Benign Epilepsy With Centrotemporal Spikes Patients Research Articles

Disrupted functional connectivity patterns of the left inferior frontal gyrus subregions in benign childhood epilepsy with centrotemporal spikes.

BackgroundBenign epilepsy with centrotemporal spikes (BECTS) is one of the most common pediatric epileptic syndromes. Recent studies have shown that BECTS can lead to significant language dysfunction. Although research supports the role of the left inferior frontal gyrus (LIFG) in BECTS, it is unclear whether the subregions of the LIFG show different change patterns in patients with this syndrome.MethodsUsing resting-state functional magnetic resonance imaging (fMRI) data in a group of 49 BECTS patients and 49 healthy controls, we investigated whether the BECTS patients show abnormal connectivity patterns of the LIFG subregions.ResultsCompared with healthy controls, the BECTS patients exhibited higher connectivity between the following: the inferior frontal sulcus (IFS) and the right anterior cingulate cortex (ACC), and the ventral area 44 (A44v) region and the left hippocampus/parahippocampus. Also, a decreased connectivity was found between the IFS and the left inferior temporal gyrus (ITG). No other significant differences in functional connectivity were found in the other 4 functional subregions of the LIFG in the BECTS.ConclusionsThese findings provide evidence for BECTS-related functional connectivity patterns of the LIFG subregions and suggest that different subregions may be involved in different neural circuits associated with language function in the BECTS.

Frequency-Dependent Interictal Neuromagnetic Activities in Children With Benign Epilepsy With Centrotemporal Spikes: A Magnetoencephalography (MEG) Study.

Objective: This study aimed to investigate interictal neuromagnetic activities in the low- to high-frequency ranges in patients with benign epilepsy with centrotemporal spikes (BECTS), especially those without interictal epileptiform discharges (IEDs).Methods: We studied 21 clinically-diagnosed BECTS patients and 11 age-matched healthy controls (HC) using high-sampling magnetoencephalography (MEG). Neuromagnetic sources were assessed with accumulated source imaging (ASI). The MEG data were analyzed in seven frequency bands. The MEG recordings distinguished BECTS without IEDs (n = 10) from those with IEDs (n = 11) and HC (n = 11).Results: At 1–4 Hz, the neuromagnetic activities in healthy subjects tended to locate at the precuneus/posterior cingulate, while those of the BECTS patients without IEDs tended to locate at the medial frontal cortex (MFC) compared to BECTS patients with IEDs. The MEG source imaging at 30–80 Hz revealed that BECTS patients without IEDs had higher occurrences of interictal brain activity in the medial temporal lobe (MTL) compared to controls and the brain activity strength seemed to be weaker. There was a significant correlation between the source strength of the interictal gamma oscillations of BECTS patients without IEDs and the duration of epilepsy.Conclusions: IEDs might disrupt the default mode network (DMN). Aberrant brain activities in BECTS patients without IEDs were associated with cognitive areas of the brain. The strength of gamma oscillations in the chronic epilepsy state reflected the duration of BECTS.Significance: MEG could reveal the aberrant neural activities in BECTS patients during the interictal period, and such abnormality is frequency-dependent. Gamma oscillations could be used to identify BECTS patients without IEDs.

Cortical thinning in benign epilepsy with centrotemporal spikes (BECTS) with or without attention-deficit/hyperactivity (ADHD)

The aim of this study is to evaluate the abnormal cortical structures associated with newly diagnosed benign epilepsy with centrotemporal spikes (BECTS) patients and assessed the effects of comorbid attention-deficit/hyperactivity (ADHD) on these abnormalities. Newly diagnosed BECTS patients (n = 33, 23 males) and age-matched healthy controls (n = 48) were evaluated by surface and volumetric MRI. CAT12 toolbox (HYPERLINK “http://www.neuro.uni-jena.de/cat/”\ “_blank” http://www.neuro.uni-jena.de/cat/, version r1109), SPM12(HYPERLINK“http://www.fil.ion.ucl.ac.uk/spm/software/spm12/”\ “_blank”http://www.fil.ion.ucl.ac.uk/spm/software/spm12/, version 6225) and MATLAB (9.5, Mathworks, Natick, MA) were used to gather CT estimates. An additional comparison was performed between BECTS children with (n = 13) and without ADHD (n = 20). BECTS patients had significantly smaller volume in left postcentral gyrus when compared to healthy controls. BECTS patients with ADHD had significantly thinner superior-inferior frontal cortex, superior temporal cortex, left pericalcarine, lingual and fusiform cortex to healthy controls. Also BECTS without ADHD patients had thinner cortical areas when compared to healthy controls, however the significance was more relevant in the BECTS with ADHD. The left fusiform cortex of BECTS patients with ADHD patients was significantly thinner than BECTS patients without ADHD. Our results showed that BECTS affects frontal, temporal, parietal and occipital lobes by cortical thinning. Our study supports the need for better characterization of patients with BECTS so identification of different phenotypes can occur. Further studies are needed to investigate the relationship between BECTS and ADHD.

