Ventral Tegmental Area as the Core Pathophysiological Hub in Bipolar Disorder: Evidence from Resting-State fMRI

ObjectivesBipolar disorder (BPD) is a major and complex psychiatric condition, clinically characterized by euthymic, depressive, and manic phases. Through the concept of "dialectic neuroscience," the ventral tegmental area (VTA) has been proposed as a potential key hub in BPD. This study utilized resting-state functional magnetic resonance imaging (rsfMRI) to investigate functional connectivity (FC) changes seeded by the VTA in BPD. MethodsMRI data from 98 participants in a publicly available dataset were analyzed (49 stable BPD patients and 49 healthy controls). Using the dopamine receptor D1 distribution template from JuSpace, the representative voxel of the VTA in the midbrain was identified based on the highest correlation with the D1 template. This voxel served as the seed for FC map construction. The FC maps were Fisher-transformed and compared statistically using an independent two-sample t-test. ResultsSignificant deviations in BPD were observed in brain regions that were highly consistent with the projections of the VTA, including the ventral and medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, and nucleus accumbens. ConclusionsThe FC analysis provided empirical support for the VTA theory in BPD. The role of VTA abnormalities in contributing to the manifestation of opposing polarities within a single disorder was discussed, offering insights into the potential physiological mechanisms and genesis of BPD. The framework of dialectic neuroscience may provide a valuable approach for developing guiding brain theories in psychiatric disorders.