The superior longitudinal fasciculus and its functional triple-network mechanisms in brooding.
ABSTRACT: Brooding, which refers to a repetitive focus on one's distress, is associated with functional connectivity within Default-Mode, Salience, and Executive-Control networks (DMN; SN; ECN), comprising the so-called "triple-network" of attention. Individual differences in brain structure that might perseverate dysfunctional connectivity of brain networks associated with brooding are less clear, however. Using diffusion and functional Magnetic Resonance Imaging, we explored multimodal relationships between brooding severity, white-matter microstructure, and resting-state functional connectivity in depressed adults (N?=?32-44), and then examined whether findings directly replicated in a demographically-similar, independent sample (N?=?36-45). Among the fully-replicated results, three core findings emerged. First, brooding severity is associated with functional integration and segregation of the triple-network, particularly with a Precuneal subnetwork of the DMN. Second, microstructural asymmetry of the Superior Longitudinal Fasciculus (SLF) provides a robust structural connectivity basis for brooding and may account for over 20% of its severity (Discovery: adj. R2?=?0.18; Replication: adj. R2?=?0.22; MSE?=?0.06, Predictive R2?=?0.22). Finally, microstructure of the right SLF and auxiliary white-matter is associated with the functional connectivity correlates of brooding, both within and between components of the triple-network (Discovery: adj. R2?=?0.21; Replication: adj. R2?=?0.18; MSE?=?0.03, Predictive R2?=?0.21-0.22). By cross-validating multimodal discovery with replication, the present findings help to reproducibly unify disparate perspectives of brooding etiology. Based on that synthesis, our study reformulates brooding as a microstructural-functional connectivity neurophenotype.
Project description:The human resting-state is characterized by spatially coherent brain activity at a low temporal frequency. The default mode network (DMN), one of so-called resting-state networks, has been associated with cognitive processes that are directed toward the self, such as introspection and autobiographic memory. The DMN's integrity appears to be crucial for mental health. For example, patients with Alzheimer's disease or other psychiatric conditions show disruptions of functional connectivity within the brain regions of the DMN. However, in prodromal or early stages of Alzheimer's disease, physiological alterations are sometimes elusive, despite manifested cognitive impairment. While functional connectivity assesses the signal correlation between brain areas, multi-scale entropy (MSE) measures the complexity of the blood-oxygen level dependent signal within an area and thus might show local changes before connectivity is affected. Hence, we investigated alterations of functional connectivity and MSE within the DMN in fifteen mild Alzheimer's disease patients as compared to fourteen controls. Potential associations of MSE with functional connectivity and cognitive abilities [i.e., mini-mental state examination (MMSE)] were assessed. A moderate decrease of DMN functional connectivity between posterior cingulate cortex and right hippocampus in Alzheimer's disease was found, whereas no differences were evident for whole-network functional connectivity. In contrast, the Alzheimer's disease group yielded lower global DMN-MSE than the control group. The most pronounced regional effects were localized in left and right hippocampi, and this was true for most scales. Moreover, MSE significantly correlated with functional connectivity, and DMN-MSE correlated positively with the MMSE in Alzheimer's disease. Most interestingly, the right hippocampal MSE was positively associated with semantic memory performance. Thus, our results suggested that cognitive decline in Alzheimer's disease is reflected by decreased signal complexity in DMN nodes, which might further lead to disrupted DMN functional connectivity. Additionally, altered entropy in Alzheimer's disease found in the majority of the scales indicated a disturbance of both local information processing and information transfer between distal areas. Conclusively, a loss of nodal signal complexity potentially impairs synchronization across nodes and thus preempts functional connectivity changes. MSE presents a putative functional marker for cognitive decline that might be more sensitive than functional connectivity alone.
Project description:This study identified structural and functional brain connectivity alterations in two independent samples of patients along the posterior cortical atrophy (PCA) disease course. Twenty-one PCA patients and 44 controls were recruited from two expert centres. Microstructural damage of white matter (WM) tracts was assessed using probabilistic tractography; resting state (RS) functional connectivity of brain networks was explored using a model free approach; grey matter (GM) atrophy was investigated using voxel-based morphometry. Compared with controls, common patterns of damage across PCA patients included: GM atrophy in the occipital-temporal-parietal regions; diffusion tensor (DT) MRI alterations of the corpus callosum and superior (SLF) and inferior longitudinal fasciculi (ILF) bilaterally; and decreased functional connectivity of the occipital gyri within the visual network and the precuneus and posterior cingulum within the default mode network (DMN). In PCA patients with longer disease duration and greater disease severity, WM damage extended to the cingulum and RS functional connectivity alterations spread within the frontal, dorsal attentive and salience networks. In PCA, reduced DMN functional connectivity was associated with SLF and ILF structural alterations. PCA patients showed distributed WM damage. Altered RS functional connectivity extends with disease worsening from occipital to temporo-parietal and frontostriatal regions, and this is likely to occur through WM connections. Future longitudinal studies are needed to establish trajectories of damage spreading in PCA and whether a combined DT MRI/RS functional MRI approach is promising in monitoring the disease progression.
