title: Thalamic functional connectivity predicts seizure laterality in individual TLE patients: application of a biomarker development strategy.
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.
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA ; Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Barron
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA ; Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA ; South Texas Veterans Health Care System, San Antonio, TX, USA ; Department of Neurology, University of TX Health Science Center, San Antonio, TX, USA ; State Key Lab for Brain and Cognitive Sciences, University of Hong Kong, Hong Kong.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Fox
authors.affiliation: Department of Neurology, New York University, New York, NY, USA.
authors.forename: Heath
authors.initials: H
authors.lastname: Pardoe
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA ; Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Lancaster
authors.affiliation: College of Education, Texas State University, San Marcos, TX, USA ; College of Science, Texas State University, San Marcos, TX, USA.
authors.forename: Larry R
authors.initials: LR
authors.lastname: Price
authors.affiliation: Department of Neurology, New York University, New York, NY, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Blackmon
authors.affiliation: Department of Neurology, New York University, New York, NY, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Berry
authors.affiliation: Department of Neurology, University of TX Health Science Center, San Antonio, TX, USA ; San Antonio Epilepsy Center of Excellence, South Texas Veterans Health Care System, San Antonio, TX, USA.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Cavazos
authors.affiliation: Department of Neurology, New York University, New York, NY, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Kuzniecky
authors.affiliation: Department of Neurology, New York University, New York, NY, USA.
authors.forename: Orrin
authors.initials: O
authors.lastname: Devinsky
authors.affiliation: Department of Neurology, New York University, New York, NY, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thesen
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001931:Brain Mapping / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology*; D012372:ROC Curve; D055815:Young Adult
keywords: Biomarker; Epilepsy; Lateralization; Resting-state fMRI; Temporal Lobe Epilepsy; Thalamus; fMRI