Explore the vast range of titles available.

This magnetoencephalography (MEG) study investigates how procedural sequence learning performance is related to prior brain resting-state functional connectivity (rsFC), and to what extent sequence learning induces rapid changes in brain rsFC in school-aged children. Procedural learning was assessed in 30 typically developing children (mean age ± SD: 9.99 years ± 1.35) using a serial reaction time task (SRTT). During SRTT, participants touched as quickly and accurately as possible a stimulus sequentially or randomly appearing in one of the quadrants of a touchscreen. Band-limited power envelope correlation (brain rsFC) was applied to MEG data acquired at rest pre- and post-learning. Correlation analyses were performed between brain rsFC and sequence-specific learning or response time indices. Stronger pre-learning interhemispheric rsFC between inferior parietal and primary somatosensory/motor areas correlated with better subsequent sequence learning performance and faster visuomotor response time. Faster response time was associated with post-learning decreased rsFC within the dorsal extra-striate visual stream and increased rsFC between temporo-cerebellar regions. In school-aged children, variations in functional brain architecture at rest within the sensorimotor network account for interindividual differences in sequence learning and visuomotor performance. After learning, rapid adjustments in functional brain architecture are associated with visuomotor performance but not sequence learning skills.

Magnetoencephalography (MEG) allows the non-invasive detection of interictal epileptiform discharges (IEDs). Clinical MEG analysis in epileptic patients traditionally relies on the visual identification of IEDs, which is time consuming and partially subjective. Automatic, data-driven detection methods exist but show limited performance. Still, the rise of deep learning (DL)—with its ability to reproduce human-like abilities—could revolutionize clinical MEG practice. Here, we developed and validated STIED, a simple yet powerful supervised DL algorithm combining two convolutional neural networks with temporal (1D time-course) and spatial (2D topography) features of MEG signals inspired from current clinical guidelines. Our DL model enabled a successful identification of IEDs in patients suffering from focal epilepsy with frequent and high amplitude spikes (FE group), with high-performance metrics—accuracy, specificity, and sensitivity all exceeding 85%—when learning from spatiotemporal features of IEDs. This performance can be attributed to our handling of input data, which mimics established clinical MEG practice. Reverse engineering further revealed that STIED encodes fine spatiotemporal features of IEDs rather than their mere amplitude. The model trained on the FE group also showed promising results when applied to a separate group of presurgical patients with different types of refractory focal epilepsy, though further work is needed to distinguish IEDs from physiological transients. This proof-of-concept study represents a first step towards the use of STIED and DL algorithms in the routine clinical MEG evaluation of epilepsy.

This paper investigates brain–behaviour associations between interictal epileptic discharges and cognitive performance in a population of children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS). Sixteen patients with SeLECTS underwent an extensive neuropsychological assessment, including verbal short-term and episodic memory, non-verbal short-term memory, attentional abilities and executive function. Two quantitative EEG indices were analysed, i.e., the Spike Wave Index (SWI) and the Spike Wave Frequency (SWF), and one qualitative EEG index, i.e., the EEG score, was used to evaluate the spreading of focal SW to other parts of the brain. We investigated associations between EEG indices and neuropsychological performance with non-parametric Spearman correlation analyses, including correction for multiple comparisons. The results showed a significant negative correlation between (i) the awake EEG score and the Block Tapping Test, a visuo-spatial short-term memory task, and (ii) the sleep SWI and the Tower of London, a visuo-spatial planning task (pcorr < 0.05). These findings suggest that, in addition to the usual quantitative EEG indices, the EEG analysis should include the qualitative EEG score evaluating the spreading of focal SW to other parts of the brain and that neuropsychological assessment should include visuo-spatial skills.

Objective Patients with Early Infantile Epileptic Encephalopathy (EIEE) 52 have inherited, homozygous variants in the gene SCN1B, encoding the voltage‐gated sodium channel (VGSC) β1 and β1B non‐pore‐forming subunits. Methods Here, we describe the detailed electroclinical features of a biallelic SCN1B patient with a previously unreported variant, p.Arg85Cys. Results The female proband showed hypotonia from birth, multifocal myoclonus at 2.5 months, then focal seizures and myoclonic status epilepticus (SE) at 3 months, triggered by fever. Auditory brainstem response (ABR) showed bilateral hearing loss. Epilepsy was refractory and the patient had virtually no development. Administration of fenfluramine resulted in a significant reduction in seizure frequency and resolution of SE episodes that persisted after a 2‐year follow‐up. The patient phenotype is more compatible with early infantile developmental and epileptic encephalopathy (DEE) than with typical Dravet syndrome (DS), as previously diagnosed for other patients with homozygous SCN1B variants. Biochemical and electrophysiological analyses of the SCN1B variant expressed in heterologous cells showed cell surface expression of the mutant β1 subunit, similar to wild‐type (WT), but with loss of normal β1‐mediated modification of human Nav1.1‐generated sodium current, suggesting that SCN1B‐p.Arg85Cys is a loss‐of‐function (LOF) variant. Interpretation Importantly, a review of the literature in light of our results suggests that the term, early infantile developmental and epileptic encephalopathy, is more appropriate than either EIEE or DS to describe biallelic SCN1B patients.

Recessive mutations in the SLC13A5 gene encoding the sodium‐dependent citrate transporter are a recently identified cause of developmental and epileptic encephalopathy. Here, we describe a child harboring a novel homozygous loss‐of‐function mutation in the SLC13A5 gene (c.1496C>T–p.Ser499Phe) and exhibiting an unusual extremely severe neonatal presentation with drug‐resistant seizures and burst‐suppression EEG pattern. Early carbamazepine use resulted in dramatic improvement both clinically and on EEG features. Follow‐up from the neonatal period to the age of 4 years is documented. This case expands the electro‐clinical phenotype associated with SLC13A5‐related disease and confirms the efficacy and safety of carbamazepine in nonstructural early‐onset epilepsies.

