Brain structural changes and molecular analyses in children with benign epilepsy with centrotemporal spikes.

BACKGROUND: Benign epilepsy with centrotemporal spikes (BECTS) is a common childhood epilepsy syndrome, accompanied by behavioral problems and cognitive impairments. Previous studies of BECTS-related brain structures applied univariate analysis and showed inconsistent results. And neurotransmitter patterns associated with brain structural alterations were still unclear. METHODS: Structural images of twenty-one drug-naïve children with BECTS and thirty-five healthy controls (HCs) were scanned. Segmented gray matter volume (GMV) images were decomposed into independent components (ICs) using the source-based morphometry method. Then spatial correlation analyses were applied to examine possible relationships between GMV changes and neurotransmitter systems. RESULTS: Compared with HCs, drug-naïve children with BECTS showed increased volume in one GMV component (IC7), including bilateral precentral gyrus, bilateral supplementary motor area, left superior frontal cortex, bilateral middle/ inferior frontal cortex and bilateral anterior/ middle cingulate cortex. A positive correlation was observed between one GMV component (IC6) and seizure frequency. There were significantly positive correlations between abnormal GMV in IC7 and serotonergic, GABAergic and glutamatergic systems. CONCLUSION: These findings provided further evidence of changed GMV in drug-naïve children with BECTS related to their behavioral problems and cognitive impairments, and associated neurotransmitters which could help to better understand neurobiological mechanisms and underlying molecular mechanisms of BECTS. IMPACT: The article provides further evidence of changed gray matter volume in drug-naïve children with BECTS related to their behavioral problems and cognitive impairments as well as associated neurotransmitters. Most literature to date has applied univariate analysis and showed inconsistent results, and neurotransmitter patterns associated with brain structural alterations were still unclear. Therefore, this article uses multivariate method and JuSpace toolbox to fill the gap. Significantly increased gray matter volume was found in drug-naïve children with BECTS compared with healthy controls. Abnormal gray matter volume was significantly correlated with clinical data and specific neurotransmitters.

Combined diffusion tensor imaging and quantitative susceptibility mapping to characterize normal-appearing white matter in self-limited epilepsy with centrotemporal spikes.

PURPOSE: In brain development, Myelination is the characteristic feature of white matter maturation, which plays an important role in efficient information transmitting. The white matter abnormality has been reported to be associated with self-limited epilepsy with centrotemporal spikes (SeLECTS). This study aimed to detect the altered white matter region in the SeLECTS patients by the combination of diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM) technique. METHODS: 27 children with SeLECTS and 23 age- and gender-matched healthy children were enrolled. All participants were scanned with 3.0-T MRI to acquire the structure, diffusion and susceptibility-weighted data. The susceptibility and diffusion weighted data were processed to obtain quantitative susceptibility map and fraction anisotropy (FA) map. Then voxel-wise tract-based spatial statistics (TBSS) were used to analyze quantitative susceptibility and FA data. RESULTS: Both DTI and QSM revealed extensive white matter alterations in the frontal, parietal, and temporal lobes in SeLECTS patients. The overlapped region of DTI and QSM analyses was located in the fiber tracts of the corona radiata. The FA values in this overlapped region were negatively correlated with the magnetic susceptibility values. CONCLUSION: Our results suggest that TBSS-based QSM can be employed as a novel approach for characterizing alterations in white matter in SeLECTS. And the combination of QSM and DTI can provide a more comprehensive evaluation of white matter integrity by utilizing different biophysical features.

Structural and functional changes in drug-naïve benign childhood epilepsy with centrotemporal spikes and their associated gene expression profiles.

Benign epilepsy with centrotemporal spikes (BECTS) is a common pediatric epilepsy syndrome that has been widely reported to show abnormal brain structure and function. However, the genetic mechanisms underlying structural and functional changes remain largely unknown. Based on the structural and resting-state functional magnetic resonance imaging data of 22 drug-naïve children with BECTS and 33 healthy controls, we conducted voxel-based morphology (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) analyses to compare cortical morphology and spontaneous brain activity between the 2 groups. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial correlation analyses were applied to explore gene expression profiles associated with gray matter volume (GMV) and fALFF changes in BECTS. VBM analysis demonstrated significantly increased GMV in the right brainstem and right middle cingulate gyrus in BECTS. Moreover, children with BECTS exhibited significantly increased fALFF in left temporal pole, while decreased fALFF in right thalamus and left precuneus. These brain structural and functional alterations were closely related to behavioral and cognitive deficits, and the fALFF-linked gene expression profiles were enriched in voltage-gated ion channel and synaptic activity as well as neuron projection. Our findings suggest that brain morphological and functional abnormalities in children with BECTS involve complex polygenic genetic mechanisms.

