Executive Control Network Functional Connectivity Research Articles

Functional Integrity of Executive Control Network Contributed to Retained Executive Abilities in Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI) is considered to be a transitional state between normal aging and Alzheimer's dementia (AD). Recent studies have indicated that executive function (EF) declines during MCI. However, only a limited number of studies have investigated the neural basis of EF deficits in MCI. Herein, we investigate the changes of regional brain spontaneous activity and functional connectivity (FC) of the executive control network (ECN) between high EF and low EF groups.Methods: According to EF composite score (ADNI-EF) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we divided MCI into two groups, including the MCI-highEF group and MCI-lowEF group. Resting-state functional MRI was utilized to investigate the fractional amplitude of low-frequency fluctuation (fALFF) and ECN functional connectivity across 23 healthy controls (HC), 11 MCI-highEF, and 14 MCI-lowEF participants. Moreover, a partial correlation analysis was carried out to examine the relationship between altered fALFF or connectivity of the ECN and the ADNI-EF.Results: Compared to HC, the MCI-highEF participants demonstrated increased fALFF in the left superior temporal gyrus (STG), as well as decreased fALFF in the right precentral gyrus, right postcentral gyrus, and left middle frontal gyrus (MFG). The MCI-lowEF participants demonstrated increased fALFF in the cerebellar vermis and decreased fALFF in the left MFG. Additionally, compared to HC, the MCI-highEF participants indicated no significant difference in connectivity of the ECN. Furthermore, the MCI-lowEF participants showed increased ECN FC in the left cuneus and left MFG, as well as decreased ECN functional connectivity in the right parahippocampal gyrus (PHG). Notably, the altered fALFF in the left MFG was positively correlated to ADNI-EF, while the altered fALFF in cerebellar vermis is negatively correlated with ADNI-EF across the two MCI groups and the HC group. Altered ECN functional connectivity in the right PHG is negatively correlated to ADNI-EF, while altered ECN functional connectivity in the left cuneus is negatively correlated to ADNI-EF across the three groups.Conclusions: Our current study demonstrates the presence of different patterns of regional brain spontaneous activity and ECN FC in the MCI-highEF group and MCI-lowEF group. Furthermore, the ECN FC of the MCI-highEF group was not disrupted, which may contribute to retained EF in MCI.

Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery.

To investigate postoperative functional connectivity (FC) alterations across impaired cognitive domains and their causal relationships with systemic inflammation. Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether FC alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remains unclear. Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for tumor necrosis factor-a and interleukin-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations, and cytokines. Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC FC with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased tumor necrosis factor-a and decreased executive function up to day 7 after cardiac surgery. The decreased FC of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits after cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.

Co-occurrence of schizo-obsessive traits and its correlation with altered executive control network functional connectivity.

The prevalence of obsessive-compulsive symptoms (OCS) in schizophrenia patients is as around 30%. Evidence suggested that mild OCS could reduce symptoms of schizophrenia, supporting the presence of compensatory functions. However, severe OCS could aggravate various impairments in schizophrenia patients, supporting the "double jeopardy hypothesis". Patients with schizo-obsessive comorbidity, schizophrenia patients and obsessive-compulsive disorder patients have been found to have similarities in executive dysfunctions and altered resting-state functional connectivity within the executive control network (ECN). Executive functions could be associated with the ECN. However, little is known as to whether such overlap exists in the subclinical populations of individuals with schizo-obsessive traits (SOT), schizotypal individuals and individuals with high levels of obsessive-compulsive symptoms (OCS). In this study, we recruited 30 schizotypal individuals, 25 individuals with OCS, 29 individuals with SOT and 29 controls for a resting-state ECN-related functional connectivity (rsFC) and a go/shift/no-go task. We found that individuals with SOT exhibited increased rsFC within the ECN compared with controls, while schizotypal individuals exhibited the opposite. Individuals with OCS exhibited decreased rsFC within the ECN and between the ECN and the default mode network (DMN), relative to controls. No significant correlational results between altered rsFC related to the ECN with executive function performance were found after corrections for multiple comparisons in three subclinical groups. Our findings showed that individuals with SOT had increased rsFC within the ECN, while schizotypal individuals and individuals with OCS showed the opposite. Our findings provide evidence for possible neural substrates of subclinical comorbidity of OCS and schizotypy.

Changes in Brain Function Networks in Patients With Amnestic Mild Cognitive Impairment: A Resting-State fMRI Study.

