Altered Structural Connectome in Temporal Lobe Epilepsy

Matthew DeSalvo

Linda Douw

Naoaki Tanaka

Claus Reinsberger

Steven Stufflebeam

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From the Athinoula A. Martinos Center for Biomedical Imaging, 149 Thirteenth St, Suite 2301, Charlestown, MA 02129 (M.N.D., L.D., N.T., C.R., S.M.S.); Department of Radiology, Massachusetts General Hospital, Charlestown, Mass (M.N.D., L.D., N.T., S.M.S.); and Department of Neurology, Brigham and Women’s Hospital, Boston, Mass (C.R.).

^{Corresponding author.}

Steven M. Stufflebeam: ude.dravrah.hgm.rmn@sms

Address correspondence to S.M.S. (e-mail: ude.dravrah.hgm.rmn@sms).

Contributed by

Author contributions: Guarantors of integrity of entire study, M.N.D., N.T., S.M.S.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, all authors; clinical studies, M.N.D., N.T., C.R.; experimental studies, N.T., C.R., S.M.S.; statistical analysis, all authors; and manuscript editing, all authors

Steven M. Stufflebeam: ude.dravrah.hgm.rmn@smsAddress correspondence to S.M.S. (e-mail: ude.dravrah.hgm.rmn@sms).

Abstract

Left temporal lobe epilepsy is associated with decreased distant structural connectivity in the default mode network and increased local connectivity in widespread cortical areas, perhaps due to altered white matter fiber orientation as a result of epileptiform activity.

Abstract

Purpose

To study differences in the whole-brain structural connectomes of patients with left temporal lobe epilepsy (TLE) and healthy control subjects.

Materials and Methods

This study was approved by the institutional review board, and all individuals gave signed informed consent. Sixty-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) magnetic resonance imaging volumes were analyzed in 24 patients with left TLE and in 24 healthy control subjects. MP-RAGE volumes were segmented into 1015 regions of interest (ROIs) spanning the entire brain. Deterministic white matter tractography was performed after voxelwise tensor calculation. Weighted structural connectivity matrices were generated by using the pairwise density of connecting fibers between ROIs. Graph theoretical measures of connectivity networks were compared between groups by using linear models with permutation testing.

Results

Patients with TLE had 22%–45% reduced (P < .01) distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with that in healthy subjects. However, local connectivity, as measured by means of network efficiency, was increased by 85%–270% (P < .01) in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE as compared with healthy subjects.

Conclusion

This study suggests that TLE involves altered structural connectivity in a network that reaches beyond the temporal lobe, especially in the default mode network.

Online supplemental material is available for this article.

Abstract

Acknowledgments

The authors acknowledge Nao Suzuki, BA, and Roberta Zanzonico, MD, for technical support, as well as Lawrence Wald, PhD, and Nikos Makris, PhD, for essential advice on diffusion acquisition and analysis.

Acknowledgments

Received May 6, 2013; revision requested June 9; revision received July 9; accepted July 19; final version accepted August 22.

Supported by the National Center for Research Resources, the National Institutes of Health Human Connectome Project, the Mental Illness and Neuroscience Discovery Institute, the Netherlands Organisation for Scientific Research (NOW) Rubicon grant, the Epilepsy Foundation of America, the Japan Epilepsy Research Foundation, and an RSNA Research Medical Student Grant.

Funding: This research was supported by the National Institutes of Health (grants P41-RR14075, R01-NS037462, R0-1NS069696, and 5R01-NS060918).

Disclosures of Conflicts of Interest: M.N.D. No relevant conflicts of interest to disclose. L.D. No relevant conflicts of interest to disclose. N.T. No relevant conflicts of interest to disclose. C.R. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: author received a consultancy from Sleep Med for the interpretation of clinical data and electroencephalograms. Other relationships: none to disclose. S.M.S. No relevant conflicts of interest to disclose.

Abbreviations:

DMN: default mode network
MP-RAGE: magnetization-prepared rapid acquisition gradient-echo
ROI: region of interest
TLE: temporal lobe epilepsy

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