The Brain’s Functional Connectivity Profile in Bipolar Disorder

What’s the science?

Differences in the brain’s connectivity or wiring are thought to underlie different psychiatric disorders. One functionally connected network in the brain is the reward network, which includes the nucleus accumbens. One role of this network is to seek out stimuli that are positive or pleasurable. In individuals with bipolar disorder, a connection between the nucleus accumbens and the ventromedial prefrontal cortex has been found to be abnormal during anticipation of reward. However, whether this altered connectivity is present in individuals with bipolar disorder while they are not experiencing symptoms is not known. This week in Biological Psychiatry, Whittaker and colleagues used functional magnetic resonance imaging (fMRI) to understand how connectivity of the brain’s reward network is altered in bipolar disorder.

How did they do it?

88 participants (35 with bipolar disorder, 30 unaffected siblings of those with bipolar disorder, and 23 healthy controls) aged 35-60 were included in the final analyses for the study. Individuals with bipolar disorder participated when they were in a euthymic state (a calm, normal mood) and had had no major mood or psychotic episodes for a month before scanning. IQ was measured in all participants using the National Adult Reading Test. fMRI data were collected while the participants were at rest (‘resting state’; not performing any task). The blood oxygen dependent level (BOLD) signal was recorded, which is a measure of fluctuations in the blood oxygen levels in the brain, (an indirect measure of brain activity). In each participant, the nucleus accumbens was identified, and the correlation between the activity of the nucleus accumbens and all other brain regions was measured (this correlation of activity between two brain regions is referred to as ‘functional connectivity’). The group of individuals with bipolar disorder was compared with the group of unaffected siblings as well as healthy controls, and the unaffected siblings were also compared with the healthy control group.

What did they find?

Across all participants, activity at rest in the nucleus accumbens was strongly positively correlated with activity in subcortical structures of the brain such as the hippocampus and amygdala, and cortical regions such as the ventromedial prefrontal cortex, anterior cingulate, and postcentral gyrus. There was a stronger functional connection between the nucleus accumbens and the ventromedial prefrontal cortex in the bipolar disorder group versus in healthy controls. The strength of this connection in the bipolar disorder group was not predicted by use of mood stabilizers (e.g. lithium). When the ventromedial prefrontal cortex was selected as a region of interest and group comparisons were performed, siblings exhibited connectivity midway between connectivity levels of the bipolar group (stronger connectivity) and the healthy control group (weaker connectivity). When depression and mania scores were included as covariates in the group comparison analyses, group differences remained. Depression and mania scores were not related to individual differences in functional connectivity amongst individuals with bipolar disorder.

                                       Brain,  S  ervier Medical Art,  image by BrainPost,  CC BY-SA 3.0

                                       Brain, Servier Medical Art, image by BrainPost, CC BY-SA 3.0

What’s the impact?

This study is the first to examine functional connectivity of a key region of the reward network (the nucleus accumbens) in individuals with bipolar disorder and unaffected siblings. Strong functional connectivity (i.e. correlated brain activity) between the nucleus accumbens and ventromedial prefrontal cortex may be a biomarker for bipolar disorder. The study has important implications for understanding the role of the reward network in bipolar disorder.


Whittaker et al., The functional connectivity between nucleus accumbens and the ventromedial prefrontal cortex as an endophenotype for bipolar disorder. Biological Psychiatry (2018). Access the original scientific publication here.