Assessing criticality in pre-seizure single-neuron activity of human epileptic cortex

Author summary In epilepsy patients, the brain regularly fails to control its activity, resulting in epileptic seizures. So far, it is not fully understood why the the brains of epilepsy patients are susceptible to seizures and what the mechanism behind seizure generation is. We investigated epilepsy from the perspective of collective neural dynamics in the brain. It has been hypothesized that epileptic seizures might be a tipping over from stable, so-called subcritical, dynamics (which are commonly found in healthy brains) to unstable, so-called supercritical dynamics. We therefore examined two potential scenarios of seizure generation: (i) epileptic brain areas might generally operate closer to instability, which would make epilepsy patients generally susceptible to seizures, or (ii) epileptic brain areas might slowly drift towards instability before seizure onset. To test these two hypotheses, we analyzed activity of single neurons recorded with micro-electrodes in epilepsy patients. Contrary to widespread expectation, we found no evidence for either scenario, thus no evidence that epilepsy involves a transition to supercritical collective neural dynamics. In fact, our results from both seizure-free and pre-seizure intervals suggest that the human epileptic brain operates in the stable regime, just like the brains of other healthy mammalians. Epileptic seizures are characterized by abnormal and excessive neural activity, where cortical network dynamics seem to become unstable. However, most of the time, during seizure-free periods, cortex of epilepsy patients shows perfectly stable dynamics. This raises the question of how recurring instability can arise in the light of this stable default state. In this work, we examine two potential scenarios of seizure generation: (i) epileptic cortical areas might generally operate closer to instability, which would make epilepsy patients generally more susceptible to seizures, or (ii) epileptic cortical areas might drift systematically towards instability before seizure onset. We analyzed single-unit spike recordings from both the epileptogenic (focal) and the nonfocal cortical hemispheres of 20 epilepsy patients. We quantified the distance to instability in the framework of criticality, using a novel estimator, which enables an unbiased inference from a small set of recorded neurons. Surprisingly, we found no evidence for either scenario: Neither did focal areas generally operate closer to instability, nor were seizures preceded by a drift towards instability. In fact, our results from both pre-seizure and seizure-free intervals suggest that despite epilepsy, human cortex operates in the stable, slightly subcritical regime, just like cortex of other healthy mammalians.