Disrupted Causal Connectivity in Mesial Temporal Lobe Epilepsy

Han Zhang,Zhiqiang Zhang,Gong-Jun Ji,Wei Liao,Yu-Feng Zang,Guangming Lu,Dong-Qiang Liu,Jue Wang,Pedro Antonio Valdes-Sosa

doi:10.1371/journal.pone.0063183

Abstract

Although mesial temporal lobe epilepsy (mTLE) is characterized by the pathological changes in mesial temporal lobe, function alteration was also found in extratemporal regions. Our aim is to investigate the information flow between the epileptogenic zone (EZ) and other brain regions. Resting-state functional magnetic resonance imaging (RS-fMRI) data were recorded from 23 patients with left mTLE and matched controls. We first identified the potential EZ using the amplitude of low-frequency fluctuation (ALFF) of RS-fMRI signal, then performed voxel-wise Granger causality analysis between EZ and the whole brain. Relative to controls, patients demonstrated decreased driving effect from EZ to thalamus and basal ganglia, and increased feedback. Additionally, we found an altered causal relation between EZ and cortical networks (default mode network, limbic system, visual network and executive control network). The influence from EZ to right precuneus and brainstem negatively correlated with disease duration, whereas that from the right hippocampus, fusiform cortex, and lentiform nucleus to EZ showed positive correlation. These findings demonstrate widespread brain regions showing abnormal functional interaction with EZ. In addition, increased ALFF in EZ was positively correlated with the increased driving effect on EZ in patients, but not in controls. This finding suggests that the initiation of epileptic activity depends not only on EZ itself, but also on the activity emerging in large-scale macroscopic brain networks. Overall, this study suggests that the causal topological organization is disrupted in mTLE, providing valuable information to understand the pathophysiology of this disorder.

Highlights

IntroductionMesial temporal lobe epilepsy (mTLE) is a common epileptic syndrome [1,2]. The mesial temporal lobe (mTL) structure is conventionally regarded to be responsible for generation of epileptic activity [3]
Mesial temporal lobe epilepsy is a common epileptic syndrome [1,2]
A positive correlation was found in patients, but not in controls. These results demonstrate that the high activity level of the epileptogenic zone is partly contributed by the abnormal driving effect from extratemporal regions, and it suggests the initiation of epileptic activity depends on EZ itself, and on the activity emerging in largescale macroscopic brain networks

Summary

Introduction

Mesial temporal lobe epilepsy (mTLE) is a common epileptic syndrome [1,2]. The mesial temporal lobe (mTL) structure is conventionally regarded to be responsible for generation of epileptic activity [3]. A number of RS-fMRI studies have found that, the abnormality of intrinsic activity is not restricted to mTL, and could be found in anatomically distant brain regions in mTLE patients. Both increased and decreased local activity can be observed in extratemporal regions using general linear model on simultaneously electroencephalograph (EEG)-fMRI data [5]. This technique, is still challenged for epilepsy study. ALFF may be a complementary approach to EEG-fMRI studies to localize the epileptogenic zone (EZ) in mTLE [10]

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