Elucidating neural network functional connectivity abnormalities in bipolar disorder: toward a harmonized methodological approach.

Bipolar disorder (BD), a mood disorder characterized by emotional lability and dysregulation, is associated with alterations in functional connectivity, particularly as assessed using functional MRI. Here, we provide an overview of the extant literature, and themes that have emerged within it. We identified published research describing functional connectivity in BD using PubMed and follow-up searches. The most consistent evidence favors abnormally heightened functional connectivity between the amygdala and the lateral regions of the ventral prefrontal cortex (PFC), both during rest or emotional processing. Altered interactions between the amygdala and more medial PFC regions have been implicated in BD, but are less consistently related to core symptoms and are sometimes associated with mood state or psychosis. Interactions between medial and lateral ventral PFC have also been reported to be altered in BD, and may mediate estimates of amygdala/vlPFC connectivity. We also describe other themes, including an emerging literature examining reward circuitry, which has highlighted abnormal functional interactions between the ventral striatum and medial prefrontal cortex, as well as the advent of examining global network abnormalities in BD. Functional connectivity studies in BD have established altered interactions between PFC and the amygdala. To address the inconsistencies in the literature, we suggest avenues for the adoption of large scale, and network-based analysis of connectivity, the integration of structural connectivity and the acknowledgement of dynamic and context-related shifts in functional connectivity as a means of clarifying the abnormal neural circuitry in the disorder.

Dissociable patterns of abnormal frontal cortical activation during anticipation of an uncertain reward or loss in bipolar versus major depression.

OBJECTIVES: Recent research has found abnormalities in reward-related neural activation in bipolar disorder (BD), during both manic and euthymic phases. However, reward-related neural activation in currently depressed individuals with BD and that in currently depressed individuals with major depressive disorder (MDD) have yet to be directly compared. Here, we studied these groups, examining the neural activation elicited during a guessing task in fronto-striatal regions identified by previous studies. METHODS: We evaluated neural activation during a reward task using fMRI in two groups of depressed individuals, one with bipolar I disorder (BD-I) (n = 23) and one with MDD (n = 40), with similar levels of illness severity, and a group of healthy individuals (n = 37). RESULTS: Reward expectancy-related activation in the anterior cingulate cortex was observed in the healthy individuals, but was significantly reduced in depressed patients (BD-I and MDD together). Anticipation-related activation was increased in the left ventrolateral prefrontal cortex in the BD-I depressed group compared with the other two groups. There were no significant differences in prediction error-related activation in the ventral striatum across the three groups. CONCLUSIONS: The findings extend previous research which has identified dysfunction within the ventrolateral prefrontal cortex in BD, and show that abnormally elevated activity in this region during anticipation of either reward or loss may distinguish depressed individuals with BD-I from those with MDD. Altered activation of the anterior cingulate cortex during reward expectancy characterizes both types of depression. These findings have important implications for identifying both common and distinct properties of the neural circuitry underlying BD-I and MDD.

State-dependent microstructural white matter changes in bipolar I depression.

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.