Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline?

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery may alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning - obtained from IQ tests (domains: Full-Scale IQ, Verbal IQ, Performance IQ, Working Memory, and Processing Speed) and tests of academic attainment (Reading, Spelling and Numeracy) - and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery (median age at surgery = 11.9 years, interquartile range = [7.8,15.0]) and neuropsychology assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all p-values ≤ 0.001; e.g., ßFSIQ = -1.9, SEFSIQ = 0.3, pFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27-43% declined by 10 or more points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (Full-Scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all p-values > 0.128). However, children who became seizure-free through surgery showed higher postoperative neuropsychological performance (e.g., rrb-FSIQ = 0.37, p < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g., ßFSIQ = 0.9, SEFSIQ = 0.3, pFSIQ = 0.004). Children who had discontinued antiseizure medication (ASM) treatment at one-year follow-up showed an eight-to-13-point advantage in postoperative Working Memory, Processing Speed, and Numeracy, and greater improvements in Verbal IQ, Working Memory, Reading, and Spelling (all p-values < 0.034) over the postoperative period compared to children who were seizure-free and still receiving ASMs. In conclusion, by providing seizure freedom and the opportunity for ASM cessation, epilepsy surgery may not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible, or potentially prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.

Functional brain connectivity in children with focal epilepsy: A systematic review of functional MRI studies.

Epilepsy is increasingly recognised as a brain network disorder and many studies have investigated functional connectivity (FC) in children with epilepsy using functional MRI (fMRI). This systematic review of fMRI studies, published up to November 2023, investigated profiles of FC changes and their clinical relevance in children with focal epilepsy compared to healthy controls. A literature search in PubMed and Web of Science yielded 62 articles. We categorised the results into three groups: 1) differences in correlation-based FC between patients and controls; 2) differences in other FC measures between patients and controls; and 3) associations between FC and disease variables (for example, age of onset), cognitive and seizure outcomes. Studies revealed either increased or decreased FC across multiple brain regions in children with focal epilepsy. However, findings lacked consistency: conflicting FC alterations (decreased and increased FC) co-existed within or between brain regions across all focal epilepsy groups. The studies demonstrated overall that 1) interhemispheric connections often displayed abnormal connectivity and 2) connectivity within and between canonical functional networks was decreased, particularly for the default mode network. Focal epilepsy disrupted FC in children both locally (e.g., seizure-onset zones, or within-brain subnetworks) and globally (e.g., whole-brain network architecture). The wide variety of FC study methodologies limits clinical application of the results. Future research should employ longitudinal designs to understand the evolution of brain networks during the disease course and explore the potential of FC biomarkers for predicting cognitive and postsurgical seizure outcomes.

Gender differences in interoceptive accuracy and emotional ability: An explanation for incompatible findings.

Most theories of emotion describe a crucial role for interoceptive accuracy, the perception of the body's internal physiological signals, in emotional experience. Despite support for interoceptive accuracy's role in emotion, findings of gender differences in emotional and interoceptive processing are incompatible with theory; women typically show poorer interoceptive accuracy, but women often outperform men on measures of emotional processing and recognition. This suggests a need to re-evaluate the relationship between interoceptive accuracy and emotion considering sex and gender. Here we extend Pennebaker and Roberts' (1992) theory of gender differences in the use of interoceptive signals for emotional experience, proposing that language socialisation may result in gender differences in the propensity to label internal state changes as physiological or emotional, respectively. Despite outstanding questions concerning the fractionation of interoceptive and emotional domains, this theory provides a plausible explanation for seemingly incompatible findings of gender differences in interoceptive and emotional abilities.

Sex differences in interoceptive accuracy: A meta-analysis.

Interoceptive accuracy, the ability to correctly perceive internal signals arising from the body, is thought to be disrupted in numerous mental and physical health conditions. Whilst evidence suggests poorer interoceptive accuracy in females compared to males, raising the possibility that interoceptive differences may relate to sex differences in mental and physical health, results concerning sex differences in interoceptive accuracy are mixed. Given such ambiguity, this meta-analysis aimed to establish the presence or absence of sex differences in interoceptive accuracy across cardiac, respiratory, and gastric domains. A review of 7956 abstracts resulted in 93 eligible studies. Results demonstrated superior accuracy in males across cardiac, but not gastric, tasks, while findings on respiratory tasks were mixed. Effect sizes were consistent across cardiac tasks, but instability and/or moderate heterogeneity was observed across other domains, likely due to the small number of eligible studies. Despite such limitations, results indicate the possibility of sex differences across interoception tasks and domains. Methodological limitations concerning the influence of physiological factors, and directions for future research are discussed.