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Updated: Nov 29, 2025

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Altered functional activity in bipolar disorder: A comprehensive review from a large-scale network perspective
Sujung Yoon1,2, Tammy D Kim1, Jungyoon Kim1,2
1Ewha Brain Institute, Ewha W. University, Seoul, South Korea.
Background:
Growing literature continues to identify brain regions that are functionally altered in bipolar disorder. However, precise functional network correlates of bipolar disorder have yet to be determined due to inconsistent results. The overview of neurological alterations from a large-scale network perspective may provide more comprehensive results and elucidate the neuropathology of bipolar disorder. Here, we critically review recent neuroimaging research on bipolar disorder using a network-based approach.
Methods:
A systematic search was conducted on studies published from 2009 through 2019 in PubMed and Google Scholar. Articles that utilized functional magnetic resonance imaging technique to examine altered functional activity of major regions belonging to a large-scale brain network in bipolar disorder were selected.
Results:
A total of 49 studies were reviewed. Within-network hypoconnectivity was reported in bipolar disorder at rest among the default mode, salience, and central executive networks. In contrast, when performing a cognitive task, hyperconnectivity among the central executive network was found. Internetwork functional connectivity in the brain of bipolar disorder was greater between the salience and default mode networks, while reduced between the salience and central executive networks at rest, compared to control.
Conclusion:
This systematic review suggests disruption in the functional activity of large-scale brain networks at rest as well as during a task stimuli in bipolar disorder. Disrupted intra- and internetwork functional connectivity that are also associated with clinical symptoms suggest altered functional connectivity of and between large-scale networks plays an important role in the pathophysiology of bipolar disorder.
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