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Brain’s ‘push-pull’ can control drug-resistant seizures

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The amount of pressure in the brain can regulate focal seizures, the kind that originate at a single point, according to new research.

The finding may revolutionize the treatment of drug-resistant epilepsy.

Epilepsy is one of the most common neurological diseases, affecting people of all ages. There are many seizure disorders, all of which fall under the umbrella of epilepsy. While many seizure disorders can be treated with medication, some patients have strains of epilepsy that are resistant to drugs, meaning that sometimes surgical intervention is necessary. In these patients, doctors can surgically remove tissue to eliminate or minimize future seizures.

The paper further shows that an imbalance of excitation-inhibition activity within an epileptic network may be a promising biomarker for the secondary generalization of focal seizures. In other words, when medical professionals see indications that the excitation and inhibition of neuron firing within the brain is out of balance, this imbalance may be an indicator as to if the seizure will propagate in the brain.

Seizures spreading through the brain

“People thought that the spread of seizures mainly depends on where seizures originate in the brain, but the propagation of a seizure is actually regulated by the surrounding tissues, which includes that seizure onset zone,” says Bin He, head of the biomedical engineering department at Carnegie Mellon University.

“By using an array of electrophysiological recordings, we found that it’s not moving outward necessarily; it depends on how much ‘pull’ a patient receives from the surrounding tissue towards the seizure onset zone, and how much ‘push’ propagates from the seizure onset zone in the same patient. If that pull is weak, then it’s going to spread. If that pull is strong, then we can contain the seizure where it is and prevent it from spreading.”

Although medical professionals recognize drug-resistant focal epilepsy as a network disease (i.e., a seizure spreads through the brain after originating from a single point) in which seizures propagate in coordination with different neuron oscillation frequencies, the mechanism by which different networks constrain the spreading of focal seizures remains unclear.

New treatments?

Researchers tackled the problem by looking at various frequencies, including both slow and fast brain rhythms. They also performed new analysis of functional networks for a given rhythmic band, or the interactions between low and high brain rhythms. By using a new “cross-frequency directionality” technique to study 24 focal drug-resistant epilepsy patients, the team found that the propagation of seizures through the brain depend on a “push-pull” antagonism control mechanism. This “push-pull” mechanism can potentially reflect connections in the epileptic network, suppressing the seizure.

“This finding will have important implications, and suggests that future treatment options should consider interventions not only upon seizure onset zones, but also the surrounding tissues,” He says. “Further delineation of critical network nodes may assist the development of treatments for epilepsy using neuromodulation.”

The research will appear in the journal Annals of Neurology.

Additional researchers from Carnegie Mellon and the Mayo Clinic contributed to the work.
Funding for the work came from the National Institute of Biomedical Imaging and Bioengineering, National Institute of Neurological Disorders, National Institute of Mental Health, and National Center for Complementary and Integrative Health of the National Institutes of Health.

Source: Emily Durham for Carnegie Mellon University