In roughly 20 million people with drug-resistant epilepsy, focal seizures originating in dysfunctional brain networks will often evolve and spread to surrounding tissue, disrupting function in otherwise normal brain regions. Understanding why and how this synchronization spreads would be a critical tool in treating severe epilepsy.  Now, a study from researchers at the University of Pennsylvania identifies the first existence of a regulatory network of neural regions that can push or pull on the synchronization of the regions directly involved in a seizure.  The team state that with further study, this regulatory network could be a more effective target for epilepsy therapies, including implantable stimulation devices that would help quiet a localized seizure before it spreads throughout the brain.  The opensource study is published in the journal Neuron.

Earlier studies from the lab looked at how the interconnections between members of a group influence the behaviour of the whole. Looking at epilepsy with this perspective developed a computer model of seizure networks based on brain recordings from Penn’s epilepsy patients.  They used this model to show that the algorithms can predict where in the brain a seizure will originate and which groups of neurons it will likely spread to.  For people with epilepsy, there are a number of areas in the brain that are really broken, that’s the seizure-generating network.  Therefore, the group hypothesized that there is a separate regulatory network which can quiet the seizure, and for people whose seizures are general and do not quiet before spreading, that regulatory network is also broken.  However, research is lacking for this regulatory network.   The current study aims to understand how focal seizures, which are limited to only a part of the brain, become general seizures, which spread throughout the brain and are therefore more dangerous and debilitating.

The current study shows that a secondary regulatory network acts on the one directly involved in the seizure, influencing whether the pathological synchronization remains confined to a local area or spreads across the brain.  Results show that seizures are more likely to spread in brain networks with a weaker regulatory capacity to limit traffic flow via desynchronizing brain regions.  The team explain that in engineering terms this regulatory network has what is known as a ‘push-pull regulatory control.’ They go on to add that there are some regions of the regulatory network which can push the seizure network into a less active state, or pull it out of that state.

The researchers state that in order to study how seizure networks synchronize and desynchronize, they used a technique known as ‘virtual cortical resection,’ where they could simulate the surgical removal of different sections of the brain.  They go on to add that resection of regions implicated in the seizure network is a last-ditch treatment for severe epilepsy; using virtual cortical resection, they could test the impact of targeting the regulatory network instead.  Data findings show that this ‘push-pull’ mechanism appears to work in a manner similar to other biological processes that maintain homeostasis, such as the regulation of heart rate or body temperature, however, their study is the first to show the existence of this kind of regulatory network for epilepsy.

The team surmise that their findings identify a network control mechanism which regulates dynamics of network synchronization in advance of seizures, providing critical insight into the mechanisms of brain self-regulation.  For the future, the researchers state that identifying the regions in a patient’s regulatory network could guide new treatment options, such as implantable stimulation devices that bolster the nodes which help quiet seizure activity, or laser surgery to eliminate the nodes that promote it.

Source: University of Pennsylvania