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.
Objective
Temporal lobe epilepsy (TLE) is the most common drug‐resistant epilepsy in adults. Although it is commonly related to hippocampal pathology, increasing evidence suggests structural changes ...beyond the mesiotemporal lobe. Functional anomalies and their link to underlying structural alterations, however, remain incompletely understood.
Methods
We studied 30 drug‐resistant TLE patients and 57 healthy controls using multimodal magnetic resonance imaging (MRI) analyses. All patients had histologically verified hippocampal sclerosis and underwent postoperative imaging to outline the extent of their surgical resection. Our analysis leveraged a novel resting‐state functional MRI framework that parameterizes functional connectivity distance, consolidating topological and physical properties of macroscale brain networks. Functional findings were integrated with morphological and microstructural metrics, and utility for surgical outcome prediction was assessed using machine learning techniques.
Results
Compared to controls, TLE patients showed connectivity distance reductions in temporoinsular and prefrontal networks, indicating topological segregation of functional networks. Testing for morphological and microstructural associations, we observed that functional connectivity contractions occurred independently from TLE‐related cortical atrophy but were mediated by microstructural changes in the underlying white matter. Following our imaging study, all patients underwent an anterior temporal lobectomy as a treatment of their seizures, and postsurgical seizure outcome was determined at a follow‐up at least 1 year after surgery. Using a regularized supervised machine learning paradigm with fivefold cross‐validation, we demonstrated that patient‐specific functional anomalies predicted postsurgical seizure outcome with 76 ± 4% accuracy, outperforming classifiers operating on clinical and structural imaging features.
Significance
Our findings suggest connectivity distance contractions as a macroscale substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance toward epileptogenesis in affected networks and that may assist in patient‐specific surgical prognostication.
Abstract Increasing evidence from behavioral and neuroimaging studies suggests that mesial temporal lobe epilepsy (mTLE) is possibly associated with the default-mode brain function. However, the ...alteration of coherent neural activities in such a default-mode network (DMN) in mTLE has yet to be investigated. The present study analyzed the resting-state functional MRI data from two groups of mTLE patients with left and right hippocampal sclerosis using independent component analysis. In comparison with healthy controls, decreased functional connectivity in the dorsal mesial prefrontal cortex, mesial temporal lobe and inferior temporal cortex was observed in these two patient groups. Moreover, the right but not left mTLE patients showed bilaterally decreased functional connectivity in the mesial temporal lobe and increased functional connectivity in the posterior cingulate cortex. The decreased functional connectivity of the mesial temporal lobe was related to the epilepsy duration, suggesting that the posterior cingulate cortex may play a compensatory role for the altered DMN in the right mTLE. These findings indicate that the DMN is widely affected even if a single network node is impaired. An extensive regional overlap between the DMN and the previously described epileptic network suggests that the widespread functional impairments in mTLE may attribute to an aberrant DMN. The distinct patterns of the DMN between the left and right mTLE support a view that there are different pathological mechanisms underlying these two types of epilepsies.
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.
► Effective connectivity of resting-state fMRI. ► Small-world of multivariate Granger causality. ► Our finding suggest that the human brain directed influence network could have a prominent small-world topological property.
The accurate prediction of general neuropsychiatric disorders, on an individual basis, using resting-state functional magnetic resonance imaging (fMRI) is a challenging task of great clinical ...significance. Despite the progress to chart the differences between the healthy controls and patients at the group level, the pattern classification of functional brain networks across individuals is still less developed. In this paper we identify two novel neuroimaging measures that prove to be strongly predictive neuroimaging markers in pattern classification between healthy controls and general epileptic patients. These measures characterize two important aspects of the functional brain network in a quantitative manner: (i) coordinated operation among spatially distributed brain regions, and (ii) the asymmetry of bilaterally homologous brain regions, in terms of their global patterns of functional connectivity. This second measure offers a unique understanding of brain asymmetry at the network level, and, to the best of our knowledge, has not been previously used in pattern classification of functional brain networks. Using modern pattern-recognition approaches like sparse regression and support vector machine, we have achieved a cross-validated classification accuracy of 83.9% (specificity: 82.5%; sensitivity: 85%) across individuals from a large dataset consisting of 180 healthy controls and epileptic patients. We identified significantly changed functional pathways and subnetworks in epileptic patients that underlie the pathophysiological mechanism of the impaired cognitive functions. Specifically, we find that the asymmetry of brain operation for epileptic patients is markedly enhanced in temporal lobe and limbic system, in comparison with healthy individuals. The present study indicates that with specifically designed informative neuroimaging markers, resting-state fMRI can serve as a most promising tool for clinical diagnosis, and also shed light onto the physiology behind complex neuropsychiatric disorders. The systematic approaches we present here are expected to have wider applications in general neuropsychiatric disorders.
