Disrupted causal connectivity in mesial temporal lobe epilepsy

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.

Figure 1. Regions showing abnormal amplitude of low-frequency fluctuation.

The warm and cold colors represent higher and lower ALFF, respectively, in patients compared with controls (P<0.05, corrected). Color bar represents t-values.

Figure 2. Granger causality analysis for seed(EZ)-to-whole-brain.

(A) Regions showing significant causal effect with the seed in patients. (B) Regions showing significant causal effect with the seed in controls. Warm and cold colors indicate positive and negative causal effects, respectively. (C) Regions showing abnormal causal effect with the seed in patients compared with controls. The scatter-plot maps show the correlations between Granger causality value in corresponding clusters and disease duration. Color bar represents t-values.

Figure 3. Granger causality analysis for whole-brain-to-seed(EZ).

(A) Regions showing significant causal effect with the seed in patients. (B) Regions showing significant causal effect with the seed in controls. Warm and cold colors indicate positive and negative causal effects, respectively. (C) Regions showing abnormal causal effect with the seed in patients compared with controls. The scatter-plot maps show the correlations between Granger causality value in corresponding clusters and disease duration. Color bar represents t-values.

Figure 4. Correlation between the amplitude of low-frequency fluctuation (ALFF) of EZ and the abnormal driven effect on it in patients (A) and controls (B).