Jurong Ding

Altered Functional Connectivity and Small-World in Mesial Temporal Lobe Epilepsy

Background The functional architecture of the human brain has been extensively described in terms of functional connectivity networks, detected from the low–frequency coherent neuronal fluctuations that can be observed in a resting state condition. Little is known, so far, about the changes in functional connectivity and in the topological properties of functional networks, associated with different brain diseases. Methodology/Principal Findings In this study, we investigated alterations related to mesial temporal lobe epilepsy (mTLE), using resting state functional magnetic resonance imaging on 18 mTLE patients and 27 healthy controls. Functional connectivity among 90 cortical and subcortical regions was measured by temporal correlation. The related values were analyzed to construct a set of undirected graphs. Compared to controls, mTLE patients showed significantly increased connectivity within the medial temporal lobes, but also significantly decreased connectivity within the frontal and parietal lobes, and between frontal and parietal lobes. Our findings demonstrated that a large number of areas in the default-mode network of mTLE patients showed a significantly decreased number of connections to other regions. Furthermore, we observed altered small-world properties in patients, along with smaller degree of connectivity, increased n-to-1 connectivity, smaller absolute clustering coefficients and shorter absolute path length. Conclusions/Significance We suggest that the mTLE alterations observed in functional connectivity and topological properties may be used to define tentative disease markers.

Altered functional–structural coupling of large-scale brain networks in idiopathic generalized epilepsy

The human brain is a large-scale integrated network in the functional and structural domain. Graph theoretical analysis provides a novel framework for analysing such complex networks. While previous neuroimaging studies have uncovered abnormalities in several specific brain networks in patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures, little is known about changes in whole-brain functional and structural connectivity networks. Regarding functional and structural connectivity, networks are intimately related and share common small-world topological features. We predict that patients with idiopathic generalized epilepsy would exhibit a decoupling between functional and structural networks. In this study, 26 patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures and 26 age- and sex-matched healthy controls were recruited. Resting-state functional magnetic resonance imaging signal correlations and diffusion tensor image tractography were used to generate functional and structural connectivity networks. Graph theoretical analysis revealed that the patients lost optimal topological organization in both functional and structural connectivity networks. Moreover, the patients showed significant increases in nodal topological characteristics in several cortical and subcortical regions, including mesial frontal cortex, putamen, thalamus and amygdala relative to controls, supporting the hypothesis that regions playing important roles in the pathogenesis of epilepsy may display abnormal hub properties in network analysis. Relative to controls, patients showed further decreases in nodal topological characteristics in areas of the default mode network, such as the posterior cingulate gyrus and inferior temporal gyrus. Most importantly, the degree of coupling between functional and structural connectivity networks was decreased, and exhibited a negative correlation with epilepsy duration in patients. Our findings suggest that the decoupling of functional and structural connectivity may reflect the progress of long-term impairment in idiopathic generalized epilepsy, and may be used as a potential biomarker to detect subtle brain abnormalities in epilepsy. Overall, our results demonstrate for the first time that idiopathic generalized epilepsy is reflected in a disrupted topological organization in large-scale brain functional and structural networks, thus providing valuable information for better understanding the pathophysiological mechanisms of generalized tonic-clonic seizures.

Selective aberrant functional connectivity of resting state networks in social anxiety disorder.

Several functional MRI (fMRI) activation studies have highlighted specific differences in brain response in social anxiety disorder (SAD) patients. Little is known, so far, about the changes in the functional architecture of resting state networks (RSNs) in SAD during resting state. We investigated statistical differences in RSNs on 20 SAD and 20 controls using independent component analysis. A diffuse impact on widely distributed RSNs and selective changes of RSN intrinsic functional connectivity were observed in SAD. Functional connectivity was decreased in the somato-motor (primary and motor cortices) and visual (primary visual cortex) networks, increased in a network including medial prefrontal cortex which is thought to be involved in self-referential processes, and increased or decreased in the default mode network (posterior cingulate cortex/precuneus, bilateral inferior parietal gyrus, angular gyrus, middle temporal gyrus, and superior and medial frontal gyrus) which has been suggested to be involved in episodic memory, and self-projection, the dorsal attention network (middle and superior occipital gyrus, inferior and superior parietal gyrus, and middle and superior frontal gyrus) which is thought to mediate goal-directed top-down processing, the core network (insula-cingulate cortices) which is associated with task control function, and the central-executive network (fronto-parietal cortices). A relationship between functional connectivity and disease severity was found in specific regions of RSNs, including medial and lateral prefrontal cortex, as well as parietal and occipital regions. Our results might supply a novel way to look into neuro-pathophysiological mechanisms in SAD patients.

