Simultaneous EEG-fMRI Investigation of Rhythm-Dependent Thalamo-Cortical Circuits Alteration in Schizophrenia.

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls ([Formula: see text]). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater ([Formula: see text]), and the degree of coupling was negatively correlated with the duration of disease ([Formula: see text], [Formula: see text]). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia.

Brain activation and connection across resting and motor-task states in patients with generalized tonic-clonic seizures.

AIMS: Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. METHODS: Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups. RESULTS: All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients. CONCLUSION: Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.

Striatum- and Cerebellum-Modulated Epileptic Networks Varying Across States with and without Interictal Epileptic Discharges.

Idiopathic generalized epilepsy (IGE) is characterized by cryptogenic etiology and the striatum and cerebellum are recognized as modulators of epileptic network. We collected simultaneous electroencephalogram and functional magnetic resonance imaging data from 145 patients with IGE, 34 of whom recorded interictal epileptic discharges (IEDs) during scanning. In states without IEDs, hierarchical connectivity was performed to search core cortical regions which might be potentially modulated by striatum and cerebellum. Node-node and edge-edge moderation models were constructed to depict direct and indirect moderation effects in states with and without IEDs. Patients showed increased hierarchical connectivity with sensorimotor cortices (SMC) and decreased connectivity with regions in the default mode network (DMN). In the state without IEDs, striatum, cerebellum, and thalamus were linked to weaken the interactions of regions in the salience network (SN) with DMN and SMC. In periods with IEDs, overall increased moderation effects on the interaction between regions in SN and DMN, and between regions in DMN and SMC were observed. The thalamus and striatum were implicated in weakening interactions between regions in SN and SMC. The striatum and cerebellum moderated the cortical interaction among DMN, SN, and SMC in alliance with the thalamus, contributing to the dysfunction in states with and without IEDs in IGE. The current work revealed state-specific modulation effects of striatum and cerebellum on thalamocortical circuits and uncovered the potential core cortical targets which might contribute to develop new clinical neuromodulation techniques.

The role of the primary sensorimotor system in generalized epilepsy: Evidence from the cerebello-cerebral functional integration.

The interaction between cerebellum and cerebrum participates widely in function from motor processing to high-level cognitive and affective processing. Because of the motor symptom, idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizure have been recognized to associate with motor abnormalities, but the functional interaction in the cerebello-cerebral circuit is still poorly understood. Resting-state functional magnetic resonance imaging data were collected for 101 IGE patients and 106 healthy controls. The voxel-based functional connectivity (FC) between cerebral cortex and the cerebellum was contacted. The functional gradient and independent components analysis were applied to evaluate cerebello-cerebral functional integration on the voxel-based FC. Cerebellar motor components were further linked to cerebellar gradient. Results revealed cerebellar motor functional modules were closely related to cerebral motor components. The altered mapping of cerebral motor components to cerebellum was observed in motor module in patients with IGE. In addition, patients also showed compression in cerebello-cerebral functional gradient between motor and cognition modules. Interestingly, the contribution of the motor components to the gradient was unbalanced between bilateral primary sensorimotor components in patients: the increase was observed in cerebellar cognitive module for the dominant hemisphere primary sensorimotor, but the decrease was found in the cerebellar cognitive module for the nondominant hemisphere primary sensorimotor. The present findings suggest that the cerebral primary motor system affects the hierarchical architecture of cerebellum, and substantially contributes to the functional integration evidence to understand the motor functional abnormality in IGE patients.

Functional and structural networks decoupling in generalized tonic-clonic seizures and its reorganization by drugs.

OBJECTIVE: To investigate potential functional and structural large-scale network disturbances in untreated patients with generalized tonic-clonic seizures (GTCS) and the effects of antiseizure drugs. METHODS: In this study, 41 patients with GTCS, comprising 21 untreated patients and 20 patients who received antiseizure medications (ASMs), and 29 healthy controls were recruited to construct large-scale brain networks based on resting-state functional magnetic resonance imaging and diffusion tensor imaging. Structural and functional connectivity and network-level weighted correlation probability (NWCP) were further investigated to identify network features that corresponded to response to ASMs. RESULTS: Untreated patients showed more extensive enhancement of functional and structural connections than controls. Specifically, we observed abnormally enhanced connections between the default mode network (DMN) and the frontal-parietal network. In addition, treated patients showed similar functional connection strength to that of the control group. However, all patients exhibited similar structural network alterations. Moreover, the NWCP value was lower for connections within the DMN and between the DMN and other networks in the untreated patients; receiving ASMs could reverse this pattern. SIGNIFICANCE: Our study identified alterations in structural and functional connectivity in patients with GTCS. The influence of ASMs may be more noticeable within the functional network; moreover, abnormalities in both the functional and structural coupling state may be improved by ASM treatment. Therefore, the coupling state of structural and functional connectivity may be used as an indicator of the efficacy of ASMs.

