Long-term characterization of cognitive phenotypes in children with seizures over 36 months.

RATIONALE: Children with new-onset epilepsies often exhibit co-morbidities including cognitive dysfunction, which adversely affects academic performance. Application of unsupervised machine learning techniques has demonstrated the presence of discrete cognitive phenotypes at or near the time of diagnosis, but there is limited knowledge of their longitudinal trajectories. Here we investigate longitudinally the presence and progression of cognitive phenotypes and academic status in youth with new-onset seizures as sibling controls. METHODS: 282 subjects (6-16 years) were recruited within 6 weeks of their first recognized seizure along with 167 unaffected siblings. Each child underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months later. Factor analysis of the neuropsychological tests revealed four underlying domains - language, processing speed, executive function, and verbal memory. Latent trajectory analysis of the mean factor scores over 36 months identified clusters with prototypical cognitive trajectories. RESULTS: Three unique phenotypic groups with distinct cognitive trajectories over the 36-month period were identified: Resilient, Average, and Impaired phenotypes. The Resilient phenotype exhibited the highest neuropsychological factor scores and academic performance that were all similar to controls; while the Impaired phenotype showed the polar opposite with the worst performances across all test metrics. These findings remained significant and stable over 36 months. Multivariate logistic regression indicated that age of onset, EEG, neurological examination, and sociodemographic disadvantage were associated with phenotype classification. CONCLUSIONS: This study demonstrates the presence of diverse latent cognitive trajectory phenotypes over 36 months in youth with new-onset seizures that are associated with a stable neuropsychological and academic performance longitudinally.

The Relationship Between Sleep, Cognition and Behavior in Children With Newly-Diagnosed Epilepsy Over 36 Months.

Introduction: There is substantial evidence that children with epilepsy experience more sleep, behavior and cognitive challenges than children without epilepsy. However, the literature is limited in describing the relationship between sleep, epilepsy, cognition and behavioral challenges and the interactions amongst these factors over time. This study aims to understand the nature and strength of the relationship between sleep, cognition, mood and behavior in children with new-onset epilepsy as assessed by multiple informants at multiple time periods using multiple different dependent measures. Methods: 332 participants (6-16years) were recruited within 6 weeks of their first recognized seizure. The comparison group was comprised of 266 healthy siblings. Participants underwent sleep evaluation by a parent using the Sleep Behavioral Questionnaire (SBQ), cognitive evaluation using a comprehensive neuropsychological test battery, a behavioral evaluation using the Child Behavior Checklist (CBCL from parents and TRF from teachers) and the Children's Depression Inventory (CDI). These evaluations were completed at baseline (B), at 18 months, and at 36 months. Results: Compared to siblings, children with new-onset epilepsy had more sleep disturbance (SBQ), higher rates of behavioral problems (CBCL and TRF), lower cognitive testing scores, and higher rates of depression; which persisted over the 36-month study. Sleep significantly correlated with behavioral problems, cognitive scores and depression. When divided into categories based of sleep disturbance scores, 39.7% of children with epilepsy experienced "Persistently Abnormal Sleep", while 14.8% experienced "Persistently Normal Sleep". Children with persistently abnormal sleep experienced the highest rates of behavioral problems, depression and cognitive impairment compared to those with persistently normal sleep, regardless of epilepsy syndrome. Younger age of seizure onset, younger age at testing, and lower grade level at baseline were associated with persistently abnormal sleep. Conclusions: To our knowledge, this is the first demonstration of the nature, strength, reliability, stability and persistence of the relationship between sleep, cognition, and behavioral problems over time in a large cohort of children with newly diagnosed epilepsy, as assessed by multiple informants at different timepoints. The results of this study indicate that children with epilepsy are at a high risk of significant persisting neurobehavioral multimorbidity. Therefore, early screening for these challenges may be essential for optimizing quality of life long-term.

Neural activation associated with outgroup helping in adolescent rats.

Prosocial behavior, helping others in need in particular, occurs preferentially in response to the perceived distress of one's own group members or ingroup. To investigate the development of ingroup bias, neural activity during a helping test was analyzed in adolescent and adult rats. Although adults selectively released trapped ingroup members, adolescent rats helped both ingroup and outgroup members, suggesting that ingroup bias emerges in adulthood. Analysis of brain-wide neural activity, indexed by expression of the early-immediate gene c-Fos, revealed increased activity for ingroup members across a broad set of regions previously associated with empathy. Adolescents showed reduced hippocampal and insular activity and increased orbitofrontal cortex activity compared to adults. Non-helper adolescents demonstrated increased amygdala connectivity. These findings demonstrate that biases for group-dependent prosocial behavior develop with age in rats and suggest that specific brain regions contribute to prosocial selectivity, pointing to possible targets for the functional modulation of ingroup bias.