Brain Networks In Major Depressive Disorder Research Articles

Linked patterns of symptoms and cognitive covariation with functional brain controllability in major depressive disorder

Controllability analysis is an approach developed for evaluating the ability of a brain region to modulate function in other regions, which has been found to be altered in major depressive disorder (MDD). Both depressive symptoms and cognitive impairments are prominent features of MDD, but the case-control differences of controllability between MDD and controls can not fully interpret the contribution of both clinical symptoms and cognition to brain controllability and linked patterns among them in MDD. Sparse canonical correlation analysis was used to investigate the associations between resting-state functional brain controllability at the network level and clinical symptoms and cognition in 99 first-episode medication-naïve patients with MDD. Average controllability was significantly correlated with clinical features. The average controllability of the dorsal attention network (DAN) and visual network had the highest correlations with clinical variables. Among clinical variables, depressed mood, suicidal ideation and behaviour, impaired work and activities, and gastrointestinal symptoms were significantly negatively associated with average controllability, and reduced cognitive flexibility was associated with reduced average controllability. These findings highlight the importance of brain regions in modulating activity across brain networks in MDD, given their associations with symptoms and cognitive impairments observed in our study. Disrupted control of brain reconfiguration of DAN and visual network during their state transitions may represent a core brain mechanism for the behavioural impairments observed in MDD. National Natural Science Foundation of China (82001795 and 82027808), National Key R&D Program (2022YFC2009900), and Sichuan Science and Technology Program (2024NSFSC0653).

Disrupted properties of functional brain networks in major depressive disorder during emotional face recognition: an EEG study via graph theory analysis.

Previous neuroimaging studies have revealed abnormal brain networks in patients with major depressive disorder (MDD) in emotional processing. While any cognitive task consists of a series of stages, little is yet known about the topology of functional brain networks in MDD for these stages during emotional face recognition. To address this problem, electroencephalography (EEG)-based functional brain networks of MDD patients at different stages of facial information processing were investigated in this study. First, EEG signals were collected from 16 patients with MDD and 18 age-, gender-, and education-matched normal subjects when performing an emotional face recognition task. Second, the global field power (GFP) method was employed to divide group-averaged event-related potentials into different stages. Third, using the phase transfer entropy (PTE) approach, the brain networks of MDD patients and normal individuals were constructed for each stage in negative and positive face processing, respectively. Finally, we compared the topological properties of brain networks of each stage between the two groups using graph theory approaches. The results showed that the analyzed three stages of emotional face processing corresponded to specific neurophysiological phases, namely, visual perception, face recognition, and emotional decision-making. It was also demonstrated that depressed patients showed abnormally decreased characteristic path length at the visual perception stage of negative face recognition and normalized characteristic path length in the stage of emotional decision-making during positive face processing compared to healthy subjects. Furthermore, while both the MDD and normal groups' brain networks were found to exhibit small-world network characteristics, the brain network of patients with depression tended to be randomized. Moreover, for patients with MDD, the centro-parietal region may lose its status as a hub in the process of facial expression identification. Together, our findings suggested that altered emotional function in MDD patients might be associated with disruptions in the topological organization of functional brain networks during emotional face recognition, which further deepened our understanding of the emotion processing dysfunction underlying MDD.

Intrinsic Organization of Occipital Hubs Predicts Depression: A Resting-State fNIRS Study.

Dysfunctional brain networks have been found in patients with major depressive disorder (MDD). In this study, to verify this in a more straightforward way, we investigated the intrinsic organization of brain networks in MDD by leveraging the resting-state functional near-infrared spectroscopy (rs-fNIRS). Thirty-four MDD patients (24 females, 38.41 ± 13.14 years old) and thirty healthy controls (22 females, 34.43 ± 5.03 years old) underwent a 10 min rest while their brain activity was recorded via fNIRS. The results showed that MDD patients and healthy controls exhibited similar resting-state functional connectivity. Moreover, the depression group showed lower small-world Lambda (1.12 ± 0.04 vs. 1.16 ± 0.10, p = 0.04) but higher global efficiency (0.51 ± 0.03 vs. 0.48 ± 0.05, p = 0.03) than the control group. Importantly, MDD patients, as opposed to healthy controls, showed a significantly lower nodal local efficiency at the left middle occipital gyrus (0.56 ± 0.36 vs. 0.81 ± 0.20, pFDR < 0.05), which predicted the level of depression in MDD (r = 0.45, p = 0.01, R2 = 0.15). In sum, we found a more integrated brain network in MDD patients with a lower nodal local efficiency at the occipital hub, which could predict depressive symptoms.