Patients with amnestic mild cognitive impairment (aMCI) are at high risk of developing dementia. This study used resting-state functional magnetic resonance imaging (rs-fMRI) and an independent component analysis (ICA) approach to explore changes in functional connectivity (FC) in the default mode network (DMN), executive control network (ECN), and salience network (SN). Thirty patients with aMCI and 30 healthy controls (HCs) were enrolled. All the participants underwent an rs-fMRI scan. The brain FC in DMN, ECN, and SN was calculated using the ICA approach. We found that the FC of brain regions in DMN decreased significantly and that of brain regions in ECN increased, which was in accordance with the findings of previous studies on Alzheimer's disease (AD) and aMCI. We also found that the FC of brain regions in SN increased, which was different from the findings of previous studies on AD. The increase in FC in brain regions in SN might result from different pathophysiological states in AD and aMCI, indicating that a decrease in FC in SN does not occur in a person with aMCI. These results are consistent with those of previous studies using the voxel-mirrored homotopic connectivity approach and seed-based correlation analysis. We therefore considered that the decrease in FC in DMN and the increase in FC in ECN and SN might be peculiar patterns observed on the rs-fMRI of a person with aMCI. These findings may contribute to the development of imaging biomarkers for the diagnosis of aMCI.

Can the Executive Control Network be Used to Diagnose Parkinson's Disease and as an Efficacy Indicator of Deep Brain Stimulation?

Objective The aim of this work was to investigate whether there are differences in the executive control network (ECN) between patients with Parkinson's disease (PD) before and after deep brain stimulation (DBS) surgery and to explore how deep brain stimulation (DBS) surgery affects ECN connectivity in patients with PD. Methods Resting-state magnetic resonance imaging (MRI) data were obtained from 23 patients with Parkinson's disease preoperatively (pre-PD) and postoperatively (post-PD) and 14 normal controls (CN). The right dorsolateral prefrontal cortex (DLPFC) was used as the seed region of interest (ROI) to study the characteristics of the functional connectivity of the ECN in these subjects. Results There were differences in the ECN among PD patients before and after surgery and between the CN. Compared with the CN group, the pre-PD patients showed significantly reduced functional connectivity (FC) between the DLPFC and the left inferior frontal gyrus, left precuneus, left cerebellum posterior lobe, right middle frontal gyrus, right inferior parietal gyrus, right posterior central gyrus, right precuneus, and right inferior frontal gyrus. Compared to the CN group, the post-PD patients showed significantly reduced FC between the DLPFC and left inferior frontal gyrus, left precuneus, left cerebellum posterior lobe, right middle frontal gyrus, right inferior frontal gyrus, and right parietal lobule. There is no difference in the ECN between the pre-PD patients and the post-PD patients. Conclusions The FC of ECN in PD patients was different from that in normal controls, but the FC of the ECN in patients with PD may not be altered by DBS. This suggests that the ECN may be considered an imaging biomarker for the identification of PD but may not be a good imaging biomarker for the evaluation of DBS efficacy.

Amyloid and cerebrovascular burden divergently influence brain functional network changes over time.

To examine the effects of baseline Alzheimer disease and cerebrovascular disease markers on longitudinal default mode network (DMN) and executive control network (ECN) functional connectivity (FC) changes in mild cognitive impairment (MCI). We studied 30 patients with amnestic MCI (aMCI) and 55 patients with subcortical vascular MCI (svMCI) with baseline Pittsburgh Compound B (PiB)-PET scans and longitudinal MRI scans. Participants were followed up clinically with annual MRI for up to 4 years (aMCI: 26 with 2 timepoints, 4 with 3 timepoints; svMCI: 13 with 2 timepoints, 16 with 3 timepoints, 26 with 4 timepoints). β-Amyloid (Aβ) burden was associated with longitudinal DMN FC declines, while cerebrovascular burden was associated with longitudinal ECN FC changes. When patients were divided into PiB+ and PiB- groups, PiB+ patients showed longitudinal DMN FC declines, while patients with svMCI showed longitudinal ECN FC increases. Direct comparisons between the 2 groups without mixed pathology (aMCI PiB+ and svMCI PiB-) recapitulated this divergent pattern: aMCI PiB+ patients showed steeper longitudinal DMN FC declines, while svMCI PiB- patients showed steeper longitudinal ECN FC increases. Finally, using baseline PiB uptake and lacune numbers as continuous variables, baseline PiB uptake showed inverse U-shape associations with longitudinal DMN FC changes in both MCI subtypes, while baseline lacune numbers showed mainly inverse U-shape relationships with longitudinal ECN FC changes in patients with svMCI. Our findings underscore the divergent effects of Aβ and cerebrovascular burden on longitudinal FC changes in the DMN and ECN in the predementia stage, which reflect the underlying pathology and may be used to track early changes in Alzheimer disease and cerebrovascular disease.

