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.

Spatiotemporal dynamics of functional connectivity and association with molecular architecture in schizophrenia.

Schizophrenia is a self-disorder characterized by disrupted brain dynamics and architectures of multiple molecules. This study aims to explore spatiotemporal dynamics and its association with psychiatric symptoms. Resting-state functional magnetic resonance imaging data were collected from 98 patients with schizophrenia. Brain dynamics included the temporal and spatial variations in functional connectivity density and association with symptom scores were evaluated. Moreover, the spatial association between dynamics and receptors/transporters according to prior molecular imaging in healthy subjects was examined. Patients demonstrated decreased temporal variation and increased spatial variation in perceptual and attentional systems. However, increased temporal variation and decreased spatial variation were revealed in higher order networks and subcortical networks in patients. Specifically, spatial variation in perceptual and attentional systems was associated with symptom severity. Moreover, case-control differences were associated with dopamine, serotonin and mu-opioid receptor densities, serotonin reuptake transporter density, dopamine transporter density, and dopamine synthesis capacity. Therefore, this study implicates the abnormal dynamic interactions between the perceptual system and cortical core networks; in addition, the subcortical regions play a role in the dynamic interaction among the cortical regions in schizophrenia. These convergent findings support the importance of brain dynamics and emphasize the contribution of primary information processing to the pathological mechanism underlying schizophrenia.

In vivo characterization of magnetic resonance imaging-based T1w/T2w ratios reveals myelin-related changes in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in adults. Although brain myelination alterations have been observed in TLE, it remains unclear how the myelination network changes in TLE. This study developed a novel method in characterization of myelination structural covariance network (mSCN) by T1-weighted and T2-weighted magnetic resonance imaging (MRI). The mSCNs were estimated in 42 left TLE (LTLE), 42 right TLE (RTLE) patients, and 41 healthy controls (HCs). The topology of mSCN was analyzed by graph theory. Voxel-wise comparisons of myelination laterality were also examined among the three groups. Compared to HC, both patient groups showed decreased myelination in frontotemporal regions, amygdala, and thalamus; however, the LTLE showed lower myelination in left medial temporal regions than RTLE. Moreover, the LTLE exhibited decreased global efficiency compared with HC and more increased connections than RTLE. The laterality in putamen was differently altered between the two patient groups: higher laterality at posterior putamen in LTLE and higher laterality at anterior putamen in RTLE. The putamen may play a transfer station role in damage spreading induced by epileptic seizures from the hippocampus. This study provided a novel workflow by combination of T1-weighted and T2-weighted MRI to investigate in vivo the myelin-related microstructural feature in epileptic patients first time. Disconnections of mSCN implicate that TLE is a system disorder with widespread disruptions at regional and network levels.

Progressive trajectories of schizophrenia across symptoms, genes, and the brain.

BACKGROUND: Schizophrenia is characterized by complex psychiatric symptoms and unclear pathological mechanisms. Most previous studies have focused on the morphological changes that occur over the development of the disease; however, the corresponding functional trajectories remain unclear. In the present study, we aimed to explore the progressive trajectories of patterns of dysfunction after diagnosis. METHODS: Eighty-six patients with schizophrenia and 120 healthy controls were recruited as the discovery dataset. Based on multiple functional indicators of resting-state brain functional magnetic resonance imaging, we conducted a duration-sliding dynamic analysis framework to investigate trajectories in association with disease progression. Neuroimaging findings were associated with clinical symptoms and gene expression data from the Allen Human Brain Atlas database. A replication cohort of patients with schizophrenia from the University of California, Los Angeles, was used as the replication dataset for the validation analysis. RESULTS: Five stage-specific phenotypes were identified. A symptom trajectory was characterized by positive-dominated, negative ascendant, negative-dominated, positive ascendant, and negative surpassed stages. Dysfunctional trajectories from primary and subcortical regions to higher-order cortices were recognized; these are associated with abnormal external sensory gating and a disrupted internal excitation-inhibition equilibrium. From stage 1 to stage 5, the importance of neuroimaging features associated with behaviors gradually shifted from primary to higher-order cortices and subcortical regions. Genetic enrichment analysis identified that neurodevelopmental and neurodegenerative factors may be relevant as schizophrenia progresses and highlighted multiple synaptic systems. CONCLUSIONS: Our convergent results indicate that progressive symptoms and functional neuroimaging phenotypes are associated with genetic factors in schizophrenia. Furthermore, the identification of functional trajectories complements previous findings of structural abnormalities and provides potential targets for drug and non-drug interventions in different stages of schizophrenia.

