Thalamus and focal to bilateral seizures: a multi-scale cognitive imaging study

Objective

To 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. As the thalamus modulates propagation of temporal-lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized, i.e. focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity and whole-brain network centrality.

Methods

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. 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 multi-scale approach, entailing analysis of SPM12-derived measures of activation, task-modulated thalamic functional connectivity (psychophysiological interaction), and graph-theoretical metrics of centrality. 

Results

Individuals 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 thalamo-motor 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.

Conclusions

In 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.

Methods
Details in relation to data collection and processing details are provided in the main manuscript text. The uploaded material contains:

-Supplementary Methods (Appendix e-1)

-Supplementary Results (Appendix e-2)

-Two supplementary Figures (Figure e-1, Figure e-2)

-Two supplementary Tables (Table e-1, Table e-2)

-Additional references (e-References), cited in the supplementary material only.