Default Mode Network Functional Connectivity Research Articles

Negative affective burden is associated with higher resting-state functional connectivity in subjective cognitive decline

Subjective cognitive decline (SCD), as expressed by older adults, is associated with negative affect, which, in turn, is a likely risk factor for Alzheimer’s Disease (AD). This study assessed the associations between negative affective burden, cognitive functioning, and functional connectivity in networks vulnerable to AD in the context of SCD. Older participants (60–90 years) with SCD (n = 51) and healthy controls (n = 50) were investigated in a cross-sectional study. Subclinical negative affective burden, quantified through a composite of self-reported negative affective factors, was related to cognitive functioning (self-perceived and objective) and functional connectivity. Seed-to-voxel analyses were carried out in default mode network (DMN) and salience network (SAL) nodes using resting-state functional magnetic resonance imaging. Greater negative affective burden was associated with lower self-perceived cognitive functioning and lower between-network functional connectivity of DMN and SAL nodes in the total sample. In addition, there was a significant moderation of SCD status. Greater negative affective burden related to higher functional connectivity within DMN (posterior cingulate-to-precuneus) and within SAL (anterior cingulate-to-insula) nodes in the SCD group, whereas in controls the inverse association was found. We show that negative affective burden is associated with functional brain alterations in older adults, regardless of SCD status. Specifically in the SCD phenotype, greater negative affective burden relates to higher functional connectivity within brain networks vulnerable to AD. Our findings imply that negative affective burden should be considered a potentially modifiable target for early intervention.

Prospective Memory and Default Mode Network Functional Connectivity in Normal and Pathological Aging.

Prospective memory (PM), the ability to execute a previously formed intention given the proper circumstance, has been proven to be vulnerable to Alzheimer's disease. Previous studies have indicated the involvement of the frontoparietal networks; however, it is proposed that PM may also be associated with other neural substrates that support stimulus-dependent spontaneous cognition. The present study aimed to examine the hypothesis that PM deficit in Alzheimer's disease is related to altered functional connectivity (FC) within the default mode network (DMN). Thirty-four patients with very mild or mild dementia (17 with Alzheimer's disease and 17 with subcortical ischemic vascular disease) and 22 cognitively-normal participants aged above 60 received a computerized PM task and resting-state functional magnetic resonance imaging study. Seed-based functional connectivity analysis was performed at group level within the DMN. We found that the dementia groups showed worse PM performance and altered FC within the DMN as compared to the normal aging individuals. The FC between the medial prefrontal cortices and precuneus/posterior cingulate cortex was significantly correlated with PM in normal aging, while the FC between the right precuneus and bilateral inferior parietal lobules was correlated with PM in patients with Alzheimer's disease. These findings support a potential role for the DMN in PM, and corroborate that PM deficit in Alzheimer's disease was associated with altered FC within the posterior hubs of the DMN, with spatial patterning different from normal aging.

Enhanced default mode network functional connectivity links with electroconvulsive therapy response in major depressive disorder

BackgroundElectroconvulsive therapy (ECT) is an effective neuromodulatory treatment for major depressive disorder (MDD), especially for cases resistant to antidepressant drugs. While the precise mechanisms underlying ECT efficacy are still unclear, it is speculated that ECT modulates brain connectivity. The current study aimed to investigate the longitudinal effects of ECT on resting-state functional connectivity (FC) in MDD patients and test if baseline FC can be used to predict therapeutic response. MethodResting-state functional magnetic resonance imaging data were collected at baseline and following ECT from 33 MDD patients. Whole-brain multi-voxel pattern analysis (MVPA) and region of interest-wise FC analysis were employed to fully investigate ECT effects on brain connectivity. Linear support vector regression was further utilized to predict the improvement in depressive symptoms based on baseline connectivity. ResultsMVPA revealed a significant ECT effect on FC in the default mode network (DMN), central executive network (CEN), sensorimotor network (SMN), and cerebellar posterior lobe. The FCs within the DMN and between DMN and CEN were enhanced in patients after ECT, and the changed FC between the medial prefrontal cortex and ventrolateral prefrontal cortex was negatively correlated with depressive symptom improvement. Moreover, baseline FC within the DMN and between the DMN and CEN could effectively predict the improvement of depressive symptoms. ConclusionsThe findings suggest that the FCs within the DMN and between DMN and CEN may be critical therapeutic targets for effective antidepressant treatment as well as neuromarkers for predicting treatment response.