Children with Rolandic epilepsy have micro- and macrostructural abnormalities in white matter constituting networks necessary for language function.

INTRODUCTION: Self-limited epilepsy with centrotemporal spikes is a transient developmental epilepsy with a seizure onset zone localized to the centrotemporal cortex that commonly impacts aspects of language function. To better understand the relationship between these anatomical findings and symptoms, we characterized the language profile and white matter microstructural and macrostructural features in a cohort of children with SeLECTS. METHODS: Children with active SeLECTS (n = 13), resolved SeLECTS (n = 12), and controls (n = 17) underwent high-resolution MRIs including diffusion tensor imaging sequences and multiple standardized neuropsychological measures of language function. We identified the superficial white matter abutting the inferior rolandic cortex and superior temporal gyrus using a cortical parcellation atlas and derived the arcuate fasciculus connecting them using probabilistic tractography. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region, and tested for linear relationships between diffusivity metrics in these regions and language scores on neuropsychological testing. RESULTS: We found significant differences in several language modalities in children with SeLECTS compared to controls. Children with SeLECTS performed worse on assessments of phonological awareness (p = 0.045) and verbal comprehension (p = 0.050). Reduced performance was more pronounced in children with active SeLECTS compared to controls, namely, phonological awareness (p = 0.028), verbal comprehension (p = 0.028), and verbal category fluency (p = 0.031), with trends toward worse performance also observed in verbal letter fluency (p = 0.052), and the expressive one-word picture vocabulary test (p = 0.068). Children with active SeLECTS perform worse than children with SeLECTS in remission on tests of verbal category fluency (p = 0.009), verbal letter fluency (p = 0.006), and the expressive one-word picture vocabulary test (p = 0.045). We also found abnormal superficial white matter microstructure in centrotemporal ROIs in children with SeLECTS, characterized by increased diffusivity and fractional anisotropy compared to controls (AD p = 0.014, RD p = 0.028, MD p = 0.020, and FA p = 0.024). Structural connectivity of the arcuate fasciculus connecting perisylvian cortical regions was lower in children with SeLECTS (p = 0.045), and in the arcuate fasciculus children with SeLECTS had increased diffusivity (AD p = 0.007, RD p = 0.006, MD p = 0.016), with no difference in fractional anisotropy (p = 0.22). However, linear tests comparing white matter microstructure in areas constituting language networks and language performance did not withstand correction for multiple comparisons in this sample, although a trend was seen between FA in the arcuate fasciculus and verbal category fluency (p = 0.047) and the expressive one-word picture vocabulary test (p = 0.036). CONCLUSION: We found impaired language development in children with SeLECTS, particularly in those with active SeLECTS, as well as abnormalities in the superficial centrotemporal white matter as well as the fibers connecting these regions, the arcuate fasciculus. Although relationships between language performance and white matter abnormalities did not pass correction for multiple comparisons, taken together, these results provide evidence of atypical white matter maturation in fibers involved in language processing, which may contribute to the aspects of language function that are commonly affected by the disorder.

A prospective 5-year longitudinal study detects neurocognitive and imaging correlates of seizure remission in self-limiting Rolandic epilepsy.

OBJECTIVE: Self-limiting Rolandic epilepsy (RE) is the most common epilepsy in school-age children. Seizures are generally infrequent, but cognitive, language, and motor coordination problems can significantly impact the child's life. To better understand brain structure and function changes in RE, we longitudinally assessed neurocognition, cortical thickness, and subcortical volumes. METHODS: At baseline, we recruited 30 participants diagnosed with RE and 24-healthy controls and followed up for 4.94 ± 0.8 years when the participants with RE were in seizure remission. Measures included were as follows: T1-weighted magnetic resonance brain imaging (MRI) with FreeSurfer analysis and detailed neuropsychological assessments. MRI and neuropsychological data were compared between baseline and follow-up in seizure remission. RESULTS: Longitudinal MRI revealed excess cortical thinning in the left-orbitofrontal (p = 0.0001) and pre-central gyrus (p = 0.044). There is a significant association (p = 0.003) between a reduction in cortical thickness in the left-orbitofrontal cluster and improved processing of filtered words. Longitudinal neuropsychology revealed significant improvements in the symptoms of developmental coordination disorder (DCD, p = 0.005) in seizure remission. CONCLUSIONS: There is evidence for altered development of neocortical regions between active seizure state and seizure remission in RE within two clusters maximal in the left-orbitofrontal and pre-central gyrus. There is significant evidence for improvement in motor coordination between active seizures and seizure remission and suggestive evidence for a decline in fluid intelligence and gains in auditory processing.

