Quantifying extra-lesional interhemispheric cortical asymmetry in focal cortical dysplasia type II

Focal cortical dysplasia type II (FCDII) is a cortical malformation representing a common cause of surgically treatable drug-resistant epilepsy. We studied whether FCDII disrupts normal structural interhemispheric asymmetry beyond the lesion location and quantified these asymmetries derived from structural magnetic resonance imaging (MRI) between individuals with FCDII and healthy controls (HC) as well as within FCDII subtypes using surface-based morphometry (SBM).

Using an open MRI dataset from University Hospital Bonn, we processed T1-weighted images from HC and individuals with FCDII aged over 15 years at the time of scan. We designed a three-stage workflow consisting of SBM using FreeSurfer, visual inspection of atlas-based cortical parcellations, and lesion projection. We extracted five cortical measures of intensity, thickness, volume, curvature, and surface area from 34 regions of interest (ROIs) and computed unsigned interhemispheric asymmetry indices beyond the lesion location.

The majority of FCDII lesions annotated in the original dataset were located in the frontal lobe (64.0%). Compared to the HC, individuals with MRI-diagnosed FCDII showed significantly reduced unsigned interhemispheric intensity asymmetry across parietal, temporal, and occipital cortices (q < 0.001). We observed an increase in the unsigned interhemispheric volume asymmetry in the lateral orbitofrontal cortex and in the unsigned interhemispheric surface-area asymmetry in the inferior temporal cortex for FCDII compared to HC (q < 0.001). Subtype analyses revealed greater unsigned interhemispheric intensity asymmetry in caudal anterior cingulate and superior temporal cortices in FCDIIb compared with FCDIIa (q < 0.001). Conversely, precentral unsigned surface-area and volume asymmetries were smaller in FCDIIb relative to FCDIIa (q < 0.001). We observed no significant differences for unsigned interhemispheric cortical thickness and curvature asymmetries after multiple-comparison corrections.

SBM-derived interhemispheric asymmetry captures cortical alterations in FCDII beyond the focal lesions. Observed differences in group-level unsigned interhemispheric intensity, volume, and surface-area asymmetry indicated cortical alterations that are consistent with distributed cortical involvement between FCDIIa and FCDIIb. These findings may enhance presurgical evaluation by highlighting cortical areas outside the primary lesion that could contribute to seizure generation and achieving seizure-freedom after the operation.

Focal cortical dysplasia type II (FCDII) is a malformation of cortical development associated with drug-resistant epilepsies. FCDII may disrupt normal cortical interhemispheric asymmetries which are understudied in focal, extratemporal epilepsies. We discovered that individuals with FCDII display altered structural cortical interhemispheric asymmetries in intensity, volume, and surface area compared to healthy volunteers, with each FCDII subtype exhibiting a distinct pattern of disrupting the natural asymmetries. Since extra-lesional abnormalities may contribute to incomplete seizure control after surgery, these interhemispheric asymmetry findings could provide complementary information for presurgical evaluations.