High Dream Recall Frequency is Associated with Increased Creativity and Default Mode Network Connectivity.

IntroductionSeveral results suggest that the frequency of dream recall is positively correlated with personality traits such as creativity and openness to experience. In addition, neuroimaging results have evidenced different neurophysiological profiles in high dream recallers (HR) and low dream recallers (LR) during both sleep and wakefulness, specifically within regions of the default mode network (DMN). These findings are consistent with the emerging view that dreaming and mind wandering pertain to the same family of spontaneous mental processes, subserved by the DMN.MethodsTo further test this hypothesis, we measured the DMN functional connectivity during resting wakefulness, together with personality and cognitive abilities (including creativity) in 28 HR and 27 LR.ResultsAs expected, HR demonstrated a greater DMN connectivity than LR, higher scores of creativity, and no significant difference in memory abilities. However, there was no significant correlation between creativity scores and DMN connectivity.DiscussionThese results further demonstrate that there are trait neurophysiological and psychological differences between individuals who frequently recall their dreams and those who do not. They support the forebrain and the DMN hypotheses of dreaming and leave open the possibility that increased activity in the DMN promotes creative-thinking during both wakefulness and sleep. Further work is needed to test whether activity in the DMN is causally associated with creative-thinking.

Default Mode Network and Neural Phase Synchronization in Healthy Aging: A Resting State EEG Study

Aging is associated with altered brain connectivity within the default mode network (DMN). Although research using functional magnetic resonance imaging has quantified age-related alterations in functional connectivity within this network during resting state, it is less clear how this may be reflected in electrophysiological measures, and how this relates to cognitive performance in older adults. The aim of this study was to quantify age differences in phase synchrony of the DMN during resting state, with particular focus on connectivity between the anterior node (i.e., medial prefrontal cortex, or mPFC) and other associated regions in this network. Electroencephalography was recorded from 55 younger adults (18–30 years, 28 females) and 34 older adults (64–88 years, 16 females) in two resting state conditions (eyes-open and -closed). Source-level functional connectivity was quantified using phase-locking value (PLV) with a spatial filter of six sources of interest, and were subjected to data-driven permutation testing between groups from 1 to 50 Hz. Older adults also completed tests of memory, language, executive functioning, and processing speed. Findings indicated decreased connectivity in the alpha2 range for older than younger adults between the mPFC and other DMN regions including the left angular gyrus and bilateral lateral temporal cortices, the latter of which were associated with lower performance in semantic fluency and executive functioning in older adults. Furthermore, greater PLV in theta and beta bands between the mPFC and posterior cingulate regions were found in older than younger adults. These results suggest age-related changes in DMN functional connectivity are non-uniform and frequency-dependent, and may reflect poorer performance in cognitive domains thought to decline with aging.

Age-Related Decrease in Default-Mode Network Functional Connectivity Is Accelerated in Patients With Major Depressive Disorder.

Major depressive disorder (MDD) is a common psychiatric disorder which is associated with an accelerated biological aging. However, little is known whether such process would be reflected by a more rapid aging of the brain function. In this study, we tested the hypothesis that MDD would be characterized by accelerated aging of the brain’s default-mode network (DMN) functions. Resting-state functional magnetic resonance imaging data of 971 MDD patients and 902 healthy controls (HCs) was analyzed, which was drawn from a publicly accessible, multicenter dataset in China. Strength of functional connectivity (FC) and temporal variability of dynamic functional connectivity (dFC) within the DMN were calculated. Age-related effects on FC/dFC were estimated by linear regression models with age, diagnosis, and diagnosis-by-age interaction as variables of interest, controlling for sex, education, site, and head motion effects. The regression models revealed (1) a significant main effect of age in the predictions of both FC strength and dFC variability; and (2) a significant main effect of diagnosis and a significant diagnosis-by-age interaction in the prediction of FC strength, which was driven by stronger negative correlation between age and FC strength in MDD patients. Our results suggest that (1) both healthy participants and MDD patients experience decrease in DMN FC strength and increase in DMN dFC variability along age; and (2) age-related decrease in DMN FC strength may occur at a faster rate in MDD patients than in HCs. However, further longitudinal studies are still needed to understand the causation between MDD and accelerated aging of brain.

