An event-related FMRI study of phonological verbal working memory in schizophrenia

Abstract

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.

Figure 1. Procedure of the phonological verbal WM task

Figure 2. Cortical activation patterns during verbal WM maintenance for the two groups.

Healthy controls (A), patients with schizophrenia (B), and significantly different activation between groups (subtraction of SZ-CO) (C) are shown. The time series plots in the middle column show activation associated with true memory maintenance (red lines) relative to the baseline activities (blue line). Bright parts in the middle of each plot represent 1-volume (1.5 s) after onset, and offset of the maintenance phase (4.5 secs). All p-values are corrected with false discovery rate of q<0.005.

Figure 3. Cortical activation patterns during false memory trials.

(A) False memory – Baseline in CO. (B) False memory – Baseline in SZ. (C) SZ – CO. All p-values are corrected with FDR of q<0.005. The time course plots show false memory related activities (yellow) and true memory related activities (red) relative to the baseline (blue).