Learning the Language of the Brain

One minute Adam Holbrook would be having an ordinary day — shopping, walking down the street, coaching a Little League game — and the next he would find himself back on combat patrol: heart racing, adrenaline coursing, the feel of his rifle in his hands, the odor of burn pits in his nose, in a world of dusty rooftops and dim alleys that all held the threat of danger and death.  

It didn’t take much to trigger a flashback. The waft of a particular smell could do it, or even a glimpse of the sawtooth mountain range behind his house: suddenly they weren’t the mountains of Arizona, but of Afghanistan. 

“And snap, I’d be back there,” said Holbrook, a U.S. Army platoon leader in Iraq and Afghanistan from 2009-2013. “It would be like I never left. Suddenly, I’m on patrol again.” 

The episodes were frequent, unpredictable, and sometimes so powerful that he suffered seizures and blacked out. He was diagnosed with severe Post-Traumatic Stress Disorder (PTSD). He tried every therapy his doctors recommended, but the dissociative episodes continued. Living a normal life was impossible. Living at all began to seem nearly so.  

“The way I was going,” Holbrook said, “I was going to be a statistic.”  

Then, via the VA Clinic in Rancho Cucamonga, California, he was referred to psychiatrist Ralph Koek, MD; neurosurgeon Jean-Phillipe Langevin, MD; and neuroscientist Nanthia Suthana, PhD, who was then at UCLA.  

Suthana, who joined the Duke Department of Neurosurgery earlier this year as a Duke Science and Technology Scholar, studies the neural mechanisms of cognition and behavior. At Duke, she is continuing the cutting-edge research she began at UCLA, using advanced neuroimaging and electrophysiology technologies to investigate and treat neurological and psychiatric disorders.   

When she met with Holbrook, she was working alongside Koek and Langevin to prepare a clinical trial to test a novel deep brain electrostimulation technique for severe PTSD. 

“They did some tests and said, ‘You’re a candidate for this test we’re doing that involves a device we implant in your skull,’” Holbrook said. “By then, I was willing to try anything. So I was like, ‘Wow. OK, cool. Let’s do that.’”  

Memory and Emotion 

Suthana is especially interested in the complex processes that drive memory and emotion, and in developing therapies using neurostimulation to treat disorders that involve those processes.  

One such disorder, of course, is Alzheimer’s disease, which robs people of their memories. The flip side of that is PTSD, in which many patients are besieged by memories they don’t want.  

“At this point, it’s a little easier to inhibit an unwanted memory than it is to enhance a specific memory,” Suthana said. “But we’re working in parallel on both sides of that issue.”  

The amygdala, in the medial temporal lobe, plays a critical role in memory processing and emotional response. By recording and analyzing data from microfine wire electrodes in the amygdala, Suthana and her colleagues discovered that signals called theta waves spike sharply when a subject experiences fear or anxiety — as in, for example, the flashbacks associated with PTSD.  

If one could interrupt that brain wave spike just as it begins, they wondered, could that prevent the flashback and emotional distress? 

A neural implant approved by the FDA a decade ago for the treatment of epilepsy gave them the opportunity to try.  

Stopping the Firestorm 

Suthana and her team developed a wireless interface for the system, which uses ultrafine electrodes and a small transmitter affixed to the skull to continuously record neural activity. They programmed it to detect the distinctive theta wave spike and instantly deliver a targeted electrical pulse.  

“That signal occurs just before they become conscious of the memory, and once that memory starts, it sets off a whole firestorm of events that can leave them unable to function,” Suthana said. “We want to stop that process before it becomes a full-blown episode.”  

Holbrook was among the subjects in the small clinical trial. The results were striking.  

“The subjects still recognize when something happens that would normally trigger an episode,” Suthana said. “They might start to feel nervous that it’s going to happen, but then they say the feeling washes over them, then passes and is gone.”   

After Holbrook had the device implanted three years ago, the flashbacks stopped. Having the disruptive dissociative episodes tamed has given him a sense of control and stability he hadn’t felt in years.    

“I’ve gotten my life back,” said Holbrook, who joined Suthana in addressing the Congressional Neuroscience Caucus on the future of the National Institutes of Health’s BRAIN Initiative in February. “I wouldn’t be here without my wife, and I wouldn’t be here without this science. It works for me, and I hope it’s going to help other veterans and individuals who are suffering from this.”  

Creative Magic 

Suthana and team hope to conduct a trial with a larger cohort of subjects, and she is also hard at work on several other promising areas of research. She was recently named one of 20 principal investigators on the Simons Collaboration on Ecological Neuroscience, a major international initiative aimed at reshaping our understanding of cognition and behavior.  

She’s also conducting research to monitor brain activities at the level of single neurons, which provides an extraordinary window into how the brain functions — and what exactly goes wrong when it malfunctions, in conditions such as seizure disorders. 

She came to Duke because it offers a wealth of potential collaborators across a multitude of disciplines — not only in the School of Medicine but also in the Pratt School of Engineering and across campus — as well as a large patient population and the Durham Veterans Affairs Medical Center right next door.  

“I’m excited to talk with people and generate new ideas across departments and schools,” she said. “There’s a kind of creative magic that happens when you start talking to people who have completely different areas of expertise.” 

“This kind of work requires clinicians, neuroscientists, neurologists, neurosurgeons, psychiatrists, and great engineers,” she said. “There are very few places that have all those things. Duke not only has them, but it has multiple top people in all those areas: the best engineers, the best surgeons, the best neuroscientists. And they all want to work together! That creates a community that is rare to find.”  

Suthana brings her unique experience and expertise to an institution that is already one of the nation’s best at the intersection of neuroscience and engineering.

“Nanthia is a generational talent who thinks like both an engineer and a clinician,” said Gerald A. Grant, MD, chair of the Department of Neurosurgery. “Her work is not just an academic pursuit — she is very focused on making an impact on patient outcomes. Duke is a leader in this neuroengineering space, and her work is key to a larger neurosciences initiative to launch our Center for Brain and Spine Health and Resilience.” 

Suthana has wasted no time taking advantage of Duke’s fertile environment for innovative research. 

“I’m excited to talk with people and generate new ideas across departments and schools,” she said. “There’s a kind of creative magic that happens when you start talking to people who have completely different areas of expertise.” 

Speaking to the Brain 

Suthana says the neuroimaging and stimulation techniques she explores have enormous potential to ultimately benefit patients with a variety of conditions. Other researchers are already adapting her team’s pioneering techniques to develop interventions for Parkinson’s disease, obsessive-compulsive disorder, and binge eating disorder.  

The key, she said, is refining our ability to interact with the brain in all its complexity.  

“You can imagine a future world where we are much better at recording what is happening in the brain and can use that information to personalize interventions for each patient,” she said. “We have to understand the language of the brain, but we also need to be able to speak to it. The better we learn to do that, the better able we will be to help patients in a more personalized manner.  

“These techniques are eventually likely to be useful not only for PTSD and seizure disorders, but for almost any neurological or psychiatric condition you can name.” 

Suthana’s research is supported by the National Institutes of Health, the Simons Foundation, and other public and private sources. 

Dave Hart is the editorial director in the Office of Strategic Communications at the Duke University School of Medicine.  

Eamon Queeney is assistant director Multimedia and Creative in the Office of Strategic Communications at the Duke University School of Medicine.