Fenglai Xiao

Real-time effects of centrotemporal spikes on cognition in rolandic epilepsy: An EEG-fMRI study

Objective: To identify the real-time effects of interictal rolandic spikes (or centrotemporal spikes [CTS]) on language, behavior, and cognitive function in patients with rolandic epilepsy (RE). Methods: We studied 22 medication-naive patients with RE using EEG-fMRI with a 3T MRI scanner. We used simultaneous EEG to define the pre-CTS, CTS, and post-CTS periods. We analyzed the dynamic functional connectivity maps of the rolandic network during the 3 interictal CTS periods. Results: The analysis of dynamic changes revealed positive correlations between the bilateral rolandic areas and the left inferior frontal gyrus (IFG; Broca area), the left inferior parietal lobe and the supramarginal gyrus (areas responsible for receptive language function), and the right IFG and left caudate. Anti-correlations were found in the default mode network (bilateral superior frontal gyrus, left middle frontal gyrus, left middle temporal gyrus, and right precuneus). Conclusions: Interictal CTS directly disrupts the functional brain networks responsible for language, behavior, and cognition in children with typical RE. It is important to suppress discharges to reduce the risk of neuropsychological impairments in children with RE.

Functional brain connectome and sensorimotor networks in rolandic epilepsy

PURPOSE Rolandic epilepsy (RE) is a form of well-characterized childhood epilepsy whose focal electroencephalographic abnormalities affect the same well-delineated local brain regions. Little is known about how the focal electroencephalographic discharges interfere with the topological organization of whole-brain networks in RE patients. METHODS Seventy-three patients RE patients and 73 healthy children underwent rsfMRI. The whole-brain functional networks were constructed by thresholding the partial correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based approaches. We used network-based statistics to evaluate functional connectivity. The correlations between the network properties and the clinical and cognitive characteristics were calculated. RESULTS The global topologic organization of the functional brain network was disrupted in RE patients, as manifested by reduced clustering coefficient and local and global efficiency and increased characteristic path length. The RE patients exhibited less connectivity among the sensorimotor areas; this reduction in the mean functional connectivity in this network correlated to altered global small-world properties. The RE patients exhibited decreased nodal centralities, predominantly in the bilateral postcentral gyrus, in the frontal, parietal and temporal lobes around the rolandic fissure and in areas related to linguistics and attention control (p<0.05, FDR-corrected). The altered nodal centralities in the bilateral postcentral gyrus and the left posterior cingulate cortex were correlated with subscales in Child Behavior Checklist. CONCLUSIONS These results support the hypothesis that RE is associated with systemic brain disorganization and that the functional defect in rolandic areas contribute to symptomatology and electrophysiology in RE. Nodal abnormalities appear to imply the disturbances in linguistics and attention observed in RE patients.

Hemispheric lateralization of microstructural white matter abnormalities in children with active benign childhood epilepsy with centrotemporal spikes (BECTS): A preliminary DTI study

PURPOSE The deficit of white matter is reported to be involved during the disease progression in patients with benign childhood epilepsy with centrotemporal spikes (BECTS). The aim of this study is to investigate patterns of white matter damage in children with BECTS with left- or right-hemispheric focus by using diffusion tensor imaging (DTI), and its relationship with the cofactors such duration, seizure frequency and handedness. METHODS Diffusion tensor imaging (DTI) was performed in twenty-eight children with BECTS and eighteen healthy controls. The data were analyzed using both tract-based spatial statistics (TBSS) and region of interest (ROI) analyses. Correlations were investigated between the fractional anisotropy (FA) values of the identified altered regions and clinical features such as age, age of onset and seizure frequency. RESULTS The TBSS analysis revealed that white matter impairment in children with rolandic spikes on the ipsilateral hemisphere was much wider. The FA value was significantly lower in the body of the corpus callosum and forceps minor in BECTS patients with spikes on the ipsilateral hemisphere. The seizure frequency correlated positively with the FA values of body of corpus callosum (CC), bilateral cingulate gyrus and left uncinate fasciculi (UA). CONCLUSION The impaired WM integrity in patients with BECTS was greater in patients with spikes on the dominant hemisphere, possibly due to the greater vulnerability of the left hemisphere and excitotoxic effects of seizures.