Functional segregation of executive control network and frontoparietal network in Alzheimer's disease

Functional connectivity pattern altered of default mode network (DMN) is gaining more attention as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease. However, the changed functional connectivity except for DMN, the longitudinal changes in executive control network (ECN) and frontoparietal network (FPN) also has attracted wide interest. Moreover, AD-related functional connectivity abnormalities within the DMN are well replicated research, but the (increased/decreased and reduced) functional connectivity in ECN and FPN weren't receive adequate attention. To address the above issues, in this paper, we adopt sparse inverse covariance estimation (SICE) approach to investigate the changed functional connectivity of ECN and FPN on the ADNI2 dataset. Our experimental results indicate the left superior frontal gyrus (SFGmed.L) and left thalamus (THA.L) regions of ECN has shown increased functional connectivity, the left anterior cingulate (ACG.L) region of ECN has shown decreased functional connectivity. The Superior Parietal Gyrus (SPG) regions and left paracentral lobule (PCL.L) of FPN has shown increased functional connectivity, the left supramarginal gyrus (SMG.L) regions has shown decreased functional connectivity in AD patients. On the other hand, the ACG.L regions in ECN, SMG.L and left inferior parietal (IPL.L) in FPN have shown significantly reduced functional connectivity. These results demonstrate that increased/decreased functional connectivity and reduced functional connectivity not only within DMN, but also associated with ECN and FPN. It also suggest that AD is associated with the characteristics of large-scale functional networks, and these changed functional connectivity possibly as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease.

APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease.

Purpose of the researchAlthough single nucleotide polymorphisms of membrane-spanning 4A (MS4A) (rs670139) and several other susceptibility genes have shown interaction effects on the risk of Alzheimer's disease (AD), little is known about the interaction effects of apolipoprotein E (APOE) with MS4A (rs670139) on cognitive performances, and the underlying pathogenesis is unclear. The study aimed to investigate the APOE-MS4A (rs670139) interaction effects on cognitive performances, cortical volumes, and functional connectivity (FC) in brain networks.Principal resultsCognitive performances were characterized in each genotypic group, and were compared between normal controls and patients in each genotypic group. APOE-MS4A interaction effects on memory and executive function scores, cortical volumes, and FC in brain networks were demonstrated. Significant effects of APOE-MS4A interactions on FC were observed in executive control network (ECN) (T maxima = 4.99, false discovery rate-corrected p < .001), the calculation score (F3, 87 = 6.218; p = .015), and the volume in prefrontal (F3, 87 = 4.374; p = .039) and orbitofrontal cortices (F3, 87 = 6.022; p = .016). The calculation score was correlated with each frontal volume (cc) (ρ = 0.304; p = .004) and genetic interaction-associated FC in ECN (ρ = 0.282; p = .008). Variations in genotypes affected the relationship between the calculation score and each frontal volume (cc).Major conclusionsThese findings indicate that the genetic interaction effects on FC in ECN might contribute to pathogenic mechanisms underlying the interaction effects of APOE-MS4A on calculation ability in AD.

Cognitive impairment in patients with kidney deficiency syndrome: A resting-state fMRI study

IntroductionAccording to traditional Chinese medicine (TCM) theory, kidney deficiency syndrome accompanies cognitive impairment, especially for memory and attention. The executive control network (ECN) plays an important role in the cognitive processing for memory and attention. Our aim was to investigate the change of ECN in patients with kidney deficiency syndrome. MethodsTwelve patients and 12 healthy subjects underwent functional magnetic resonance imaging (fMRI) examination and neuropsychological tests. ResultsCompared with healthy subjects, patients with kidney deficiency syndrome revealed significantly decreased functional connectivity (FC) within ECN. Furthermore, the FC value was positively correlated with the 4-actual number of responses (4-ANR), and this FC value was negatively correlated with the number of wrong responses. ConclusionsOur findings suggest that patients with kidney deficiency syndrome are associated with abnormal FC of ECN, and provides new evidence on neuroimaging to support the notion that the kidney deficiency syndrome could lead to cognitive impairment.

Cerebrovascular disease influences functional and structural network connectivity in patients with amnestic mild cognitive impairment and Alzheimer\u2019s disease

BackgroundPatients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach.MethodsWe examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains.ResultsWe demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition.ConclusionsWe demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment.

