Connectivity strength, time lag structure and the epilepsy network in resting-state fMRI

Abstract

The relationship between the epilepsy network, intrinsic brain networks and hypersynchrony in epilepsy remains incompletely understood. To converge upon a synthesized understanding of these features, we studied two elements of functional connectivity in epilepsy: correlation and time lag structure using resting state fMRI data from both SEEG-defined epileptic brain regions and whole-brain fMRI analysis. Functional connectivity (FC) was analyzed in 15 patients with epilepsy and 36 controls. Correlation strength and time lag were selected to investigate the magnitude of and temporal interdependency across brain regions. Zone-based analysis was carried out investigating directed correlation strength and time lag between both SEEG-defined nodes of the epilepsy network and between the epileptogenic zone and all other brain regions. Findings were compared between patients and controls and against a functional atlas. FC analysis on the nodal and whole brain levels identifies consistent patterns of altered correlation strength and altered time lag architecture in epilepsy patients compared to controls. These patterns include 1) broadly distributed increased strength of correlation between the seizure onset node and the remainder of the brain, 2) decreased time lag within the seizure onset node, and 3) globally increased time lag throughout all regions of the brain not involved in seizure onset or propagation. Comparing the topographic distribution of findings against a functional atlas, all resting state networks were involved to a variable degree. These local and whole brain findings presented here lead us to propose the network steal hypothesis as a possible mechanistic explanation for the non-seizure clinical manifestations of epilepsy.

Keywords: Epilepsy network; Functional connectivity; Resting state networks.

Fig. 1

Cortical and subcortical surface projection. Top row demonstrates the mid-cortical surface alignment on the T1 and average EPI with a magnified panel depicting a close-up representation of the right hemispheric cortical surface. Bottom row demonstrates the thalamic surface projection on the T1 and average EPI with a magnified panel depicting the projection filter centered on the green dot.

Fig. 2

Results from epilepsy network node-based lag analysis. Connection widths reflect relative nodal synchronization and are proportional to t-values (indicated adjacent to each connection; increased lag corresponds to decreased synchronization while decreased lag corresponds to increased synchronization). Significant findings are indicated by an asterisk (p < 0.005, FDR corrected). .

Fig. 3

Results from whole brain functional connectivity analysis. Top panel depicts cortical regions of increased connectivity when selecting the seizure onset node, EZ, as the seed for whole brain functional connectivity analysis. Comparison was made at the group level across all patients compared to all control subjects. Colorbar demonstrates significant t-values for both the cortical and subcortical surfaces. Bottom panel depicts findings at the subcortical surfaces with magnified panel demonstrating findings within the right caudate and putamen. A: anterior, P: posterior, S: superior, R: right (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).

Fig. 4

Results from whole brain time lag analysis. Top panel depicts cortical regions of both increased and decreased time lag when selecting the seizure onset node (EZ) as the seed for whole brain time lag analysis. Comparison was made at the group level across all patients compared to all control subjects. Colorbar demonstrates significant t-values for both the cortical and subcortical surfaces. Bottom panel depicts findings at the subcortical surfaces. A: anterior, P: posterior, S: superior, L: left. .