Functional connectivity differences in speech production networks in Chinese children with Rolandic epilepsy.

Previous studies have demonstrated that language impairments are frequently observed in patients with benign epilepsy with centrotemporal spikes (BECTS). However, how BECTS affects language processing in the Chinese population remains unclear. With the use of functional magnetic resonance imaging (fMRI) in an overt picture-naming task, the present study examined functional connectivity in 27 children with BECTS and 26 healthy controls. The results indicated that children with BECTS showed altered functional connectivity associated with speech production between the left precuneus and the right cerebellum, between the right precuneus and the bilateral thalamus and the left superior temporal gyrus, between the right cuneus and the right postcentral gyrus and the right inferior parietal lobule, and between the right cerebellum and right middle frontal gyrus. Collectively, the findings in this study demonstrate the abnormal functional connectivity basis of speech production in Chinese children with BECTS, providing clues to understanding the brain mechanisms of language-related network in patients with BECTS.

Delayed brain development of Rolandic epilepsy profiled by deep learning-based neuroanatomic imaging.

OBJECTIVES: Although Rolandic epilepsy (RE) has been regarded as a brain developmental disorder, neuroimaging studies have not yet ascertained whether RE has brain developmental delay. This study employed deep learning-based neuroanatomic biomarker to measure the changed feature of "brain age" in RE. METHODS: The study constructed a 3D-CNN brain age prediction model through 1155 cases of typically developing children's morphometric brain MRI from open-source datasets and further applied to a local dataset of 167 RE patients and 107 typically developing children. The brain-predicted age difference was measured to quantitatively estimate brain age changes in RE and further investigated the relevancies with cognitive and clinical variables. RESULTS: The brain age estimation network model presented a good performance for brain age prediction in typically developing children. The children with RE showed a 0.45-year delay of brain age by contrast with typically developing children. Delayed brain age was associated with neuroanatomic changes in the Rolandic regions and also associated with cognitive dysfunction of attention. CONCLUSION: This study provided neuroimaging evidence to support the notion that RE has delayed brain development. KEY POINTS: • The children with Rolandic epilepsy showed imaging phenotypes of delayed brain development with increased GM volume and decreased WM volume in the Rolandic regions. • The children with Rolandic epilepsy had a 0.45-year delay of brain-predicted age by comparing with typically developing children, using 3D-CNN-based brain age prediction model. • The delayed brain age was associated with morphometric changes in the Rolandic regions and attentional deficit in Rolandic epilepsy.

Alterations in white matter integrity and asymmetry in patients with benign childhood epilepsy with centrotemporal spikes and childhood absence epilepsy: An automated fiber quantification tractography study.

PURPOSE: To investigate whether patients with benign childhood epilepsy with centrotemporal spikes (BECTS) and childhood absence epilepsy (CAE) show distinct patterns of white matter (WM) alterations and structural asymmetry compared with healthy controls and the relationship between WM alterations and epilepsy-related clinical variables. METHODS: We used automated fiber quantification to create tract profiles of fractional anisotropy (FA) and mean diffusivity (MD) in twenty-six patients with BECTS, twenty-nine patients with CAE, and twenty-four healthy controls. Group differences in FA and MD were quantified at 100 equidistant nodes along the fiber tract and these alterations and epilepsy-related clinical variables were correlated. A lateralization index (LI) representing the structural asymmetry of the fiber tract was computed and compared between both patient groups and controls. RESULTS: Compared with healthy controls, the BECTS group showed widespread FA reduction in 43.75% (7/16) and MD elevation in 50% (8/16) of identified fiber tracts, and the CAE group showed regional FA reduction in 31.25% (5/16) and MD elevation in 25% (4/16) of identified fiber tracts. In the BECTS group, FA and MD in the right anterior thalamic radiation positively and negatively correlated with the number of antiepileptic drugs, respectively, and MD in the right arcuate fasciculus (AF) positively correlated with seizure frequency. In the CAE group, the LI values were significantly lower in the inferior fronto-occipital fasciculus and the AF. CONCLUSION: The two childhood epilepsy syndromes display different patterns of WM alterations and structural asymmetry, suggesting that neuroanatomical differences may underlie the different profiles of BECTS and CAE.

Persistent abnormalities in Rolandic thalamocortical white matter circuits in childhood epilepsy with centrotemporal spikes.

