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.

Alterations in Social Brain Network Topology at Rest in Children With Autism Spectrum Disorder

BackgroundUnderconnectivity in the resting brain is not consistent in autism spectrum disorder (ASD). However, it is known that the default mode network is mainly decreased in childhood ASD. This study investigated the brain network topology as the changes in the connection strength and network efficiency in childhood ASD, including the early developmental stages.MethodsIn this study, 31 ASD children aged 2–11 years were compared with 31 age and sex-matched children showing typical development. We explored the functional connectivity based on graph filtration by assessing the single linkage distance and global and nodal efficiencies using resting-state functional magnetic resonance imaging. The relationship between functional connectivity and clinical scores was also analyzed.ResultsUnderconnectivities within the posterior default mode network subregions and between the inferior parietal lobule and inferior frontal/superior temporal regions were observed in the ASD group. These areas significantly correlated with the clinical phenotypes. The global, local, and nodal network efficiencies were lower in children with ASD than in those with typical development. In the preschool-age children (2–6 years) with ASD, the anterior-posterior connectivity of the default mode network and cerebellar connectivity were reduced.ConclusionsThe observed topological reorganization, underconnectivity, and disrupted efficiency in the default mode network subregions and social function-related regions could be significant biomarkers of childhood ASD.

Disrupting The Resting State: Meta-Analytic Evidence That Mindfulness Training Alters Default Mode Network Connectivity

This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to structurally-equivalent programs, with the hypothesis that that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of standardized mindfulness-based interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge’s g = .234, p = 0288, I2 = 15.87), located within the SN, and the posterior cingulate cortex, a focal hub of the DMN. Egger’s test for publication bias was nonsignificant, bias = 2.17, p = .162. In support of our hypothesis, results suggest that MT targets internetwork (SN-DMN) connectivity implicated in the flexible control of internally-oriented attention.

Temporoparietal Connectivity Within Default Mode Network Associates With Clinical Improvements in Schizophrenia Following Modified Electroconvulsive Therapy

Although modified electroconvulsive therapy (ECT) has been reported to be effective for the treatment of schizophrenia (SCZ), its action mechanism is unclear. To elucidate the underlying ECT mechanisms of SCZ, this study used a longitudinal cohort including 21 SCZ patients receiving only antipsychotics (DSZ group) and 21 SCZ patients receiving a regular course of ECT combining with antipsychotics (MSZ group) for 4 weeks. All patients underwent magnetic resonance imaging (MRI) scans at baseline (t1) and follow-up (t2) time points. A matched healthy control (HC) group included 23 individuals who were only scanned at baseline. Functional connectivity (FC) within the default mode network (DMN) was evaluated before and after ECT. Significant interaction of the group over time was found in FC between angular gyrus (AG) and middle temporal gyrus (MTG). Post-hoc analysis showed a significantly enhanced FC of left AG(AG.L) and right MTG (MTG.R) in the MSZ group relative to the DSZ group. In addition, the right AG (AG.R) showed significantly enhanced FC between MTG.R and left MTG (MTG.L) after ECT in the MSZ group, but no in the DSZ group. In particular, the FCs change in AG.L-MTG.R and AG.R-MTG.R were positively correlated with the Positive and Negative Syndrome Scale (PANSS) negative score reduction. Furthermore, the FC change in AG.L-MTG.R was also positively correlated with the PANSS general psychopathology score reduction. These findings confirmed a potential relationship between ECT inducing hyperconnectivity within DMN and improvements in symptomatology of SCZ, suggesting that ECT controls mental symptoms by regulating the temporoparietal connectivity within DMN.

Transcranial stimulation of alpha oscillations up-regulates the default mode network

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain’s functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous electroencephalography and functional MRI (EEG-fMRI), we demonstrated that α-tACS (versus Sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can up-regulate the DMN further highlights an effective noninvasive intervention to normalize DMN functioning in various disorders.