Selective Impairment of Long-Range Default Mode Network Functional Connectivity as a Biomarker for Preclinical Alzheimer's Disease in People with Down Syndrome.

Down syndrome (DS) is associated with increased risk for Alzheimer's disease (AD). In neurotypical individuals, clinical AD is preceded by reduced resting state functional connectivity in the default mode network (DMN), but it is unknown whether changes in DMN connectivity predict clinical onset of AD in DS. Does lower DMN functional connectivity predict clinical onset of AD and cognitive decline in people with DS? Resting state functional MRI (rsfMRI), longitudinal neuropsychological, and clinical assessment data were collected on 15 nondemented people with DS (mean age = 51.66 years, SD = 5.34 years, range = 42-59 years) over four years, during which 4 transitioned to dementia. Amyloid-β (Aβ) PET data were acquired on 13 of the 15 participants. Resting state fMRI, neuropsychological, and clinical assessment data were also acquired on an independent, slightly younger unimpaired sample of 14 nondemented people with DS (mean age = 44.63 years, SD = 7.99 years, range = 38-61 years). Lower functional connectivity between long-range but not short-range DMN regions predicts AD diagnosis and cognitive decline in people with DS. Aβ accumulation in the inferior parietal cortex is associated with lower regional DMN functional connectivity. Reduction of long-range DMN connectivity is a potential biomarker for AD in people with DS that precedes and predicts clinical conversion.

Voxel-wise Functional Connectivity of the Default Mode Network in Epilepsies: A Systematic Review and Meta-Analysis.

Background:Default Mode Network (DMN) is recognized to be involved in the generation and propagation of epileptic activities in various epilepsies. Converging evidence has suggested disturbed Functional Connectivity (FC) in epilepsies, which was inferred to be related to underlying pathological mechanisms. However, abnormal changes of FC in DMN revealed by different studies are controversial, which obscures the role of DMN in distinct epilepsies.Objective:The present work aims to investigate the voxel-wise FC in DMN across epilepsies.Methods:A systematic review was conducted on 22 published articles before October 2020, indexed in PubMed and Web of Science. A meta-analysis with a random-effect model was performed using the effect-size signed differential mapping approach. Subgroup analyses were performed in three groups: Idiopathic Generalized Epilepsy (IGE), mixed Temporal Lobe Epilepsy (TLE), and mixed Focal Epilepsy (FE) with different foci.Results:The meta-analysis suggested commonly decreased FC in mesial prefrontal cortices across different epilepsies. Additionally decreased FC in posterior DMN was observed in IGE. The TLE showed decreased FC in temporal lobe regions and increased FC in the dorsal posterior cingulate cortex. Interestingly, an opposite finding in the ventral and dorsal middle frontal gyrus was observed in TLE. The FE demonstrated increased FC in the cuneus.

Abnormalities of the Default Mode Network Functional Connectivity in Patients with Insomnia Disorder.

Objective This paper aimed to probe changes in the default mode network (DMN) functional connectivity (DMNFC) of the brain of patients with insomnia disorder (ID) under the resting state. Methods A total of 67 patients with ID and 67 graphically matched healthy controls were selected. Then, their general information was collected, followed by a psychological scale valuation. Resting state functional magnetic resonance imaging (rs-fMRI) scanning was conducted. Subsequently, collected statistics were processed, bilateral precuneus and medial superior frontal gyrus were defined as regions of interest (ROI), and the difference in intensity between these two groups was compared. Results Compared with the healthy control group, the patients in the ID group were observed with abnormalities of DMNFC. Specifically, a significant increase in the functional connectivity (FC) could be observed between the left medial superior frontal gyrus and left central anterior gyrus, the left medial superior frontal gyrus and anterior cingulate gyrus, the right medial superior frontal gyrus and left central anterior gyrus, the left anterior cuneiform and left central anterior/posterior gyrus, the left anterior cuneiform and left superior occipital gyrus, as well as the right anterior cuneiform and left central posterior gyrus. However, the FC between the left anterior cuneiform and the right middle frontal gyrus was weakened, as well as between the left anterior cuneiform and the right angle gyrus and between the right precuneus and the left inferior temporal gyrus. Conclusion ID patients may suffer changes in FC. The decline of FC in DMN may be one of the underlying causes of ID; the enhancement of FC between DMN and the visual-spatial attention network may play a key role in the mechanisms of impaired brain functional networks of ID.