Electroencephalographic Resting-State Functional Connectivity of Benign Epilepsy with Centrotemporal Spikes.

Background and PurposeWe aimed to reveal resting-state functional connectivity characteristics based on the spike-free waking electroencephalogram (EEG) of benign epilepsy with centrotemporal spikes (BECTS) patients, which usually appears normal in routine visual inspection.MethodsThirty BECTS patients and 30 disease-free and age- and sex-matched controls were included. Eight-second EEG epochs without artifacts were sampled and then bandpass filtered into the delta, theta, lower alpha, upper alpha, and beta bands to construct the association matrix. The weighted phase lag index (wPLI) was used as an association measure for EEG signals. The band-specific connectivity, which was represented as a matrix of wPLI values of all edges, was compared for analyzing the connectivity itself. The global wPLI, characteristic path length (CPL), and mean clustering coefficient were compared.ResultsThe resting-state functional connectivity itself and the network topology differed in the BECTS patients. For the lower-alpha-band and beta-band connectivity, edges that showed significant differences had consistently lower wPLI values compared to the disease-free controls. The global wPLI value was significantly lower for BECTS patients than for the controls in lower-alpha-band connectivity (mean±SD; 0.241±0.034 vs. 0.276±0.054, p=0.024), while the CPL was significantly longer for BECTS in the same frequency band (mean±SD; 4.379±0.574 vs. 3.904±0.695, p=0.04). The resting-state functional connectivity of BECTS showed decreased connectivity, integration, and efficiency compared to controls.ConclusionsThe connectivity differed significantly between BECTS patients and disease-free controls. In BECTS, global connectivity was significantly decreased and the resting-state functional connectivity showed lower efficiency in the lower alpha band.

Language-Related White-Matter-Tract Deficits in Children with Benign Epilepsy with Centrotemporal Spikes: A Retrospective Study.

Background and PurposeBenign epilepsy with centrotemporal spikes (BECTS) is one of the most common pediatric epilepsies, and it generally has a good prognosis. However, recent research has indicated that the epileptic activity of BECTS can cause cognitive defects such as language, visuospatial, and auditory verbal memory deficits. This study assessed language-delivery deficits in BECTS patients using diffusion-tensor magnetic resonance imaging (DTI).MethodsT1-weighted MRI, DTI, and language tests were conducted in 16 BECTS patients and 16 age-matched controls. DTI data were analyzed using the TRActs Constrained by Underlying Anatomy tool in FreeSurfer 5.3, and 18 major white-matter tracts were extracted, which included 4 language-related tracts: the inferior longitudinal fasciculus, superior longitudinal fasciculus-parietal terminations, superior longitudinal fasciculus-temporal terminations, and uncinate fasciculus (UNC). Language tests included the Korean version of the Receptive and Expressive Vocabulary Test, Test of Problem-Solving Abilities (TOPS), and the mean length of utterance in words.ResultsThe BECTS group exhibited decreased mean fractional anisotropy and increased mean radial diffusivity, with significant differences in both the superior longitudinal fasciculus and the left UNC (p<0.05), which are the language-related white-matter tracts in the dual-loop model. The TOPS language test scores were significantly lower in the BECTS group than in the control group (p<0.05).ConclusionsIt appears that BECTS patients can exhibit language deficits. Seizure activities of BECTS could alter DTI scalar values in the language-related white-matter tracts.

