Thalamic Functional Connectivity Predicts Seizure Laterality in Individual TLE Patients: Application of a Biomarker Development Strategy

Date

2015-08

Authors

Barron, Daniel S.
Fox, Peter T.
Pardoe, Heath
Lancaster, Jack
Price, Larry R.
Blackmon, Karen
Berry, Kristen
Cavazos, Jose
Kuzniecky, Ruben
Devinsky, Orrin

Journal Title

Journal ISSN

Volume Title

Publisher

Elsevier

Abstract

Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied. No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses.

Description

Keywords

epilepsy, lateralization, resting-state fMRI, temporal lobe epilepsy, thalamus, fMRI, biomarker

Citation

Barron, D. S., Fox, P. T., Pardoe, H., Lancaster, J., Price, L. R., Blackmon, K., Berry, K., Cavazos, J. E., Kuzniecky, R., Devinsky, O., & Thesen, T. (2015). Thalamic functional connectivity predicts seizure laterality in individual TLE patients: Application of a biomarker development strategy. NeuroImage: Clinical, 7, pp. 273–280.

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© 2014 The Authors.

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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