Network-level dysconnectivity in patients with nasopharyngeal carcinoma (NPC) early post-radiotherapy: longitudinal resting state fMRI study

In this study, we seek to longitudinally investigate the network-level functional connectivity (FC) alternations and its association with irradiation dose and cognition changes in the early stage post radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients. We performed independent component analysis (ICA) of resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) from 39 newly diagnosed NPC patients before receiving treatment (baseline), and 3months post-RT. the default mode network (DMN), salience network (SN), and executive control network (ECN) were extracted with well-validated software (GIFT). Inter-network connectivity was assessed using the functional network connectivity (FNC) toolbox. The inter- and intra-network FC was compared between time points, and the z value of FC alternation was correlated with the RT dose value and cognitive changes. Compared with baseline, the FC of the left anterior cingulate cortex (ACC) within the DMN, and the right insular within the SN, significantly reduced 3months post-RT, with greater effects at higher doses in the right insular. Bilateral ECN FC was also significantly lower 3months post-RT compared to the baseline. Chemotherapy was not associated with inter- and intra- network FC change. We found intra- and inter-network FC disruption in NPC patients 3months post-RT, with the right insular showing a dose-dependent effect. Thus, this network-level FC may serve as a potential biomarker of the RT-induced brain functional impairments, and provide valuable targets for further functional recovery treatment.

Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our findings demonstrate the differential neural network structural and functional changes in Alzheimer's disease with and without cerebrovascular disease, suggesting that the underlying pathology of Alzheimer's disease patients with cerebrovascular disease might differ from those without cerebrovascular disease and reflect a combination of more severe cerebrovascular disease and less severe Alzheimer's disease network degeneration phenotype.

Abnormal Connectivity Within Executive Resting-State Network in Migraine With Aura.

To evaluate the executive control network connectivity integrity in patients with migraine with aura, in the interictal period, in comparison to patients with migraine without aura and healthy controls. Using resting-state functional magnetic resonance imaging, we compared executive control network functional connectivity in 20 patients with migraine with aura vs 20 sex and age-matched patients with migraine without aura and 20 healthy controls, and assessed the correlation between executive control network functional connectivity and clinical features of patients with migraine. We used voxel-based morphometry and diffusion tensor imaging to investigate potential structural or microstructural changes. Neuropsychological data revealed no significant executive dysfunction in patients with migraine. Resting-state functional magnetic resonance imaging showed significant group differences in right middle frontal gyrus (Talairach coordinates x, y, z: +26, +2, +48) and dorsal anterior cingulate cortex (Talairach coordinates x, y, z: +6, +13, +49), indicating that these areas had a decreased component activity in both patients with migraine with and without aura when compared with healthy controls. Conversely, there were no significant differences in the executive control network functional connectivity between patients with migraine with and without aura (P < .05, cluster-level corrected). These functional abnormalities are independent of structural and microstructural changes and did not significantly correlate with clinical parameters. Our data demonstrate a disrupted executive control network functional connectivity in patients with migraine with and without aura, in the interictal period. Although this functional phenomenon is present in the absence of clinically relevant executive deficits, it may reflect a vulnerability to executive high-demanding conditions of daily living activities in patients with migraine.

Reduced left executive control network functional connectivity is associated with alcohol use disorders.

Altered functional connectivity in critical networks has been associated with chronic alcohol abuse. In turn, changes in connectivity in executive control networks (ECNs) may undermine the ability to control alcohol consumption. It was hypothesized that network connectivity would be reduced in individuals with problematic alcohol use (ALC) compared with controls and that diminished network connectivity would be associated with greater failure to control drinking. Resting-state functional magnetic resonance imaging was analyzed to identify 14 previously identified intrinsic connectivity networks (ICNs) using a priori regions of interest in cases ranging from binge drinkers to those with severe alcohol use disorder, as well as control subjects. Analyses tested for differences in network connectivity strength between 255 ALC cases and 87 age- and gender-matched controls. Further, structural equation analysis, using 383 ALC cases, tested whether functional connectivity strength mediated the relationship between years of regular drinking and alcohol problems. The age- and gender-matched analysis showed that ALC had significantly lower network connectivity strength than controls in the left executive control (LECN), basal ganglia, and primary visual networks. For all ALC, LECN connectivity strength is negatively correlated with failed control and alcohol disorder severity. Edges connecting parietal regions with dorsolateral prefrontal, middle frontal, and temporal regions within the LECN drove these relationships. A positive association between years of drinking and severity of alcohol problems was mediated by reduced ECN connectivity. This study reports relationships between network strength and problematic alcohol use, suggesting that chronic drinking negatively impacts brain connectivity, specifically in the LECN. Altered functional connectivity, related to chronic alcohol abuse, may contribute to the etiology of alcohol dependence and relapse.