Researchers have found new clues as to how brain plasticity can overcome a genetic predisposition to bipolar disorder.

Reporting their findings online January 5 in Translational Psychiatry, a research team compared connections between different brain regions among people with bipolar disorder, their relatives who shared features predicting bipolar disorder but showed no symptoms, and unrelated people without bipolar disorder.

The team focused on brain regions that contribute to working memory — the ability to hold on to new information temporarily.  They also tested how those in the study interpreted faces displaying different emotions. Both of these faculties are often impaired in bipolar disorder. Participants underwent imaging to measure brain activity during one working memory task where they tracked letters presented on cards, and another task where they distinguished between human faces showing different emotions or  neutral expressions.

The paper’s first author was 2014 NARSAD Young Investigator grantee Danai Dima, Ph.D., of King’s College London and the Icahn School of Medicine at Mount Sinai. The team was led by 2002 Young Investigator and 2008 Independent Investigator grantee Sophia Frangou, M.D., Ph.D., also of the Icahn School of Medicine at Mount Sinai. The team also included Ed Roberts, Ph.D., of Imperial College London.

The study’s key findings concerned communication patterns within the brain. Both the participants with bipolar disorder and their relatives showed increased connections between the amygdala, crucial for emotional responses, and the ventromedial prefrontal cortex, part of the brain’s executive center that helps inhibit emotions and make decisions. These increased connections seem to reflect a propensity toward bipolar disorder.

This raises the question of why the unaffected relatives had never shown signs of the illness, despite having this same pattern of greater connectivity. A possible answer comes from the finding that these relatives additionally showed increased connections between brain regions involved in visual processing, particularly face recognition. These connections may compensate for any processing dysfunction caused by the unusual amygdala-ventromedial prefrontal cortex connectivity.

Thus, the brain appears to have the capacity to “defeat” a predisposition to bipolar disorder, or at least delay onset of the disease, since none of the relatives in this study showed any history of symptoms and were all past the age range in which bipolar typically appears. This insight could help identify strategies to prevent bipolar disorder among people genetically predisposed to it, the researchers say.

The study participants with bipolar disorder uniquely showed reduced connections between the brain regions responsible for working memory. Those connections grew less robust the longer people had been living with the illness, and they predicted the level of working memory deficits. However, the researchers note, other studies suggest that working memory is sensitive to irregularities in other brain connection, and thus is not specific to bipolar disorder.