More Complex Cognitive Tasks Increasingly Connect Functionally Dissimilar Brain Regions.

Objective To explore the neural profile of functional connectivity of default mode network (DMN), central-executive network(CEN) , and salience network (SN) in patients with schizophrenia during a resting-state functional magnetic resonance imaging(rs-fMRI). Methods The SPM8, DPARSFA, CONN softwares combined with data-driven region of interest (ROI) analysis were used to investigate functional connectivity (FC) of the DMN, CEN, and SN in 74 patients with schizophrenia (SZ) and 79 age-and gender-matched normal controls (NC). Medial prefrontal cortex (MPFC) was selected as seed region for identifying the DMN and CEN while right anterior insula (rAI) for the SN. Voxel-wise functional connectivity analyses were performed between MPFC and rAI while pair-wise functional connectivity analyses were conducted across DMN, CEN, and SN. Results Concerning the MPFC, SZ showed increased functional connectivity, comparing with NC, with bilateral dorsolateral prefrontal cortex (left: - 0.02 ± 0.18 vs. - 0.12±0.12, t=4.25, P<0.01; right: -0.02±0.11 vs. -0.10±0.10,t=5.40,P<0.01) and bilateral putamen (left: 0.14± 0.12 vs. 0.04±0.10,t=5.03,P<0.01; right: 0.13±0.11 vs. 0.03±0.98, t=4.96,P<0.01). With regard to rAI, increased functional connectivity between rAI and left middle frontal cortex (-0.05±0.17 vs. -0.07±0.17,t= 4.60,P<0.01) and between rAI and precuneus/posterior cingulate cortex (0.01±0.13 vs. -0.09±0.14,t=4.01, P<0.01) were found in SZ comparison to NC (gaussian random field thaeory-corrected; voxel level P<0.01, cluster level P<0.05). Additionally, SZ also showed enhanced interconnectivity strengths of DMN-CEN and DMN-SN (Bonferroni-corrected, P<0.05). Furthermore, partial correlation analyses showed that the increased functional connectivity between rAI and precuneus/posterior cingulate cortex was significantly correlated with PANSS-positve symptoms (r=0.232,P=0.025). Positive relationships were found between the duration of illness and functional connectivity between rAI and left middle frontal cortex (r=0.288, P=0.007) and between rAI and precuneus/posterior cingulate cortex (r=0.196, P=0.049). Conclusions This study provides evidence for resting state functional connectivity abnormalities of DMN, CEN, and SN in patients with schizophrenia. These aberrant functional connectivities between some key brain regions of three networks may be responsible for certain schizophrenic symptoms, which could contribute to exploring the pathophysiological mechanisms of schizophrenia. Key words: Schizophrenia; Magnetic resonance imaging; Default mode network; Central-executive network; Salience network; Functional connectivity

Impact of vascular factors and tau deposition on functional brain network connectivity in participants of the Framingham Heart Study

Editor's evaluation: Task-evoked metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks

The default mode network normally decreases in activity during externally directed tasks. Although default mode network connectivity is disrupted in numerous brain pathologies, default mode network deactivation has not been studied in patients with brain tumors. We investigated default mode network deactivation with language task-based fMRI by measuring the anticorrelation of a critical default mode network node, the posterior cingulate cortex, in patients with gliomas and controls; furthermore, we examined default mode network functional connectivity in these patients with task-based and resting-state fMRI. In 10 healthy controls and 30 patients with gliomas, the posterior cingulate cortex was identified on task-based fMRI and was used as an ROI to create connectivity maps from task-based and resting-state fMRI data. We compared the average correlation in each default mode network region between patients and controls for each correlation map and stratified patients by tumor location, hemisphere, and grade. Patients with gliomas (P = .001) and, in particular, patients with tumors near the posterior default mode network (P < .001) showed less posterior cingulate cortex anticorrelation in task-based fMRI than controls. Patients with both left- and right-hemisphere tumors, as well as those with grade IV tumors, showed significantly lower posterior cingulate cortex anticorrelation than controls (P = .02, .03, and <.001, respectively). Functional connectivity in each default mode network region was not significantly different between task-based and resting-state maps. Task-based fMRI showed impaired deactivation of the default mode network in patients with gliomas. The functional connectivity of the default mode network in both task-based and resting-state fMRI in patients with gliomas using the posterior cingulate cortex identified in task-based fMRI as an ROI for seed-based correlation analysis has strong overlap.