Background Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results Pathogenic variants in ASPM and WDR62 were the most frequent causes in non‐consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non‐consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients. Phenotyping and genetic analyses in 169 probands referred for primary microcephaly produced a molecular diagnosis in 38, with ASPM and WDR62 most prevalent in non‐consanguineous patients, and a total diagnostics rate of 67% in consanguineous patients. Our series includes 11 novel pathogenic variants and reveals epilepsy as a more frequent feature than previously reported.

Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials. In this case-control study, samples were collected prospectively from patients with mutation-proven AGS. The expression of six interferon-stimulated genes (ISGs) was measured by quantitative PCR, and the median fold change, when compared with the median of healthy controls, was used to create an interferon score for each patient. Scores higher than the mean of controls plus two SD (>2·466) were designated as positive. Additionally, we collated historical data for interferon activity, measured with a viral cytopathic assay, in CSF and serum from mutation-positive patients with AGS. We also undertook neutralisation assays of interferon activity in serum, and looked for the presence of autoantibodies against a panel of interferon proteins. 74 (90%) of 82 patients had a positive interferon score (median 12·90, IQR 6·14–20·41) compared with two (7%) of 29 controls (median 0·93, IQR 0·57–1·30). Of the eight patients with a negative interferon score, seven had mutations in RNASEH2B (seven [27%] of all 26 patients with mutations in this gene). Repeat sampling in 16 patients was consistent for the presence or absence of an interferon signature on 39 of 41 occasions. Interferon activity (tested in 147 patients) was negatively correlated with age (CSF, r=−0·604; serum, r=−0·289), and was higher in CSF than in serum in 104 of 136 paired samples. Neutralisation assays suggested that measurable antiviral activity was related to interferon α production. We did not record significantly increased concentrations of autoantibodies to interferon subtypes in patients with AGS, or an association between the presence of autoantibodies and interferon score or serum interferon activity. AGS is consistently associated with an interferon signature, which is apparently sustained over time and can thus be used to differentiate patients with AGS from controls. If future studies show that interferon status is a reactive biomarker, the measurement of an interferon score might prove useful in the assessment of treatment efficacy in clinical trials. European Union's Seventh Framework Programme; European Research Council.

This study aims at testing the hypothesis that neurodevelopmental abilities at age 2years are related with local brain microstructure of preterm infants at term equivalent age. Forty-one preterm infants underwent brain MRI with diffusion tensor imaging sequences to measure mean diffusivity (MD), fractional anisotropy (FA), longitudinal and transverse diffusivity (λ// and λ⊥) at term equivalent age. Neurodevelopment was assessed at 2years corrected age using the Bayley III scale. A voxel-based analysis approach, statistical parametric mapping (SPM8), was used to correlate changes of the Bayley III scores with the regional distribution of MD, FA, λ// and λ⊥. We found that language abilities are negatively correlated to MD, λ// and λ⊥ in the left superior temporal gyrus in preterm infants. These findings suggest that higher MD, λ// and λ⊥ values at term-equivalent age in the left superior temporal gyrus are associated with poorer language scores in later childhood. Consequently, it highlights the key role of the left superior temporal gyrus for the development of language abilities in children. Further studies are needed to assess on an individual basis and on the long term the prognostic value of brain DTI at term equivalent age for the development of language. •Voxel-based DTI study in a population of 41 preterm infants.•Correlation between DTI indices at term age and neurodevelopment at 2 years•Language is negatively correlated to DTI indices in the left superior temporal gyrus•Highlights the key role of the left superior temporal gyrus for language development

This study aims at testing the hypothesis that neurodevelopmental abilities at age 2 years are related with local brain microstructure of preterm infants at term equivalent age. Forty-one preterm infants underwent brain MRI with diffusion tensor imaging sequences to measure mean diffusivity (MD), fractional anisotropy (FA), longitudinal and transverse diffusivity (λ// and λ[perpendicular]) at term equivalent age. Neurodevelopment was assessed at 2 years corrected age using the Bayley III scale. A voxel-based analysis approach, statistical parametric mapping (SPM8), was used to correlate changes of the Bayley III scores with the regional distribution of MD, FA, λ// and λ[perpendicular]. We found that language abilities are negatively correlated to MD, λ// and λ[perpendicular] in the left superior temporal gyrus in preterm infants. These findings suggest that higher MD, λ// and λ[perpendicular] values at term-equivalent age in the left superior temporal gyrus are associated with poorer language scores in later childhood. Consequently, it highlights the key role of the left superior temporal gyrus for the development of language abilities in children. Further studies are needed to assess on an individual basis and on the long term the prognostic value of brain DTI at term equivalent age for the development of language.

In this MRI study, we aimed to provide new in vivo structural markers of asymmetry in motor and language networks in a population of healthy preterm neonates scanned at term equivalent age. Using diffusion tensor imaging and probabilistic tractography, we showed that, besides volume and microstructural asymmetries in the parieto-temporal part of the superior longitudinal fasciculus (SLF) and a trend towards microstructural asymmetry in the corticospinal tract (CST), volume asymmetry in the motor part of the superior thalamic radiations (STR) and a trend towards volume asymmetry in the CST are already present in the neonatal period. No asymmetry was found in the sensory part of the STR, the anterior thalamic radiations (ATR), and posterior thalamic radiations (PTR) neither in the fronto-parietal part of the SLF. These results suggest that structural asymmetries in the motor and language networks are present in healthy preterm neonates at term equivalent age, well before the development of speech and hand preference.