Altered attention networks in benign childhood epilepsy with centrotemporal spikes (BECTS): A resting-state fMRI study.

It is noteworthy that some children with benign childhood epilepsy with centrotemporal spikes (BECTS) show attention problems despite their favorable seizure outcome. Resting-state functional magnetic resonance imaging (fMRI) is a method widely used to detect brain network alterations in neuropsychiatric diseases. We used resting-state functional magnetic resonance imaging (fMRI) to investigate specific brain networks related to attention deficit in children with BECTS. Resting-state fMRI was performed in patients with BECTS with ADHD (n=15) and those with BECTS without ADHD (n=15) and in healthy controls (n=15). Unbiased seed-based whole-brain functional connectivity analysis was used to study the connectivity pattern of three resting-state networks, including the ventral attention network (VAN) and the dorsal attention network (DAN) and the default mode network (DMN). Patients with BECTS with ADHD displayed decreased functional connectivity in the DAN compared with other two groups, while patients with BECTS without ADHD showed increased functional connectivity in the DAN. Moreover, we found increased functional connectivity in the VAN and in the DMN in patients with BECTS with or without ADHD when comparing with controls. These results showed that the newly-diagnosed children with BECTS displayed brain activity alterations in the ventral and dorsal attention networks. The difference in the extent of impairment in the dorsal attention network of patients with BECTS with ADHD and patients with BECTS without ADHD may lead to improved understanding of the underlying neuropathophysiology and treatment of BECTS with ADHD and BECTS without ADHD.

White Matter Abnormalities in Post-traumatic Stress Disorder Following a Specific Traumatic Event

Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the regions established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.

Validation of the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) in West China

OBJECTIVE We aimed to validate the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) for Chinese people with epilepsy (PWE). METHODS The NDDI-E was translated into a Chinese version. A consecutive cohort of PWE from West China Hospital was recruited to test the reliability and validity of the Chinese version of the NDDI-E (C-NDDI-E). Each patient underwent the Mini International Neuropsychiatric Interview (MINI) and C-NDDI-E. RESULTS A total of 202 PWE completed the psychiatric evaluation. The C-NDDI-E was easily comprehended and quickly completed by all participants. Fifty-four patients (26.7%) had current major depressive disorder (MDD) according to the MINI criteria. The Cronbachs α coefficient for the C-NDDI-E was 0.825. Receiver operating characteristic analyses showed an area under the curve of 0.936 (95% CI=0.904-0.968). At a cutoff score of >12, the C-NDDI-E had a sensitivity of 0.926, a specificity of 0.804, a positive predictive value of 0.633, and a negative predictive value of 0.967. CONCLUSION The C-NDDI-E is a valuable instrument for screening MDD in Chinese PWE.

Functional MRI-based connectivity analysis: A promising tool for the investigation of the pathophysiology and comorbidity of epilepsy

Epilepsy has been recognized as a brain network disorder. Therefore, functional MRI (fMRI)-based connectivity is an ideal technique for exploring the complex effects of epilepsy on the brain. Functional connectivity studies have provided insights into the physiopathogenesis of the epileptic network underlying focal epilepsies, genetic generalized epilepsy, and specific epileptic syndromes. An increasing number of studies have focused on the deleterious effects of epilepsy on other brain networks to help to explain cognitive deficits and psychiatric symptoms. Anti-epileptic treatment studies have yielded information about the side effects and the restoration of functional abnormalities after using the drug. Researchers who have examined predictors of surgical outcomes have suggested that there might be identifiable pre-surgical patterns of functional connectivity that are associated with a greater likelihood of positive cognitive or seizure outcomes. However, knowledge regarding the role of fMRI connectivity remains limited in clinical settings. Further validation through invasive investigations and follow-up studies is required for its reliable application in the clinical management of individual patients.