OBJECTIVE: Childhood epilepsy with centrotemporal spikes (CECTS) is a common, focal, transient, developmental epilepsy syndrome characterized by unilateral or bilateral, independent epileptiform spikes in the Rolandic regions of unknown etiology. Given that CECTS presents during a period of dramatic white matter maturation and thatspikes in CECTS are activated during non-rapid eye movement (REM) sleep, we hypothesized that children with CECTS would have aberrant development of white matter connectivity between the thalamus and the Rolandic cortex. We further tested whether Rolandic thalamocortical structural connectivity correlates with spike rate during non-REM sleep. METHODS: Twenty-three children with CECTS (age = 8-15 years) and 19 controls (age = 7-15 years) underwent 3-T structural and diffusion-weighted magnetic resonance imaging and 72-electrode electroencephalographic recordings. Thalamocortical structural connectivity to Rolandic and non-Rolandic cortices was quantified using probabilistic tractography. Developmental changes in connectivity were compared between groups using bootstrap analyses. Longitudinal analysis was performed in four subjects with 1-year follow-up data. Spike rate was quantified during non-REM sleep using manual and automated techniques and compared to Rolandic connectivity using regression analyses. RESULTS: Children with CECTS had aberrant development of thalamocortical connectivity to the Rolandic cortex compared to controls (P = .01), where the expected increase in connectivity with age was not observed in CECTS. There was no difference in the development of thalamocortical connectivity to non-Rolandic regions between CECTS subjects and controls (P = .19). Subjects with CECTS observed longitudinally had reductions in thalamocortical connectivity to the Rolandic cortex over time. No definite relationship was found between Rolandic connectivity and non-REM spike rate (P > .05). SIGNIFICANCE: These data provide evidence that abnormal maturation of thalamocortical white matter circuits to the Rolandic cortex is a feature of CECTS. Our data further suggest that the abnormalities in these tracts do not recover, but are increasingly dysmature over time, implicating a permanent but potentially compensatory process contributing to disease resolution.

Electrical status epilepticus in sleep affects intrinsically connected networks in patients with benign childhood epilepsy with centrotemporal spikes.

BACKGROUND: Although outcomes of benign childhood epilepsy with centrotemporal spikes (BECTS) are frequently excellent, some atypical forms of BECTS, especially electrical status epilepticus in sleep (ESES), are characterized by worse outcomes and negative impacts on cognitive development. METHODS: To explore specific ESES-related brain networks in patients with BECTS, we used resting-state functional magnetic resonance imaging (fMRI) to scan patients with BECTS with ESES (n = 9), patients with BECTS without ESES (n = 17), and healthy controls (n = 36). Unbiased seed-based whole-brain functional connectivity (FC) was adopted to explore the connectivity mode of three resting-state cerebral networks: the default mode network (DMN), salience network (SN), and central executive network (CEN). RESULTS: Compared with the other two groups, patients with BECTS with ESES showed FC in the SN or in the CEN decreased, but not in the DMN. Moreover, we found the FC in the CEN in patients with BECTS without ESES decreased when compared with controls. Our currently intrinsically defined anticorrelated networks strength was disrupted in BECTS and connote greater deactivation than the results from FC for a seed region in children with BECTS. CONCLUSION: These results indicated that children with BECTS with ESES showed brain activity altered in the CEN and the SN. The difference of impairment in the SN and CEN may lead to improve the understanding of the underlying neuropathophysiology, and to assess the activity of patients with BECTS with ESES, which is crucial for measuring disease activity, improving patient care, and assessing the effect of antiepilepsy therapy.

Network analysis of prospective brain development in youth with benign epilepsy with centrotemporal spikes and its relationship to cognition.

OBJECTIVE: Benign epilepsy with centrotemporal spikes (BECTS) is the most common childhood idiopathic localization-related epilepsy syndrome. BECTS presents normal routine magnetic resonance imaging (MRI); however, quantitative analytic techniques have captured subtle cortical and subcortical magnetic resonance anomalies. Network science, including graph theory (GT) analyses, facilitates understanding of brain covariance patterns, potentially informing in important ways how this common self-limiting epilepsy syndrome may impact normal patterns of brain and cognitive development. METHODS: GT analyses examined the developmental covariance among cortical and subcortical regions in children with new/recent onset BECTS (n = 19) and typically developing healthy controls (n = 22) who underwent high-resolution MRI and cognitive assessment at baseline and 2 years later. Global (transitivity, global efficiency, and modularity index [Q]) and regional measures (local efficiency and hubs) were investigated to characterize network development in each group. Associations between baseline-based GT measures and cognition at both time points addressed the implications of GT analyses for cognition and prospective cognitive development. Furthermore, an individual contribution measure was investigated, reflecting how important for cognition it is for BECTS to resemble the correlation matrices of controls. RESULTS: Groups exhibited similar Q and overall network configuration, with BECTS presenting significantly higher transitivity and both global and local efficiency. Furthermore, both groups presented a similar number of hubs, with BECTS showing a higher number in temporal lobe regions compared to controls. The investigated measures were negatively associated with 2-year cognitive outcomes in BECTS. SIGNIFICANCE: Children with BECTS present a higher-than-normal global developmental configuration compared to controls, along with divergence from normality in terms of regional configuration. Baseline GT measures demonstrate potential as a cognitive biomarker to predict cognitive outcome in BECTS 2 years after diagnosis. Similarities and differences in developmental network configurations and their implications for cognition and behavior across common epilepsy syndromes are of theoretical interest and clinical relevance.

