The role of hippocampus dysfunction in deficient memory encoding and positive symptoms in schizophrenia

Background: Declarative memory disturbances, known to substantially contribute to cognitive impairment in schizophrenia, have previously been attributed to prefrontal as well as hippocampal dysfunction. Aims: To characterize the role of prefrontal and mesolimbic/hippocampal dysfunction during memory encoding in schizophrenia. Method: Neuronal activation in schizophrenia patients and controls was assessed using functional magnetic resonance imaging (fMRI) during encoding of words in a deep (semantic judgement) and shallow (case judgment) task. A free recall (no delay) and a recognition task (24 h delay) were performed. Results: Free recall, but not recognition performance was reduced in patients. Reduced performance was correlated with positive symptoms which in turn were related to increased left hippocampal activity during successful encoding. Furthermore, schizophrenia patients displayed a hippocampal hyperactivity during deep encoding irrespective of encoding success along with a reduced anterior cingulate cortex (ACC) and dorsomedial prefrontal cortex (DMPFC) activity in successful encoding but an intact left inferior frontal cortex (LIFC) activity. Conclusions: This study provides the first evidence directly linking positive symptoms and memory deficits to dysfunctional hippocampal hyperactivity. It thereby underscores the pivotal pathophysiological role of a hyperdopaminergic mesolimbic state in schizophrenia.