Unbalance between working memory task-activation and task-deactivation networks in epilepsy: Simultaneous EEG-fMRI study.

Working memory (WM) is a cognitive function involving emergent properties of theta oscillations and large-scale network interactions. The synchronization of WM task-related networks in the brain enhanced WM performance. However, how these networks regulate WM processing is not well known, and the alteration of the interaction among these networks may play an important role in patients with cognitive dysfunction. In this study, we used simultaneous EEG-fMRI to examine the features of theta oscillations and the functional interactions among activation/deactivation networks during the n-back WM task in patients with idiopathic generalized epilepsy (IGE). The results showed that there was more enhancement of frontal theta power along with WM load increase in IGE, and the theta power was positively correlated with the accuracy of the WM tasks. Moreover, fMRI activations/deactivations correlated with n-back tasks were estimated, and we found that the IGE group had increased and widespread activations in high-load WM tasks, including the frontoparietal activation network and task-related deactivation areas, such as the default mode network and primary visual and auditory networks. In addition, the network connectivity results demonstrated decreased counteraction between the activation network and deactivation network, and the counteraction was correlated with the higher theta power in IGE. These results indicated the important role of the interactions between activation and deactivation networks during the WM process, and the unbalance among them may indicate the pathophysiological mechanism of cognitive dysfunction in generalized epilepsy.

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.

Influencing factors of two-way social support for the old adults in China: A cross-sectional study.

This study aims to investigate the status and influencing factors of two-way social support among old adults. A cross-sectional study of 408 convenient samples of old adults was conducted using socio-demographic questionnaire, Brief 2-Way Social Support Scale, Modified Barthel index, General Well-being Schedule, Family APGAR Index, and Lubben Social Network Scale 6. The two-way social support score for old adults in China was (43.74±7.86), with the receiving and giving social support scoring (22.80±4.06) and (20.94±4.52), respectively. The multiple linear regression analysis revealed that family care, residence place, socioeconomic status, and social network were associated with both receiving and giving social support. Chronic diseases and religious beliefs were related to receiving social support, while gender, general well-being, and residence form were related to giving social support. Tailored interventions based on the distinct influencing factors are needed to enhance old adults' social support both as recipients and providers.

Effects of group mindfulness-based cognitive therapy and group cognitive behavioural therapy on symptomatic generalized anxiety disorder: a randomized controlled noninferiority trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. METHODS: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. RESULTS: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: - 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. CONCLUSIONS: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. TRIAL REGISTRATION: Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

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.

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.

Cerebello-cerebral connectivity in idiopathic generalized epilepsy.

