TY - JOUR

T1 - Neuronal underpinnings of cognitive impairment in bipolar disorder

T2 - A large data-driven functional magnetic resonance imaging study

AU - Zarp Petersen, Jeff

AU - Varo, Cristina

AU - Skovsen, Cecilie F.

AU - Ott, Caroline V.

AU - Kjærstad, Hanne L.

AU - Vieta, Eduard

AU - Harmer, Catherine J.

AU - Knudsen, Gitte M.

AU - Kessing, Lars V.

AU - Macoveanu, Julian

AU - Miskowiak, Kamilla W.

N1 - Funding Information: The study was supported by the Lundbeck Foundation (grant R215–20154121) awarded to Kamilla Miskowiak; the Lundbeck Foundation had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Funding Information: We thank Dr Julie Lyng Forman for supervision and advices on the multiple imputation analyses. KWM holds a five‐year Lundbeck Foundation Fellowship which also funded the current fMRI study (grant no. R215‐2015‐4121). EV 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 co‐financed by the ISCIII‐Subdirección General 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 Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357. CJH was supported by the NIHR Oxford Health Biomedial Research Centre, Oxford. Publisher Copyright: © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

PY - 2022

Y1 - 2022

N2 - Objectives: Cognitive impairment occurs in approximately 50% of remitted patients with bipolar disorder (BD). However, there exists no treatment with replicated and robust efficacy on cognition in BD. This is partially due to limited insight into the neuronal underpinnings of cognitive impairment in these patients. This is the first study to investigate neuronal underpinnings of cognitive impairment in a large functional magnetic resonance imaging (fMRI) dataset comparing neural activity patterns between distinct neurocognitive subgroups of partially or fully remitted patients with BD. Methods: Patients (n = 153) and healthy controls (HC) (n = 52) underwent neuropsychological assessment and fMRI, during which they performed a verbal N-back working memory (WM) task. Based on hierarchical cluster analysis of neuropsychological test performance, patients were grouped into one of two neurocognitive subgroups (cognitively impaired, n = 91; cognitively normal compared to HC, n = 62) that were compared on WM-related neural activity. Results: Cognitively impaired patients displayed WM-related hypo-activity in left dorsolateral prefrontal cortex and frontal and parietal regions within a cognitive control network (CCN) as well as hyper-activity in the default mode network (DMN) compared to cognitively normal patients. In contrast, cognitively normal patients only exhibited hypo-activity within a small cluster in the superior frontal gyrus relative to HC. Conclusions: Cognitive impairment in BD seems to originate from a failure to recruit key regions in the CCN and to suppress task-irrelevant DMN activity during cognitive performance. These results highlight modulation of aberrant dorsal prefrontal and DMN activity as a putative target for pro-cognitive treatment in BD.

AB - Objectives: Cognitive impairment occurs in approximately 50% of remitted patients with bipolar disorder (BD). However, there exists no treatment with replicated and robust efficacy on cognition in BD. This is partially due to limited insight into the neuronal underpinnings of cognitive impairment in these patients. This is the first study to investigate neuronal underpinnings of cognitive impairment in a large functional magnetic resonance imaging (fMRI) dataset comparing neural activity patterns between distinct neurocognitive subgroups of partially or fully remitted patients with BD. Methods: Patients (n = 153) and healthy controls (HC) (n = 52) underwent neuropsychological assessment and fMRI, during which they performed a verbal N-back working memory (WM) task. Based on hierarchical cluster analysis of neuropsychological test performance, patients were grouped into one of two neurocognitive subgroups (cognitively impaired, n = 91; cognitively normal compared to HC, n = 62) that were compared on WM-related neural activity. Results: Cognitively impaired patients displayed WM-related hypo-activity in left dorsolateral prefrontal cortex and frontal and parietal regions within a cognitive control network (CCN) as well as hyper-activity in the default mode network (DMN) compared to cognitively normal patients. In contrast, cognitively normal patients only exhibited hypo-activity within a small cluster in the superior frontal gyrus relative to HC. Conclusions: Cognitive impairment in BD seems to originate from a failure to recruit key regions in the CCN and to suppress task-irrelevant DMN activity during cognitive performance. These results highlight modulation of aberrant dorsal prefrontal and DMN activity as a putative target for pro-cognitive treatment in BD.

KW - bipolar disorder

KW - cognition

KW - cognitive impairment

KW - fMRI

KW - neural

KW - pro-cognitive

KW - treatment

U2 - 10.1111/bdi.13100

DO - 10.1111/bdi.13100

M3 - Journal article

C2 - 33955648

AN - SCOPUS:85104870203

VL - 24

SP - 69

EP - 81

JO - Bipolar Disorders, Supplement

JF - Bipolar Disorders, Supplement

SN - 1399-2406

IS - 1

ER -