Dartmouth Medical School professor Alan Green and researchers from MIT and Harvard recently discovered that hyperactivation and hyperconnectivity of the default mode of brain may contribute to disturbances of thought in schizophrenia and in first-degree relatives (i.e. parents, siblings and offspring) of persons with schizophrenia. The finding was published last month in PNAS.

Schizophrenia is a severe psychiatric disorder marked by disturbed thoughts and emotions, accompanied by mental impairments, including attention and working memory (WM). Often in schizophrenia patients, the boundary blurs between internal and external realities causing hallucinations.

The researchers examined the default mode in the brain, which is active when people are at rest and thinking about nothing or about themselves, and typically suppressed when performing challenging mental tasks. The studied revealed that even during tasks, the default mode was comparatively much more active in schizophrenia patients and relatives than typical, healthy individuals.
The researchers studied three groups of 13 subjects each: schizophrenia patients, non-psychotic first-degree relatives of patients and healthy controls. Using functional magnetic resonance imaging (fMRI), patients, relatives and controls alternated between rest and performance of working memory (WM) tasks. When performing tasks, controls suppressed the activation in the default network as expected, including medial prefrontal cortex (MPFC), a region associated with self-reflection and autobiographical memories. However, schizophrenia patients and relatives exhibited significantly reduced suppression in MPFC. These results imply that schizophrenia patients and relatives cannot seem to turn off the default system, thereby causing an exaggerated focus on self.
Further, it has long been thought that the characteristics of schizophrenia like disturbances in thoughts, perceptions and emotions are caused by disconnections among the brain regions that control these functions. This study revealed that schizophrenia in fact also triggers excessive connectivity between the default brain regions.

These results “may help us understand why people who have schizophrenia may be more focused on their inner thoughts than on things outside of them,” said Green in an email to DUJS.

Relatives were found to exhibit some of the abnormalities of the patients, suggesting that certain abnormalities may be linked to genetic inheritance. In fact, schizophrenia is known to have a strong genetic component; first-degree relatives of patients are 10 times more likely to develop the disease than the general population.

According to Susan Whitfield-Gabrieli of MIT, first author of the paper, “We are happy with these findings. One possible future direction is that these brain imaging measures could be used to PREDICT treatment outcome. For example, the default network activation and connectivity profile may be used to predict which patients respond to which treatments.”