PURPOSE: The present study aims to investigate structural and functional connectivity (SC and FC) in cerebello-cerebral circuit in idiopathic generalized epilepsy (IGE). METHODS: Diffusion tensor imaging and resting-state imaging data were collected from 57 patients with IGE and 66 controls in the present study. First, we performed bidirectional probabilistic fiber tracking between cerebellum and cerebral cortex, consisting of cerebellar efferent and afferent fibers. Then, strength of structural connectivity (SCS), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were extracted and compared between groups. Finally, cerebellar FC with cerebral cortex was evaluated with seeding at dentate nucleus. Between-group comparisons were performed using t tests with a significant level setting at p < 0.05 with threshold-free cluster enhancement correction. RESULTS: The patients with IGE showed decreased SCS in cerebellar efferent fibers to sensorimotor cortex in anterior corona radiate and increased SCS in efferent fibers to occipital cortex in posterior corona radiata. The SCS in cerebellar afferent fibers in corticospinal tract from frontal and in retrolenticular part of the internal capsule from occipital cortices were increased in IGE, and SCS in afferent fibers in posterior limb of internal capsule from parietal cortex was decreased. Decreased FA and increased MD and RD were observed in cerebello-cerebral tracts. Besides, decreased cerebellar FC with putamen and motor cortex was observed in IGE. CONCLUSION: The patients with IGE demonstrated distinct alterations in efferent and afferent pathways between cerebellum and different cerebral cortices, which might be the pathological anatomical basis for cerebellar modulation effect on epileptic activities and contribute to motor deficits. KEY POINTS: • IGE showed decreased SCS in cerebellar efferent fibers to the sensorimotor cortex and increased SCS in efferent fibers to the occipital cortex. • Patients demonstrated increased SCS in cerebellar afferent fibers from the frontal and the occipital cortex and decreased SCS in afferent fibers from parietal cortex. • Decreased FC between motor-related regions and dentate nucleus was observed in IGE.

Alterations of functional connectivity density in a Chinese family with a mild phenotype associated with a novel inherited variant of SCN8A.

OBJECTIVE: Only a few heritable SCN8A variants have been described in patients with a mild phenotype of epilepsy. Here, we describe a Chinese family with a novel inherited SCN8A variant and investigate changes in spontaneous cerebral activity during the resting-state in magnetic resonance imaging (MRI)-negative patients with epilepsy and their unaffected siblings. METHODS: A gene panel targeting 535 epilepsy genes was performed on the proband and his parents. The identified variant was confirmed in other affected members by Sanger sequencing. Resting-state functional MRI (fMRI) data were gathered from the family (4 affected individuals and 3 unaffected siblings) and 72 healthy controls (HCs). Functional connectivity density (FCD) was used to assess whether distant or local functional network changes occurred in patients with epilepsy. RESULTS: A heterozygous missense variant (c.4568C>A; p.A1523D) in SCN8A was identified in the Chinese family, with a total of 7 members who presented with a mild phenotype (childhood seizures and normal cognition). All patients remained seizure-free, and one patient remained seizure-free without medication. Increased FCD values in the thalamocortical network and basal ganglia network were observed in both patients with epilepsy and their unaffected siblings compared with the HCs. Direct comparison between SCN8A variant patients and unaffected siblings showed that more serious and distributed abnormal changes occurred in the mesial frontal regions of patients with epilepsy. CONCLUSIONS: We identified a novel SCN8A variant with a mild familial epilepsy phenotype. A similar pattern of FCD alterations in patients and their unaffected siblings might represent an endophenotype of benign epilepsy associated with the SCN8A inherited variant, and more extensive alterations in mesial frontal regions may help us to further understand the pathogenesis of SCN8A-related mild epilepsy.

BOLD-fMRI reveals the association between renal oxygenation and functional connectivity in the aging brain.

Aging is accompanied by a decline in physical and cognitive function. Vascular aging may provide a major influence on these measures. The purpose of this study was to explore the relationship between renal oxygenation and functional connectivity of the aging brain because of the anatomic and hemodynamic similarities between cerebral and renal vessels. Fifty-two healthy older adults were recruited to undergo a BOLD-fMRI scan of the brain and kidneys, and forty-four healthy younger subjects were recruited as the control group. First, cerebral functional connectivity density (FCD) was used to evaluate functional connectivity. Renal medullary and cortical R2* values were extracted respectively, and the ratio of medullary and cortical R2* values (MCR) was calculated. Then, the association between brain FCD and renal MCR was analyzed. Compared with younger adults, the elderly group showed higher renal medullary R2* and MCR, which might reflect a slight abnormality of renal oxygenation with aging. The older subjects also showed enhanced FCD in bilateral motor-related regions and decreased FCD in regions of the default mode network (DMN). The findings indicated that the functional connectivity in the DMN and motor cortices was vulnerable to aging. Moreover, the altered brain FCD values in the watershed regions, DMN and motor cortices were significantly correlated with the renal MCR value in the elderly group. The association between renal oxygenation abnormalities and spontaneous activity in the brain might reflect vascular aging and its influence on the kidney and brain during aging to some extent. This study provided a new perspective for understanding the relationship between tissue oxygenation and brain functional connectivity.