Physical activity moderates the association between executive function and functional connectivity in older adults.

Recent evidence suggests that physical activity may influence the functional connectivity of the aging brain. The purpose of this study was to examine the influence of physical activity on the association between executive function and functional connectivity of key brain networks and graph theory metrics in community-dwelling older adults. Participants were 47 older adults (M = 73 years; SD = 5.92) who participated in neuropsychological testing, physical activity measurements, and magnetic resonance imaging (MRI). Seed-to-voxel moderation analyses and graph theory analyses were conducted. Physical activity was significantly positively associated with default mode network functional connectivity (DMN FC; Posterior Cingulate Gyrus, p-FDR = 0.005; Frontal Pole (L), p-FDR = 0.005; Posterior Cingulate Gyrus, p-FDR = 0.006; Superior Frontal Gyrus (L), p-FDR = 0.016) and dorsal attention network functional connectivity (DAN FC; Inferior Frontal Gyrus Pars Opercularis (R), p-FDR = 0.044). The interaction between physical activity and executive function on the DMN FC and DAN FC was analyzed. The interaction between executive function and physical activity was significantly associated with DMN FC. When this significant interaction was probed, the association between physical activity and DMN FC differed between levels of high and low executive function such that the association was only significant at levels of high executive function. These results suggest that greater physical activity in later life is associated with greater DMN and DAN FC and provides evidence for the importance of physical activity in cognitively healthy older adults.

Influence of endogenous estrogen on a network model of female brain integrity.

Recent reports document sex differences in midlife brain integrity and metabolic health, such that more relationships are detectable between metabolic syndrome (MetS) components and markers of brain health in females than in males. Midlife is characterized by a rapid decrease in endogenous estrogen levels for women which is thought to increase risk for cardiometabolic disease and neurocognitive decline. Our study used network models, designed to explore the interconnectedness and organization of relationships among many variables at once, to compare the influence of endogenous estrogen and chronological age on a network of brain and metabolic health in order to investigate the utility of estrogen as a biomarker for brain vulnerability. Data were analyzed from 82 females (ages 40-62). Networks consisted of known biomarkers of risk for late-life cognitive decline: the five components of MetS; Brain-predicted age difference calculated on gray and white matter volume; white matter hyperintensities; Default Mode Network functional connectivity; cerebral concentrations of N-acetyl aspartate, glutamate and myo-inositol; and serum concentrations of estradiol. A second network replaced estradiol with chronological age. Expected influence (EI) of estradiol on the network was -1.190, relative to chronological age at -0.524, indicating that estradiol had a stronger expected influence over the network than age. A negative expected influence indicates that higher levels of estradiol would be expected to decrease the number of relationships in the model, which is thought to indicate lower risk. Overall, levels of estradiol appear more influential than chronological age at midlife for relationships between brain integrity and metabolic health.

Task-induced subjective fatigue and resting-state striatal connectivity following traumatic brain injury

BackgroundPeople with traumatic brain injury (TBI) often experience fatigue, but an understanding of the neural underpinnings of fatigue following TBI is still lacking. This study used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between functional connectivity (FC) changes and task-induced changes in subjective fatigue in people with moderate-severe TBI. MethodsSixteen people with moderate-severe TBI and 17 matched healthy controls (HC) performed an adaptive N-back task (working memory task) to induce cognitive fatigue. Before and after the task they rated their state fatigue level and underwent rs-fMRI. Seed-to-voxel analyses with seeds in areas involved in cognitive fatigue, namely the striatum and default mode network (DMN) including, medial prefrontal cortex and posterior cingulate cortex, were performed. ResultsThe adaptive N-back task was effective in inducing fatigue in both groups. Subjective task-induced fatigue was positively associated with FC between striatum and precuneus in people with TBI, while there was a negative association in HC. In contrast, subjective task-induced fatigue was negatively associated with FC between striatum and cerebellum in the TBI group, while there was no association in HC. Similar associations between task-induced subjective fatigue and DMN FC were found across the groups. ConclusionsOur results suggest that the subjective experience of fatigue was linked to DMN connectivity in both groups and was differently associated with striatal connectivity in people with moderate-severe TBI compared to HC. Defining fatigue-induced neuronal network changes is pertinent to the development of treatments that target abnormal neuronal activity after TBI.

