Phase-amplitude coupling between interictal high-frequency activity and slow waves in epilepsy surgery

Objective We hypothesized that the modulation index (MI), a summary measure of the strength of phase-amplitude coupling between high-frequency activity (>150 Hz) and the phase of slow waves (3-4 Hz), would serve as a useful interictal biomarker for epilepsy presurgical evaluation. Methods Results We investigated 123 patients who underwent focal cortical resection following extraoperative electrocorticography recording and had at least 1 year of postoperative follow-up. We examined whether consideration of MI would improve the prediction of postoperative seizure outcome. MI was measured at each intracranial electrode site during interictal slow-wave sleep. We compared the accuracy of prediction of patients achieving International League Against Epilepsy class 1 outcome between the full multivariate logistic regression model incorporating MI in addition to conventional clinical, seizure onset zone (SOZ), and neuroimaging variables, and the reduced logistic regression model incorporating all variables other than MI. Ninety patients had class 1 outcome at the time of most recent follow-up (mean follow-up = 5.7 years). The full model had a noteworthy outcome predictive ability, as reflected by regression model fit R-2 of 0.409 and area under the curve (AUC) of receiver operating characteristic plot of 0.838. Incomplete resection of SOZ (P < 0.001), larger number of antiepileptic drugs at the time of surgery (P = 0.007), and larger MI in nonresected tissues relative to that in resected tissue (P = 0.020) were independently associated with a reduced probability of class 1 outcome. The reduced model had a lower predictive ability as reflected by R-2 of 0.266 and AUC of 0.767. Anatomical variability in MI existed among nonepileptic electrode sites, defined as those unaffected by magnetic resonance imaging lesion, SOZ, or interictal spike discharges. With MI adjusted for anatomical variability, the full model yielded the outcome predictive ability of R-2 of 0.422, AUC of 0.844, and sensitivity/specificity of 0.86/0.76. Significance MI during interictal recording may provide useful information for the prediction of postoperative seizure outcome.