Abstract
ObjectiveTo investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality.MethodsFBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multiscale approach, entailing analysis of statistical parametric mapping (SPM) 12–derived measures of activation, task-modulated thalamic functional connectivity (psychophysiologic interaction), and graph-theoretical metrics of centrality.ResultsIndividuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS.ConclusionsIn TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization.
Highlights
In temporal lobe epilepsy (TLE)-focal to bilateral tonic-clonic seizures (FBTCS), we found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality
Demographic and clinical characteristics There were no differences between TLE-focal seizures (FS) and TLE-FBTCS for demographic and clinical variables, including temporal pathology subtype, number of antiepileptic drugs (AEDs), and usage of topiramate or zonisamide, which both affect verbal fluency activations[28]
Propensity for FBTCS was similar in LTLE and RTLE subgroups (χ2 = 2.66, p = 0.10)
Summary
FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Participants For this cross-sectional investigation, we consecutively recruited 113 patients with drug-resistant TLE (55 left [30 female]; 58 right [43 female]), who underwent presurgical evaluation at the National Hospital for Neurology and Neurosurgery (NHNN), London, United Kingdom, between 2008 and 2013 (table 1).
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