Neurometabolic and functional changes of default-mode network relate to clinical recovery in first-episode psychosis patients: A longitudinal 1H-MRS and fMRI study

BackgroundAntipsychotic treatment has improved the disrupted functional connectivity (FC) and neurometabolites levels of the default mode network (DMN) in schizophrenia patients, but a direct relationship between FC change, neurometabolic level alteration, and symptom improvement has not been built. This study examined the association between the alterations in DMN FC, the changes of neurometabolites levels in the medial prefrontal cortex (MPFC), and the improvementsinpsychopathology in a longitudinal study of drug-naïve first-episode psychosis (FEP) patients. MethodsThirty-two drug-naïve FEP patients and 30 matched healthy controls underwent repeated assessments with the Positive and Negative Syndrome Scale (PANSS) and 3T proton magnetic resonance spectroscopy as well as resting-state functional magnetic resonance imaging. The levels of γ-aminobutyric acid, glutamate, N-acetyl-aspartate in MPFC, and the FC of DMN were measured. After 8-week antipsychotic treatment, 24 patients were re-examined. ResultsAfter treatment, the changes in γ-aminobutyric acid were correlated with the alterations of FC between the MPFC and DMN, while the changes in N-acetyl-aspartate were associated with the alterations of FC between the posterior cingulate cortex/precuneus and DMN. The FC changes of both regions were correlated with patients PANSS positive score reductions. The structural equation modeling analyses revealed that the changes of DMN FC mediated the relationship between the changes of neurometabolites and the symptom improvements of the patients. ConclusionsThe derived neurometabolic-functional changes underlying the clinical recovery provide insights into the prognosis of FEP patients. It is noteworthy that this is an exploratory study, and future work with larger sample size is needed to validate our findings.

Correlations Between the DMN and the Smoking Cessation Outcome of a Real-Time fMRI Neurofeedback Supported Exploratory Therapy Approach: Descriptive Statistics on Tobacco-Dependent Patients.

The aim of this study was to explore the potential of default mode network (DMN) functional connectivity for predicting the success of smoking cessation in patients with tobacco dependence in the context of a real-time function al MRI (RT-fMRI) neurofeedback (NF) supported therapy.Fifty-four tobacco-dependent patients underwent three RT-fMRI-NF sessions including resting-state functional connectivity (RSFC) runs over a period of 4 weeks during professionally assisted smoking cessation. Patients were randomized into two groups that performed either active NF of an addiction-related brain region or sham NF. After preprocessing, the RSFC baseline data were statistically evaluated using seed-based ROI (SBA) approaches taking into account the smoking status of patients after 3 months (abstinence/relapse).The results of the real study group showed a widespread functional connectivity in the relapse subgroup (n = 10) exceeding the DMN template and mainly low correlations and anticorrelations in the within-seed analysis. In contrast, the connectivity pattern of the abstinence subgroup (n = 8) primarily contained the core DMN in the seed-to-whole-brain analysis and a left lateralized correlation pattern in the within-seed analysis. Calculated Multi-Subject Dictionary Learning (MSDL) matrices showed anticorrelations between DMN regions and salience regions in the abstinence group. Concerning the sham group, results of the relapse subgroup (n = 4) and the abstinence subgroup (n = 6) showed similar trends only in the within-seed analysis.In the setting of a RT-fMRI-NF-assisted therapy, a widespread intrinsic DMN connectivity and a low negative coupling between the DMN and the salience network (SN) in patients with tobacco dependency during early withdrawal may be useful as an early indicator of later therapy nonresponse.

Maladaptive self-focused attention and default mode network connectivity: a transdiagnostic investigation across social anxiety and body dysmorphic disorders.

Maladaptive self-focused attention (SFA) is a bias toward internal thoughts, feelings and physical states. Despite its role as a core maintaining factor of symptoms in cognitive theories of social anxiety and body dysmorphic disorders (BDDs), studies have not examined its neural basis. In this study, we hypothesized that maladaptive SFA would be associated with hyperconnectivity in the default mode network (DMN) in self-focused patients with these disorders. Thirty patients with primary social anxiety disorder or primary BDD and 28 healthy individuals were eligible and scanned. Eligibility was determined by scoring greater than 1SD or below 1SD of the Public Self-Consciousness Scale normative mean, respectively, for each group. Seed-to-voxel functional connectivity was computed using a DMN posterior cingulate cortex (PCC) seed. There was no evidence of increased DMN functional connectivity in patients compared to controls. Patients (regardless of diagnosis) showed reduced functional connectivity of the PCC with several brain regions, including the bilateral superior parietal lobule (SPL), compared to controls, which was inversely correlated with maladaptive SFA but not associated with social anxiety, body dysmorphic, depression severity or rumination. Abnormal PCC-SPL connectivity may represent a transdiagnostic neural marker of SFA that reflects difficulty shifting between internal versus external attention.

