Abstract
Alterations in activity and connectivity of brain circuits implicated in emotion processing and emotion regulation have been observed during resting-state for different clinical phases of bipolar disorders (BD), but longitudinal investigations across different mood states in the same patients are still rare. Furthermore, measuring dynamics of functional connectivity patterns offers a powerful method to explore changes in the brain’s intrinsic functional organization across mood states. We used a novel co-activation pattern (CAP) analysis to explore the dynamics of amygdala connectivity at rest in a cohort of 20 BD patients prospectively followed-up and scanned across distinct mood states: euthymia (20 patients; 39 sessions), depression (12 patients; 18 sessions), or mania/hypomania (14 patients; 18 sessions). We compared them to 41 healthy controls scanned once or twice (55 sessions). We characterized temporal aspects of dynamic fluctuations in amygdala connectivity over the whole brain as a function of current mood. We identified six distinct networks describing amygdala connectivity, among which an interoceptive-sensorimotor CAP exhibited more frequent occurrences during hypomania compared to other mood states, and predicted more severe symptoms of irritability and motor agitation. In contrast, a default-mode CAP exhibited more frequent occurrences during depression compared to other mood states and compared to controls, with a positive association with depression severity. Our results reveal distinctive interactions between amygdala and distributed brain networks in different mood states, and foster research on interoception and default-mode systems especially during the manic and depressive phase, respectively. Our study also demonstrates the benefits of assessing brain dynamics in BD.
Highlights
To achieve good monitoring of bipolar disorder (BD) patients’ state and prognosis, psychiatric research needs to better characterize the neural processes that distinguish different clinical phases of the disease
Co-activation patterns: different network interactions of the amygdala Our dynamic connectivity analyses identified six distinct coactivation pattern (CAP), each interacting in a distinctive manner with the amygdala seed region
The reported associations between CAP occurrences and clinical scores were still significant even after controlling for antidepressant effect, except for the elated mania subscore (Y2) and INT CAP metrics. These findings indicate that, medication may be associated with changes in the temporal brain dynamics of BD patients, such effects are unlikely to explain the specific alterations that we described in relation to mood changes
Summary
To achieve good monitoring of bipolar disorder (BD) patients’ state and prognosis, psychiatric research needs to better characterize the neural processes that distinguish different clinical phases of the disease. Resting-state brain imaging studies of BD, initially limited to Independent Component Analysis (ICA) and seed-based functional connectivity (FC), and later enriched by graph theory methods, have contributed to the demonstration of widespread FC disruptions [1,2,3]. This literature incriminates different brain areas and networks such as the default-mode network, limbic and reward circuits, and more recently sensorimotor networks [4,5,6,7]. A few investigations segregated different states, they compared different patients [2, 7, 13] rather than the same patients across different phases
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