Aberrant resting-state functional connectivity underlies cognitive and functional impairments in remitted patients with bipolar disorder

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Background: Bipolar disorder (BD) is commonly associated with cognitive impairments, that directly contribute to patients' functional disability. However, there is no effective treatment targeting cognition in BD. A key reason for the lack of pro-cognitive interventions is the limited insight into the brain correlates of cognitive impairments in these patients. This is the first study investigating the resting-state neural underpinnings of cognitive impairments in different neurocognitive subgroups of patients with BD. Method: Patients with BD in full or partial remission and healthy controls (final sample of n = 144 and n = 50, respectively) underwent neuropsychological assessment and resting-state functional magnetic resonance imaging. We classified the patients into cognitively impaired (n = 83) and cognitively normal (n = 61) subgroups using hierarchical cluster analysis of the four cognitive domains. We used independent component analysis (ICA) to investigate the differences between the neurocognitive subgroups and healthy controls in resting-state functional connectivity (rsFC) in the default mode network (DMN), executive central network (ECN), and frontoparietal network (FPN). Results: Cognitively impaired patients displayed greater positive rsFC within the DMN and less negative rsFC within the ECN than healthy controls. Across cognitively impaired patients, lower positive connectivity within DMN and lower negative rsFC within ECN correlated with worse global cognitive performance. Conclusion: Cognitive impairments in BD seem to be associated with a hyper-connectivity within the DMN, which may explain the failure to suppress task-irrelevant DMN activity during the cognitive performance, and blunted anticorrelation in the ECN. Thus, aberrant connectivity within the DMN and ECN may serve as brain targets for pro-cognitive interventions.

TidsskriftActa Psychiatrica Scandinavica
Udgave nummer6
Sider (fra-til)570-582
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
Funding for this study was provided by a five‐year Lundbeck Foundation Fellowship to Kamilla W. Miskowiak (R215‐2015‐4121). Joaquim Radua and Lydia Fortea were supported by the Instituto de Salud Carlos III ‐ Subdirección General de Evaluación y Fomento de la Investigación: Miguel Servet Research Contract (CPII19/0009 to Joaquim Radua), and the PFIS contract (FI20/00047 to Lydia Fortea). Eduard Vieta thanks the support of the Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I + D + I and cofinanced by the ISCIII‐ Subdirección de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats I Recerca del Departament d'Economia I Coneixement (2017 SGR 1365); the CERCA Programme, and the Department de Salut de la Generalitat de Catalunya for the PERIS grant (SLT006/17/00357).

Publisher Copyright:
© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.

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