Vascular feature as a modulator of the aging brain.

The cerebral functional reorganization and declined cognitive function of aging might associate with altered vascular features. Here, we explored the altered cerebral hierarchical functional network of 2 conditions (task-free and naturalistic stimuli) in older adults and its relationship with vascular features (systemic microvascular and perfusion features, measured by magnetic resonance imaging) and behavior. Using cerebral gradient analysis, we found that compressive gradient of resting-state mainly located on the primary sensory-motor system and transmodal regions in aging, and further compress in these regions under the continuous naturalistic stimuli. Combining cerebral functional gradient, vascular features, and cognitive performance, the more compressive gradient in the resting-state, the worse vascular state, the lower cognitive function in older adults. Further modulation analysis demonstrated that both vascular features can regulate the relationship between gradient scores in the insula and behavior. Interestingly, systemic microvascular oxygenation also can modulate the relationship between cerebral gradient and cerebral perfusion. Furthermore, the less alteration of the compressive gradient with naturalistic stimuli came with lower cognitive function. Our findings demonstrated that the altered cerebral hierarchical functional structure in aging was linked with changed vascular features and behavior, offering a new framework for studying the physiological mechanism of functional connectivity in aging.

Distinct effects of the basal ganglia and cerebellum on the thalamocortical pathway in idiopathic generalized epilepsy.

The aberrant thalamocortical pathways of epilepsy have been detected recently, while its underlying effects on epilepsy are still not well understood. Exploring pathoglytic changes in two important thalamocortical pathways, that is, the basal ganglia (BG)-thalamocortical and the cerebellum-thalamocortical pathways, in people with idiopathic generalized epilepsy (IGE), could deepen our understanding on the pathological mechanism of this disease. These two pathways were reconstructed and investigated in this study by combining diffusion and functional MRI. Both pathways showed connectivity changes with the perception and cognition systems in patients. Consistent functional connectivity (FC) changes were observed mainly in perception regions, revealing the aberrant integration of sensorimotor and visual information in IGE. The pathway-specific FC alterations in high-order regions give neuroimaging evidence of the neural mechanisms of cognitive impairment and epileptic activities in IGE. Abnormal functional and structural integration of cerebellum, basal ganglia and thalamus could result in an imbalance of inhibition and excitability in brain systems of IGE. This study located the regulated cortical regions of BG and cerebellum which been affected in IGE, established possible links between the neuroimaging findings and epileptic symptoms, and enriched the understanding of the regulatory effects of BG and cerebellum on epilepsy.

Connective profiles and antagonism between dynamic and static connectivity underlying generalized epilepsy.

This study aims to characterize the connective profiles and the coupling relationship between dynamic and static functional connectivity (dFC and sFC) in large-scale brain networks in patients with generalized epilepsy (GE). Functional, structural and diffuse MRI data were collected from 83 patients with GE and 106 matched healthy controls (HC). Resting-state BOLD time course was deconvolved to neural time course using a blind hemodynamic deconvolution method. Then, five connective profiles, including the structural connectivity (SC) and BOLD/neural time course-derived sFC/dFC networks, were constructed based on the proposed whole brain atlas. Network-level weighted correlation probability (NWCP) were proposed to evaluate the association between dFC and sFC. Both the BOLD signal and neural time course showed highly concordant findings and the present study emphasized the consistent findings between two functional approaches. The patients with GE showed hypervariability and enhancement of FC, and notably decreased SC in the subcortical network. Besides, increased dFC, weaker anatomic links, and complex alterations of sFC were observed in the default mode network of GE. Moreover, significantly increased SC and predominantly increased sFC were found in the frontoparietal network. Remarkably, antagonism between dFC and sFC was observed in large-scale networks in HC, while patients with GE showed significantly decreased antagonism in core epileptic networks. In sum, our study revealed distinct connective profiles in different epileptic networks and provided new clues to the brain network mechanism of epilepsy from the perspective of antagonism between dynamic and static functional connectivity.

Dynamic Temporospatial Patterns of Functional Connectivity and Alterations in Idiopathic Generalized Epilepsy.