Default mode network dissociation linking cerebral beta amyloid retention and depression in cognitively normal older adults

AbstractBackgroundTo date, cerebral beta amyloid (Aß) deposition and late‐life depression (LLD) are known to be associated with trajectory of Alzheimer’s disease (AD). However, their neurobiological link is not clear. Although previous studies showed aberrant functional connectivity (FC) change of default mode network (DMN) in early Aß deposition and LLD respectively, its mediating role is not elucidated. The aim of this study is to investigate distinctive association pattern of DMN FC linking LLD and Aß retention in the cognitively normal older adults.MethodTwo hundred thirty‐five cognitively normal older adults with (N=118) and without depression (N=117) underwent resting state functional magnetic resonance image and 18F‐Flutemetamol positron emission tomography. We investigated associations among Aß burden, depression, and DMN FC.ResultIndependent component analysis showed increased anterior DMN FC and decreased posterior DMN FC in depression group compared with no depression group. Global cerebral Aß retention correlated positively with anterior and negatively with posterior DMN FC. Anterior DMN FCs were positively correlated with depression severity whereas posterior DMN FCs were negatively correlated with cognitive function. In addition, effect of global cerebral Aß retention on depression severity was mediated by subgenual anterior cingulate FC.ConclusionOur results of anterior and posterior DMN FC dissociation pattern might play pivotal role in linking cerebral Aß pathology and LLD in the course of AD progression. Further longitudinal studies would be needed to confirm causal relationships between cerebral Aß retention and LLD.

Executive control network (ECN) and default mode network (DMN) functional connectivity in older adults with remitted depression, mild cognitive impairment, Alzheimer’s dementia, or normal cognition

AbstractBackgroundMajor Depressive Disorder (MDD) is associated with an increased risk of developing Alzheimer’s dementia (AD). The present study aims to understand risk for AD by comparing resting state functional connectivity (FC) in putatively shared vulnerability networks; executive control network (ECN) or default mode network (DMN) among older adults who are either healthy or have a history of MDD, MCI, or AD.MethodWe assessed brain functional alterations in ECN and DMN in five groups at‐risk for dementia: remitted MDD, non‐amnestic mild cognitive impairment (naMCI), MDD+naMCI, amnestic MCI (aMCI), and MDD+aMCI. The analysis also included individuals with AD and healthy controls (HC). Resting‐state functional MRI data were acquired on the same 3T scanner. Following quality control (n=330), dual regression was conducted. The ECN and DMN group‐ICA (independent component analysis) were selected from the Smith atlas. Next, the group difference in the functional connectivity (FC) of each network was calculated using PALM (Permutation Analysis of Linear Models).ResultFor within‐network FC in the ECN or DMN, we found no difference between participant groups. For between‐network FC, we found a significant difference between the DMN and the superior parietal lobe (SPL); post‐hoc tests showed decreased anti‐correlation between the AD group compared to the MDD and HC groups (p<0.05).ConclusionThe between‐network difference in DMN among groups was driven by the AD group. There was minimal distinction among those with remitted MDD or MCI. It is possible that remitted MDD may not act as mechanistic risk for AD in ECN or DMN networks.

Abnormal Dynamic Functional Network Connectivity Estimated from Default Mode Network Predicts Symptom Severity in Major Depressive Disorder.