Changes in background electroencephalographic activity in benign childhood epilepsy with centrotemporal spikes after oxcarbazepine treatment: a standardized low-resolution brain electromagnetic tomography (sLORETA) study.

BACKGROUND: Several neuroimaging studies have reported neurophysiological alterations in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS). However, reported outcomes have been inconsistent, and the progression of these changes in the brain remains unresolved. Moreover, background electroencephalography (EEG) in cases of BCECTS has not been performed often. METHODS: We investigated background EEG activity changes after six months of oxcarbazepine treatment to better understand the neurophysiological alterations and progression that occur in BCECTS. In 18 children with BCECTS, non-parametric statistical analyses using standardized low resolution brain electromagnetic tomography (sLORETA) were performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between untreated and treated conditions. RESULTS: Background EEG activity for the delta frequency band was significantly decreased in the fronto-temporal and limbic regions of the left hemisphere after oxcarbazepine treatment (threshold log-F-ratio = ±2.729, P < 0.01). The maximum current density difference was found in the parahippocampal gyrus of the left limbic lobe (Montreal Neurological Institute coordinate [x, y, z = 25, - 20, - 10], Brodmann area 28) (log-F-ratio = 3.081, P < 0.01). CONCLUSIONS: Our results indicate the involvement of the fronto-temporal and limbic cortices in BCECTS, and limbic lobe involvement, including the parahippocampal gyrus, was noted. In addition to evidence of the involvement of the fronto-temporal and limbic cortices in BCECTS, this study also found that an antiepileptic drug could reduce the delta frequency activity of the background EEG in these regions.

Differential patterns of dynamic functional connectivity variability of striato-cortical circuitry in children with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is characterized by abnormal (static) functional interactions among cortical and subcortical regions, regardless of the active or chronic epileptic state. However, human brain connectivity is dynamic and associated with ongoing rhythmic activity. The dynamic functional connectivity (dFC) of the distinct striato-cortical circuitry associated with or without interictal epileptiform discharges (IEDs) are poorly understood in BECTS. Herein, we captured the pattern of dFC using sliding window correlation of putamen subregions in the BECTS (without IEDs, n = 23; with IEDs, n = 20) and sex- and age-matched healthy controls (HCs, n = 28) during rest. Furthermore, we quantified dFC variability using their standard deviation. Compared with HCs and patients without IEDs, patients with IEDs exhibited excessive variability in the dorsal striatal-sensorimotor circuitry related to typical seizure semiology. By contrast, excessive stability (decreased dFC variability) was found in the ventral striatal-cognitive circuitry (p < .05, GRF corrected). In addition, correlation analysis revealed that the excessive variability in the dorsal striatal-sensorimotor circuitry was related to highly frequent IEDs (p < .05, uncorrected). Our finding of excessive variability in the dorsal striatal-sensorimotor circuitry could be an indication of increased sensitivity to regional fluctuations in the epileptogenic zone, while excessive stability in the ventral striatal-cognitive circuitry could represent compensatory mechanisms that prevent or postpone cognitive impairments in BECTS. Overall, the differentiated dynamics of the striato-cortical circuitry extend our understanding of interactions among epileptic activity, striato-cortical functional architecture, and neurocognitive processes in BECTS.

Could Rolandic spikes be a prognostic factor of the neurocognitive outcome of children with BECTS?

