Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect

Abstract

Background: The negative symptoms of schizophrenia have been proposed to reflect prefrontal cortex dysfunction. However, this proposal has not been consistently supported in functional imaging studies, which have also used executive tasks that may not capture key aspects of negative symptoms such as lack of volition. Method: Twenty-four DSM-5 schizophrenic patients with high negative symptoms (HNS), 25 with absent negative symptoms (ANS) and 30 healthy controls underwent fMRI during performance of the Computerized Multiple Elements Test (CMET), a task designed to measure poor organization of goal directed behaviour or 'goal neglect'. Negative symptoms were rated using the PANSS and the Clinical Assessment Interview for Negative Symptoms (CAINS). Results: On whole brain analysis, the ANS patients showed no significant clusters of reduced activation compared to the healthy controls. In contrast, the HNS patients showed hypoactivation compared to the healthy controls in the left anterior frontal cortex, the right dorsolateral prefrontal cortex (DLPFC), the anterior insula bilaterally and the bilateral inferior parietal cortex. When compared to the ANS patients, the HNS patients showed reduced activation in the left anterior frontal cortex, the left DLPFC and the left inferior parietal cortex. After controlling for disorganization scores, differences remained in clusters in the left anterior frontal cortex and the bilateral inferior parietal cortex. Conclusions: This study provides evidence that reduced prefrontal activation, perhaps especially in the left anterior frontal cortex, is a brain functional correlate of negative symptoms in schizophrenia. The simultaneous finding of reduced inferior parietal cortex activation was unexpected, but could reflect this region's involvement in cognitive control, particularly the 'regulative' component of this.