A functional discrepancy exists in adolescents between frontal and subcortical regions due to differential regional maturational trajectories. It remains unknown how this functional discrepancy ...alters and whether the influence from the subcortical to the frontal system plays a primacy role in medication naïve adolescent with major depressive disorder (MDD).
Eighteen MDD and 18 healthy adolescents were enrolled. Depression and anxiety severity was assessed by the Short Mood and Feeling Questionnaire (SMFQ) and Screen for Child Anxiety Related Emotional Disorders (SCARED) respectively. The functional discrepancy was measured by the amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signal. Correlation analysis was carried out between ALFF values and SMFQ and SCARED scores. Resting brain activity levels measured by ALFF was higher in the frontal cortex than that in the subcortical system involving mainly (para) limbic-striatal regions in both HC and MDD adolescents. The difference of ALFF values between frontal and subcortical systems was increased in MDD adolescents as compared with the controls.
The present study identified an increased imbalance of resting-state brain activity between the frontal cognitive control system and the (para) limbic-striatal emotional processing system in MDD adolescents. The findings may provide insights into the neural correlates of adolescent MDD.
Neuroimaging evidence suggested that the thalamic nuclei may play different roles in the progress of idiopathic generalized epilepsy (IGE). This study aimed to demonstrate the alterations in ...morphometry and functional connectivity in the thalamic nuclei in IGE.
Fifty-two patients with IGE characterized by generalized tonic-clonic seizures and 67 healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted MRI data were acquired for voxel-based morphometry (VBM) analysis, and resting-state blood-oxygenation level functional MRI data were acquired for functional connectivity analysis. The thalamic nuclei of bilateral medial dorsal nucleus (MDN) and pulvinar, as detected with decreased gray matter volumes in patients with IGE through VBM analysis, were selected as seed regions for functional connectivity analysis.
Different alteration patterns were found in functional connectivity of the thalamic nuclei with decreased gray matter volumes in IGE. Seeding at the MDN, decreased connectivity in the bilateral orbital frontal cortex, caudate nucleus, putamen and amygdala were found in the patients (P<0.05 with correction). However, seeding at the pulvinar, no significant alteration of functional connectivity was found in the patients (P<0.05 with correction).
Some specific impairment of thalamic nuclei in IGE was identified using morphological and functional connectivity MRI approaches. These findings may strongly support the different involvement of the thalamocortical networks in IGE.
Abstract Recent functional magnetic resonance imaging (fMRI) studies have demonstrated that the resting state networks (RSNs) are impaired in various neuropsychiatric disorders. However, little is ...known about the changes in the functional architecture of the RSNs in idiopathic generalized epilepsy patients with generalized tonic–clonic seizures (GTCS). Resting state fMRI data were acquired from 16 GTCS patients and 16 healthy subjects. The data were acquired during interictal without combined EEG confirmation. Functional connectivity among the RSNs was examined using individual-based independent component analysis. Six RSNs were identified in both the GTCS and control groups. Compared with the healthy subjects, decreased functional connectivity in the self-referential, somatosensory, visual, and auditory networks, and both the decreased and increased functional connectivities in the classic default-mode and dorsal attention networks were found in the GTCS patients. Furthermore, the present study revealed a negative correlation between the seizure duration and functional connectivity changes in the medial prefrontal cortex in the GTCS patients. These results indicate that there are impairments in the RSNs and possible reorganization of the default-mode network and dorsal attention network in patients with GTCS. Our findings may also suggest that the medial prefrontal cortex and its associated network play a role in the development of GTCS.
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