Itziar Alonso-Colmenero

The development of cognitive control during childhood is characterized by progressive improvements in attentional processing and response inhibition. The present study examined neural activity associated with visual attention and inhibitory control in typically developing children aged 6 to 12 years, using quantitative high-density electroencephalography (HD-EEG).A total of 172 typically developing children aged 6 to 12 years participated in the study. Participants completed a computerized Go/NoGo task while EEG activity was recorded. Behavioural performance, event-related potentials (ERPs), and time-frequency EEG features were analysed, including median frequency (MF), spectral entropy (SE), and relative power (RP) in the theta (θ) and beta1 (β1) frequency bands. Differences were observed both between task conditions and across age groups. P300 amplitude and latency decreased linearly with age across conditions. NoGo trials elicited larger P300 amplitudes and longer latencies than Go trials. Time-frequency analyses showed reductions in MF and SE with increasing age. During task performance, RP (θ) increased and RP (β1) decreased relative to the pre-stimulus baseline. These time-frequency changes were observed across all age groups but were more pronounced in older children. All time-frequency measures differentiated Go and NoGo trials, with stronger effect observed during NoGo trials. These patterns suggest that with age, children become progressively more capable of synchronizing their frequency-specific neural activity to meet the functional demands of the task. Together, these findings indicate that HD-EEG biomarkers are useful to study the maturation of large-scale coordination mechanisms and inhibitory control networks across childhood.

Objective To describe the genetic mutation and its action mechanism in patients with compatible diagnosis of fundus albipunctatus (FAP). Subjects and methods We describe the clinical evolution and genetic findings of two female Spanish children of 14 and 16 years old who have been followed at the children’s hospital Sant Joan de Déu (Barcelona, Spain). Nyctalopia without detectable field constriction was the initial symptom. Retinal fundus was compatible with FAP or retinitis punctata albescens (RPA). We have registered ophthalmological examination from each visit, including visual acuity, visual field assessment, wide-field fundoscopy imaging, fundus autofluorescence and optical coherence tomography. Full-field electroretinogram (ERG) was also performed. DNA sampling was analysed by next-generation sequency (NGS). Results Compound heterozygous pathogenic variants in the LRAT gene were identified in both children. Interestingly, these were the same two pathogenic variants, despite the families being unrelated. No additional genetic alterations were found that could explain the disease in our patients. Conclusions To the best of our knowledge, up to the present time, only a single clinical case involving a genetic variant in the LRAT gene leading to an FAP phenotype has been reported in the literature. LRAT genetic variants, despite their low frequency in clinical practice, seem to lead to a FAP-like phenotype, in addition to their established association with Leber congenital amaurosis (LCA) and Early Onset Severe Retinal Dystrophy (EOSRD).

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 16 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.