Abstract
BACKGROUND AND OBJECTIVE: Executive dysfunction (ExD) is a common comorbidity of focal epilepsy. Focal cortical dysplasia (FCD) is the most common lesional cause of epilepsy in children. We aimed to investigate clinical, etiologic (pathology), and anatomic vs functional network associations with ExD in FCD-related epilepsy. FCD lesion-network interactions may underlie ExD. The primary analysis was to evaluate whether FCD colocalization to frontoparietal control network or attention networks is associated with ExD. We also evaluated whether FCD type I pathology is associated with ExD because it is reported to be associated with worse intellectual function. METHODS: Patients with FCD were included from retrospective surgical/radiologic databases at Children's National Hospital from January 2000 to January 2022 if they had preoperative neuropsychological testing. FCD colocalization to the Yeo 7-network atlas was determined. Clinical, radiologic, and pathologic factors were evaluated for association with ExD. The primary outcome measure was ExD measured categorically (ExD/Not ExD) and linearly (Behavior Rating Inventory of Executive Function [BRIEF]-Global Executive Composite [GEC] T-score). RESULTS: Ninety-three patients with FCD (45% female) had preoperative BRIEF-GEC T-scores sampled at 11.4 years (SD 4.5 years). Control network colocalization (odds ratio [OR] 3.6, 95% CI 0.94-13.9, p < 0.05) and FCD type I (OR 4.45, 95% CI 1.39-14.3, p = 0.009) are associated with ExD (BRIEF-GEC T-score ≥65). Control network colocalization is associated with Cognitive Regulation Index (mean difference 8.3, 95% CI 0.7-15.9, p = 0.03) and Plan/Organize subscale (8.4, 95% CI 0.9-16.0, p = 0.028). FCD type I is associated with BRIEF-GEC T-score (8.3, 95% CI 2.3-14.2, p = 0.007), Cognitive Regulation Index (7.1, 95% CI 1.2-13.1, p = 0.019), Working Memory (7.4, 95% CI 1.2-13.6, p = 0.021), Plan/Organize (6.0, 95% CI 0.21-11.8, p = 0.042), Shift (8.1, 95% CI 1.6-14.7, p = 0.015), and Emotional Control (8.5, 95% CI 2.5-14.5, p = 0.006) subscales. These findings were not related to Full Scale IQ. FCD colocalization to attentional network (dorsal or ventral), lobar location, or age seizure onset was not associated with ExD. DISCUSSION: These data demonstrate the importance of lesion-network interaction in neuropsychological comorbidity (ExD) in focal epilepsy, unrelated to lesion size or lobar location. FCD colocalization to the Frontoparietal Control network is associated with ExD in a heterogeneous cohort of FCD-related epilepsy. A network-level structure-function correlation is suggested as the most affected processes of cognitive regulation (e.g., planning/organization) are domains regulated by this network. This work contributes toward a more unified theory of focal epilepsy, by beginning to explain common neuropsychological deficits seen across the epilepsies by cortical lesion-network interaction and regardless of lobar location.