Intracranial EEG Structure-Function Coupling and Seizure Outcomes After Epilepsy Surgery.

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 affects 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 after surgery. METHODS: We constructed functional and structural brain networks in patients with drug-resistant focal epilepsy by using presurgery functional data from intracranial EEG (iEEG) recordings, presurgery and postsurgery structural data from T1-weighted MRI, and presurgery diffusion-weighted MRI. We quantified the relationship (coupling) between structural and functional connectivity by using the Spearman rank correlation and analyzed this structure-function coupling at 2 spatial scales: (1) global iEEG network level and (2) individual iEEG electrode contacts using virtual surgeries. We retrospectively predicted postoperative seizure freedom by incorporating the structure-function connectivity coupling metrics and routine clinical variables into a cross-validated predictive model. RESULTS: 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 patients compared with those with seizure recurrence (p = 0.002, d = 0.76, area under the receiver operating characteristic curve [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%. DISCUSSION: 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 presurgical 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 the outcome from surgical resection for treatment-resistant focal epilepsy.

Contribution of White Matter Fiber Bundle Damage to Language Change After Surgery for Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: In medically refractory temporal lobe epilepsy (TLE), 30%-50% of patients experience substantial language decline after resection in the language-dominant hemisphere. In this study, we investigated the contribution of white matter fiber bundle damage to language change at 3 and 12 months after surgery. METHODS: We studied 127 patients who underwent TLE surgery from 2010 to 2019. Neuropsychological testing included picture naming, semantic fluency, and phonemic verbal fluency, performed preoperatively and 3 and 12 months postoperatively. Outcome was assessed using reliable change index (RCI; clinically significant decline) and change across timepoints (postoperative scores minus preoperative scores). Functional MRI was used to determine language lateralization. The arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus, middle longitudinal fasciculus (MLF), and uncinate fasciculus were mapped using diffusion MRI probabilistic tractography. Resection masks, drawn comparing coregistered preoperative and postoperative T1 MRI scans, were used as exclusion regions on preoperative tractography to estimate the percentage of preoperative tracts transected in surgery. Chi-squared assessments evaluated the occurrence of RCI-determined language decline. Independent sample t tests and MM-estimator robust regressions were used to assess the impact of clinical factors and fiber transection on RCI and change outcomes, respectively. RESULTS: Language-dominant and language-nondominant resections were treated separately for picture naming because postoperative outcomes were significantly different between these groups. In language-dominant hemisphere resections, greater surgical damage to the AF and IFOF was related to RCI decline at 3 months. Damage to the inferior frontal subfasciculus of the IFOF was related to change at 3 months. In language-nondominant hemisphere resections, increased MLF resection was associated with RCI decline at 3 months, and damage to the anterior subfasciculus was related to change at 3 months. Language-dominant and language-nondominant resections were treated as 1 cohort for semantic and phonemic fluency because there were no significant differences in postoperative decline between these groups. Postoperative seizure freedom was associated with an absence of significant language decline 12 months after surgery for semantic fluency. DISCUSSION: We demonstrate a relationship between fiber transection and naming decline after temporal lobe resection. Individualized surgical planning to spare white matter fiber bundles could help to preserve language function after surgery.