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. 2016 Jul;123:20-8.
doi: 10.1016/j.eplepsyres.2016.04.001. Epub 2016 Apr 5.

Low Functional Robustness in Mesial Temporal Lobe Epilepsy

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Free PMC article

Low Functional Robustness in Mesial Temporal Lobe Epilepsy

C Garcia-Ramos et al. Epilepsy Res. .
Free PMC article

Abstract

Objectives: Brain functional topology was investigated in patients with mesial temporal lobe epilepsy (mTLE) by means of graph theory measures in two differentially defined graphs. Measures of segregation, integration, and centrality were compared between subjects with mTLE and healthy controls (HC).

Methods: Eleven subjects with mTLE (age 36.5±10.9years) and 15 age-matched HC (age 36.8±14.0years) participated in this study. Both anatomically and functionally defined adjacency matrices were used to investigate the measures. Binary undirected graphs were constructed to study network segregation by calculating global clustering and modularity, and network integration by calculating local and global efficiency. Node degree and participation coefficient were also computed in order to investigate network hubs and their classification into provincial or connector hubs. Measures were investigated in a range of low to medium graph density.

Results: The group of patients presented lower global segregation than HC while showing higher global but lower local integration. They also failed to engage regions that comprise the default-mode network (DMN) as hubs such as bilateral medial frontal regions, PCC/precuneus complex, and right inferior parietal lobule, which were present in controls. Furthermore, the cerebellum in subjects with mTLE seemed to be playing a major role in the integration of their functional networks, which was evident through the engagement of cerebellar regions as connector hubs.

Conclusions: Functional networks in subjects with mTLE presented both global and local abnormalities compared to healthy subjects. Specifically, there was significant separation between groups, with lower global segregation and slightly higher global integration observed in patients. This could be indicative of a network that is working as a whole instead of in segregated or specialized communities, which could translate into a less robust network and more prone to disruption in the group with epilepsy. Furthermore, functional irregularities were also observed in the group of patients in terms of the engagement of cerebellar regions as hubs while failing to engage DMN-related areas as major hubs in the network. The use of two differentially defined graphs synergistically contributed to findings.

Keywords: Functional hubs; Graph theory analysis; Mesial temporal lobe epilepsy; Resting-state fMRI.

Figures

Figure 1
Figure 1. Global efficiency
Global efficiency in anatomically defined (left) and functionally defined (right) graphs across a range of network densities between mTLE (red) and healthy subjects (blue). Both kinds of networks show moderately higher global efficiency in patients compared to controls. * Significant at p<0.05, corrected for multiple comparisons.
Figure 2
Figure 2. Global clustering
Global clustering in the anatomically defined (left) and the functionally defined (right) graphs across a range of network densities between mTLE (red) and healthy subjects (blue). In both kinds of networks, patients show lower global clustering when compared to controls. * Significant at p<0.05, corrected for multiple comparisons.
Figure 3
Figure 3. Modularity index
Modularity index in anatomically (left) and functionally defined (right) networks across a range of network densities between mTLE (red) and healthy subjects (blue). No significant differences were obtained at any density level.
Figure 4
Figure 4. Local efficiency
Local efficiency in anatomically (top) and functionally defined (bottom) networks between mTLE (red) and healthy subjects (blue). Filled nodes are those that presented significant differences at FDR correction. Calculated at a density threshold of 37%.
Figure 5
Figure 5. 2D visualization of modularity
Modularity in anatomically (top) and functionally defined (bottom) networks in HC (left) and mTLE (right). Hubs are represented as bigger spheres. Different colors represent different modules. Anatomically defined network: green= cerebellar regions; cyan= mainly parietal, temporal, and occipital regions; red=mainly frontal and parietal; blue=frontal, insular and subcortical in HC, only subcortical in mTLE. Functionally defined network: red=mostly SM, visual, attention, and task control; green=mainly task control, and salience in controls, and salience and subcortical areas in mTLE; cyan= cerebellar (in controls only); blue=mainly DMN. Nodes with stronger and higher number of connections are spatially closer while those with weaker and lower number of connections are farther in space. Calculated at a density threshold of 37%.
Figure 6
Figure 6. Functional hubs
Provincial (small spheres) and connector (bigger spheres) hubs of the anatomically defined (top) and the functionally defined (bottom) networks in healthy subjects (left) and patients with mTLE (right). Different colors represent different locations (anatomically defined) or different functional systems (functionally defined). Anatomically defined network: red=frontal; blue=parietal; green=temporal; yellow=occipital; cyan=cerebellar; pink=insular; magenta=cingulate cortex. Functionally defined network: red=somatomotor; green= auditory; blue=DMN; pink=ventral attention; magenta=cingulo-opercular task control; yellow=visual; brown=salience; orange=fronto-parietal task control; teal=dorsal attention. Calculated at a density threshold of 37%.

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