Abstracts

Rationale: An anterior to posterior gradient exists in the rodent hippocampus (HC) with distinct connections and functions. The ventral HC (homologous to anterior in humans), is mainly connected to subcortical regions important for emotionality i.e. amygdala. In contrast, the dorsal HC (posterior in humans), is primarily connected to cognitive regions in the neocortex. Here, we explored this basic principle of hippocampal gradient in humans and examine whether temporal lobe epilepsy alters these connections. Methods: MRI data was obtained in 11 subjects with left TLE (36.6 3.8 yrs; mean SEM) and 17 controls (29.8 2.5 yrs), including DTI (64 directions, b value = 800 s/mm2) and T1-weighted MP-Rage scans (sense coil 2.4, TR 8.4 ms, TE 3.7 ms). Parcellation of HC, amygdala, medial temporal, and posterior cingulate was performed in each subject using Freesurfer (http://surfer.nmr.mgh.harvard.edu/). FSL tools (http://www.fmrib.ox.ac.uk/fsl/) were used to register DTI data to these masks, and then probabilistic tractography was performed to asses for probability of connectivity between HC and the three target regions. The resultant probability maps were thresholded, and the mean probability of connectivity was calculated for each target mask. Hard segmentation was performed to determine regions of HC with the highest probability of connection to each target mask. Results were aligned along the long axis of the HC and the number of voxels with the highest probability of connectivity to each target mask was recorded for each slice, normalized for total cross-sectional area of HC. Results: Maps of probability of connectivity showed a clear anterior/posterior gradient in control HC (Fig 1), as follows: 1) amygdala = greatest in anterior one-third, with relatively minor connectivity in middle and posterior HC, 2) posterior cingulate = greatest in posterior one-fourth, with relatively minor connectivity throughout the middle and anterior HC, and 3) medial temporal lobe = greatest in middle HC, with decreases near anterior and posterior HC. In TLE, there is a relative increase in proportion of connectivity to amygdala, with a decrease to medial temporal regions, along the entire course of the HC (Fig 2). When comparing the mean probability of connectivity between healthy controls and TLE, a significant difference was found for amygdala on the left (p = 0.049) and posterior cingulate on the right (p = 0.003), after controlling for age.Conclusions: This study is to our knowledge the first to document an anterior to posterior gradient of connectivity for the HC in humans, as has been previously shown in rodent. The larger proportion of HC connected to the amygdala might be the neurobiological correlate of increase emotionality in TLE. Future studies will investigate if the chronic stress of TLE may lead to a shunting of connectivity to emotionality regions, which may therefore contribute to alterations in mood and cognition.