Functional Connectivity Within the Default Mode Network in Response to Exercise During Return-to-Sport Following Concussion

ObjectiveThe aim of this pilot study is to explore changes in EEG derived functional connectivity of the default mode network in response to physical exercise during return-to-sports (RTS) after sports related concussion (SRC).BackgroundThe rehabilitation of athletes with SRC is challenging. Presently, there are no objective biomarkers to predict effects of exercise during RTS. SRC associated diffuse axonal injuries predominantly affect the Default Mode Network (DMN). Assessing exercise induced changes in functional connectivity of the DMN may therefore be a potential target.Design/MethodsEleven athletes were examined during the early stages of RTS after SRC (age: 23.90 ± 4.81) and compared to 13 control athletes (age: 24.00 ± 4.90). Resting state 128-channel EEGs were collected before and after a progressive ergometer exercise protocol working up to 70% of the maximal heart rate. DMN connectivity was assessed by calculating the phase locking value (PLV) in 3 frequency bands (theta: 3–7, alpha: 7–13, beta: 14–25). Wilcoxon Signed Rank Tests were used to explore statistical significance between pre- and post-exercise.ResultsIn SRC athletes PLV within the alpha band decreased significantly post-exercise (median [Mdn] = 0.445, interquartile range [IQR = 0.069) in comparison to pre-exercise (Mdn = 0.436, IQR = 0.047; Z = −1.956, p < 0.05), whereas no difference was observed in the control group (post-exercise [Mdn = 0.476, IQR = 0.072] compared to pre-exercise [Mdn = 0.461, IQR = 0.100; Z = −0.175, p = 0.86]). PLVs in the theta and beta band before and after exercise differed neither in the patient nor in the control group.ConclusionsExercise induced changes of functional connectivity of the DMN within the alpha band were only present in post-concussed athletes and may be suitable as a potential objective marker to reflect pathophysiologic changes in further clinical studies to guide RTS.

Dysfunctional Interaction Between the Dorsal Attention Network and the Default Mode Network in Patients With Type 2 Diabetes Mellitus

The risk of cognitive impairment in patients with type 2 diabetes mellitus (T2DM) is significantly higher than that in the general population, but the exact neurophysiological mechanism underlying this is still unclear. An abnormal change in the intrinsic anticorrelation of the dorsal attention network (DAN) and the default mode network (DMN) is thought to be the mechanism underlying cognitive deficits that occur in many psychiatric disorders, but this association has rarely been tested in T2DM. This study explored the relationship between the interaction patterns of the DAN-DMN and clinical/cognitive variables in patients with T2DM. Forty-four patients with T2DM and 47 sex-, age-, and education-matched healthy controls (HCs) underwent neuropsychological assessments, independent component analysis (ICA), and functional network connection analysis (FNC). The relationship of DAN-DMN anticorrelation with the results of a battery of neuropsychological tests was also assessed. Relative to the HC group, the DMN showed decreased functional connectivity (FC) in the right precuneus, and the DAN showed decreased FC in the left inferior parietal lobule (IPL) in patients with T2DM. Subsequent FNC analysis revealed that, compared with the HC group, the T2DM patients displayed significantly increased inter-network connectivity between the DAN and DMN. These abnormal changes were correlated with the scores of multiple neuropsychological assessments (P &lt; 0.05). These findings indicate abnormal changes in the interaction patterns of the DAN-DMN may be involved in the neuropathology of attention and general cognitive dysfunction in T2DM patients.

The Effect of Seed Location on Functional Connectivity: Evidence from an Image-Based Meta-Analysis

Default mode network (DMN) is the most involved network in the study of brain development and brain diseases. Resting-state functional connectivity (rs-FC) is the most used method to study DMN, but different studies are inconsistent in the selection of seed. To evaluate the effect of different seed selection on rs-FC, we conducted an image-based meta-analysis (IBMA). We identified 59 coordinates of seed regions of interest (ROIs) within the default mode network (DMN) from 11 studies (retrieved from Web of Science and Pubmed) to calculate the functional connectivity; then, the uncorrected t maps were obtained from the statistical analyses. The IBMA was performed with the t maps. We demonstrate that the overlap of meta-analytic maps across different seeds’ ROIs within DMN is relatively low, which cautions us to be cautious with seeds’ selection. Future studies using the seed-based functional connectivity method should take the reproducibility of different seeds into account. The choice of seed may significantly affect the connectivity results.