Background: Major depressive disorder (MDD) is a severe mental illness marked by a continuous sense of sadness and a loss of interest. The default mode network (DMN) is a group of brain areas that are more active during rest and deactivate when engaged in task-oriented activities. The DMN of MDD has been found to have aberrant static functional network connectivity (FNC) in recent studies. In this work, we extend previous findings by evaluating dynamic functional network connectivity (dFNC) within the DMN subnodes in MDD. Methods: We analyzed resting-state functional magnetic resonance imaging data of 262 patients with MDD and 277 healthy controls (HCs). We estimated dFNCs for seven subnodes of the DMN, including the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and precuneus (PCu), using a sliding window approach, and then clustered the dFNCs into five brain states. Classification of MDD and HC subjects based on state-specific FC was performed using a logistic regression classifier. Transition probabilities between dFNC states were used to identify relationships between symptom severity and dFNC data in MDD patients. Results: By comparing state-specific FNC between HC and MDD, a disrupted connectivity pattern was observed within the DMN. In more detail, we found that the connectivity of ACC is stronger, and the connectivity between PCu and PCC is weaker in individuals with MDD than in those of HC subjects. In addition, MDD showed a higher probability of transitioning from a state with weaker ACC connectivity to a state with stronger ACC connectivity, and this abnormality is associated with symptom severity. This is the first research to look at the dFC of the DMN in MDD with a large sample size. It provides novel evidence of abnormal time-varying DMN configuration in MDD and offers links to symptom severity in MDD subjects. Impact Statement This study is the first attempt that explored the temporal change on default mode network (DMN) connectivity in a relatively large cohort of patients with major depressive disorder (MDD). We also introduced a new hypothesis that explains the inconsistency in DMN functional network connectivity (FNC) comparison between MDD and healthy control based on static FNC in the previous literature. Additionally, our findings suggest that within anterior cingulate cortex connectivity and the connectivity between the precuneus and posterior cingulate cortex are the potential biomarkers for the future intervention of MDD.

Altered intrinsic default mode network functional connectivity in patients with remitted geriatric depression and amnestic mild cognitive impairment.

Patients with geriatric depression exhibit a spectrum of symptoms ranging from mild to severe cognitive impairment which could potentially lead to the development of Alzheimer's disease (AD). The aim of the study is to assess the alterations of the default mode network (DMN) in remitted geriatric depression (RGD) patients and whether it could serve as an underlying neuropathological mechanism associated with the risk of progression of AD. Cross-sectional study. A total of 154 participants, comprising 66 RGD subjects (which included 27 patients with comorbid amnestic mild cognitive impairment [aMCI] and 39 without aMCI [RGD]), 45 aMCI subjects without a history of depression (aMCI), and 43 matched healthy comparisons (HC), were recruited. All participants completed neuropsychological tests and underwent resting-state functional magnetic resonance imaging (fMRI). Posterior cingulate cortex (PCC)-seeded DMN functional connectivity (FC) along with cognitive function were compared among the four groups, and correlation analyses were conducted. In contrast to HC, RGD, aMCI, and RGD-aMCI subjects showed significant impairment across all domains of cognitive functions except for attention. Furthermore, compared with HC, there was a similar and significant decrease in PCC-seed FC in the bilateral medial superior frontal gyrus (M-SFG) in the RGD, aMCI, and RGD-aMCI groups. The aberrations in rsFC of the DMN were associated with cognitive deficits in RGD patients and might potentially reflect an underlying neuropathological mechanism for the increased risk of developing AD. Therefore, altered connectivity in the DMN could serve as a potential neural marker for the conversion of geriatric depression to AD.

Cognitive and Affective Empathy as Indirect Paths Between Heterogeneous Depression Symptoms on Default Mode and Salience Network Connectivity in Adolescents.

Depression amongst adolescents is a prevalent disorder consisting of heterogeneous emotional and functional symptoms-often involving impairments in social domains such as empathy. Cognitive and affective components of empathy as well as their associated neural networks (default mode network for cognitive empathy and salience network for affective empathy) are affected by depression. Depression commonly onsets during adolescence, a critical period for brain development underlying empathy. However, the available research in this area conceptualizes depression as a homogenous construct, and thereby miss to represent the full spectrum of symptoms. The present study aims to extend previous literature by testing whether cognitive and affective empathy indirectly account for associations between brain network connectivity and heterogeneous depression symptoms in adolescents. Heterogeneous functional and emotional symptoms of depression were measured using the child depression inventory. Our results indicate that cognitive empathy mediates the association between default mode network functional connectivity and emotional symptoms of depression. More specifically, that adolescents with a stronger positive association between the default mode network and cognitive empathy show lower emotional depression symptoms. This finding highlights the importance of cognitive empathy in the relationship between brain function and depression symptoms, which may be an important consideration for existing models of depression in adolescents.