BACKGROUND AND OBJECTIVES: Surgery is an effective treatment for drug-resistant epilepsy, which modifies the brain's structure and networks to regulate seizure activity. Our objective was to examine the relationship between brain structure and function to determine the extent to which this relationship impacts the success of the surgery in controlling seizures. We hypothesized that a stronger association between brain structure and function would lead to improved seizure control following surgery.
METHOD: We constructed functional and structural brain networks in patients with drug-resistant focal epilepsy by using pre-surgery functional data from intracranial EEG (iEEG) recordings, pre- and post-surgery structural data from T1-weighted MRI, and pre-surgery diffusion-weighted MRI. We quantified the relationship (coupling) between structural and functional connectivity by using Spearman rank correlation and analyzed this structure-function coupling at two spatial scales: (i) global iEEG network level and (ii) individual iEEG electrode contacts using "virtual surgeries". We retrospectively predicted post-operative seizure freedom, by incorporating the structure-function connectivity coupling metrics and routine clinical variables into a cross-validated predictive model.
RESULT: We conducted a retrospective analysis on data from 39 patients who met our inclusion criteria. Brain areas implanted with iEEG electrodes had stronger structure-function coupling in seizure-free subjects compared to those with seizure recurrence (p=0.002, d=0.76, AUC=0.78 [95%CI 0.62, 0.93]). Virtual surgeries on brain areas that resulted in stronger structure-function coupling of the remaining network were associated with seizure-free outcomes (p=0.007, d=0.96, AUC=0.73 [95%CI 0.58, 0.89]). The combination of global and local structure-function coupling measures accurately predicted seizure outcomes with a cross-validated AUC of 0.81 [95%CI 0.67, 0.94]. These measures were complementary to other clinical variables and, when included for prediction, resulted in a cross-validated AUC of 0.91 [95%CI 0.82, 1.0], accuracy of 92%, sensitivity of 93%, and specificity of 91%.
CONCLUSION: Our study showed that the strength of structure-function connectivity coupling may play a crucial role in determining the success of epilepsy surgery. By quantitatively incorporating structure-function coupling measures and standard-of-care clinical variables into pre-surgical evaluations, we may be able to better localize epileptogenic tissue and select patients for epilepsy surgery.
CLASSIFICATION OF EVIDENCE: This is a Class IV retrospective case series showing that structure-function mapping may help determine outcome from surgical resection for treatment-resistant focal epilepsy.