Objective: Prefrontal cortical dysfunction has been implicated in the pathophysiology of schizophrenia but it is unclear to what extent these are related to changes in symptomatology as well as task demand. Method: We examined the neural correlates of symptom change and task demand during a longitudinal functional magnetic resonance imaging (fMRI) study using a verbal fluency task with differential task demands in patients with schizophrenia and matched healthy control subjects. The fMRI data were acquired using clustered acquisition technique, enabling ongoing monitoring of behavioural responses, in the patient group on two occasions separated by 6-8weeks, and the control group at baseline. Results: Positive psychotic symptoms were significantly reduced over the 6-8-week duration of the study. This change was associated with increased activation within the left middle frontal gyrus and decreased activation of the left precuneus. An interaction between symptom change and task demand was evident in the activation of the left middle frontal gyrus. The decrease in positive symptoms was associated with normalisation of activation in the dorsolateral prefrontal cortex and a decrease in parietal activation during the verbal fluency task. Conclusion: The data supports the role of dysfunctional prefronto-parietal relationships in the genesis of positive psychotic symptoms. © 2010 John Wiley & Sons A/S.