Abstract
Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased ‘false memory’ errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased “false memory” errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research.
Highlights
Working memory is a limited-capacity, active short-term memory system that guides and controls behavior in context
The second goal of this study was to test the less invasive nearinfrared spectroscopy (NIRS) as a viable alternative to functional magnetic resonance imaging (fMRI) using the same task employed in Experiment 1. fMRI has become the standard brain imaging method to examine the neural correlates of cognitive function, but the MRI environment can lead to difficulties in recruiting psychiatric patients because of stringent exclusion criteria
The patients showed a greater activation compared with the controls in the left middle frontal gyrus (MFG), the left inferior frontal gyrus (IFG), the left CG as well as the left inferior parietal lobule (IPL) and the left superior temporal gyrus (STG)
Summary
Working memory is a limited-capacity, active short-term memory system that guides and controls behavior in context. The working memory deficit in schizophrenia, first reported in the early 90s [1] has become an important cornerstone in understanding the pathophysiology of this disorder. Individuals at risk for schizophrenia, such as healthy, unmedicated first-degree relatives of schizophrenic subjects [3,4,5] and psychometrically-ascertained schizotypal subjects show working memory deficits [6,7,8,9]. In schizophrenic subjects, working memory deficit is permanent and stable even when their clinical symptoms are largely in remission [10,11]. The persistent and trait-like nature of working memory deficit in schizophrenic patients and in healthy first-degree relatives suggests that it may be an endophenotypic marker for schizophrenia [3,12,13], and a potential aid to discovering the genetic basis of this disorder. It is important to specify the origins and consequences of the deficit but we do not know yet know much about the reasons for the deficit
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