Patients who suffer from the devastating psychiatric illness schizophrenia are plagued by hallucinations, bizarre behavior, and delusional ideas, such as believing that they are controlled by malevolent outside forces. A fundamental human cognitive operation that may contribute to these hallmark symptoms is the ability to maintain accurate and coherent self-referential processing over time, such as occurs during reality monitoring (distinguishing self-generated from externally perceived information). However, the neural bases for a disturbance in this operation in schizophrenia have not been fully explored. Using functional magnetic resonance imaging, we asked clinically stable schizophrenia patients to remember whether or not they had generated a target word during an earlier sentence completion task. We found that, during accurate performance of this self-referential source memory task, the schizophrenia subjects manifest a deficit in rostral medial prefrontal cortex (mPFC) activity - a brain region critically implicated in both the instantiation and the retrieval of self-referential information in healthy subjects. Impairment in rostral mPFC function likely plays a key role in the profound subjective disturbances that characterize schizophrenia and that are the aspect of the disorder most troubling to patients and to society at large.
Bibliographical noteFunding Information:
San Francisco Department of Veterans Affairs Medical Center (to S.V.); University of California, San Francisco Research and Education Allocation Committee (to S.V.); National Institutes of Health (grant MH068725-01A1 to S.V.; F32 MH64295 and K01 AG027369 to T.L.L.; and NS45171 to G.V.S.); Howard Hughes Medical Institute (to B.J.S.).
- Medial prefrontal cortex
- Self-referential processes
- Source memory