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 magnetic resonance imaging. 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) 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/ventrolateral PFC 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 analyses 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.