Regionally Specific Disturbance of Dorsolateral Prefrontal–Hippocampal Functional Connectivity in Schizophrenia

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Abstract
Much interest in schizophrenia research has centered on the dorsolateral prefrontal cortex (DLPFC)1 and the hippocampal formation (HF),2 brain regions where multiple abnormalities are demonstrated by converging evidence from neuropathologic findings3,4 and structural5 and functional6,7 neuroimaging. Since the HF provides important input to the DLPFC8 and because neonatal HF lesions in animals induce postpubertally manifested changes in prefrontal cortex9 mimicking aspects of schizophrenic pathophysiology, it has been hypothesized that the interaction between these two regions might be particularly disturbed in the disorder.10,11 This so-called “disconnection” hypothesis12 is also attractive since the HF is selectively vulnerable to some obstetrical insults,13 and a disturbed interaction with the DLPFC would thus offer an explanation of epidemiological data linking schizophrenia to early neurodevelopmental disturbances.14 Previous neuroimaging studies of schizophrenia have observed patterns of abnormal activity prominently involving temporal lobe areas and the DLPFC.15,16 However, no neuroimaging data exist that specifically target the HF to examine its functional connections in schizophrenia.