The focal alteration and causal connectivity in children with new-onset benign epilepsy with centrotemporal spikes

The aim of the current study was to find the epileptic focus and examine its causal relationship to other brain regions in children with new-onset benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 66 children with BECTS and 37 matched control children. We compared the amplitude of low frequency fluctuation (ALFF) signals between the two groups to find the potential epileptogenic zone (EZ), then used Granger causality analysis (GCA) to explore the causal effects of EZ on the whole brain. Children with BECTS had significantly increased ALFF in the right Broca’s area, and decreased ALFF in bilateral fusiform gyrus. The patients also showed increased driving effect from the EZ in Broca’s area to the right prefrontal lobe, and decreased effects to the frontal lobe and posterior parts of the language network. The causal effect on left Wernicke’s area negatively correlated with verbal IQ (VIQ) score. Our research on new-onset BECTS patients illustrates a possible compensatory mechanism in the language network at early stages of BECTS, and the negative correlation of GCA and VIQ suggest the disturbance of epileptiform activity on language. These findings shed light on the mechanisms of and language dysfunction in BECTS.

Clinical and Electroencephalographic (EEG) Features Associated With Refractoriness in Benign Childhood Epilepsy With Centrotemporal Spikes

The aim of this study is to identify clinical or electroencephalographic (EEG) features associated with refractoriness to the initial antiepileptic drug in typical benign childhood epilepsy with centrotemporal spikes. A total of 87 children with typical benign childhood epilepsy with centrotemporal spikes were retrospectively reviewed in the analyses. The patients were subdivided into 2 groups: patients whose seizures were controlled with monotherapy and patients requiring 2 medications. Sixty-three children achieved seizure freedom with monotherapy, whereas 24 received 2 medications for seizure control. Diffusing foci at the follow-up EEG and delayed treatment (duration >1 year) are 2 main risk factors associated with more refractory cases (P < .001). Delayed diagnosis (37.1%) and nonadherence to treatment (57.2%) contributed to delayed treatment. Our findings suggested that diffusing foci on EEG and delayed treatment are associated with more frequent seizures and refractoriness in benign childhood epilepsy with centrotemporal spikes. Diagnostic delays and nonadherence hindered timely care, which may represent opportunities for improved intervention.

Frequency-specific alterations in the amplitude and synchronization of resting-state spontaneous low-frequency oscillations in benign childhood epilepsy with centrotemporal spikes

OBJECTIVES Spontaneous low-frequency oscillations in different frequency bands have diverse physiological meanings. The amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) in different frequency bands in Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) are unknown and worth exploring. METHOD Resting-state functional magnetic resonance imaging data were collected in 51 drug-naïve BECTS patients and 76 healthy controls. The ALFF was calculated for the typical (0.01 - 0.08 Hz), slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and slow-3 (0.073-0.198 Hz) frequency bands. The bilateral precuneus/posterior cingulate cortex (PCU/PCC) showed a common alteration of ALFF in different frequency bands, and was selected as the seed for calculating FC per voxel. RESULTS In the typical band, BECTS patients showed increased ALFF in the left rolandic operculum and the right pre/postcentral gyrus, and decreased ALFF in the bilateral PCU/PCC, some of which were shared by the slow-5, slow-4, and slow-3 bands. Decreased ALFF in the left angular gyrus was also found in the slow-3 band. Only the bilateral PCU/PCC showed a frequency-dependent correlation with the total seizure frequency and full-scale intelligence quotient. Regions having degenerated FC with the bilateral PCU/PCC in BECTS patients were mainly in the left prefrontal cortex and bilateral anterior cingulate cortex for the typical and slow-5 bands, and in the bilateral temporal limbic system and striatum for the slow-4 and slow-3 bands. CONCLUSION Alteration of the ALFF and FC differed with distinct frequency bands. Therefore, employing different frequency bands would provide more meaningful findings for BECTS patients.