This study investigated changes in cerebral activation related to emotion processing in schizophrenia patients with blunted or flat affect (FA+) during treatment with quetiapine. Using functional magnetic resonance imaging (fMRI), brain activation in 12 FA+ schizophrenia patients during passive viewing of sad film excerpts was studied before and after a median of 5.5-months treatment with quetiapine. Random-effects 'paired sample t-test' analyses of brain activation before quetiapine (contrast=sad-neutral, before-after) revealed significant activation in the brainstem (pons, medulla). After quetiapine, the same contrast showed significant prefrontal activation (BA 9, 10 and 11). Activation of key prefrontal areas involved in emotion processing and significant symptoms improvement as measured by the subjective rating scale and PANSS suggests the potential effect of quetiapine in improving blunted affect related symptoms (i.e., passive withdrawal, emotional withdrawal, social avoidance) in schizophrenia.