Dysfunctional white-matter networks in medicated and unmedicated benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECT) is the most common childhood idiopathic focal epilepsy syndrome, which characterized with white-matter abnormalities in the rolandic cortex. Although diffusion tensor imaging research could characterize white-matter structural architecture, it cannot detect neural activity or white-matter functions. Recent studies demonstrated the functional organization of white-matter by using functional magnetic resonance imaging (fMRI), suggesting that it is feasible to investigate white-matter dysfunctions in BECT. Resting-state fMRI data were collected from 24 new-onset drug-naive (unmedicated [NMED]), 21 medicated (MED) BECT patients, and 27 healthy controls (HC). Several white-matter functional networks were obtained using a clustering analysis on voxel-by-voxel correlation profiles. Subsequently, conventional functional connectivity (FC) was calculated in four frequency sub-bands (Slow-5:0.01-0.027, Slow-4:0.027-0.073, Slow-3:0.073-0.198, and Slow-2:0.198-0.25 Hz). We also employed a functional covariance connectivity (FCC) to estimate the covariant relationship between two white-matter networks based on their correlations with multiple gray-matter regions. Compared with HC, the NMED showed increased FC and/or FCC in rolandic network (RN) and precentral/postcentral network, and decreased FC and/or FCC in dorsal frontal network, while these alterations were not observed in the MED group. Moreover, the changes exhibited frequency-specific properties. Specifically, only two alterations were shared in at least two frequency bands. Most of these alterations were observed in the frequency bands of Slow-3 and Slow-4. This study provided further support on the existence of white-matter functional networks which exhibited frequency-specific properties, and extended abnormalities of rolandic area from the perspective of white-matter dysfunction in BECT.

Evaluation of functional connectivity in subdivisions of the thalamus in schizophrenia.

BACKGROUND: Previous studies in schizophrenia revealed abnormalities in the cortico-cerebellar-thalamo-cortical circuit (CCTCC) pathway, suggesting the necessity for defining thalamic subdivisions in understanding alterations of brain connectivity.AimsTo parcellate the thalamus into several subdivisions using a data-driven method, and to evaluate the role of each subdivision in the alterations of CCTCC functional connectivity in patients with schizophrenia. METHOD: There were 54 patients with schizophrenia and 42 healthy controls included in this study. First, the thalamic structural and functional connections computed, based on diffusion magnetic resonance imaging (MRI, white matter tractography) and resting-state functional MRI, were clustered to parcellate thalamus. Next, functional connectivity of each thalamus subdivision was investigated, and the alterations in thalamic functional connectivity for patients with schizophrenia were inspected. RESULTS: Based on the data-driven parcellation method, six thalamic subdivisions were defined. Loss of connectivity was observed between several thalamic subdivisions (superior-anterior, ventromedial and dorsolateral part of the thalamus) and the sensorimotor system, anterior cingulate cortex and cerebellum in patients with schizophrenia. A gradual pattern of dysconnectivity was observed across the thalamic subdivisions. Additionally, the altered connectivity negatively correlated with symptom scores and duration of illness in individuals with schizophrenia. CONCLUSIONS: The findings of the study revealed a wide range of thalamic functional dysconnectivity in the CCTCC pathway, increasing our understanding of the relationship between the CCTCC pathway and symptoms associated with schizophrenia, and further indicating a potential alteration pattern in the thalamic nuclei in people with schizophrenia.Declaration of interestNone.