INTRODUCTION: Rolandic epilepsy, also known as benign childhood epilepsy with centrotemporal spikes (BECTS), is one of the most common epileptic syndromes in previously healthy children. Despite what was known about the benignity of this syndrome, there is always more evidence about the involvement of the cognitive functions with different deficits in several domains to be investigated. AIM OF THE STUDY: The aim of our study was to describe prognostic electroencephalogram (EEG) pattern of an adverse cognitive development to recognize patients at higher risk of lasting cognitive deficits that could need antiepileptic drugs (AEDs) or an improved neurocognitive therapy. In addition, we wanted to investigate the existence of a possible linkage between the number of interictal epileptiform discharges (IEDs) in the EEG and the more pronounced cognitive deficits. MATERIAL AND METHODS: We performed a case-control study on a cohort of 16 patients (10 male and 6 female) aged 4-14, diagnosed with BECTS who underwent EEG, magnetic resonance imaging (MRI), and neurocognitive assessment at the Pediatric Neurology Unit at the Umberto I Hospital, Sapienza University of Rome. Patients were divided into two groups according to the percentage of IEDs evaluated based on their sleep EEG: group A with less than 50% of the entire EEG invaded by discharges in more than 70% of the total number of EEG performed, so-called with low or intermediate activation. On the contrary, group B had a high activation, with more than 50% of the entire EEG invaded by discharges in the same percentage of the EEG performed. All children were assessed based on a protocol designed to study neuropsychological functions with specific tests chosen depending on age (Wechsler Intelligence Scale for Children IV: WISC IV; Wechsler Preschool and Primary Scale of Intelligence III: WPPSI III). Groups were compared for cognitive outcomes achieved by each patient through Student's t-test with a significance level of p<0.05 (two-tailed). RESULTS: There is no statistically significant difference in the cognitive outcomes of these patients: Student's t-test showed a statistical significance (p) for each cognitive index always higher than 0.05, demonstrating that the intellectual quotient (IQ) and all other indexes analyzed (verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI)) are not affected by the difference in EEG anomalies presented by our patients. Interestingly, all patients had an IQ equal to or greater than the Italian average (12 out of 16 patients showed an IQ>100), with selective drops, particularly significant in the WMI and also in the PSI. CONCLUSIONS: Our results clearly demonstrate the importance of a proper evaluation of patients with this kind of epilepsy, without paying attention only to those with the greatest number of IEDs or seizures because all of them had a neurocognitive impairment, especially in memory. These data may be reinforced by a larger sample for an even more significant statistical value. These results also highlight the importance of a neurocognitive therapy for these children to treat for their specific needs.

Cognitive and behavioral comorbidities in Rolandic epilepsy and their relation with default mode network's functional connectivity and organization.

OBJECTIVE: Rolandic epilepsy (RE) is characterized by typical interictal-electroencephalogram (EEG) patterns mainly localized in centrotemporal and parietooccipital areas. An aberrant intrinsic organization of the default mode network (DMN) due to repeated disturbances from spike-generating areas may be able to account for specific cognitive deficits and behavioral problems in RE. The aim of the present study was to investigate cognitive development (CD) and socioemotional development (SED) in patients with RE during active disease in relation to DMN connectivity and network topology. METHODS: In 10 children with RE and active EEG, CD was assessed using the Wechsler Intelligence Scale for Children-IV (WISC-IV); SED was assessed using the Fünf-Faktoren-Fragebogen für Kinder (FFFK), a Big-Five inventory for the assessment of personality traits in children. Functional connectivity (FC) in the DMN was determined from a 15-minute resting state functional magnetic resonance imaging (fMRI), and network properties were calculated using standard graph-theoretical measures. RESULTS: More severe deficits of verbal abilities tended to be associated with an earlier age at epilepsy onset, but were not directly related to the number of seizures and disease duration. Nonetheless, at the network level, disease duration was associated with alterations of the efficiency and centrality of parietal network nodes and midline structures. Particularly, centrality of the left inferior parietal lobe (IPL) was found to be linked with CD. Reduced centrality of the left IPL and alterations supporting a rather segregated processing within DMN's subsystems was associated with a more favorable CD. A more complicated SED was associated with high seizure frequency and long disease duration, and revealed links with a less favorable CD. SIGNIFICANCE: An impaired CD and - because of their interrelation - SED might be mediated by a common pathomechanism reflected in an aberrant organization, and thus, a potential functional deficit of the DMN. A functional segregation of (left) parietal network nodes from the DMN and a rather segregated processing mode within the DMN might have positive implications/protective value for CD in patients with RE.

Decreased Network Efficiency in Benign Epilepsy with Centrotemporal Spikes.

