The neural basis of relational memory deficits in schizophrenia

Context: Memory deficits are common in schizophrenia. Recent studies have demonstrated that relational memory is particularly impaired. Objective: To study the neural correlates of relational memory in schizophrenia using functional magnetic resonance imaging. Design: Cross-sectional case-control study. Setting: Academic medical center. Subjects: Twenty patients with schizophrenia and 17 control subjects. Main Outcome Measures: Behavioral performance and brain activity were assessed during the discrimination of previously seen and novel pairs of visual stimuli, which varied in the degree of relational memory load. We performed whole-brain and region-of-interest (hippocampus) analyses. Results: Schizophrenic subjects displayed normal activation of the presupplementary motor area and ventral prefrontal cortex, but significantly decreased recruitment of the right parietal cortex and anterior cingulate cortex when discriminating novel pairs derived from a sequence of stimuli. Discrimination accuracy was decreased in schizophrenia only when the flexible representation of a sequence was required. This selective deficit was associated with decreased activation of the right parietal cortex and left hippocampus. Conclusions: Schizophrenia is characterized by a specific deficit of relational memory, which is associated with impaired function of the parietal cortex and hippocampus. Abnormal relational memory may be at the core of 2 prominent features of schizophrenia, ie, cognitive deficits and psychosis.