Abstracts

Rationale: Normal cognitive development is characterized by the age-dependent harmonious improvement of multiple ability areas including language, memory, spatial skills and executive function. How childhood-onset epilepsy alters the interrelationship among diverse cognitive systems remains to be characterized. Objective: To map the global landscape of cognitive integration in children with epilepsy compared to normally developing children, charting the networks of inter-relationship between multiple cognitive skills, employing graph theory to analyze the community structure of these networks.Methods: A neuropsychological battery was administered to 127 children with epilepsy and 80 age and gender matched healthy controls (ages 8-18) assessing multiple domains including intelligence, academic skills, language, memory, executive function and cognitive/psychomotor speed (Table 1). For patients and controls, we constructed an adjacency matrix representing pair-wise correlation coefficients between each combination of tests. Tests were adjusted to reflect a higher score for better performance, and only positive correlation coefficients were maintained. A weighted non-directed graph was constructed where each node corresponded to a behavioral test and each link corresponded to the correlation coefficient between the tests. Only links with a correlation coefficient greater than 0.7 were maintained, and the community structure from each graph was calculated. The spatial distribution of nodes representing their inter-relationship was plotted using a Force Atlas algorithm and modularity was qualitatively assessed. Finally, as a secondary analysis we tested the hypothesis that executive function was more likely dissociated from language performance in patients compared with controls by evaluating the relative frequency of participation of both tests in the same module using a heuristic approach.Results: We observed a community structure composed of fewer and larger modules in controls characterized by two main modules representing close relationships between: 1) academic skills, visuospatial processes, inhibiton, and memory, and 2) language and executive function. Conversely, patients exhibited a relative disconnection between cognitive functions, which segregated into more numerous and smaller modules consisting of 1) language and visuospatial processing, 2) academic skills and memory, and 3) executive function (Figure 1, Table 1). Executive function was more likely dissociated from language performance in patients (p<0.001).Conclusions: Cognitive development in children with epilepsy is associated with a fragmentation of the typical patterns of interrelationship across multiple cognitive abilities. While healthy children exhibit a higher association of different modalities of cognitive abilities, children with epilepsy demonstrate a dissociated pattern of development, with multiple independent and sub-optimally inter-related domains. Notably, children with epilepsy also exhibited dissociation between executive function and language, suggesting an atypical pattern of cognitive development.