Default mode network alterations during language task performance in children with benign epilepsy with centrotemporal spikes (BECTS).

Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic epileptic disorder in children. Besides reported cognitive deficits, functional alterations mostly in the reorganization of language areas have also been described. In several publications, it has been reported that activation of the default mode network (DMN) can be reduced or altered in different neuropsychiatric and neurological disorders in adults. Whether this also holds true for children with epilepsy has so far not been clarified. To determine the functional activation of the DMN in children with BECTS, 20 patients and 16 healthy controls were examined using functional magnetic resonance imaging (fMRI), while a sentence generation task and a reading task were applied in a block design manner. To study the default mode network and the functional alterations between groups, an independent component analysis (ICA) was computed and further analyzed using SPM5. Compared with controls, children with BECTS showed not only significantly less activation of the DMN during the rest condition but also less deactivation during cognitive effort. This was most apparent in the precuneus, a key region of the DMN, while subjects were generating sentences. From these findings, we hypothesize that children with BECTS show a functional deficit that is reflected by alterations in the DMN.

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

PURPOSE: 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. METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.

6-year course of sleep homeostasis in a case with epilepsy-aphasia spectrum disorder.

The epilepsy-aphasia spectrum consists of epilepsies with a strong activation of epileptic discharges during non-rapid-eye-movement (NREM) sleep, variable seizure burden and language problems. The homeostatic decrease of slow waves (SW) during NREM sleep (i.e. their amplitude/slope and power) has been related to brain recovery and cognitive function. Epileptic discharges during NREM-sleep were related to an impairment of the decrease of the slope of SW and to cognitive deficits. In this longitudinal case study, we aim to relate this electrophysiological marker, i.e. overnight change of slope of SW, to imaging and behavior. We report a young girl with a fluctuating course in the epilepsy-aphasia spectrum, ranging from the benign end with self-limited childhood epilepsy with centrotemporal spikes (SLECTS) to the severe end with epileptic encephalopathy with continuous spike waves during sleep (CSWS) with two phases of cognitive regression. She was documented over a period of six years including 12 PSGs, six language fMRIs and seven neuropsychological assessments. We longitudinally studied focal and total spike wave index (SWI), detected SW during NREM sleep, calculated their slopes (first and last hour of NREM sleep and overnight change). Deterioration of overnight decrease of the slope of SW was paralleled by the occurrence of the EEG picture of bilateral synchronous electrical status epilepticus during sleep (ESES) and neuropsychological deficits, and this impairment was reversible with resolution of ESES and was accompanied by cognitive improvement. A laterality switch from left to right sided language dominance occurred during recovery from the second regression phase. This might reflect a compensating process. Later, the laterality switched back to the left, possibly facilitated by a low SWI on the left hemisphere. The qualitative analysis of this case supports the view that the longitudinal course of the overnight change of the slope of SW, as an objective, quantitative EEG measure, is related to the course of cognitive function and functional language MR analysis.

Effects of gestational age on brain volume and cognitive functions in generally healthy very preterm born children during school-age: A voxel-based morphometry study.

OBJECTIVE: To determine whether the relationship of gestational age (GA) with brain volumes and cognitive functions is linear or whether it follows a threshold model in preterm and term born children during school-age. STUDY DESIGN: We studied 106 children (M = 10 years 1 month, SD = 16 months; 40 females) enrolled in primary school: 57 were healthy very preterm children (10 children born 24-27 completed weeks' gestation (extremely preterm), 14 children born 28-29 completed weeks' gestation, 19 children born 30-31 completed weeks' gestation (very preterm), and 14 born 32 completed weeks' gestation (moderately preterm)) all born appropriate for GA (AGA) and 49 term-born children. Neuroimaging involved voxel-based morphometry with the statistical parametric mapping software. Cognitive functions were assessed with the WISC-IV. General Linear Models and multiple regressions were conducted controlling age, sex, and maternal education. RESULTS: Compared to groups of children born 30 completed weeks' gestation and later, children born <28 completed weeks' gestation had less gray matter volume (GMV) and white matter volume (WMV) and poorer cognitive functions including decreased full scale IQ, and processing speed. Differences in GMV partially mediated the relationship between GA and full scale IQ in preterm born children. CONCLUSIONS: In preterm children who are born AGA and without major complications GA is associated with brain volume and cognitive functions. In particular, decreased brain volume becomes evident in the extremely preterm group (born <28 completed weeks' gestation). In preterm children born 30 completed weeks' gestation and later the relationship of GA with brain volume and cognitive functions may be less strong as previously thought.

