An epilepsy network derived from human brain lesions and deep brain stimulation

Abstract Background: Focal epilepsy is increasingly conceptualized as a disease of brain networks, but the network localization remains poorly understood. Lesion locations associated with epilepsy may help identify epilepsy networks and lead to new treatment targets. Methods: We studied 701 stroke patients and analyzed the lesion locations associated with epilepsy (n = 76) or control (n = 625). Lesion locations were mapped to a common brain atlas and the brain network functionally connected to each lesion location was computed using human connectome data (n = 1000). Functional connections associated with stroke-related epilepsy were identified using lesion-network mapping. Generalizability to epilepsy associated with other lesion types (n = 452) was assessed using a leave-one-lesion-type-out cross-validation. Finally, therapeutic relevance of these connections was assessed using outcome data from patients who received thalamic deep brain stimulation for drug resistant epilepsy (n = 30). Results: Lesion locations associated with stroke-related epilepsy map to a specific brain network defined by functional connectivity to nodes in the cerebellum, substantia nigra, and globus pallidus (P < 0.01). Connectivity to this network was associated with the risk of epilepsy across different lesion types (P = 0.0001) and with therapeutic response to thalamic deep brain stimulation (R = 0.63, P = 0.00017). Conclusions: Brain lesions associated with epilepsy map to a specific brain network, with therapeutic potential for neuromodulation in epilepsy. Keywords: epilepsy, lesions, brain networks, neuromodulation