Parcellation of the Hippocampus Using Resting Functional Connectivity in Temporal Lobe Epilepsy

Abstract

We have previously shown that the connectivity of the hippocampus to other regions of the default mode network (DMN) is a strong indicator of memory ability in people with temporal lobe epilepsy (TLE). Recent work in the cognitive neuroscience literature has suggested that the anterior and posterior aspects of the hippocampus have distinct connections to the rest of the DMN and may support different memory operations. Further, structural analysis of epileptogenic hippocampi has found greater atrophy, characterized by mesial temporal sclerosis, in the anterior region of the hippocampus. Here, we used resting state FMRI data to parcellate the hippocampus according to its functional connectivity to the rest of the brain in people with left lateralized TLE (LTLE) and right lateralized TLE (RTLE), and in a group of neurologically healthy controls. We found similar anterior and posterior compartments in all groups. However, there was weaker connectivity of the epileptogenic hippocampus to multiple regions of the DMN. Both TLE groups showed reduced connectivity of the posterior hippocampus to key hubs of the DMN, the posterior cingulate cortex (PCC) and the medial pre-frontal cortex (mPFC). In the LTLE group, the anterior hippocampus also showed reduced connectivity to the DMN, and this effect was influenced by the presence of mesial temporal sclerosis. When we explored brain-behavior relationships, we found that reduced connectivity of the left anterior hippocampus to the DMN hubs related to poorer verbal memory ability in people with LTLE, and reduced connectivity of the right posterior hippocampus to the PCC related to poorer visual memory ability in those with RTLE. These findings may inform models regarding functional distinctions of the hippocampal anteroposterior axis.

Keywords: default mode network; epilepsy; hippocampus; long axis; memory; resting state.

Figure 1

(Top) Group level clusters from k-means clustering procedure, projected onto the standard MNI brain showing an anterior (yellow) and posterior (blue) cluster for both the left and right hippocampus derived from patients with left temporal lobe epilepsy, healthy controls, and patients with right temporal lobe epilepsy. (Bottom) Anterior hippocampal connectivity contrasted against posterior hippocampal connectivity in people with left temporal lobe epilepsy (LTLE), healthy controls, and people with right temporal lobe epilepsy (RTLE) presented without statistical thresholding. Warm colors indicate anterior > posterior hippocampal connectivity, while cool colors indicate posterior > anterior hippocampal connectivity. The color bars depict t-values.

Figure 2

Contrast maps of differences in connectivity between patients with left temporal lobe epilepsy compared to controls, seeding from either the anterior hippocampal seeds (top) or the posterior hippocampal seeds (bottom), thresholded at p < 0.05 FDR cluster correction, using 5,000 permutations. Areas of increased connectivity in LTLE, depicted in red, were only significant using a small volume correction in the entorhinal cortex. Areas of reduced connectivity in LTLE compared to controls are shown in cool colors. Bar plots depict mean group connectivity and standard error at voxels of peak difference between the LTLE group and controls, with the LTLE group separated into those with mesial temporal sclerosis (LMTS+), and those without (LMTS−). These peaks are presented below in Table 2. The color bars depict t-values. ACC, anterior cingulate cortex; ERC, entorhinal cortex; PCC, posterior cingulate cortex; R, right.

Figure 3

Contrast maps of differences in connectivity between patients with right temporal lobe epilepsy compared to controls, seeding from the right posterior hippocampal seed, thresholded at p < 0.05 FDR cluster correction, using 5,000 permutations. Areas of reduced connectivity in RTLE compared to controls are shown in cool colors. Bar plots depict connectivity at areas of peak difference between the RTLE group and controls, with the RTLE group separated into those with mesial temporal sclerosis (RMTS+) and those without (RMTS−). These peaks are presented below in Table 3. The color bars depict t values. L, left; mPFC, medial pre-frontal cortex; PCC, posterior cingulate cortex; R, right.

Figure 4

Correlation matrix depicting the relationship of functional connectivity to verbal and visual memory in the LTLE and RTLE groups. Thick black outlines delineate relationships of interest. Ant, anterior; L, left; LTLE, left temporal lobe epilepsy; HPC, hippocampus; mPFC, medial pre-frontal cortex; PCC, posterior cingulate cortex; Post, posterior; R, right; RTLE, right temporal lobe epilepsy.