Sub-cortical brain morphometry and its relationship with cognition in rolandic epilepsy.

PURPOSE: Rolandic epilepsy (RE), also called benign epilepsy with centrotemporal spikes (BECTS) is the most common childhood epilepsy syndrome. RE is associated with cognitive difficulties, which can affect children's quality of life. The underlying causes of these cognitive impairments are unclear. The objective of this prospective study is to investigate sub-cortical morphological alterations in RE children with left, right, or bilateral hemispheric focus and its association with cognition. METHODS: Participants include 41 children with rolandic epilepsy and 38 healthy controls (age 8-14 years), recruited from CHU Sainte-Justine Montreal Children Hospital (N=40) and Basel's Children Hospital (N=39). Quantitative volumetric assessment of putamen and caudate structures was performed on T1-weighted MR scans along with the morphological analysis to test for differences between patients and controls. These analyses were performed considering the side of epilepsy focus in all participants. Correlations were investigated between the sub-cortical morphometry and cognitive indices such as intelligence quotient (IQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI). RESULTS: Children with bilateral BECTS showed statistically significant volume reduction in right caudate (p<.05), while no statistically significant putamen volumetric changes were detected in BECTS participants compared to normal controls. According to a spectral-based groupwise shape analysis, regional alterations were found in both putamen and caudate structures of children with BECTS. In particular, children with left BECTS showed significant outward local deformity in left putamen and individuals with bilateral BECTS showed inward local group differences in both right putamen and right caudate. The correlation assessment showed positive association between the volume of the left caudate and cognitive indices in the group containing all BECTS participants. Negative correlation was found between putamen sub-regional shape alterations and cognition in individuals with right BECTS and in all BECTS participants. Negative associations between caudate sub-regional morphologies and cognitive indices were detected in left cohort. SIGNIFICANCE: We have confirmed putamen and caudate shape alterations in children with BECTS. However, our results further suggest that variations in sub-cortical shape affect cognitive functions. Importantly, we have demonstrated that shape alterations and their relation with cognition depend on the side of epilepsy focus. Our results point to different syndromic entities in the BECTS population.

Statistical shape analysis of subcortical structures using spectral matching.

Studying morphological changes of subcortical structures often predicate neurodevelopmental and neurodegenerative diseases, such as Alzheimer's disease and schizophrenia. Hence, methods for quantifying morphological variations in the brain anatomy, including groupwise shape analyses, are becoming increasingly important for studying neurological disorders. In this paper, a novel groupwise shape analysis approach is proposed to detect regional morphological alterations in subcortical structures between two study groups, e.g., healthy and pathological subjects. The proposed scheme extracts smoothed triangulated surface meshes from segmented binary maps, and establishes reliable point-to-point correspondences among the population of surfaces using a spectral matching method. Mean curvature features are incorporated in the matching process, in order to increase the accuracy of the established surface correspondence. The mean shapes are created as the geometric mean of all surfaces in each group, and a distance map between these shapes is used to characterize the morphological changes between the two study groups. The resulting distance map is further analyzed to check for statistically significant differences between two populations. The performance of the proposed framework is evaluated on two separate subcortical structures (hippocampus and putamen). Furthermore, the proposed methodology is validated in a clinical application for detecting abnormal subcortical shape variations in Alzheimer's disease. Experimental results show that the proposed method is comparable to state-of-the-art algorithms, has less computational cost, and is more sensitive to small morphological variations in patients with neuropathologies.