Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures
- Leonardo Bonilha1,
- Travis Nesland1,
- Gabriel U Martz1,
- Jane E Joseph1,
- Maria V Spampinato2,
- Jonathan C Edwards1,
- Ali Tabesh2
- 1Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA
- 2Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, South Carolina, USA
- Correspondence to Dr L Bonilha, 96 Jonathan Lucas St, 3rd floor CSB, Division of Neurology, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA;
Contributors All authors have contributed to the production of this study and are in agreement with its content. As per the International Committee of Medical Journal Editors, authorship credit should be based on: (1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of the data; (2) drafting the article or revising it critically for important intellectual content; and (3) final approval of the version to be published. The authors of the this paper met the following conditions: LB: (1), (2), (3); TN: (2); GUM: (1), (2); JEJ: (1), (2), (3); MVS: (2); JCE: (2); AT: (1), (2), (3).
- Received 8 February 2012
- Revised 30 April 2012
- Accepted 4 June 2012
- Published Online First 4 July 2012
Background It has been hypothesised that seizure induced neuronal loss and axonal damage in medial temporal lobe epilepsy (MTLE) may lead to the development of aberrant connections between limbic structures and eventually result in the reorganisation of the limbic network. In this study, limbic structural connectivity in patients with MTLE was investigated, using diffusion tensor MRI, probabilistic tractography and graph theory based network analysis.
Methods 12 patients with unilateral MTLE and hippocampal sclerosis (five left and seven right MTLE) and 26 healthy controls were studied. The connectivity of 10 bilateral limbic regions of interest was mapped with probabilistic tractography, and the probabilistic fibre density between each pair of regions was used as the measure of their weighted structural connectivity. Binary connectivity matrices were then obtained from the weighted connectivity matrix using a range of fixed density thresholds. Graph theory based properties of nodes (degree, local efficiency, clustering coefficient and betweenness centrality) and the network (global efficiency and average clustering coefficient) were calculated from the weight and binary connectivity matrices of each subject and compared between patients and controls.
Results MTLE was associated with a regional reduction in fibre density compared with controls. Paradoxically, patients exhibited (1) increased limbic network clustering and (2) increased nodal efficiency, degree and clustering coefficient in the ipsilateral insula, superior temporal region and thalamus. There was also a significant reduction in clustering coefficient and efficiency of the ipsilateral hippocampus, accompanied by increased nodal degree.
Conclusions These results suggest that MTLE is associated with reorganisation of the limbic system. These results corroborate the concept of MTLE as a network disease, and may contribute to the understanding of network excitability dynamics in epilepsy and MTLE.
Funding This work was supported in part by the National Science Foundation/EPSCoR under grant No EPS-0919440. This publication was supported by the South Carolina Clinical and Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, through NIH grant Nos UL1 RR029882 and UL1 TR000062.
Competing interests None.
Ethics approval The study was approved by the institutional review board of the Medical University of South Carolina.
Provenance and peer review Not commissioned; externally peer reviewed.
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