Focal epilepsy is commonly caused by brain lesions, but it remains unclear why some lesion locations result in epilepsy while others do not. One possibility is that some brain regions or networks are more vulnerable than others. Identifying the brain regions or networks related to epilepsy could inform prognosis and guide interventions.

Lesion locations from patients with ischemic stroke-related epilepsy (n = 76) and control lesions (n = 625) were mapped to a common brain atlas. Traditional lesion mapping methods were used to test for associations between epilepsy and lesion location. Next, we computed the brain network functionally connected to each lesion location using human brain connectome data (n = 1000). Network connections associated with epilepsy were identified. Generalizability to other lesion types was assessed using independent datasets of four different lesion etiologies (n = 772) and a leave-one-dataset-out analysis. These connections were then used to generate a brain network map that best encompasses lesion locations related to epilepsy. Finally, we tested whether thalamic deep brain stimulation sites that improve seizure control were connected to this same network (n = 30).

We found that lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these heterogenous lesion locations were part of a common brain network defined by functional connectivity to the basal ganglia and cerebellum (Vmax = 6.8, P < 0.001). Functional connectivity to these regions was associated with the risk of epilepsy across different lesion types (χ2 = 205.3, P < 0.001) and with therapeutic response to thalamic deep brain stimulation (r = 0.63, P < 0.005).

Lesion locations related to epilepsy map to a common brain network defined by functional connectivity to the basal ganglia and cerebellum.