest that a wider network of frontal and parietal regions support WM maintenance in correct trials compared with error trials in both groups. Furthermore, a more extensive and dynamic pattern of recruitment of the frontal and parietal networks for true memory was observed in healthy controls compared with schizophrenia patients. These results underscore the value of parsing the sources of memory errors in fMRI studies because of the non-linear nature of the brain-behavior relationship, and suggest that group comparisons need to be interpreted in more specific behavioral contexts. - Funding: Supported by MH-073028 and the Discovery Grant to Sohee Park. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Working memory (WM) deficit in schizophrenia is a cardinal feature of the disorder and is a potential candidate for an endophenotypic marker [1]. WM is a limited-capacity, active short-term memory system that guides and controls behavior in context [2,3]. A majority of patients with schizophrenia show stable WM deficits [4] across diverse paradigms, modalities and methods [5]. Impaired verbal WM predicts poor functional outcome [6] and WM deficits have become a major therapeutic target for pharmacological treatments. Therefore it has become increasingly important to understand and specify the reasons for this deficit. Clear evidence exists for the central role of the dorsolateral prefrontal cortex (DLPFC) in WM and its regulation of higher cognitive functions in non-human primates [7]. Past studies using single cell recording revealed that maintenance of WM representations is coded by increased firing rate of cells in the principal sulcus (PS, Area 46) and this robust increase of prefrontal activity during WM maintenance is correlated with accuracy of the task performance [810]. Similarly, WM accuracy is correlated with increased DLPFC activation in healthy humans in neuroimaging studies [1113]. However, numerous neuroimaging studies of WM have demonstrated task-related hypofrontality in schizophrenia patients [14,15]. On the other hand, some studies have also observed hyperfrontality in schizophrenia [16,17]. This discrepancy may arise from different WM loads across studies [18]. In healthy people DLPFC activity increases with WM load until the capacity of WM is exceeded at which point, it decreases [19,20]. This relationship between WM load and DLPFC activity, often described as an inverted U, appears to be shifted in schizophrenia patients such that peak DLPFC activation is reached at a lower memory load compared with healthy controls. This hypothesis is supported by studies that demonstr (...truncated)


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Jejoong Kim, Natasha L. Matthews, Sohee Park. An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia, PLOS ONE, 2010, Volume 5, Issue 8, DOI: 10.1371/journal.pone.0012068