Altered Dynamic Functional Network Connectivity in Frontal Lobe Epilepsy.

Frontal lobe epilepsy has recently been associated with disrupted brain functional connectivity; variations among various resting-state networks (RSNs) across time remains largely unclear. This study applied dynamic functional network connectivity (dFNC) analysis to investigate functional patterns in the temporal and spatial domains of various functional systems in FLE. Resting-state fMRI data were acquired from 19 FLE patients and 18 controls. Independent component analysis was used to decompose RSNs, which were grouped into seven functional systems. Sliding windows and clustering approach were used to identify the dFNC patterns. Then, state-specific connectivity pattern and dynamic functional state interactions (dFSIs) were evaluated. Compared with healthy controls, FLE patients exhibited decreased dFNC in almost all four patterns, changes that were mostly related to the frontoparietal system, suggesting a disturbed communication of the frontoparietal system with other systems in FLE. Additionally, regarding the fundamental connectivity pattern (state 3 in this study), FLE showed decreased time spent in this state. Moreover, the duration positively correlated with seizure onset. Furthermore, significantly reduced dynamic connections in this state were observed in the frontoparietal system linked to the cerebellar and subcortical systems. These findings imply abnormal fundamental dynamic interactions and dysconnectivity associated with the subcortical and cerebellar regulation of dysfunctions in frontoparietal regions in FLE. Finally, based on the developed FSI analysis, temporal dynamic abnormalities among states were observed in FLE. Therefore, this altered dynamic FNC extended our understanding of the abnormalities in the frontoparietal system in FLE. The dynamic FNC provided novel insight into the fundamental pathophysiological mechanisms in FLE.

The efficacy of group cognitive-behavioural therapy plus duloxetine for generalised anxiety disorder versus duloxetine alone.

OBJECTIVE: To explore whether and how group cognitive-behavioural therapy (GCBT) plus medication differs from medication alone for the treatment of generalised anxiety disorder (GAD). METHODS: Hundred and seventy patients were randomly assigned to the GCBT plus duloxetine (n=89) or duloxetine group (n=81). The primary outcomes were Hamilton Anxiety Scale (HAMA) response and remission rates. The explorative secondary measures included score reductions from baseline in the HAMA total, psychic, and somatic anxiety subscales (HAMA-PA, HAMA-SA), the Hamilton Depression Scale, the Severity Subscale of Clinical Global Impression Scale, Global Assessment of Functioning, and the 12-item Short-Form Health Survey. Assessments were conducted at baseline, 4-week, 8-week, and 3-month follow-up. RESULTS: At 4 weeks, HAMA response (GCBT group 57.0% vs. control group 24.4%, p=0.000, Cohen's d=0.90) and remission rates (GCBT group 21.5% vs. control group 6.2%, p=0.004; d=0.51), and most secondary outcomes (all p<0.05, d=0.36-0.77) showed that the combined therapy was superior. At 8 weeks, all the primary and secondary significant differences found at 4 weeks were maintained with smaller effect sizes (p<0.05, d=0.32-0.48). At 3-month follow-up, the combined therapy was only significantly superior in the HAMA total (p<0.045, d=0.43) and HAMA-PA score reductions (p<0.001, d=0.77). Logistic regression showed superiority of the combined therapy for HAMA response rates [odds ratio (OR)=2.12, 95% confidence interval (CI) 1.02-4.42, p=0.04] and remission rates (OR=2.80, 95% CI 1.27-6.16, p=0.01). CONCLUSIONS: Compared with duloxetine alone, GCBT plus duloxetine showed significant treatment response for GAD over a shorter period of time, particularly for psychic anxiety symptoms, which may suggest that GCBT was effective in changing cognitive style.

Abnormal subsurface hydrogen diffusion behaviors in heterogeneous hydrogenation reactions.