Network characteristics in benign epilepsy with centro-temporal spikes patients indicating defective connectivity during spindle sleep: A partial directed coherence study of EEG signals

ObjectiveTo investigate the changes in EEG connectivity in children with the typical presentation of benign epilepsy with centro-temporal spikes (BECTS). MethodsWe compared awake and spindle-sleep EEG recordings obtained by a standard electrode array in patients with lateralised (10 Right, 9 Left-BECTS) or bilateral spikes (10 MF-BECTS) and in 17 age-matched controls. We analysed EEG activity using partial directed coherence, an estimator of connectivity based on the multivariate autoregressive models and calculated in- and out-degrees, strength, clustering coefficient and betweenness centrality. ResultsIn comparison with the controls, the awake EEG recordings of the patients with lateralised BECTS showed a minimal increase in out-degrees on F4 and F3. The greater differences, found during sleep, included significant reductions in both in- and out-degrees and strength in all of the patient groups, but in T4 or T3 showing increased out-degrees and strength in Right and Left-BECTS. Betweenness centrality was significantly reduced on C3 and C4 in the patients with MF-BECTS. ConclusionsOur observations suggest that the main finding in BECTS patients is widely reduced local connectivity. SignificanceThe network changes in BECTS can be interpreted as a permissive condition occurring in a developmental window that predisposes to seizure generation during spindle-sleep.

Spike persistence and normalization in benign epilepsy with centrotemporal spikes – Implications for management

PurposeThis study was performed 1) to determine the timing of spike normalization in patients with benign epilepsy with centrotemporal spikes (BECTS); 2) to identify relationships between age of seizure onset, age of spike normalization, years of spike persistence and treatment; and 3) to assess final outcomes between groups of patients with or without spikes at the time of medication tapering. MethodsRetrospective analysis of BECTS patients confirmed by clinical data, including age of onset, seizure semiology and serial electroencephalography (EEG) from diagnosis to remission. Age at spike normalization, years of spike persistence, and time of treatment onset to spike normalization were assessed. Final seizure and EEG outcome were compared between the groups with or without spikes at the time of AED tapering. ResultsOne hundred and thirty-four patients were included. Mean age at seizure onset was 7.52 ± 2.11 years. Mean age at spike normalization was 11.89 ± 2.11 (range: 6.3–16.8) years. Mean time of treatment onset to spike normalization was 4.11 ± 2.13 (range: 0.24–10.08) years. Younger age of seizure onset was correlated with longer duration of spike persistence (r = −0.41, p < 0.001). In treated patients, spikes persisted for 4.1 ± 1.95 years, compared with 2.9 ± 1.97 years in untreated patients. No patients had recurrent seizures after AED was discontinued, regardless of the presence/absence of spikes at time of AED tapering. ConclusionYears of spike persistence was longer in early onset BECTS patients. Treatment with AEDs did not shorten years of spike persistence. Persistence of spikes at time of treatment withdrawal was not associated with seizure recurrence.

S13. Local and distant dysregulation of synchronization around interictal spikes in BECTS

High Density electroencephalography (HD EEG) is the reference non-invasive technique to investigate the dynamics of neuronal networks in Benign Epilepsy with Centro-Temporal Spikes (BECTS). Analysis of local dynamic changes surrounding Interictal Epileptic Spikes (IES) might improve our knowledge of the mechanisms that propel neurons to the hypersynchronization of IES in BECTS. Transient distant changes in the dynamics of neurons populations may also interact with neuronal networks involved in various functions that are impaired in BECTS patients. HD EEG (64 electrodes) of eight well characterized BECTS patients (8 males; mean age: 7.2 years, range: 5–9 years) were analyzed. Unilateral IES were selected in 6 patients. They were bilateral and independent in 2 other patients. This resulted in a total of 10 groups of IES. Time–frequency analysis was performed on HD EEG epochs around the peak of the IES (±1000 ms), including phase-locked and non-phase-locked activities to the IES. The time frequency analyses were calculated for the frequencies between 4 and 200 Hz Time–frequency analysis revealed two patterns of dysregulation of the synchronization between neuronal networks preceding and following hypersynchronization of interictal spikes (±400 ms) in the epileptogenic zone. Dysregulation consists of either desynchronization (n = 6) or oscillating synchronization (n = 4) (4–50 Hz) surrounding the IES. The 2 patients with bilateral IES exhibited only local desynchronization whatever the IES considered. Distant desynchronization in low frequencies within the same window occurs simultaneously in bilateral frontal, temporal and occipital areas (n = 7). Using time–frequency analysis of HD EEG data in a well-defined population of BECTS, we demonstrated repeated complex changes in the dynamics of neuronal networks not only during, but also, before and after the IES. In the epileptogenic zone, our results found more complex reorganization of the local network than initially thought. In line with previous results obtained at a microscopic or macroscopic level, these changes suggested the variability strategies of neuronal assemblies to raise IES. Distant changes from the epileptogenic zone in desynchronization observed in the same time window suggested interactions between larger embedded networks and opened new avenues about their possible role in the underlying mechanism leading to cognitive deficits.