Disrupted intrinsic functional brain topology in patients with major depressive disorder

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Altered temporal reachability highlights the role of sensory perception systems in major depressive disorder

BackgroundThe latest studies have considered the time-dependent structures in dynamic brain networks. However, the effect of periphery structures on the temporal flow of information remains unexplored in patients with major depressive disorder (MDD). In this work, we aimed to explore the pattern of interactions between brain regions in MDD across space and time. MethodsWe concentrated on the temporal reachability of nodes in temporal brain networks derived from the resting-state functional magnetic resonance imaging (rs-fMRI) of 55 MDD patients and 62 sex-, age-matched healthy controls. Specifically, temporal connectedness and temporal efficiency (TEF) were estimated based on the length of temporal paths between node pairs. Subsequently, the temporal clustering coefficient (TCC) and temporal distance were jointly employed to explore the patterns in which a node's periphery structure affects its reachability. ResultsSignificantly higher TEF and lower TCC were found in temporal brain networks in MDD. Besides, significant between-group differences of nodal TCC were detected in regions of sensory perception systems. Considering the temporal paths that begin or end at these regions, MDD patients showed several altered temporal distances. ConclusionOur results showed that the temporal reachability of specific brain regions in MDD could be affected as their periphery structures evolve, which may explain the dysfunction of sensory perception systems in the spatiotemporal domain.

Diagnosis of major depressive disorder using whole-brain effective connectivity networks derived from resting-state functional MRI

Objective. It is important to improve identification accuracy for possible early intervention of major depressive disorder (MDD). Recently, effective connectivity (EC), defined as the directed influence of spatially distant brain regions on each other, has been used to find the dysfunctional organization of brain networks in MDD. However, little is known about the ability of whole-brain resting-state EC features in identification of MDD. Here, we employed EC by whole-brain analysis to perform MDD diagnosis. Approach. In this study, we proposed a high-order EC network capturing high-level relationship among multiple brain regions to discriminate 57 patients with MDD from 60 normal controls (NC). In high-order EC networks and traditional low-order EC networks, we utilized the network properties and connection strength for classification. Meanwhile, the support vector machine (SVM) was employed for model training. Generalization of the results was supported by 10-fold cross-validation. Main results. The classification results showed that the high-order EC network performed better than the low-order EC network in diagnosing MDD, and the integration of these two networks yielded the best classification precision with 95% accuracy, 98.83% sensitivity, and 91% specificity. Furthermore, we found that the abnormal connections of high-order EC in MDD patients involved multiple widely concerned functional subnets, particularly the default mode network and the cerebellar network. Significance. The current study indicates whole-brain EC networks, measured by our high-order method, may be promising biomarkers for clinical diagnosis of MDD, and the complementary between high-order and low-order EC will better guide patients to get early interventions as well as treatments.

Graph theory analysis of directed functional brain networks in major depressive disorder based on EEG signal

Objective. Analysis of functional and structural brain networks has suggested that major depressive disorder (MDD) is associated with a disruption in brain networks. This paper aims to investigate the abnormalities of brain networks in MDD. Approach. To this aim, we constructed weighted directed functional networks based on electroencephalography (EEG) signals of 26 MDD patients and 23 normal (N) subjects. The nodes of networks were 19 EEG electrodes, and the edges were phase transfer entropy (PTE) between each pair of electrodes. PTE is a model-free, phase-based effective connectivity measure that is relatively robust to noise and linear mixing. Since the correct instantaneous phase of a signal is computed for narrow frequency bands, the networks were analyzed in eight frequency sub-bands including delta, theta, alpha1, alpha2, beta1, beta2, beta3, and beta4. To assess the alteration in the topology of brain networks in MDD patients, graph theory metrics consisting of global efficiency, local efficiency, node betweenness centrality, node degree, and node strength were analyzed by statistical tests and classification. Furthermore, directed differential connectivity graphs (dDCGs) for the MDD and N groups were studied. Main results. These analyses revealed a higher node degree and strength in the dDCGs of the MDD group than the normal group. It was also found that MDD brain networks have a more randomized structure than the N group. Moreover, our results indicated that the out-degree of networks classified MDD and N subjects with an accuracy of 92%; thus, our method can be considered as a powerful tool for depression detection. Significance. Our analysis may provide new insights into developing biomarkers for depression detection based on brain networks.

Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Aberrant Dynamic Functional Network Connectivity and Graph Properties in Major Depressive Disorder.

Major depressive disorder (MDD) is a complex mood disorder characterized by persistent and overwhelming depression. Previous studies have identified abnormalities in large scale functional brain networks in MDD, yet most of them were based on static functional connectivity. In contrast, here we explored disrupted topological organization of dynamic functional network connectivity (dFNC) in MDD based on graph theory. One hundred and eighty-two MDD patients and 218 healthy controls were included in this study, all Chinese Han people. By applying group information guided independent component analysis (GIG-ICA) to resting-state functional magnetic resonance imaging (fMRI) data, the dFNCs of each subject were estimated using a sliding window method and k-means clustering. Network properties including global efficiency, local efficiency, node strength and harmonic centrality, were calculated for each subject. Five dynamic functional states were identified, three of which demonstrated significant group differences in their percentage of state occurrence. Interestingly, MDD patients spent much more time in a weakly-connected State 2, which includes regions previously associated with self-focused thinking, a representative feature of depression. In addition, the FNCs in MDD were connected differently in different states, especially among prefrontal, sensorimotor, and cerebellum networks. MDD patients exhibited significantly reduced harmonic centrality primarily involving parietal lobule, lingual gyrus and thalamus. Moreover, three dFNCs with disrupted node properties were commonly identified in different states, and also correlated with depressive symptom severity and cognitive performance. This study is the first attempt to investigate the dynamic functional abnormalities in MDD in a Chinese population using a relatively large sample size, which provides new evidence on aberrant time-varying brain activity and its network disruptions in MDD, which might underscore the impaired cognitive functions in this mental disorder.

Abnormal Dynamic Functional Network Connectivity and Graph Theoretical Analysis in Major Depressive Disorder.

Major depressive disorder (MDD) is a complex mood disorder characterized by persistent and overwhelming depression. Previous studies have identified abnormalities in large scale functional brain networks in MDD, yet most of them were based on static functional connectivity. By contrast, here we explored disrupted topological organization of dynamic functional network connectivity (dFNC) in MDD based on graph theory. 182 MDD patients and 218 healthy controls were included in this study, all Chinese Han people. By applying group information guided independent component analysis (GIG-ICA) on resting-state fMRI data, the dFNCs of each subject were estimated using a sliding window method and k-means clustering. Five dynamic functional states were identified, three of which demonstrated significant group difference on the percentage of state occurrence. Interestingly, MDD patients spent much more time in a weakly-connected state 2, which is associated with self-focused thinking, a representative feature of depression. In addition, the abnormal FNCs in MDD were observed connecting different networks, especially among prefrontal, sensorimotor and cerebellum networks. As to network properties, MDD patients exhibited increased node efficiency in prefrontal and cerebellum. Moreover, three dFNCs with disrupted node properties were commonly identified in different states, which are also correlated with depressive symptom severity and cognitive performance. This study is the first attempt to investigate the dynamic functional abnormalities in Chinese MDD using a relatively large sample size, which provides new evidence on aberrant time-varying brain activity and its network disruptions in MDD, which might underscore the impaired cognitive functions in this mental disorder.

Functional reorganization of intra- and internetwork connectivity in major depressive disorder after electroconvulsive therapy.

