All Fired Up

Your brain is composed of billions of tiny elements, each communicating with the other through a series of electrical impulses. The aggregate of all these electrical signals makes you who you are – enabling you to use your senses, integrate information, make plans, dream. But when the signals don’t come together as they should, it can result in a psychiatric disorder like schizophrenia.

Flavio Frohlich, Ph.D., has a theory on how to get those neurons back in sync. He thinks that superficial brain stimulation – applied through the firing of a few simple electrodes on the scalp -- could retrain neural networks to follow normal electrical activity patterns. Frohlich has already tested the approach in ferrets, and is using an NC TraC$ 50K pilot award to explore whether it could work in humans.

For a basic scientist like Frohlich, that is a big leap.

“I am going from being an engineer and an animal electrophysiologist to trying out some of my ideas with humans, and NC TraCS [North Carolina Translational and Clinical Sciences Institute] has made that possible. I would have never been able to do this without their help,” said Frohlich, who joined UNC-CH a year ago as an assistant professor of psychiatry, cell and molecular physiology, and biomedical engineering. “It's not just the money; it's the support and the mentoring they provide. It is the active encouragement to go beyond your own horizons -- which I love to do anyway – and the infrastructure to increase your chances of success.”

NC TraCS is UNC’s home of the NIH Clinical and Translational Science Awards (CTSA), a national consortium focused on speeding up the pace of translational research.

Frohlich’s own research focuses on the cerebral cortex, the convoluted outmost shell of the brain that is responsible for most of our higher-order functions. A lot of what scientists know about the cortex has come from electroencephalograms or EEGs, a technique developed over a hundred years ago. EEGs essentially give a global measure of brain activity, recording the overall hum or sound of a large group of neurons talking to each other. Researchers have found that neurons coordinate their communication through rhythmic activity patterns, or oscillations. Depending on your behavioral state -- whether you are in a deep sleep or trying to understand these words on the page -- those patterns appear at a different frequency.

These different frequencies all go by Greek letters – delta for the pattern that corresponds with taking that long nap, gamma for the one that appears when you are trying to digest new information. For people with neuropsychiatric illnesses, there are very specific deficits in certain rhythms. For example, the gamma oscillations are not as strong in patients with schizophrenia as they are in normal individuals.

Frohlich thinks that within this basic observation lies a new treatment for schizophrenia and other mental illnesses. So he proposed a pilot project in collaboration with senior faculty psychiatrist John Gilmore, M.D., and senior faculty neurologist Bradley Vaughn, M.D., to test his idea.

“Rather than giving someone a pill that might change some biochemical properties of brain cells, which hopefully affects how brain cells talk to each other, which hopefully affects how these large scale signals arise, which hopefully affects behavior, we're going to take a massive shortcut,” said Frohlich. “We’re going to bypass all this molecular and cellular complexity and just use electrical stimulation to tell the brain how to get its act together.”

Frohlich’s approach is different from other researchers who have tried to use a constant electrical current to treat such deficiencies. Instead, Frohlich is using his basic knowledge of the brain’s communication patterns to apply specific electrical frequencies as a way of nudging the brain’s wiring back into a specific rhythm.

“Using constant stimulation would be like trying to have a conversation by me yelling at you at constant pitch and volume and not really having any temporal structure in my speech,” said Frohlich. “We want to use electrical stimulation to more intelligently converse with the brain, to tell it when it is out of step and give it a hint of how to correct its behavior. Almost like a dance teacher.”

He has just started his pilot project, which tests brain stimulation in 16 volunteers with no history of neuropsychiatric illnesses. Though there will be no deficiency to correct in the study subjects, Frohlich says that people’s brain functioning can always get better. If he finds that brain stimulation has a positive effect, then he will move on to assess its effects in patients with schizophrenia.

The Swiss-born son of two physicians, Frohlich is happy to push his work closer to the clinic. While he wants to focus on patients with schizophrenia first, he thinks his approach could also help treat autism, attention deficit disorder, depression and dementia, all of which have neural communication that is out of sync.

“Down the road, I’m probably going to want to do it all, but I also realize that we have to take a number of smaller or bigger steps first,” said Frohlich. “I’m happy to have help in making my research truly translational.”