Intrinsic functional connectivity correlates of cognitive deficits involving sustained attention and executive function in bipolar disorder

(2023) 23:584 Wu et al. BMC Psychiatry https://doi.org/10.1186/s12888-023-05083-2 BMC Psychiatry RESEARCH Open Access Intrinsic functional connectivity correlates of cognitive deficits involving sustained attention and executive function in bipolar disorder Yan‑Kun Wu1†, Yun‑Ai Su1†, Lin‑Lin Zhu1, Ji‑Tao Li1, Qian Li1, You‑Ran Dai1, Jing‑Yu Lin1, Ke Li2 and Tian‑Mei Si1* Abstract Background The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further inves‑ tigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the dif‑ ferent relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs). Methods Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic reso‑ nance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clini‑ cal assessment. A seed-based approach was used to evaluate the intrinsic FC alterations in three core neurocognitive networks (the default mode network [DMN], the central executive network [CEN] and the salience network [SN]). Finally, we examined the relationship between FC and cognitive performance by using linear regression analyses. Results Decreased FC was observed within the DMN, in the DMN-SN and DMN-CEN and increased FC was observed in the SN-CEN in BD. The alteration direction of regional FC was consistent with that of FC at the brain network level. Decreased FC between the left posterior cingulate cortex and right anterior cingulate cortex was associated with longer WCST completion time in BD patients (but not in HCs). Conclusions These findings emphasize the dominant role of the DMN in the psychopathology of BD and provide evidence that cognitive deficits in BD may be associated with aberrant FC between the anterior and posterior DMN. Keywords Magnetic resonance imaging, Bipolar disorder, Default mode network, Executive function, Attention † Yan-Kun Wu and Yun-Ai Su contributed equally to this work. *Correspondence: Tian‑Mei Si Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wu et al. BMC Psychiatry (2023) 23:584 Background Although mood instability is the core characteristic of bipolar disorder (BD), deficits in cognitive performance are also common but underestimated. Cognitive deficits exist persistently across acute episodes and euthymic states and may track illness progression independently of illness severity [1]. However, reliable treatments targeted at cognition are lacking [2], which is partially attributed to limited insight into the neurobiological underpinnings of cognitive deficits. The neural correlate of cognitive deficits is an issue of profound clinical and research interest that warrants further investigation. The default mode network (DMN), central executive network (CEN) and salience network (SN) are three core neurocognitive networks that have been identified in the human brain in terms of their important roles in higher cognition [3]. The CEN is crucial for supporting executive functions, such as working memory and problem solving, whereas the DMN is responsible for episodic memory retrieval and social cognitive processes [3]. The SN serves as a bridge between the external-oriented CEN and internal-oriented DMN by detecting and mapping external stimuli and internal mental events [4]. Neuroimaging studies have demonstrated that functional connectivity alterations in these three brain networks are implicated in mood dysregulation in BD [5–8], but there are relatively few studies that have investigated the cognitive implications of these brain networks. Commonly observed cognitive deficits in BD are related to the domains of executive function and sustained attention [9]. Several task-related functional imaging studies have supported the idea that aberrant activations in the DMN, CEN and SN [10, 11] play a pivotal role in cognitive deficits in BD. For example, hypoactivation in the dorsolateral prefrontal cortex (dlPFC) and the parietal cortex in the CEN may elicit working memory dysfunction [12–14]. Aberrant activation in the ventrolateral prefrontal cortex (vlPFC) [15, 16] and insula [11, 17] in the SN is associated with response inhibition and sustained attention dysfunction, respectively. In addition, restingstate functional connectivity (FC) offers an opportunity to examine the intrinsic activity of neural circuitry associated with cognitive deficits. A negative association was observed between inferior temporal gyrus-dorsal caudal putamen FC and the ability to discriminate a signal (target) from background noise (the nontarget) [9], whereas a positive association was found between perigenual anterior cingulate cortex (ACC)-related FC and sustained attention function [18]. However, another study did not find any significant correlation between inferior frontal gyrus (IFG) seed-based FC and visual sustained attention performance [19]. The contradictory findings related to the relationship between resting-state FC and cognitive Page 2 of 13 measure likely due to differences in neuropsychological tests used, the cognitive domains explored, technical issues related to measuring FC, etc. [20]. Despite this progress in neural correlates underlying cognitive deficits, there are several limitations to the literature. For example, there are relatively few studies examining how brain regions interplay in a temporal manner to inform executive function performance in the absence of task demands, with a particular lack of data that simultaneously assess executive function and sustained attention [9]. Furthermore, although the aberrant activations in the brain network sugge (...truncated)