Hippocampus-associated causal network of structural covariance measuring structural damage progression in temporal lobe epilepsy.

In mesial temporal lobe epilepsy (mTLE), the causal relationship of morphometric alterations between hippocampus and the other regions, that is, how the hippocampal atrophy leads to progressive morphometric alterations in the epileptic network regions remains largely unclear. In this study, a causal network of structural covariance (CaSCN) was proposed to map the causal effects of hippocampal atrophy on the network-based morphometric alterations in mTLE. It was hypothesized that if cross-sectional morphometric MRI data could be attributed temporal information, for example, by sequencing the data according to disease progression information, GCA would be a feasible approach for constructing a CaSCN. Based on a large cohort of mTLE patients (n = 108), the hippocampus-associated CaSCN revealed that the hippocampus and the thalamus were prominent nodes exerting causal effects (i.e., GM reduction) on other regions and that the prefrontal cortex and cerebellum were prominent nodes being subject to causal effects. Intriguingly, compensatory increased gray matter volume in the contralateral temporal region and post cingulate cortex were also detected. The method unraveled richer information for mapping network atrophy in mTLE relative to the traditional methods of stage-specific comparisons and structured covariance network. This study provided new evidence on the network spread mechanism in terms of the causal influence of hippocampal atrophy on progressive brain structural alterations in mTLE. Hum Brain Mapp 38:753-766, 2017. © 2016 Wiley Periodicals, Inc.