Hydrogen adsorption and diffusion behaviors on noble metal model catalyst surfaces and into the subsurfaces are of paramount significance in the exploration of novel heterogenous catalytic hydrogenation reactions. We present an in-depth study of hydrogen adsorption on and diffusion into the subsurfaces of three typical 5d noble metals from three-dimensional electronically adiabatic potential energy surfaces (PESs) by interpolating plenty of ab initio density functional theory (DFT) configuration-energy points. The surfaces and subsurfaces regions of the relaxed Ir(100) and (111), Pt(100) and (111), and Au(100) and (111) surfaces, are, respectively, taken into account. For hydrogen adsorption on the (100) surfaces, the lowest adsorption energy site is the Bridge site, instead of the traditional Hollow site. Hydrogen prefers to follow the indirect pathway with a lower diffusion barrier, in the competition with the direct pathway with much higher diffusion barrier. For hydrogen diffusion on the (111) surfaces, hydrogen follows the pathway from Top site to fcc site on the surface and prefers an up-down direct pathway into the subsurface. Importantly, the nudged elastic band (NEB) based on the PESs can reproduce those results calculated from the NEB(DFT) very well. The developed highly-accurate and efficient approach based on the PESs helps us to further investigate the more complex reactant diffusion dynamics at surfaces.

Altered Structural and Functional Connectivity of Juvenile Myoclonic Epilepsy: An fMRI Study.

The aim of this study was to investigate the structural and functional connectivity (FC) of juvenile myoclonic epilepsy (JME) using resting state functional magnetic resonance imaging (rs-fMRI). High-resolution T1-weighted magnetic resonance imaging (MRI) and rs-fMRI data were collected in 25 patients with JME and in 24 control subjects. A FC analysis was subsequently performed, with seeding at the regions that demonstrated between-group differences in gray matter volume (GMV). Then, the observed structural and FCs were associated with the clinical manifestations. The decreased GMV regions were found in the bilateral anterior cerebellum, the right orbital superior frontal gyrus, the left middle temporal gyrus, the left putamen, the right hippocampus, the bilateral caudate, and the right thalamus. The changed FCs were mainly observed in the motor-related areas and the cognitive-related areas. The significant findings of this study revealed an important role for the cerebellum in motor control and cognitive regulation in JME patients, which also have an effect on the activity of the occipital lobe. In addition, the changed FCs were related to the clinical features of JME patients. The current observations may contribute to the understanding of the pathogenesis of JME.

Complex discharge-affecting networks in juvenile myoclonic epilepsy: A simultaneous EEG-fMRI study.

Juvenile myoclonic epilepsy (JME) is a common subtype of idiopathic generalized epilepsies (IGEs) and is characterized by myoclonic jerks, tonic-clonic seizures and infrequent absence seizures. The network notion has been proposed to better characterize epilepsy. However, many issues remain not fully understood in JME, such as the associations between discharge-affecting networks and the relationships among resting-state networks. In this project, eigenspace maximal information canonical correlation analysis (emiCCA) and functional network connectivity (FNC) analysis were applied to simultaneous EEG-fMRI data from JME patients. The main findings of our study are as follows: discharge-affecting networks comprising the default model (DMN), self-reference (SRN), basal ganglia (BGN) and frontal networks have linear and nonlinear relationships with epileptic discharge information in JME patients; the DMN, SRN and BGN have dense/specific associations with discharge-affecting networks as well as resting-state networks; and compared with controls, significantly increased FNCs between the salience network (SN) and resting-state networks are found in JME patients. These findings suggest that the BGN, DMN and SRN may play intermediary roles in the modulation and propagation of epileptic discharges. These roles further tend to disturb the switching function of the SN in JME patients. We also postulate that emiCCA and FNC analysis may provide a potential analysis platform to provide insights into our understanding of the pathophysiological mechanism of epilepsy subtypes such as JME. Hum Brain Mapp 37:3515-3529, 2016. © 2016 Wiley Periodicals, Inc.