Brain activation patterns during a selective attention test — a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia

Abstract

In a previous functional magnetic resonance imaging (fMRI) study of high functioning outpatients with remitted schizophrenia, we found increased activity compared with healthy subjects across multiple areas of the brain, including the dorsolateral frontal cortex and the anterior cingulate, during a modified Stroop task. The same fMRI procedure was used in this subsequent study to investigate eight unmedicated patients during an acute episode of schizophrenia and eight healthy control subjects. Patients showed a reduced activation in dorsolateral prefrontal, anterior cingulate and parietal regions and a higher activation in temporal regions and posterior cingulate compared to healthy controls. Healthy controls showed a trend towards higher accuracy in the modified Stroop task compared to schizophrenia patients. Treatment with second generation antipsychotics may improve executive performance in patients with schizophrenia and facilitate a normalization of functional hypofrontality after symptomatic improvement.

Introduction

Attention and working memory deficits are among the earliest and most severe cognitive impairments observed in schizophrenia patients (Heinrichs and Zakzanis, 1998, Barch et al., 1999, Rund and Borg, 1999). Functional imaging studies of attention and working memory have produced mixed findings in patients with schizophrenia, with some studies showing reduced prefrontal cortex activation (Weinberger et al., 1988, Weinberger et al., 1992, Callicott et al., 1998, Carter et al., 1998, Fletcher et al., 1998, Stevens et al., 1998, Curtis et al., 1998, Barch et al., 2001, Perlstein et al., 2001) and others reporting equal or increased frontal activity (Frith et al., 1995, Mellers et al., 1998, Curtis et al., 1998, Manoach et al., 1999, Manoach et al., 2000, Manoach et al., 2003, Callicott et al., 2000). Discrepant findings may be due to methodological inhomogeneity mainly regarding factors such as medication, task performance, task design and differences in task demands.

In a previous functional magnetic resonance imaging (fMRI) study, we compared the cortical activation patterns during a modified Stroop task in healthy volunteers and outpatients with remitted schizophrenia who were pre-selected on the basis of good performance on this selective attention test (Weiss et al., 2003). The modified Stroop task is similar in critical aspects to more familiar response-competition tasks such as the original Stroop task or the go/no-go task and engages a similar network of regional cerebral activity as the traditional Stroop task in healthy subjects (Weiss et al., 2003). In patients with schizophrenia, we found increased activity across multiple areas of the brain, including the dorsolateral frontal cortex and the anterior cingulate. Although both schizophrenia patients and healthy control subjects recruited the prefrontal cortex during the modified Stroop task, this activation was bilateral in schizophrenia patients, whereas for the controls it was primarily seen in the left hemisphere, suggesting that patients with schizophrenia recruited more prefrontal regions to perform the task with the same accuracy as healthy controls (Weiss et al., 2003).

However, all patients in this study were treated with second generation antipsychotics, which are believed to have beneficial effects on cognitive functioning (Weiss et al., 2002b). Furthermore, only patients who had been clinically stable for a period of at least 6 months were included. To address these limitations, we have now investigated activation patterns in unmedicated patients during an acute episode of schizophrenia. We hypothesized that unmedicated patients during an acute episode of schizophrenia would show a reduced activation of the prefrontal cortex compared with healthy control subjects.