Electroconvulsive therapy (ECT) is an effective and rapid treatment for major depressive disorder (MDD). However, the neurobiological underpinnings of ECT are still largely unknown. Recent studies have identified dysregulated brain networks in MDD. Therefore, we hypothesized that ECT may improve MDD symptoms through reorganizing these networks. To test this hypothesis, we used resting-state functional connectivity to investigate changes to the intra- and internetwork architecture of five reproducible resting-state networks: the default mode network (DMN), dorsal attention network (DAN), executive control network (CON), salience network (SAL), and sensory-motor network. Twenty-three MDD patients were assessed before and after ECT, along with 25 sex-, age-, and education-matched healthy controls. At the network level, enhanced intranetwork connectivities were found in the CON in MDD patients after ECT. Furthermore, enhanced internetwork connectivities between the DMN and SAL, and between the CON and DMN, DAN, and SAL were also identified. At the nodal level, the posterior cingulate cortex had increased connections with the left posterior cerebellum, right posterior intraparietal sulcus (rpIPS), and right anterior prefrontal cortex. The rpIPS had increased connections with the medial PFC (mPFC) and left anterior cingulate cortex. The left lateral parietal had increased connections with the dorsal mPFC (dmPFC), left anterior prefrontal cortex, and right anterior cingulate cortex. The dmPFC had increased connection with the left anterolateral prefrontal cortex. Our findings indicate that enhanced interactions in intra- and internetworks may contribute to the ECT response in MDD patients. These findings provide novel and important insights into the neurobiological mechanisms underlying ECT.

Anomalous single-subject based morphological cortical networks in drug-naive, first-episode major depressive disorder.

Major depressive disorder (MDD) has been associated with disruptions in the topological organization of brain morphological networks in group-level data. Such disruptions have not yet been identified in single-patients, which is needed to show relations with symptom severity and to evaluate their potential as biomarkers for illness. To address this issue, we conducted a cross-sectional structural brain network study of 33 treatment-naive, first-episode MDD patients and 33 age-, gender-, and education-matched healthy controls (HCs). Weighted graph-theory based network models were used to characterize the topological organization of brain networks between the two groups. Compared with HCs, MDD patients exhibited lower normalized global efficiency and higher modularity in their whole-brain morphological networks, suggesting impaired integration and increased segregation of morphological brain networks in the patients. Locally, MDD patients exhibited lower efficiency in anatomic organization for transferring information predominantly in default-mode regions including the hippocampus, parahippocampal gyrus, precuneus and superior parietal lobule, and higher efficiency in the insula, calcarine and posterior cingulate cortex, and in the cerebellum. Morphological connectivity comparisons revealed two subnetworks that exhibited higher connectivity strength in MDD mainly involving neocortex-striatum-thalamus-cerebellum and thalamo-hippocampal circuitry. MDD-related alterations correlated with symptom severity and differentiated individuals with MDD from HCs with a sensitivity of 87.9% and specificity of 81.8%. Our findings indicate that single subject grey matter morphological networks are often disrupted in clinically relevant ways in treatment-naive, first episode MDD patients. Circuit-specific changes in brain anatomic network organization suggest alterations in the efficiency of information transfer within particular brain networks in MDD. Hum Brain Mapp 38:2482-2494, 2017. © 2017 Wiley Periodicals, Inc.

Altered dynamics of brain connectivity in major depressive disorder at-rest and during task performance

Major depressive disorder (MDD) has been associated with alterations in several functional brain networks. Previous studies investigating brain networks in MDD during the performance of a task have yielded inconsistent results with the function of the brain at rest. In this study, we used functional magnetic resonance imaging at rest and during a goal-directed task to investigate dynamics of functional connectivity in 19 unmedicated patients with MDD and 19 healthy controls across both experimental paradigms. Patients had spatial differences in the default mode network (DMN), in the executive network (EN), and in the dorsal attention network (DAN) compared to controls at rest and during task performance. In patients the amplitude of the low frequency (LFO) oscillations was reduced in the motor and in the DAN networks during both paradigms. There was a diagnosis by paradigm interaction on the LFOs amplitude of the salience network, with increased amplitude change between task and rest in patients relative to controls. Our findings suggest that the function of several networks could be intrinsically affected in MDD and this could be viable phenotype for the investigation on the neurobiological mechanisms of this disorder and its treatment.