Default mode network abnormalities in mesial temporal lobe epilepsy: a study combining fMRI and DTI.

Studies of in mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS) have reported reductions in both functional and structural connectivity between hippocampal structures and adjacent brain regions. However, little is known about the connectivity among the default mode network (DMN) in mTLE. Here, we hypothesized that both functional and structural connectivity within the DMN were disturbed in mTLE. To test this hypothesis, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were applied to examine the DMN connectivity of 20 mTLE patients, and 20 gender‐ and age‐matched healthy controls. Combining these two techniques, we explored the changes in functional (temporal correlation coefficient derived from fMRI) and structural (path length and connection density derived from DTI tractography) connectivity of the DMN. Compared to the controls, we found that both functional and structural connectivity were significantly decreased between the posterior cingulate cortex (PCC)/precuneus (PCUN) and bilateral mesial temporal lobes (mTLs) in patients. No significant between‐group difference was found between the PCC/PCUN and medial prefrontal cortex (mPFC). In addition, functional connectivity was found to be correlated with structural connectivity in two pairwise regions, namely between the PCC/PCUN and bilateral mTLs, respectively. Our results suggest that the decreased functional connectivity within the DMN in mTLE may be a consequence of the decreased connection density underpinning the degeneration of structural connectivity. Hum Brain Mapp, 2011.

Evaluating the effective connectivity of resting state networks using conditional Granger causality

The human brain has been documented to be spatially organized in a finite set of specific coherent patterns, namely resting state networks (RSNs). The interactions among RSNs, being potentially dynamic and directional, may not be adequately captured by simple correlation or anticorrelation. In order to evaluate the possible effective connectivity within those RSNs, we applied a conditional Granger causality analysis (CGCA) to the RSNs retrieved by independent component analysis (ICA) from resting state functional magnetic resonance imaging (fMRI) data. Our analysis provided evidence for specific causal influences among the detected RSNs: default-mode, dorsal attention, core, central-executive, self-referential, somatosensory, visual, and auditory networks. In particular, we identified that self-referential and default-mode networks (DMNs) play distinct and crucial roles in the human brain functional architecture. Specifically, the former RSN exerted the strongest causal influence over the other RSNs, revealing a top-down modulation of self-referential mental activity (SRN) over sensory and cognitive processing. In quite contrast, the latter RSN was profoundly affected by the other RSNs, which may underlie an integration of information from primary function and higher level cognition networks, consistent with previous task-related studies. Overall, our results revealed the causal influences among these RSNs at different processing levels, and supplied information for a deeper understanding of the brain network dynamics.

Altered Effective Connectivity Network of the Amygdala in Social Anxiety Disorder: A Resting-State fMRI Study

The amygdala is often found to be abnormally recruited in social anxiety disorder (SAD) patients. The question whether amygdala activation is primarily abnormal and affects other brain systems or whether it responds “normally” to an abnormal pattern of information conveyed by other brain structures remained unanswered. To address this question, we investigated a network of effective connectivity associated with the amygdala using Granger causality analysis on resting-state functional MRI data of 22 SAD patients and 21 healthy controls (HC). Implications of abnormal effective connectivity and clinical severity were investigated using the Liebowitz Social Anxiety Scale (LSAS). Decreased influence from inferior temporal gyrus (ITG) to amygdala was found in SAD, while bidirectional influences between amygdala and visual cortices were increased compared to HCs. Clinical relevance of decreased effective connectivity from ITG to amygdala was suggested by a negative correlation of LSAS avoidance scores and the value of Granger causality. Our study is the first to reveal a network of abnormal effective connectivity of core structures in SAD. This is in support of a disregulation in predescribed modules involved in affect control. The amygdala is placed in a central position of dysfunction characterized both by decreased regulatory influence of orbitofrontal cortex and increased crosstalk with visual cortex. The model which is proposed based on our results lends neurobiological support towards cognitive models considering disinhibition and an attentional bias towards negative stimuli as a core feature of the disorder.