Epileptic Discharge Related Functional Connectivity Within and Between Networks in Benign Epilepsy with Centrotemporal Spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is a common childhood epilepsy syndrome associated with abnormalities in neurocognitive domains, particularly during interictal epileptiform discharges (IEDs). Here, we investigated the effects of IEDs on brain's intrinsic connectivity networks in 43 BECTS patients and 28 matched healthy controls (HCs). Patients were further divided into IED and non-IED subgroups based on simultaneous EEG-fMRI recordings. Functional connectivity within and between five networks, corresponding to seizure origination and cognitive processes, were analyzed to measure IED effects. We found that patients exhibited increased connectivity within the auditory network (AN) and the somato-motor network (SMN), and decreased connectivity within the basal ganglia network and the dorsal attention network, suggesting that both transient and chronic seizure activity may disturb normal network organization. The IED group showed decreased functional connectivity within the default mode network (DMN) compared with the non-IED group and HCs, implying that the DMN was selectively impaired during epileptiform discharges associated with altered self-referential cognitive functions. Moreover, the IED group exhibited increased positive correlations between the AN and the SMN, which suggests a possible excessive influence of centrotemporal spiking on information processing in the auditory system. The association between epileptic activity and network dysfunctions highlights their importance in investigating the pathological mechanism underlying BECTS.

P233 Local and distant dysregulation of synchronization around interictal spikes in bects

Introduction High Density electroencephalography (HD EEG) is the reference non-invasive technique to investigate the dynamics of neuronal networks in Benign Epilepsy with Centro-Temporal Spikes (BECTS). Analysis of local dynamic changes surrounding Interictal Epileptic Spikes (IES) might improve our knowledge of the mechanisms that propel neurons to the hypersynchronization of IES in BECTS. Transient distant changes in the dynamics of neurons populations may also interact with neuronal networks involved in various functions that are impaired in BECTS patients. Methods HD EEG (64 electrodes) of eight well characterized BECTS patients (8 males; mean age: 7.2 years, range: 5–9 years) were analyzed. Unilateral IES were selected in 6 patients. They were bilateral and independent in 2 other patients. This resulted in a total of 10 groups of IES. Time–frequency analysis was performed on HD EEG epochs around the peak of the IES (±1000 ms), including phase-locked and non-phase-locked activities to the IES. The time frequency analyses were calculated for the frequencies between 4 and 200 Hz Results Time–frequency analysis revealed two patterns of dysregulation of the synchronization between neuronal networks preceding and following hypersynchronization of interictal spikes (±400 ms) in the epileptogenic zone. Dysregulation consists of either desynchronization (n = 6) or oscillating synchronization (n = 4) (4–50 Hz) surrounding the IES. The 2 patients with bilateral IES exhibited only local desynchronization whatever the IES considered. Distant desynchronization in low frequencies within the same window occurs simultaneously in bilateral frontal, temporal and occipital areas (n = 7). Conclusion Using time–frequency analysis of HD EEG data in a well-defined population of BECTS, we demonstrated repeated complex changes in the dynamics of neuronal networks not only during, but also, before and after the IES. In the epileptogenic zone, our results found more complex reorganization of the local network than initially thought. In line with previous results obtained at a microscopic or macroscopic level, these changes suggested the variability strategies of neuronal assemblies to raise IES. Distant changes from the epileptogenic zone in desynchronization observed in the same time window suggested interactions between larger embedded networks and opened new avenues about their possible role in the underlying mechanism leading to cognitive deficits.