Purpose To investigate the functional connectome alterations in benign epilepsy with centrotemporal spikes with respect to the occurrence of interictal epileptic discharges (IEDs) during functional magnetic resonance (MR) imaging. Materials and Methods This prospective study was approved by the local institutional review board and was HIPAA compliant. All participants were consecutively enrolled with written informed consent. Forty-three right-handed patients were classified into IED (n = 20, 13 girls and seven boys; mean age ± standard deviation, 9.00 years ± 1.95) and non-IED (n = 23, 11 girls and 12 boys; mean age, 10.22 years ± 2.13) groups on the basis of electroencephalographic data simultaneously recorded during resting-state functional MR imaging at 3.0 T. The functional connectome features (estimated with graph theoretical analysis) in patient groups and control subjects who were matched for sex, age, and education level (n = 28, all right-handed, 13 girls and 15 boys; mean age, 10.00 years ± 2.31) were compared by using one-way analysis of variance. Results Patients with IEDs and those without IEDs showed consistently abnormal global topology in their functional networks (ie, decreased global efficiency; P < .05) relative to that of control subjects, with no differences between the two patient groups (P > .05). Decreased regional efficiency and connectivity strength were observed in the patients with IEDs and those without (mainly in the perirolandic and frontal areas) relative to control subjects (P < .05). Moreover, the altered functional features significantly correlated with clinical characteristics (ie, disease duration and age at symptom onset, P < .05). Conclusion These findings suggest that decreased global and regional efficiency are prominent functional deficits in children with benign epilepsy with centrotemporal spikes and can be readily identified with resting-state functional MR imaging, irrespective of IEDs. © RSNA, 2016 Online supplemental material is available for this article.

Wavelet entropy of BOLD time series: An application to Rolandic epilepsy.

PURPOSE: To assess the wavelet entropy for the characterization of intrinsic aberrant temporal irregularities in the time series of resting-state blood-oxygen-level-dependent (BOLD) signal fluctuations. Further, to evaluate the temporal irregularities (disorder/order) on a voxel-by-voxel basis in the brains of children with Rolandic epilepsy. MATERIALS AND METHODS: The BOLD time series was decomposed using the discrete wavelet transform and the wavelet entropy was calculated. Using a model time series consisting of multiple harmonics and nonstationary components, the wavelet entropy was compared with Shannon and spectral (Fourier-based) entropy. As an application, the wavelet entropy in 22 children with Rolandic epilepsy was compared to 22 age-matched healthy controls. The images were obtained by performing resting-state functional magnetic resonance imaging (fMRI) using a 3T system, an 8-element receive-only head coil, and an echo planar imaging pulse sequence ( T2*-weighted). The wavelet entropy was also compared to spectral entropy, regional homogeneity, and Shannon entropy. RESULTS: Wavelet entropy was found to identify the nonstationary components of the model time series. In Rolandic epilepsy patients, a significantly elevated wavelet entropy was observed relative to controls for the whole cerebrum (P = 0.03). Spectral entropy (P = 0.41), regional homogeneity (P = 0.52), and Shannon entropy (P = 0.32) did not reveal significant differences. CONCLUSION: The wavelet entropy measure appeared more sensitive to detect abnormalities in cerebral fluctuations represented by nonstationary effects in the BOLD time series than more conventional measures. This effect was observed in the model time series as well as in Rolandic epilepsy. These observations suggest that the brains of children with Rolandic epilepsy exhibit stronger nonstationary temporal signal fluctuations than controls. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1728-1737.

Altered brain functional connectivity induced by physical exercise may improve neuropsychological functions in patients with benign epilepsy.

OBJECTIVE: The objective of this study was to elucidate alteration in functional connectivity (FC) in patients with benign epilepsy with centrotemporal spikes (BECTS) as induced by physical exercise therapy and their correlation to the neuropsychological (NP) functions. METHODS: We analyzed 115 artifact- and spike-free 2-second epochs extracted from resting state EEG recordings before and after 5weeks of physical exercise in eight patients with BECTS. The exact Low Resolution Electromagnetic Tomography (eLORETA) was used for source reconstruction. We evaluated the cortical current source density (CSD) power across five different frequency bands (delta, theta, alpha, beta, and gamma). Altered FC between 34 regions of interests (ROIs) was then examined using lagged phase synchronization (LPS) method. We further investigated the correlation between the altered FC measures and the changes in NP test scores. RESULTS: We observed changes in CSD power following the exercise for all frequency bands and statistically significant increases in the right temporal region for the alpha band. There were a number of altered FC between the cortical ROIs in all frequency bands of interest. Furthermore, significant correlations were observed between FC measures and NP test scores at theta and alpha bands. CONCLUSION: The increased localization power at alpha band may be an indication of the positive impact of exercise in patients with BECTS. Frequency band-specific alterations in FC among cortical regions were associated with the modulation of cognitive and NP functions. The significant correlation between FC and NP tests suggests that physical exercise may mitigate the severity of BECTS, thereby enhancing NP function.