Neural markers of pathophysiological processes underlying the dimension of subsyndromal-syndromal-level depression severity can provide objective, biologically informed targets for novel interventions to help prevent the onset of depressive and other affective disorders in individuals with subsyndromal symptoms, and prevent worsening symptom severity in those with these disorders. Greater functional connectivity (FC) among the central executive network (CEN), supporting emotional regulation (ER) subcomponent processes such as working memory (WM), the default mode network (DMN), supporting self-related information processing, and the salience network (SN), is thought to interfere with cognitive functioning and predispose to depressive disorders. We examined in young adults (1) relationships among activity and FC in these networks and current depression severity, using a paradigm designed to examine WM and ER capacity in n = 90, age = 21.7 (2.0); (2) the extent to which these relationships were specific to depression versus mania/hypomania; (3) whether findings in a first, "discovery" sample could be replicated in a second, independent, "test" sample of young adults n = 96, age = 21.6 (2.1); and (4) whether such relationships also predicted depression at up to 12 months post scan and/or mania/hypomania severity in (n = 61, including participants from both samples, age = 21.6 (2.1)). We also examined the extent to which there were common depression- and anxiety-related findings, given that depression and anxiety are highly comorbid. In the discovery sample, current depression severity was robustly predicted by greater activity and greater positive functional connectivity among the CEN, DMN, and SN during working memory and emotional regulation tasks (all ps < 0.05 qFDR). These findings were specific to depression, replicated in the independent sample, and predicted future depression severity. Similar neural marker-anxiety relationships were shown, with robust DMN-SN FC relationships. These data help provide objective, neural marker targets to better guide and monitor early interventions in young adults at risk for, or those with established, depressive and other affective disorders.

An evolutionary gap in primate default mode network organization

Introduction Spleen deficiency syndrome (SDS), a common clinical syndrome of traditional Chinese medicine, is manifested with digestive symptoms and cognitive impairments. However, the cognitive neural mechanism in brain networks of SDS still remained unclear. Our aim was to investigate the changes between the default mode, dorsal attention, and frontoparietal networks in SDS. Methods Twenty nonorganic gastrointestinal disorder (NOGD) patients with SDS and eighteen healthy controls were enrolled to attend functional magnetic resonance imaging scan and participated a continuous performance test (CPT) before scanning. Results Compared with healthy controls, NOGD patients with SDS showed the significantly increased functional connectivity (FC) between dorsal attention network (DAN) and left frontal-parietal control network (LFPN) and significantly decreased FC between LFPN and default mode network (DMN). The functional network connectivity analysis showed positive correlation coefficients between the DAN and LFPN and DAN and DMN as well as negative correlation between LFPN and DMN in NOGD patients with SDS compared with healthy controls. Correlation analysis revealed that the increased FC between LFPN and DAN was positively correlated with 4-digitnumber reaction time mean (RTM) and 3-digitnumber RTM. Conclusion Our study may provide novel insights into the relationship among the DMN, DAN, and FPN in NOGD patients with SDS to deepen our understanding of the neuropsychological mechanisms of SDS.

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

Smartphones provide convenience in everyday life. Smartphones, however, can elicit adverse effects when used excessively. The purpose of this study was to examine the underlying neurobiological alterations that arise from problematic smartphone use. We performed resting state seed-based functional connectivity (FC) analysis of 44 problematic smartphone users and 54 healthy controls. This analysis assessed the salience, central executive, default mode, and affective networks. Compared to controls, problematic smartphone users showed enhanced FC within the salience network and between the salience and default mode network. Moreover, we observed decreased FC between the salience and central executive network in problematic smartphone users, compared to controls. These results imply that problematic smartphone use is associated with aberrant FC in key brain networks. Our results suggest that changes in FC of key networks centered around the salience network might be associated with problematic smartphone use.

Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder. Recently, there has been increasing attention to evaluate the effect of ECT on resting-state functional magnetic resonance imaging (rs-fMRI). This study aims to compare rs-fMRI of depressive disorder (DEP) patients with healthy participants, investigate whether pre-ECT dynamic functional network connectivity network (dFNC) estimated from patients rs-fMRI is associated with an eventual ECT outcome, and explore the effect of ECT on brain network states.Method: Resting-state functional magnetic resonance imaging (fMRI) data were collected from 119 patients with depression or depressive disorder (DEP) (76 females), and 61 healthy (HC) participants (34 females), with an age mean of 52.25 (N = 180) years old. The pre-ECT and post-ECT Hamilton Depression Rating Scale (HDRS) were 25.59 ± 6.14 and 11.48 ± 9.07, respectively. Twenty-four independent components from default mode (DMN) and cognitive control network (CCN) were extracted, using group-independent component analysis from pre-ECT and post-ECT rs-fMRI. Then, the sliding window approach was used to estimate the pre-and post-ECT dFNC of each subject. Next, k-means clustering was separately applied to pre-ECT dFNC and post-ECT dFNC to assess three distinct states from each participant. We calculated the amount of time each subject spends in each state, which is called “occupancy rate” or OCR. Next, we compared OCR values between HC and DEP participants. We also calculated the partial correlation between pre-ECT OCRs and HDRS change while controlling for age, gender, and site. Finally, we evaluated the effectiveness of ECT by comparing pre- and post-ECT OCR of DEP and HC participants.Results: The main findings include (1) depressive disorder (DEP) patients had significantly lower OCR values than the HC group in state 2, where connectivity between cognitive control network (CCN) and default mode network (DMN) was relatively higher than other states (corrected p = 0.015), (2) Pre-ECT OCR of state, with more negative connectivity between CCN and DMN components, is linked with the HDRS changes (R = 0.23 corrected p = 0.03). This means that those DEP patients who spent less time in this state showed more HDRS change, and (3) The post-ECT OCR analysis suggested that ECT increased the amount of time DEP patients spent in state 2 (corrected p = 0.03).Conclusion: Our finding suggests that dynamic functional network connectivity (dFNC) features, estimated from CCN and DMN, show promise as a predictive biomarker of the ECT outcome of DEP patients. Also, this study identifies a possible underlying mechanism associated with the ECT effect on DEP patients.

<h3>Abstract</h3> While brain default mode network (DMN) activation in human subjects has been associated with mind wandering, meditation practice has been found to suppress it and to increase psychological well-being. Additionally to DMN activity reduction, experienced meditators during meditation practice show and increased connectivity between the DMN and the central executive network (CEN). However, the gradual change between DMN and CEN configuration from pre-meditation, during meditation, and post-meditation are unknown. Here we investigated the change in DMN and CEN configuration by means of brain activity and functional connectivity analyses in experienced meditators across three back-to-back functional magnetic resonance imaging scans: Pre-meditation baseline (trait), meditation (state), and post-meditation (state-to-trait). Pre-meditation baseline group comparison was also performed between experienced meditators and healthy controls. Meditation trait was characterized by a significant reduction in activity and functional connectivity within DMN and increased anticorrelations between DMN and CEN. Conversely, meditation state and meditation state-to-trait periods showed increased activity and functional connectivity within the DMN and between DMN and CEN. However, the latter anticorrelations were only present in experienced meditators with limited practice. The interactions between networks during these states by means of Positive Diametric Activity (PDA) of the fractional Amplitude of Low-Frequency Fluctuations (fALFF) defined as <math xmlns="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"><mrow><mover accent="true"><mrow><mi>C</mi><mi>E</mi><mi>N</mi><mrow><mtext></mtext></mrow><mi>f</mi><mrow><mtext></mtext></mrow><mi>A</mi><mi>L</mi><mi>F</mi><mi>F</mi></mrow><mo stretchy="true">¯</mo></mover><mrow><mtext></mtext></mrow><mo>−</mo><mrow><mtext></mtext></mrow><mover accent="true"><mrow><mi>D</mi><mi>M</mi><mi>N</mi><mrow><mtext></mtext></mrow><mi>f</mi><mrow><mtext></mtext></mrow><mi>A</mi><mi>L</mi><mi>F</mi><mi>F</mi></mrow><mo stretchy="true">¯</mo></mover></mrow></math> revealed no trait differences, but significant increases during meditation state that persisted in meditation state-to-trait. The gradual reconfiguration in DMN and CEN suggest a neural mechanism by which the CEN negatively regulates the DMN and is probably responsible for the long-term trait changes seen in meditators and reported psychological well-being. <b>Significance Statement</b> We introduce a Positive Diametric Activity (PDA) metric to measure the relation between two anticorrelated rs-fMRI networks in experienced meditators. PDA as well as functional connectivity (FC) are increased during meditation compared to resting state and persists in the post meditation resting state. Conversely, meditation trait is characterized by positive PDA but with significant reduction in activity and functional connectivity within Default Mode Network (DMN) and increased anticorrelations between DMN and central executive network (CEN). PDA and FC between DMN and CEN distinguish meditation state-to-trait effects.

