Controlling seizure propagation in large-scale brain networks

Abstract

Information transmission in the human brain is a fundamentally dynamic network process. In partial epilepsy, this process is perturbed and highly synchronous seizures originate in a local network, the so-called epileptogenic zone (EZ), before recruiting other close or distant brain regions. We studied patient-specific brain network models of 15 drug-resistant epilepsy patients with implanted stereotactic electroencephalography (SEEG) electrodes. Each personalized brain model was derived from structural data of magnetic resonance imaging (MRI) and diffusion tensor weighted imaging (DTI), comprising 88 nodes equipped with region specific neural mass models capable of demonstrating a range of epileptiform discharges. Each patient’s virtual brain was further personalized through the integration of the clinically hypothesized EZ. Subsequent simulations and connectivity modulations were performed and uncovered a finite repertoire of seizure propagation patterns. Across patients, we found that (i) patient-specific network connectivity is predictive for the subsequent seizure propagation pattern; (ii) seizure propagation is characterized by a systematic sequence of brain states; (iii) propagation can be controlled by an optimal intervention on the connectivity matrix; (iv) the degree of invasiveness can be significantly reduced via the proposed seizure control as compared to traditional resective surgery. To stop seizures, neurosurgeons typically resect the EZ completely. We showed that stability analysis of the network dynamics, employing structural and dynamical information, estimates reliably the spatiotemporal properties of seizure propagation. This suggests novel less invasive paradigms of surgical interventions to treat and manage partial epilepsy.

Author summary

Epilepsy is characterized by perturbed dynamics that originate in a local network before spreading to other brain regions. We studied patient-specific brain network models of epilepsy patients, comprising 88 nodes equipped with region specific neural mass models capable of demonstrating epileptiform discharges. Applying stability analysis led to a seizure control strategy that is significantly less invasive than the traditional surgery, which typically resects the epileptogenic regions. The invasiveness of the procedure correlates with graph theoretical importance of the nodes. The novel method subsequently removes the most unstable links, a procedure possible by advent of novel surgery techniques. Our approach is entirely based on structural data, allowing creation of a brain model based on purely non-invasive data prior to any surgery.