Abnormal asymmetry in benign epilepsy with unilateral and bilateral centrotemporal spikes: A combined fMRI and DTI study

Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic focal childhood epilepsy associated with either unilateral or bilateral epileptic discharge. Asymmetry as an important characteristic of the human brain is beneficial for brain functions. However, little is known about on asymmetry of BECTS patients with different epileptic spikes pattern. In the present study, we investigated functional and structural asymmetries in unilateral spikes BECTS (U_BECTS) patients and bilateral spikes BECTS (B_BECTS) patients using resting state functional magnetic resonance images and diffusion tensor imaging. Compared with the controls, we observed a decreased voxel-mirrored interhemispheric functional connectivity (FC) in primary sensorimotor cortex (SM1) in U_BECTS and B_BECTS groups, and reduced fractional anisotropy (FA) values of the corpus callosum (CC) connecting bilateral SM1 were also observed in B_BECTS group. Further region-based FC map analysis of SM1 demonstrated increased functional asymmetry with ipsilateral hemisphere, contralateral hemisphere and the whole brain in U_BECTS and increased functional asymmetry with the contralateral hemisphere and the whole brain in B_BECTS groups. The correlation between functional asymmetry of SM1 and intelligence quotient scores was found in the U_BECTS group. The altered asymmetries of the SM1 further indicated the important role of SM1 in the pathophysiology of the BECTS. Furthermore, the B_BECTS group also showed abnormal voxel-mirrored interhemispheric FC in the temporal pole, the lobule IX of the cerebellum, the caudate and the occipital cortex relative to the controls. Altogether, our findings provide additional insight into the neuronal mechanism of BECTS with different epileptic spikes pattern and cognitive impairments with BECTS patients.

Changes in functional organization and functional connectivity during story listening in children with benign childhood epilepsy with centro-temporal spikes

Children with Benign Epilepsy with Centrotemporal Spikes (BECTS), despite high likelihood for seizure remission, are reported to have subtle difficulties in language and other cognitive skills. We used functional MRI and a story listening task to examine the effect of BECTS on patterns of activation and connectivity. Language and cognitive skills were assessed using standardized measures. Twenty-four children with recently diagnosed BECTS and 40 typically-developing children participated. In a functionally-defined region of interest in right inferior frontal gyrus, BECTS patients showed a lower level of activation. Across both groups combined, increased activation in superior/middle temporal regions of interest was associated with better language scores. Connectivity in the story processing network was similar between groups, but connectivity within left inferior frontal gyrus was decreased in children with BECTS. These results suggest that language networks are largely maintained in new-onset BECTS, but some subtle changes in activation and connectivity can be observed.

Local and Distant Dysregulation of Synchronization Around Interictal Spikes in BECTS.

Objective: High Density electroencephalography (HD EEG) is the reference non-invasive technique to investigate the dynamics of neuronal networks in Benign Epilepsy with Centro-Temporal Spikes (BECTS). Analysis of local dynamic changes surrounding Interictal Epileptic Spikes (IES) might improve our knowledge of the mechanisms that propel neurons to the hypersynchronization of IES in BECTS. Transient distant changes in the dynamics of neurons populations may also interact with neuronal networks involved in various functions that are impaired in BECTS patients.Methods: HD EEG (64 electrodes) of eight well-characterized BECTS patients (8 males; mean age: 7.2 years, range: 5–9 years) were analyzed. Unilateral IES were selected in 6 patients. They were bilateral and independent in 2 other patients. This resulted in a total of 10 groups of IES. Time-frequency analysis was performed on HD EEG epochs around the peak of the IES (±1000 ms), including phase-locked and non-phase-locked activities to the IES. The time frequency analyses were calculated for the frequencies between 4 and 200 Hz.Results: Time-frequency analysis revealed two patterns of dysregulation of the synchronization between neuronal networks preceding and following hypersynchronization of interictal spikes (±400 ms) in the epileptogenic zone. Dysregulation consists of either desynchronization (n = 6) or oscillating synchronization (n = 4) (4–50 Hz) surrounding the IES. The 2 patients with bilateral IES exhibited only local desynchronization whatever the IES considered. Distant desynchronization in low frequencies within the same window occurs simultaneously in bilateral frontal, temporal and occipital areas (n = 7).Significance: Using time-frequency analysis of HD EEG data in a well-defined population of BECTS, we demonstrated repeated complex changes in the dynamics of neuronal networks not only during, but also, before and after the IES. In the epileptogenic zone, our results found more complex reorganization of the local network than initially thought. In line with previous results obtained at a microscopic or macroscopic level, these changes suggested the variability strategies of neuronal assemblies to raise IES. Distant changes from the epileptogenic zone in desynchronization observed in the same time window suggested interactions between larger embedded networks and opened new avenues about their possible role in the underlying mechanism leading to cognitive deficits.