Decision letter: Disruption in structural–functional network repertoire and time-resolved subcortical fronto-temporoparietal connectivity in disorders of consciousness

Objectives: The specific intrinsic network coupling abnormalities in mild traumatic brain injury (mTBI) patients are poorly understood. Our objective is to compare the correlations among the default mode, salience, and central executive networks in patients with mTBI and healthy controls.Methods: This 2-year prospective study included 32 acute mTBI patients and 37 healthy comparisons. We calculated the functional connectivity scores among the default mode, salience, and central executive networks. Then we conducted multilevel correlation analysis to investigate component correlations, global graph, and local functional connectivity changes.Results: Patients with mTBI showed significant increased functional connectivity between the anterior part of the default mode network and the salience network compared with controls (p = 0.013, false discovery rate correction). Hyper-connectivity between the default mode and salience network was significantly positively correlated with the dimensional change card sort score in patients with mTBI (r = 0.40, p = 0.037). The average path length of mTBI patients was significantly higher than that of controls (p = 0.028).Conclusions: Aberrant functional coupling between the default mode and salience networks were identified in acute mTBI patients. Our finding has great potential to improve our understanding of the network architecture of mTBI.

BackgroundStronger resting-state functional connectivity of the default mode and frontoparietal control networks has been associated with cognitive resilience to Alzheimer’s disease related pathology and neurodegeneration in smaller cohort studies.ObjectivesWe investigated whether these networks are associated with longitudinal CR to AD biomarkers of beta-amyloid (Aβ).DesignLongitudinal mixed.SettingThe Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study and its natural history observation arm, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study.ParticipantsA sample of 1,021 cognitively unimpaired older adults (mean age = 71.2 years [SD = 4.7 years], 61% women, 42% APOEε4 carriers, 52% Aβ positive).MeasurementsGlobal cognitive performance (Preclinical Alzheimer’s Cognitive Composite) was assessed over an average 5.4 year follow-up period (SD = 2 years). Cortical Aβ and functional connectivity (left and right frontoparietal control and default mode networks) were estimated from fMRI and PET, respectively, at baseline. Covariates included baseline age, APOEε4 carrier status, years of education, adjusted gray matter volume, head motion, study group, cumulative treatment exposure, and cognitive test version.ResultsMixed effects models revealed that functional connectivity of the left frontoparietal control network moderated the negative effect of Aβ on cognitive change (p =.025) such that stronger connectivity was associated with reduced Aβ-related cognitive decline.ConclusionsOur results demonstrate a potential protective effect of functional connectivity in preclinical AD, such that stronger connectivity in this network is associated with slower Aβ-related cognitive decline.

Research shows that older adults can have a decline in three key resting state networks (default mode network, central executive network, and salience network) after total knee arthroplasty and that patients' pre-surgery brain and cognitive integrity predicts decline. First, to assess resting state network connectivity decline from the perspective of nodal connectivity changes in a larger older adult surgery sample. Second, to compare pre-post functional connectivity changes in mild cognitive impairment (MCI) versus non-MCI. Surgery (n = 69) and non-surgery (n = 65) peers completed a comprehensive preoperative neuropsychological evaluation and pre- and acute (within 48 hours) post-surgery/pseudo-surgery functional brain magnetic resonance imaging scan. MCI was classified within both (MCI surgery, n = 13; MCI non-surgery, n = 10). Using standard coordinates, we defined default mode network, salience network, central executive network, and the visual network (serving as a control network). The functional connectivity of these networks and brain areas (nodes) that make up these networks were examined for pre-post-surgery changes through paired samples t-test and ANOVA. There was a decline in RSN connectivity after surgery (p < 0.05) only in the three cognitive networks (not the visual network). The default mode and salience network showed nodal connectivity changes (p < 0.01). MCI surgery had greater functional connectivity decline in DMN and SN. Non-surgery participants showed no significant functional connectivity change. Surgery with general anesthesia selectively alters functional connectivity in major cognitive resting state networks particularly in DMN and SN. Participants with MCI appear more vulnerable to these functional changes.