Abstracts

Rationale: Although not a primary language area, the left hippocampus plays a large role in verbal memory and hippocampal activation has been found during language functional magnetic resonance imaging (fMRI). In epilepsy, language functioning may be affected after resection targeting the hippocampus, suggesting a functional connection between the hippocampus and language network. We examined left hippocampal functional connectivity (FC) using Psychophysiological Interaction (PPI) during language fMRI in children with left focal epilepsy. PPI is a novel method that uses linear regression to examine relationships between a seed region (left hippocampus) and other voxels in the brain (whole brain search) during a behavioral condition (e.g., language task compared to baseline) (O’Reilly et al., 2012).Methods: We used the SPM8 PPI toolbox to assess FC during an auditory description decision fMRI task in children with left focal epilepsy (n=15; M age=10.1±2.1) and typically developing controls (n=36; M age=9.9±1.9). We chose the left hippocampus as the seed region and conducted a voxel-wise whole brain search. We used results from individual subject PPI analyses to conduct second-level analysis restricted to that seed region. Given the impact of motion on FC (Power et al, 2015), all subjects passed stringent motion criteria (Wilke, 2012; Power et al., 2012). We also assessed associations between FC, age, and language ability (Expressive One-Word Vocabulary Test, EOWPVT).Results: Controls demonstrated increased left hippocampal FC with left (supramarginal gyrus, supplementary motor area, cerebellum, mid-cingulum) and right (mid-frontal gyrus, Brodmann area 38, superior temporal gyrus) brain regions (p<0.005, k>50). No regions showed greater left hippocampal FC in the epilepsy group compared to controls. We found a group by age interaction effect in the right anterior cingulum, such that controls demonstrated increased FC between this region and left hippocampus with increasing age, and the epilepsy group did not. We also found a group by EOWPVT interaction in right MFG; for the epilepsy group, increased FC between this region and left hippocampus resulted in higher EOWPVT scores, while controls showed the opposite effect.Conclusions: Our results demonstrate important left hippocampal FC differences for controls compared to children with left focal epilepsy. For controls, the left hippocampus was more connected to both left and right regions involved in language. These connections suggest that the hippocampus is functionally connected to language regions and may explain the clinical findings of language difficulties following resection targeting the hippocampus in epilepsy. Controls also demonstrated increased connectivity with age between the left hippocampus and a traditional attention region, the right anterior cingulum. For patients, increased connectivity between the left hippocampus and right MFG in focal epilepsy was associated with stronger naming performance suggesting that the MFG route, important for executive functioning (EF) skills, may be an alternative pattern that supports better performance in patients.