Impact of frequency and lateralization of interictal discharges on neuropsychological and fine motor status in children with benign epilepsy with centrotemporal spikes.

Despite a positive prognosis for seizure remission, children with benign epilepsy with centrotemporal spikes (BECTS) have been reported to exhibit subtle neuropsychological difficulties. We examined the relationship between patterns of centrotemporal spikes (the typical electroencephalography [EEG] finding in BECTS) and neuropsychological and motor outcomes in children with new-onset BECTS. Thirty-four patients with new-onset BECTS (not taking antiepileptic medication) and 48 typically developing children participated in the study. In BECTS patients, centrotemporal spikes (CTS) were evaluated in the first hour awake and first 2 h of sleep in a 24-h EEG recording and left or right-sided origin was noted. General intellectual function, language, visuospatial skill, processing speed, and fine motor skill were assessed in all participants. We found no significant difference between BECTS patients and controls on measures of general intellectual function, or visuospatial or language testing. There were significant differences in processing speed index and nondominant hand fine motor scores between groups. Significant negative relationships were observed between rates of left-sided CTS and right hand fine motor scores. This suggests that psychomotor and fine motor speed are affected in BECTS, but the extent of affected domains may be more limited than previously suggested, especially in untreated patients early in the course of their epilepsy.

Mutation screening of the PRRT2 gene for benign epilepsy with centrotemporal spikes in Chinese mainland population

Proline-rich transmembrane protein 2 gene (PRRT2) mutations are reported to cause common paroxysmal neurological disorders and show a remarkable pleiotropy. Benign epilepsy with centrotemporal spikes (BECTS) is considered to be the most common epilepsy syndrome in childhood. It is placed among the idiopathic localization related epilepsies. Recently, it was reported that a girl with a PRRT2 mutation c.649_650insC developed infantile focal epilepsy with bilateral spikes which resembled the rolandic spikes. Hereby we performed a comprehensive genetic mutation screening of PRRT2 gene in a cohort of 53 sporadic BECTS patients. None of the 53 sporadic BECTS patients and other 250 controls carried mutations including c.649_650insC in PRRT2. Our data indicated that the PRRT2 mutations might most likely not be associated with BECTS in Chinese mainland population.

Intrinsic brain activity as a diagnostic biomarker in children with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting-state functional magnetic resonance imaging (RS-fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age-matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS-fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878-3889, 2015. © 2015 Wiley Periodicals, Inc.

Resting-state oscillatory dynamics in sensorimotor cortex in benign epilepsy with centro-temporal spikes and typical brain development.

Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a common childhood epilepsy associated with deficits in several neurocognitive domains. Neurophysiological studies in BECTS often focus on centro-temporal spikes, but these correlate poorly with morphology and cognitive impairments. To better understand the neural profile of BECTS, we studied background brain oscillations, thought to be integrally involved in neural network communication, in sensorimotor areas. We used independent component analysis of temporally correlated sources on magnetoencephalography recordings to assess sensorimotor resting-state network activity in BECTS patients and typically developing controls. We also investigated the variability of oscillatory characteristics within focal primary motor cortex (M1), localized with a separate finger abduction task. We hypothesized that background oscillations would differ between patients and controls in the sensorimotor network but not elsewhere, especially in the beta band (13-30 Hz) because of its role in network communication and motor processing. The results support our hypothesis: in the sensorimotor network, patients had a greater variability in oscillatory amplitude compared to controls, whereas there was no difference in the visual network. Network measures did not correlate with age. The coefficient of variation of resting M1 peak frequency correlated negatively with age in the beta band only, and was greater than average for a number of patients. Our results point toward a "disorganized" functional sensorimotor network in BECTS, supporting a neurodevelopmental delay in sensorimotor cortex. Our findings further suggest that investigating the variability of oscillatory peak frequency may be a useful tool to investigate deficits of disorganization in neurodevelopmental disorders.

