Abstracts

Rationale: Resting state functional connectivity identifies broad networks of correlated brain activity, which have been shown to be affected in MTLE. We investigated whether adult temporal lobe epilepsy patients with no anatomic abnormality of the hippocampus showed similar alterations to functional connectivity of the hippocampus. Methods: 14 adult patients with lesion-negative temporal lobe epilepsy (11 males, age range 27-57 years) were compared to 12 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (2 males, age range 24-55 years), and to 16 healthy non-epileptic controls (8 males, age range 23-52 years). The lesion-negative group showed no abnormality of the hippocampus on routine MRI. Diagnosis was confirmed on video-EEG monitoring and the side of ictal onset ascertained (lesion-negative: 7 left, 5 right, 2 bilateral; hippocampal sclerosis: 5 left, 7 right). A seed based connectivity analysis was performed using resting state BOLD data, acquired on a 3T MRI scanner over 10 minutes (3x3x3mm voxels, TE 30ms, TR 3000ms, 210 volumes). Standard data pre-processing techniques were used including band-pass filtering of 0.1 Hz to 0.005 Hz, and regression of the mean CSF and white matter signals. Participants with right sided ictal onset had their images flipped right-to-left, before non-linear registration to a symmetric brain template. Individual hippocampal seeds were generated using an automated approach, and the mean time-course from this region was correlated against all brain voxels. The resulting statistic maps of hippocampal connectivity were compared between groups using voxel-wise t-tests (threshold p<0.01 uncorrected), and significant clusters reported after false-discovery rate cluster correction at p<0.05. Results: The lesion-negative group (LNTLE) showed regions of reduced connectivity compared to controls. The regions affected were the bilateral anterior cingulate cortex, mesial frontal cortex, bilateral superior frontal gyrus (peak t-value 5.6) and bilateral precuneus/posterior cingulate gyrus (peak t-value 5.2). Comparison of the hippocampal sclerosis group (MTLE-HS) to controls also showed reduced connectivity in the bilateral precuneus/posterior cingulate cortex and in the right superior frontal gyrus. Direct comparison of lesion-negative versus hippocampal sclerosis showed reduced connectivity to the mesial frontal cortex in the lesion-negative group. Conclusions: Patients with lesion-negative temporal lobe epilepsy show reduced resting state functional connectivity between the hippocampus and regions involved in the anterior and posterior parts of the default mode network. Alteration of large scale brain networks may occur in LNTLE, notably in the absence of structural changes, and in a pattern that is similar to, but also distinct from, that seen in MTLE with hippocampal sclerosis.