Advancing Basic Science for Humanity
12/04/2014 - Brain Stimulation Counteracts Dangerous Side Effect of Seizures
(Originally published by Yale University)
December 4, 2014
Loss of consciousness is a common and dangerous side effect of epileptic seizures. A new Yale-led study, however, shows that activation of electrodes in key brain areas can awaken rats with induced seizures.
“At least a quarter of people with epilepsy have seizures that can’t be controlled,” said Dr. Hal Blumenfeld, professor of neurology, neurobiology, and neurosurgery, a member of the Kavli Institute for Neuroscience and senior author of the study. “Our hope is that for this population, brain stimulation can help reduce injuries and deaths that result from a loss of consciousness.”
Blumenfeld and colleagues brought rats back to consciousness after seizures by stimulating the thalamus and areas of the brain stem known to play a role in wakefulness. The rats immediately began to explore their cages again.
Additional testing needs to be done to determine if such brain stimulation can be conducted safely in humans, he said.
There may be as many as 500,000 epilepsy patients in the United States who suffer from chronic, treatment-resistant seizures, Blumenfeld estimated. These patients might be aided by implants of electrodes that could prevent loss of consciousness during and following seizures, he said.
Lead author of the paper is Yale’s Abhijeet Gummadavelli.
Primary funding for the research was provided by the National Institutes of Health.
For more information on seizures and consciousness read the Q&A from Dr. Hal Blumenfeld below [Kavli Institute for Neuroscience]
For centuries, the nature of consciousness has been a question for philosophers. That began to change in the late 20th century when scientists such as Francis Crick, the co-discoverer of DNA, argued that it is a tractable scientific problem. Yale’s Hal Blumenfeld is helping to prove Crick right by using the increasingly sophisticated tools of neuroscience to find the biological basis of consciousness. With this new knowledge, he is aiming to prevent or reverse the loss of consciousness—and the dangerous consequences of it—that often accompany seizures in individuals with epilepsy.
Blumenfeld is Professor of Neurology, of Neurobiology and of Neurosurgery at the Yale School of Medicine. He is also Director of the Yale Clinical Neuroscience Imaging Center and a member of the Kavli Institute for Neuroscience. By asking what has changed in the brain as it shifts from a conscious to unconscious state of awareness, he has identified brain structures, circuits and activity patterns essential to wakefulness.
In an interview with the Kavli Institute for Neuroscience, Blumenfeld discusses the significance of the new study and the brain imaging tools that are helping neuroscientists unravel the question of consciousness.
Kavli Institute for Neuroscience: What is the focus of your research on epilepsy?
Blumenfeld: I’m interested in investigating consciousness and in particular how consciousness is interrupted by neurological disorders such as epilepsy. Understanding this is of tremendous practical importance for epilepsy patients and could lead to new treatment strategies. But it also gives us insights into normal consciousness and the brain systems that control it.
KIN: How does your clinical practice influence your research?
Blumenfeld: When I see patients with epilepsy who have impaired consciousness and difficulty at work or school because of it, it gives me more incentive to find ways to try to improve their quality of life. The other thing is that patients die from epilepsy. This is often because there is loss of consciousness causing suffocation at night or a driving accident. As a neurologist, I have discussions with my patients about these risks. My hope is that my lab’s studies will give us a better understanding of the neurobiology of impaired consciousness and help us prevent some of these deaths.
KIN: How do you use brain imaging tools to study impaired consciousness?
Blumenfeld: We use neuroimaging tools to map the brain during seizures to see what the functional changes are and to understand how seizures disrupt the mechanisms that are responsible for normal consciousness. The results provide us with a guide to which parts of the brain are disrupted either with abnormal increased or decreased activity during seizures. Then we relate those brain activity changes to behavioral changes in patients. After that, on a more fundamental level, we use animal models to investigate the cellular and molecular basis for brain dysfunction during seizures.
KIN: Can you give me an example?
Blumenfeld: Sure. We’ve looked at impaired consciousness in a very common form of epilepsy: temporal lobe seizures. They are focal, meaning they occur in one localized area of the temporal lobe. It makes sense that a seizure that involves a big area of the brain should disrupt consciousness. But why is it that during a seizure many people with temporal lobe epilepsy look like sleep-walkers, unable to respond normally to their environment? That was a mystery. So we did imaging in people during temporal lobe seizures and discovered that those seizures affect a whole network in the brain, including the subcortical structures that are important for keeping the cortex awake. It turns out that localized seizures in the temporal lobe turn on the deep sleep circuit aberrantly, which turns off the arousal network. No one really knew that before.
KIN: How have you extended this work in animals?
Blumenfeld: We've used animal models to figure out exactly which neurons are turned on and off. Normally, you think of seizures as turning things on but we think temporal lobe seizures are turning off the arousal circuits that keep people awake. We have a program in animals where we're doing deep brain stimulation and optogenetics, a technique that uses light to activate neurons. We can stimulate the arousal circuits in the thalamus and the brainstem to reverse the seizures and wake the cortex back up again. It's working in the rats. We're hoping we can translate that to the clinic to help patients with epilepsy.
KIN: Right. Your new study shows that activating the right part of the brain can restore consciousness in rats that experience seizures. How is stimulation affecting the brain?
Blumenfeld: After a seizure the brain usually shows a lot of slow wave activity resembling deep sleep. We found that stimulating the thalamus immediately after seizures converts the brain to an awake activity pattern. Instead of lying on the bottom of their cages, rats wake up and resume normal exploration of their environment. This happens because the stimulation reactivates the normal arousal circuits in the brain.
KIN: What are the next steps to translating this work to the clinic?
Blumenfeld: Before testing in humans we want to see if we can wake up the brain not just after seizures but also while a seizure is still going on. We hope that by automatically detecting when the seizure starts we can trigger stimulation early on and prevent loss of consciousness altogether. The devices and techniques for brain stimulation are already in use for other clinical disorders like Parkinson’s disease and chronic pain. So once we determine the best ways to stimulate during seizures it should be possible to translate this approach to human seizures relatively soon.