Cognition in patients with benign epilepsy with centrotemporal spikes: A study with long-term VEEG and RS-fMRI.

OBJECTIVE: The purpose of this study was to investigate the relationship between alterations of functional brain network and cognition in patients with benign epilepsy with centrotemporal spikes (BECTS) as a function of spike-wave index (SWI) during slow wave sleep. METHODS: Resting-state functional magnetic resonance imaging (RS-fMRI) data and Intelligence Quotient (IQ) were collected from two groups of patients with BECTS, including a SWI<50% group (5 cases) and a SWI≥50% group (7 cases). The SWI was calculated from the long-term video-electroencephalogram monitoring (one sleep cycle was included at least). The RS-fMRI data were analyzed by regional homogeneity (ReHo) method. RESULTS: There were three main findings. Firstly, Full Intelligence Quotient (FIQ), Verbal Intelligence Quotient (VIQ), and Performance Intelligence Quotient (PIQ) of the SWI≥50% group were significantly lower than SWI<50% group (p<0.05). Secondly, there was a negative correlation between the FIQ, VIQ, PIQ, and SWI (p<0.05), and the FIQ, VIQ, and PIQ were not dependent on age, age of onset, disease course, years of education, and total number of seizures (p>0.05). Finally, compared with the SWI<50% group, the SWI≥50% group showed increased ReHo in the bilateral precentral gyrus, bilateral premotor area, bilateral subcortical structure, right temporal lobe, and bilateral insular lobe, while they showed decreased ReHo in the posterior cingulate cortex and posterior of right inferior temporal lobe. CONCLUSIONS: The alterations of functional brain network caused by the frequent discharges during slow wave sleep could affect cognition in patients with BECTS.

The executive profile of children with Benign Epilepsy of Childhood with Centrotemporal Spikes and Temporal Lobe Epilepsy.

RATIONALE: Benign Epilepsy of Childhood with Centrotemporal Spikes (BECTS) and temporal lobe epilepsy (TLE) represent two distinct models of focal epilepsy of childhood. In both, there is evidence of executive dysfunction. The purpose of the present study was to identify particular deficits in the executive function that would distinguish children with BECTS from children with TLE. METHODS: We prospectively evaluated 19 consecutive children and adolescents with TLE with hippocampal sclerosis (HS) (57.9% male; mean 11.74years [SD 2.05]; mean IQ 95.21 [SD 15.09]), 19 with BECTS (36.8% male; mean 10.95years [SD 2.33]; mean IQ 107.40 [SD 16.01]), and 21 age and gender-matched controls (33.3% male; mean 11.86years [SD 2.25]; mean IQ 108.67 [15.05]). All participants underwent a neuropsychological assessment with a comprehensive battery for executive and attentional functions. We used ANOVA and chi-square to evaluate differences on demographic aspects among groups (BECTS, TLE-HS, and control groups). Group comparisons on continuous variables were complemented by MANOVA and Bonferroni posthoc comparisons. RESULTS: Patients with BECTS had worse performance than controls in: Matching Familiar Figures Test, time (p=0.001); Matching Familiar Figures Test, time×errors index (p<0.001); Verbal Fluency for foods (p=0.038); Trail Making Test, part B time (p=0.030); Trail Making Test, part B number of errors (p=0.030); and WCST, number of categories achieved (p=0.043). Patients with BECTS had worse performance than patients with TLE-HS on Matching Familiar Figures Test, time (p=0.004), and Matching Familiar Figures Test, time×errors index (p<0.001). Patients with TLE-HS had worse performance than controls on the following tests: Verbal Fluency for foods (p=0.004); Wisconsin Card Sorting Test, the number of categories achieved (p<0.001); and Wisconsin Card Sorting Test, the number of perseverative errors (p=0.028). Patients with TLE-HS had worse performance than patients with BECTS on Digit Backward (p=0.002); and the Wisconsin Card Sorting Test, the number of perseverative errors (p<0.001). CONCLUSIONS: Patients with TLE and BECTS present distinct cognitive profiles. Patients with TLE-HS had worse performance in mental flexibility, concept formation, and working memory compared to BECTS. Patients with BECTS had worse inhibitory control compared to children with TLE-HS. Both TLE-HS and BECTS had a higher number of errors on an inhibitory control test. However, patients with BECTS had a slower mental processing even when compared to patients with TLE-HS. Rehabilitation programs for children with epilepsy must include children with benign epilepsies and must take into account the epileptic syndrome and its particular neurocognitive phenotype.