Project description:Rumination, and particularly ruminative brooding, perpetuates dysphoric mood states and contributes to the emergence of depression. Studies of adults and older adolescents have characterized the association between rumination and intrinsic functional connectivity within default mode (DMN), salience (SN) and executive control (ECN) networks; we know little, however, about the brain network basis of rumination during early puberty, a sensitive period for network reorganization. 112 early puberty boys and girls completed resting-state scans, the Ruminative Response Scale, and the Youth Self-Report questionnaire. Using independent components analysis and dual regression, we quantified coherence for each individual in networks of interest (SN, ECN, DMN) and in non-relevant networks (motor, visual) in which we predicted no correlations with behavioral measures. Boys and girls did not differ in levels of rumination or internalizing symptoms, or in coherence for any network. The relation between SN network coherence and rumination; however, and specifically ruminative brooding, was moderated by sex: greater SN coherence was associated with higher levels of brooding in girls but not in boys. Further, in girls, brooding mediated the relation between SN coherence and internalizing symptoms. These results point to coherence within the SN as a potential neurodevelopmental marker of risk for depression in early pubertal girls.
Project description:Resting-state functional connectivity changes in the default mode network (DMN) of patients with major depressive disorder (MDD) have been linked to rumination. The DMN is divided into three subsystems: a midline Core, a dorsal medial prefrontal cortex (DMPFC) subsystem, and a medial temporal lobe (MTL) subsystem. We examined resting-state functional connectivity within and between DMN subsystems in MDD and its association with rumination. First, we conducted a meta-analysis on a large multi-site dataset of 618 MDD and 683 controls to quantify the differences in DMN subsystem functional connectivity between MDD and controls. Second, we tested the association of DMN subsystem functional connectivity and rumination in a sample of 115 unmedicated participants with symptoms of anxiety/depression and 48 controls. In our meta-analysis, only functional connectivity in the DMN Core was significantly reduced in MDD compared to controls (g = -0.246, CI = [-0.417; -0.074], pFDR = 0.048). Functional connectivity in the DMPFC subsystem and between the Core and DMPFC subsystems was slightly reduced but not significantly (g = -0.162, CI = [-0.310; -0.013], pFDR = 0.096; g = -0.249, CI = [-0.464; -0.034], pFDR = 0.084). Results were heterogeneous across sites for connectivity in the Core and between Core and DMPFC (I<sup>2</sup> = 0.348 and I<sup>2</sup> = 0.576 respectively). Prediction intervals consistently encompassed 0. In the independent sample we collected, functional connectivity within the DMN Core, DMPFC and between Core and DMPFC was not reduced in MDD compared to controls (all pFDR > 0.05). Trait rumination did not predict connectivity within and between DMN subsystems (all pFDR > 0.05). We conclude that MDD as a diagnostic category shows slightly reduced functional connectivity within the DMN Core, independent of illness duration, treatment, symptoms and trait rumination. However, this effect is small, highly variable and heterogeneous across samples, so that we could only detect it at the meta-analytic level, with a sample size of several hundreds. Our results indicate that reduced Core DMN connectivity has significant limitations as a potential clinical or prognostic marker for the diagnosis of MDD and might be more relevant to consider as a characteristic distinguishing a subgroup of individuals within this diagnostic category.
Project description:<h4>Purpose</h4>Resting state functional magnetic resonance imaging (rsfMRI) is an emerging tool to explore the functional connectivity of different brain regions. We aimed to assess the disruption of functional connectivity of the Default Mode Network (DMN), Dorsal Attention Network(DAN) and Fronto-Parietal Network (FPN) in patients with glial tumors.<h4>Methods</h4>rsfMRI data acquired on 3T-MR of treatment-naive glioma patients prospectively recruited (2015-2019) and matched controls from the 1000 functional-connectomes-project were analyzed using the CONN functional toolbox. Seed-Based Connectivity Analysis (SBCA) and Independent Component Analysis (ICA, with 10 to 100 components) were performed to study reliably the three networks of interest.<h4>Results</h4>35 patients with gliomas (17 WHO grade I-II, 18 grade III-IV) and 70 controls were included. Global increased DMN connectivity was consistently found with SBCA and ICA in patients compared to controls (Cluster1: Precuneus, height: p < 10<sup>-6</sup>; Cluster2: subcallosum; height: p < 10<sup>-5</sup>). However, an area of decreased connectivity was found in the posterior corpus callosum, particularly in high-grade gliomas (height: p < 10<sup>-5</sup>). The DAN demonstrated small areas of increased connectivity in frontal and occipital regions (height: p < 10<sup>-6</sup>). For the FPN, increased connectivity was noted in the precuneus, posterior cingulate gyrus, and frontal cortex. No difference in the connectivity of the networks of interest was demonstrated between low- and high-grade gliomas, as well as when stratified by their IDH1-R132H (isocitrate dehydrogenase) mutation status.<h4>Conclusion</h4>Altered functional connectivity is reliably found with SBCA and ICA in the DMN, DAN, and FPN in glioma patients, possibly explained by decreased connectivity between the cerebral hemispheres across the corpus callosum due to disruption of the connections.