EEG resting state analysis of cortical sources in patients with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic childhood epilepsy, which is often associated with developmental disorders in children. In the present study, we analyzed resting state EEG spectral changes in the sensor and source spaces in eight BECTS patients compared with nine age-matched controls. Using high-resolution scalp EEG data, we assessed statistical differences in spatial distributions of EEG power spectra and cortical sources of resting state EEG rhythms in five frequency bands: δ (0.5–3.5 Hz), θ (4–8 Hz), α (8.5–13 Hz), β1 (13.5–20 Hz) and β2 (20.5–30 Hz) under the eyes-closed resting state condition. To further investigate the impact of centrotemporal spikes on EEG spectra, we split the EEG data of the patient group into EEG portions with and without spikes. Source localization demonstrated the homogeneity of our population of BECTS patients with a common epileptic zone over the right centrotemporal region. Significant differences in terms of both spectral power and cortical source densities were observed between controls and patients. Patients were characterized by significantly increased relative power in θ, α, β1 and β2 bands in the right centrotemporal areas over the spike zone and in the right temporo-parieto-occipital junction. Furthermore, the relative power in all bands significantly decreased in the bilateral frontal and parieto-occipital areas of patients regardless of the presence or absence of spikes in EEG segments. However, the spectral differences between patients and controls were more pronounced in the presence of spikes. This observation emphasized the impact of benign epilepsy on cortical source power, especially in the right centrotemporal regions. Spectral changes in bilateral frontal and parieto-occipital areas may also suggest alterations in the default mode network in BECTS patients.

Cognitive impairment and cortical reorganization in children with benign epilepsy with centrotemporal spikes

Benign epilepsy with centrotemporal spikes (BECTS) is associated with mild cognitive deficits, especially language impairment. This study aimed to clarify whether children with BECTS with left- or right-hemispheric, or bilateral focus have specific neuropsychological language deficits when compared to healthy controls, whether these deficits correlate functionally with language network organization (typical vs. atypical), and whether cofactors such as duration, handedness, and medication have a relevant impact on language reorganization processes. Twenty-seven patients and 19 healthy controls were examined with several neuropsychological tests (German version of the Wechsler Intelligence Scale for Children [WISC-IV], Regensburger verbal fluency test [RWT], Corsiblock forward and backward and Hand-Dominanz-Test [HDT]) and with two language paradigms on functional magnetic resonance imaging (fMRI): silent reading of word-pairs and silent generation of simple sentences. Although neuropsychological test results only differed by trend between BECTS patients and controls, language laterality indices (LIs) in fMRI were significantly lower in patients than in controls. In particular, the anterior language network with Broca's area and the supplementary motor area (SMA) revealed the lowest LIs and showed the most bilateral or right hemispheric activations in the sentence generation task. Medication and duration of epilepsy did not have any significant effect on language reorganization and patients' performances. Language reorganization in BECTS patients takes place in bilateral or right hemispheric language networks, with a strong focus in anterior language regions. These functional changes can be interpreted as important compensatory strategies of the central nervous system (CNS) to stabilize cognitive, especially language performance.

Focal epileptiform spikes do not show a canonical BOLD response in patients with benign rolandic epilepsy (BECTS)

Simultaneous EEG and functional MRI (EEG-fMRI) studies of focal epileptiform spikes commonly use the canonical haemodynamic response function (HRF) to model the blood-oxygenation-level-dependent (BOLD) response to these events. Support for the use of the canonical HRF has come from large studies that contain mixed cohorts of epilepsy syndromes and discharge types, and has demonstrated plausible epileptic localisation results in the majority of patients. Other studies, however, have reported that some patients show a BOLD response that differs markedly from a canonical HRF. Our aim in this study was to see if the BOLD response is well modelled by a canonical HRF in a homogeneous cohort of patients with benign epilepsy with centrotemporal spikes (BECTS), an idiopathic partial epilepsy with stereotypical centrotemporal spikes on the EEG. We studied eight well-characterised and typical BECTS patients and found that the shape of the average BOLD response was different to the canonical HRF. Furthermore, a localisation analysis using the group-average response provided increased sensitivity and specificity compared to the canonical HRF. Our findings suggest that the canonical HRF may not provide the best model for the BOLD response in some epilepsy syndromes or spike-types. In studies of homogeneous patient groups, therefore, localisation results may be improved by using a group-specific BOLD response.