fMRI sheds some light on schizophrenia

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Schizophrenia may blur the boundary between internal and external realities by over-activating a brain system that is involved in self-reflection, and thus causing an exaggerated focus on self, according to a study in the Jan.19 advance online issue of the Proceedings of the National Academy of Sciences.

The researchers found 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 we are thinking about nothing in particular, or thinking about ourselves.

"People normally suppress this default system when they perform challenging tasks, but we found that patients with schizophrenia don't do this," said study author John D. Gabrieli, a professor in the McGovern Institute for Brain Research at Massachusetts Institute of Technology in Cambridge, Mass. "We think this could help to explain the cognitive and psychological symptoms of schizophrenia."

Schizophrenia has a genetic component, and first-degree relatives of patients 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 thus studied three carefully matched groups of 13 subjects each: schizophrenia patients, non-psychotic first-degree relatives of patients and healthy controls. They selected patients who were recently diagnosed, so that differences in prior treatment or psychotic episodes would not bias the results.

Investigators scanned subjects by functional MRI (fMRI), while resting and while performing easy or hard memory tasks. The researchers said that they were interested in the default system—a network of brain regions whose activity is suppressed when people perform demanding mental tasks. The network includes the medial prefrontal cortex and the posterior cingulate cortex, regions that are associated with self-reflection and autobiographical memories and which become connected into a synchronously active network when the mind is allowed to wander.

They found that in schizophrenia patients, the default system was both hyperactive and hyperconnected during rest, and it remained so as they performed the memory tasks. In other words, 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, according to the researchers.

“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," the authors explained.

The hyperactive default system could also help to explain hallucinations and paranoia by making neutral external stimuli seem inappropriately self-relevant, Gabrieli and colleagues wrote. For instance, if brain regions whose activity normally signifies 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.

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