Project description:<b>Purpose:</b> This study aimed to explore alterations in functional connectivity (FC) within and between default mode network (DMN), central executive network, and salience network in autism spectrum disorder (ASD) with co-occurring attention deficit hyperactivity disorder (ADHD). <b>Method:</b> A total of 135 individuals' date of the Autism Brain Imaging Data Exchange II was used to compare the ASD+ADHD group with the ASD group in relation to the abnormal within-network and between-network connectivity of the ASD group relative to the TD group; consequently, the correlation analysis between abnormal FC and behavior was performed. <b>Results:</b> The ASD+ADHD group exhibited decreased within-network connectivity in the precuneus of the ventral DMN compared with the ASD group. Among the three groups, the ASD+ADHD group showed lower connectivity, whereas the ASD group had higher connectivity than the TD group, although the effect of the separate <i>post hoc</i> test was not significant. Meanwhile, the ASD+ADHD group showed increased between-network connectivity between the ventral DMN and dorsal DMN and between the ventral DMN and left executive control network, compared with the ASD and TD groups. <b>Conclusion:</b> Dysfunction of DMN in the "triple-network model" is the core evidence for ASD with co-occurring ADHD.
Project description:The triple network model that consists of the default-mode network (DMN), central-executive network (CEN), and salience network (SN) has been suggested as a powerful paradigm for investigation of network mechanisms underlying various cognitive functions and brain disorders. A crucial hypothesis in this model is that the fronto-insular cortex (FIC) in the SN plays centrally in mediating interactions between the networks. Using a machine learning approach based on independent component analysis and Bayesian network (BN), this study characterizes the directed connectivity architecture of the triple network and examines the role of FIC in connectivity of the model. Data-driven exploration shows that the FIC initiates influential connections to all other regions to globally control the functional dynamics of the triple network. Moreover, stronger BN connectivity between the FIC and regions of the DMN and the CEN, as well as the increased outflow connections from the FIC are found to predict individual performance in memory and executive tasks. In addition, the posterior cingulate cortex in the DMN was also confirmed as an inflow hub that integrates information converging from other areas. Collectively, the results highlight the central role of FIC in mediating the activity of large-scale networks, which is crucial for individual cognitive function.
Project description:Deactivation of the default mode network (DMN) is one of the most reliable observations from neuroimaging and has significant implications in development, aging, and various neuropsychiatric disorders. However, the neural mechanism underlying DMN deactivation remains elusive. As the coordination of regional neurochemical substrates and interregional neural interactions are both essential in support of brain functions, a quantitative description of how they impact DMN deactivation may provide new insights into the mechanism. Using an n-back working memory task fMRI and magnetic resonance spectroscopy, we probed the pairwise relationship between task-induced deactivation, interregional functional connectivity and regional excitation-inhibition balance (evaluated by glutamate/GABA ratio) in the posterior cingulate cortex/precuneus (PCC/PCu). Task-induced PCC/PCu deactivation correlated with its excitation-inhibition balance and interregional functional connectivity, where participants with lower glutamate/GABA ratio, stronger intra-DMN connections and stronger antagonistic DMN-SN (salience network)/ECN (executive control network) inter-network connections had greater PCC/PCu deactivation. Mediation analyses revealed that the DMN-SN functional interactions partially mediated the relationship between task-induced deactivation and the excitation-inhibition balance at the PCC/PCu. The triple-relationship discovered in the present study has the potential to bridge DMN-deactivation related findings from various neuroimaging modalities and may provide new insights into the neural mechanism of DMN deactivation. Moreover, this finding may have significant implications for neuropsychiatric disorders related to the DMN dysfunction and suggests an integrated application of pharmacological and neuromodulation-based strategies for rescuing DMN deactivation deficits.
Project description:The aim of this study was to explore modifications of functional connectivity in multiple resting-state networks (RSNs) after moderate to severe traumatic brain injury (TBI) and evaluate the relationship between functional connectivity patterns and cognitive abnormalities. Forty-three moderate/severe TBI patients and 34 healthy controls (HC) underwent resting-state fMRI. Group ICA was applied to identify RSNs. Between-subject analysis was performed using dual regression. Multiple linear regressions were used to investigate the relationship between abnormal connectivity strength and neuropsychological outcome. Forty (93%) TBI patients showed moderate disability, while 2 (5%) and 1 (2%) upper severe disability and low good recovery, respectively. TBI patients performed worse than HC on the domains attention and language. We found increased connectivity in sensorimotor, visual, default mode (DMN), executive, and cerebellar RSNs after TBI. We demonstrated an effect of connectivity in the sensorimotor RSN on attention (p < 10<sup>-3</sup>) and a trend towards a significant effect of the DMN connectivity on attention (p = 0.058). A group-by-network interaction on attention was found in the sensorimotor network (p = 0.002). In TBI, attention was positively related to abnormal connectivity within the sensorimotor RSN, while in HC this relation was negative. Our results show altered patterns of functional connectivity after TBI. Attention impairments in TBI were associated with increased connectivity in the sensorimotor network. Further research is needed to test whether attention in TBI patients is directly affected by changes in functional connectivity in the sensorimotor network or whether the effect is actually driven by changes in the DMN.