The dynamic profile of brain function has received much attention in recent years and is also a focus in the study of epilepsy. The present study aims to integrate the dynamics of temporal and spatial characteristics to provide comprehensive and novel understanding of epileptic dynamics. Resting state fMRI data were collected from eighty-three patients with idiopathic generalized epilepsy (IGE) and 87 healthy controls (HC). Specifically, we explored the temporal and spatial variation of functional connectivity density (tvFCD and svFCD) in the whole brain. Using a sliding-window approach, for a given region, the standard variation of the FCD series was calculated as the tvFCD and the variation of voxel-wise spatial distribution was calculated as the svFCD. We found primary, high-level, and sub-cortical networks demonstrated distinct tvFCD and svFCD patterns in HC. In general, the high-level networks showed the highest variation, the subcortical and primary networks showed moderate variation, and the limbic system showed the lowest variation. Relative to HC, the patients with IGE showed weaken temporal and enhanced spatial variation in the default mode network and weaken temporospatial variation in the subcortical network. Besides, enhanced temporospatial variation in sensorimotor and high-level networks was also observed in patients. The hyper-synchronization of specific brain networks was inferred to be associated with the phenomenon responsible for the intrinsic propensity of generation and propagation of epileptic activities. The disrupted dynamic characteristics of sensorimotor and high-level networks might potentially contribute to the driven motion and cognition phenotypes in patients. In all, presently provided evidence from the temporospatial variation of functional interaction shed light on the dynamics underlying neuropathological profiles of epilepsy.

Altered Static and Dynamic Spontaneous Neural Activity in Drug-Naïve and Drug-Receiving Benign Childhood Epilepsy With Centrotemporal Spikes.

The present study aims to investigate intrinsic abnormalities of brain and the effect of antiepileptic treatment on brain activity in Benign childhood epilepsy with centrotemporal spikes (BECTS). Twenty-six drug-naïve patients (DNP) and 22 drug-receiving patients (DRP) with BECTS were collected in this study. Static amplitude of low frequency fluctuation (sALFF) and dynamic ALFF (dALFF) were applied to resting-state fMRI data. Functional connectivity (FC) analysis was further performed for affected regions identified by static and dynamic analysis. One-way analysis of variance and post hoc statistical analyses were performed for between-group differences. Abnormal sALFF and dALFF values were correlated with clinical features of patients. Compared with healthy controls (HC), DNP group demonstrated alterations of sALFF and/or dALFF in medial prefrontal cortex (MPFC), supplementary motor areas (SMA), cerebellum, hippocampus, pallidum and cingulate cortex, in which the values were close to normal in DRP. Notably, sALFF and dALFF showed specific sensitivity in detecting abnormalities in basal ganglia and cerebellum. Additionally, DRP showed additional changes in precuneus, inferior temporal gyrus, superior frontal gyrus and occipital visual cortex. Compared with HC, the DNP showed increased FC in default network and motion-related networks, and the DRP showed decreased FC in default network. The MPFC, hippocampus, SMA, basal ganglia and cerebellum are indicated to be intrinsically affected regions and effective therapeutic targets. And the FC profiles of default and motion-related networks might be potential core indicators for clinical treatment. This study revealed potential neuromodulatory targets and helped understand pathomechanism of BECTS. Static and dynamic analyses should be combined to investigate neuropsychiatric disorders.

Reconfiguration of dynamic large-scale brain network functional connectivity in generalized tonic-clonic seizures.

An increasing number of studies in patients with generalized tonic-clonic seizures (GTCS) have reported the alteration of functional connectivity (FC) in many brain networks. However, little is known about the underlying temporal variability of FC in large-scale brain functional networks in patients. Recently, dynamic FC could provide novel insight into the physiological mechanisms in the brain. Here, we recruited 63 GTCS and 65 age- and sex-matched healthy controls. Dynamic FC approaches were used to evaluate alterations in the temporal variability of FC in patients at the region- and network-levels. In addition, two kinds of brain templates (>102 and > 103 regions) and two kinds of temporal variability FC approaches were adopted to verify the stability of the results. Patients showed increased FC variability in regions of the default mode network (DMN), ventral attention network (VAN) and motor-related areas. The DAN, VAN, and DMN illustrated enhanced FC variability at the within-network level. In addition, increased FC variabilities between networks were found between the DMN and cognition-related networks, including the VAN, dorsal attention network and frontal-parietal network in GTCS. Meanwhile, the alterations in FC variability were relatively consistent across different methods and templates. Therefore, the consistent alteration of FC variability would reflect a dynamic restructuring of the large-scale brain networks in patients with GTCS. Overly frequent information communication among cognition-related networks, especially in the DMN, might play a role in the epileptic activity and/or cognitive dysfunction in patients.