Abstracts

Rationale: Anxiety and depression are a prevalent cause of poor quality of life in individuals with temporal lobe epilepsy (TLE). A strong neuroanatomical relationship exists among TLE, anxiety, and depression. Specifically, the hippocampus, being the most frequently identified epileptogenic zone in TLE, is connected to the same limbic structures involved in mood disorders. Therefore, in this study, we test the hypothesis that the hippocampal amygdala connectivity on the side of seizure focus is 1) increased in patients with TLE relative to controls, and 2) this augmented connectivity is associated with anxiety and depression in TLE.Methods: MRI data (T1-weighted MP-Rage, 64-direction DTI) was obtained in 27 subjects with TLE (16 left, 11 right) and 20 healthy controls. Parcellation of hippocampus, amygdala, medial temporal, and posterior cingulate were performed using Freesurfer (http://surfer.nmr.mgh.harvard.edu/). FSL (http://www.fmrib.ox.ac.uk/fsl/) was used to register segmentations to DTI data, and then probabilistic tractography was run from hippocampus to target structures. Connectivity maps were converted to hard segmentations, generating hippocampal maps of maximum probability of connectivity. Voxels associated with each target mask were recorded along the hippocampal axis (normalized for cross-sectional area), and then divided into anterior, middle, and posterior thirds. Area under the curve (AUC) for maximum connectivity to each region was determined. Becks Anxiety and Depression scores (obtained in 25 TLE and 19 HC) were then compared to the AUC using Spearman s rho. Results: An anterior-posterior gradient was found in all subjects, with an altered connectivity profile (i.e. increased amygdala) mainly within the middle hippocampus (Fig. 1). Significantly different connectivities from middle hippocampus to amygdala were found when comparing all three groups for both left (p = 0.006) and right sides (p = 0.01). Left TLE had significantly increased connectivity to left amygdala only (p = 0.05), whereas in right TLE increases were found for both left (p = 0.002) and right amygdala (p = 0.006). Among all subjects, Beck Anxiety scores correlated with middle hippocampus connectivity to left (p = 0.003) and right amygdala (p = 0.01). For individuals with TLE, connectivity from middle hippocampus to amygdala contralateral to side of seizure onset significantly correlated with Beck Anxiety scores (p = 0.03) (Fig 2). There were no significant correlations between Beck Depression score and the degree of hippocampal-amygdala connectivity.Conclusions: This study shows differential alterations in connectivity from middle hippocampus to amygdala between right (increased ipsilateral and contralateral) and left (increased ipsilateral) TLE. Furthermore, this increased connectivity is associated with increased anxiety, but not depression; notably, it is the contralateral changes in connectivity that correlate with anxiety measures. This suggests that compensatory shifts in contralateral connectivity may contribute to increased anxiety in TLE.