Small-world directed networks in the human brain: Multivariate Granger causality analysis of resting-state fMRI

Small-world organization is known to be a robust and consistent network architecture, and is a hallmark of the structurally and functionally connected human brain. However, it remains unknown if the same organization is present in directed influence brain networks whose connectivity is inferred by the transfer of information from one node to another. Here, we aimed to reveal the network architecture of the directed influence brain network using multivariate Granger causality analysis and graph theory on resting-state fMRI recordings. We found that some regions acted as pivotal hubs, either being influenced by or influencing other regions, and thus could be considered as information convergence regions. In addition, we observed that an exponentially truncated power law fits the topological distribution for the degree of total incoming and outgoing connectivity. Furthermore, we also found that this directed network has a modular structure. More importantly, according to our data, we suggest that the human brain directed influence network could have a prominent small-world topological property.

Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder ☆

In social anxiety disorder (SAD), impairments in limbic/paralimbic structures are associated with emotional dysregulation and inhibition of the medial prefrontal cortex (MPFC). Little is known, however, about alterations in limbic and frontal regions associated with the integrated morphometric, functional, and structural architecture of SAD. Whether altered gray matter volume is associated with altered functional and structural connectivity in SAD. Three techniques were used with 18 SAD patients and 18 healthy controls: voxel-based morphometry; resting-state functional connectivity analysis; and diffusion tensor imaging tractography. SAD patients exhibited significantly decreased gray matter volumes in the right posterior inferior temporal gyrus (ITG) and right parahippocampal/hippocampal gyrus (PHG/HIP). Gray matter volumes in these two regions negatively correlated with the fear factor of the Liebowitz Social Anxiety Scale. In addition, we found increased functional connectivity in SAD patients between the right posterior ITG and the left inferior occipital gyrus, and between the right PHF/HIP and left middle temporal gyrus. SAD patients had increased right MPFC volume, along with enhanced structural connectivity in the genu of the corpus callosum. Reduced limbic/paralimbic volume, together with increased resting-state functional connectivity, suggests the existence of a compensatory mechanism in SAD. Increased MPFC volume, consonant with enhanced structural connectivity, suggests a long-time overgeneralization of structural connectivity and a role of this area in the mediation of clinical severity. Overall, our results may provide a valuable basis for future studies combining morphometric, functional and anatomical data in the search for a comprehensive understanding of the neural circuitry underlying SAD.

Resting-State Functional Connectivity Bias of Middle Temporal Gyrus and Caudate with Altered Gray Matter Volume in Major Depression

Magnetic resonance imaging (MRI) studies have indicated that the structure deficits and resting-state functional connectivity (FC) imbalances in cortico-limbic circuitry might underline the pathophysiology of MDD. Using structure and functional MRI, our aim is to investigate gray matter abnormalities in patients with treatment-resistant depression (TRD) and treatment-responsive depression (TSD), and test whether the altered gray matter is associated with altered FC. Voxel-based morphometry was used to investigate the regions with gray matter abnormality and FC analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain. Using one-way analysis of variance, we found significant gray matter abnormalities in the right middle temporal cortex (MTG) and bilateral caudate among the TRD, TSD and healthy controls. For the FC of the right MTG, we found that both the patients with TRD and TSD showed altered connectivity mainly in the default-mode network (DMN). For the FC of the right caudate, both patient groups showed altered connectivity in the frontal regions. Our results revealed the gray matter reduction of right MTG and bilateral caudate, and disrupted functional connection to widely distributed circuitry in DMN and frontal regions, respectively. These results suggest that the abnormal DMN and reward circuit activity might be biomarkers of depression trait.

Regional homogeneity changes in social anxiety disorder: A resting-state fMRI study

The previous task-based or resting perfusion studies in social anxiety disorder (SAD) patients have highlighted specific differences in brain response. Little is known about the changes in the local synchronization of spontaneous functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signals that occur in SAD during the resting state. We investigated altered neural activity in the resting state using a regional homogeneity (ReHo) analysis on 20 SAD and 20 healthy controls (HC). Compared with HC, SAD patients exhibited decreased coherence (ReHo) in the bilateral angular gyrus and the left medial prefrontal cortex within the default mode network (DMN), suggesting functional impairment of the perception of socially relevant emotional state and self-related mental representations; and also in the right dorsolateral prefrontal cortex and right inferior parietal gyrus within the central-executive network (CEN), reflecting the deficit of cognitive control of social anxiety. Significantly increased coherence (ReHo) was found in the left middle occipital gyrus, which would be consistent with their hypervigilance and hyperprosexia to the social communication even in the resting state. Our results might supply a novel way to look into neuro-pathophysiological mechanisms in SAD patients.