Altered Brain Activity in Schizophrenics May Direct Focus on Self

But a new study, appearing January 19, 2009, in the advance online issue of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS), revealed that schizophrenia also involves an excess of connectivity between the so-called default brain regions, which are involved in self-reflection and become active when individuals are thinking about nothing in particular, or thinking about themselves.

"People normally suppress this default system when they perform challenging tasks, but we found that patients with schizophrenia don't do this,” said Dr. John D. Gabrieli, a professor in the McGovern Institute for Brain Research at the Massachusetts Institute of Technology (MIT; Cambridge, MA, USA) and one of the study's 13 authors. "We think this could help to explain the cognitive and psychological symptoms of schizophrenia.”

Dr. Gabrieli added that he hopes the study might lead to ways of predicting or tracking individual patients' response to treatments for this mental illness, which occurs in approximately 1% of the population. Schizophrenia has a strong genetic component, and first-degree relatives of patients (who share half their genes) are 10 times more likely to develop the disease than the general population. The identities of these genes and how they affect the brain are largely unknown.

The researchers therefore examined three carefully matched groups of 13 study participants each: schizophrenia patients, nonpsychotic first-degree relatives of patients, and healthy controls. They chose patients who were recently diagnosed, so that differences in earlier treatment or psychotic episodes would not bias the results.

The participants were scanned by functional magnetic resonance imaging (fMRI) while resting and while performing easy or hard memory tasks. The behavioral and clinical testing were performed by Dr. Larry J. Seidman and colleagues at Harvard Medical School (Cambridge, MA, USA), and the imaging data were analyzed by first author Dr. Susan Whitfield-Gabrieli, a research scientist at the MIT Martinos Imaging Center at the McGovern Institute.

The researchers were especially interested in the default system, a network of brain regions whose activity is suppressed when people perform demanding mental tasks. This network includes the medial prefrontal cortex and the posterior cingulate cortex, areas that are associated with self-reflection and autobiographic memories, which become connected into a synchronously active network when the mind is allowed to roam.

Dr. Whitfield-Gabrieli discovered that in the schizophrenia patients, the default system was both hyperactive and hyperconnected during rest, and it remained so as they performed the memory tasks. Meaning, the patients were less able than healthy control subjects to suppress the activity of this network during the task. Interestingly, the less the suppression and the greater the connectivity, the worse they performed on the hard memory task, and the more severe their clinical symptoms.

"We think this may reflect an inability of people with schizophrenia to direct mental resources away from internal thoughts and feelings and toward the external world in order to perform difficult tasks,” Dr. Whitfield-Gabrieli explained.

The hyperactive default system could also help to explain hallucinations and paranoia by making neutral external stimuli seem inappropriately self-relevant. For instance, if brain regions whose activity typically indicates self-focus are active while listening to a voice on television, the person may perceive that the voice is speaking directly to them.

The default system is also overactive, though to a lesser extent, in first-degree relatives of schizophrenia patients who did not themselves have the disease. This suggests that overactivation of the default system may be linked to the genetic cause of the disease rather than its consequences, according to the investigators.

The default system is a hot topic in brain imaging, according to Dr. Gabrieli, partly because it is easy to measure and because it is affected in different ways by different disorders.

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