Network Colocalization Correlates of Depression and Anxiety in Pediatric Focal Cortical Dysplasia-Related Epilepsy

Focal cortical dysplasia (FCD) is the most common cause of surgically treatable, drug-resistant epilepsy in children. Anxiety and depression are frequent comorbidities in epilepsy. This study examined whether FCD overlap with large-scale functional networks, the default mode network (DMN) and the limbic network, is associated with parent-reported anxiety or depressive symptoms.

Sixty-nine patients with FCD-related epilepsy completed the Child Behavior Checklist (CBCL), among whom 56 finished the 6 to 18 years version of CBCL (CBCL_6-18). FCD overlap (%) with Yeo 7-networks was calculated. General linear models tested FCD_DMN or FCD_limbic overlap with CBCL Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM)-Anxiety Problems or DSM-Depressive Problems Scores controlling for age and gender.

Fifty-six patients had preoperative CBCL_6-18 (median age = 12.8 years, 55% male patients). FCD_DMN overlap (B = 0.08, 95% confidence interval [CI] = 0.002-0.16, partial η² = 0.086, p = 0.045) and female gender were associated with higher DSM-Depressive Problems T-scores. This lesion-network depressive-symptoms effect was stronger in an adolescent-only model (52% male patients): FCD_DMN overlap (B = 0.19, 95% CI = 0.068-0.32, partial η² = 0.37, p = 0.004). Network overlap was not associated with DSM-Anxiety Problems in any age group.

FCD_DMN overlap is associated with increased depressive symptoms, particularly for adolescents, whereas FCD_limbic overlap is not. These findings underscore the importance of lesion-network colocalization contributing to depression vulnerability in developmental epilepsy and highlight DMN colocalization involvement as a potential neurobiological marker of depressive risk. ANN NEUROL 2026;100:84-94.