Disrupted network switching in euthymic bipolar disorder: Working memory and self-referential paradigms

Background: Patients with bipolar disorder (BD) frequently suffer from neurocognitive deficits that can persist during periods of clinical stability. Specifically, impairments in executive functioning such as working memory and in self-processing have been identified as the main components of the neurocognitive profile observed in euthymic BD patients. The study of the neurobiological correlates of these state-independent alterations may be a prerequisite to develop reliable biomarkers in BD.Methods: A sample of 27 euthymic BD patients and 25 healthy participants (HC) completed working memory and self-referential functional Magnetic Resonance Imaging (fMRI) tasks. Activation maps obtained for each group and contrast images (i.e., 2-back > 1-back/self > control) were used for comparisons between patients and HC.Results: Euthymic BD patients, in comparison to HC, showed a higher ventromedial prefrontal cortex activation during working memory, a result driven by the lack of deactivation in BD patients. In addition, euthymic BD patients displayed a greater dorsomedial and dorsolateral prefrontal cortex activation during self-reference processing. Limitations: Pharmacotherapy was described but not included as a confounder in our models. Sample size was modest. Conclusion: Our findings revealed a lack of deactivation in the anterior default mode network (aDMN) during a working memory task, a finding consistent with prior research in BD patients, but also a higher activation in frontal regions within the central executive network (CEN) during self-processing. These results suggest that an imbalance of neural network dynamics underlying external/internal oriented cognition (the CEN and the aDMN, respectively) may be one of the first reliable biomarkers in euthymic bipolar patients.

Automated summary

Patients with bipolar disorder (BD) frequently experience neurocognitive deficits during periods of clinical stability. Investigating the neurobiological correlates of these state-independent alterations may help develop reliable biomarkers in BD. In this study, euthymic BD patients and healthy participants completed working memory and self-reference functional Magnetic Resonance Imaging (fMRI) tasks. The results showed increased activation in the ventromedial prefrontal cortex during working memory and in the dorsomedial and dorsolateral prefrontal cortex during self-reference processing in BD patients. These findings suggest an imbalance of neural network dynamics as a potential biomarker in euthymic bipolar patients.