Abstracts

Rationale: Working memory (WM) impairments are a common co-morbidity of pediatric epilepsy. Research in adults with temporal lobe epilepsy suggests that brain networks established in long-term memory are also involved in WM. For example, Stretton et al.¹ found progressive deactivation in the hippocampus with increasing WM demand during a visuo-spatial n-back fMRI task. It is not yet known whether these findings extend to children with focal epilepsies. Hence, this study sought to examine the neuroanatomical underpinnings of WM impairments in children with epilepsy. Specifically, we aimed to establish whether the hippocampus is involved in WM and whether hippocampal involvement is related to cognitive impairments in children with focal epilepsy.

Methods: We evaluated (i) brain activity during an auditory WM n-back functional magnetic resonance imaging (fMRI) task in 14 children with left hemisphere localization-related epilepsy compared to 14 age-matched controls, and (ii) whether there was an association between brain activity in the hippocampus and cognitive performance on neuropsychological tests of WM (Digit Span Backwards and Spatial Span Backwards from the Wechsler Intelligence Scale for Children; Trail Making Test Letter/Number Switching Condition, Verbal Fluency Switching Condition, and Color Work Inference Inhibition Switching Condition from the Delis-Kaplan Executive Function System).

Results: As a group, patients and controls demonstrated deactivation in the bilateral hippocampus during the n-back fMRI task. Patients with epilepsy had significantly less deactivation in the left, but not right, hippocampus relative to age-matched controls. Less deactivation in the left hippocampus was associated with worse performance (i.e., taking longer to complete the task) on the Trail Making Test Letter/Number Switching Condition (r = -0.46, p =.004). There was also a trend for less deactivation in the left hippocampus to be associated with worse performance (i.e., lower accuracy) on a Spatial Span Backwards task (r = -0.31, p = .06). The magnitude of deactivation in the left hippocampus was not correlated with performance on the remaining WM tasks.

Conclusions: This is the first study to examine hippocampal involvement during WM in children with epilepsy. Our results suggest that children with epilepsy exhibit hippocampal dysfunction ipsilateral to the side of seizure focus that places them at risk of working memory deficits. This study contributes to our understanding of WM in pediatric epilepsy and may inform future pre-surgical evaluation of WM in clinical practice.

References
1. Stretton, J., Winston, G., Sidhu, M. et al. (2012). Neural correlates of working memory in Temporal Lobe Epilepsy – An fMRI study. NeuroImage, 60, 1696-1703. doi: 10.1016/j.neuroimage.2012.01.126

Funding: Please list any funding that was received in support of this abstract.: This research was funded by a grant from NINDS 1K23NS065121-01A2 awarded to Dr. Berl. Dr. Phillips was supported by a project grant from the Mitacs Globalink Research Award, as well as funding the Savoy Foundation Post-Doctoral Fellowship and from the SickKids Foundation.