Thalamic medial dorsal nucleus atrophy in medial temporal lobe epilepsy: A VBM meta-analysis

Abstract

Purpose: Medial temporal lobe epilepsy (MTLE) is associated with MTLE network pathology within and beyond the hippocampus. The purpose of this meta-analysis was to identify consistent MTLE structural change to guide subsequent targeted analyses of these areas.

Methods: We performed an anatomic likelihood estimation (ALE) meta-analysis of 22 whole-brain voxel-based morphometry experiments from 11 published studies. We grouped these experiments in three ways. We then constructed a meta-analytic connectivity model (MACM) for regions of consistent MTLE structural change as reported by the ALE analysis.

Key findings: ALE reported spatially consistent structural change across VBM studies only in the epileptogenic hippocampus and the bilateral thalamus; within the thalamus, the medial dorsal nucleus of the thalamus (MDN thalamus) represented the greatest convergence (P < 0.05 corrected for multiple comparisons). The subsequent MACM for the hippocampus and ipsilateral MDN thalamus demonstrated that the hippocampus and ipsilateral MDN thalamus functionally co-activate and are nodes within the same network, suggesting that MDN thalamic damage could result from MTLE network excitotoxicity.

Significance: Notwithstanding our large sample of studies, these findings are more restrictive than previous reports and demonstrate the utility of our inclusion filters and of recently modified meta-analytic methods in approximating clinical relevance. Thalamic pathology is commonly observed in animal and human studies, suggesting it could be a clinically useful indicator. Thalamus-specific research as a clinical marker awaits further investigation.

Keywords: All epilepsy/seizures; Cortical localization; Hippocampal sclerosis; Volumetric MRI.

Fig. 1

Significant areas of convergence in the VBM-ALE analysis in rectified (A), right medial temporal lobe epilepsy (B), and left medial temporal lobe epilepsy (C) groups. MACM analyses (D) of the left (green) and right (red) hippocampal tissue labels; note co-activation in the medial dorsal nucleus thalamus. All clusters thresholded at P < 0.05, corrected for multiple comparisons. See Supplementary materials for full montages of (A), (B) and (C).