51�ԹϺ���

The is set up for a unique experiment with laminated images on the walls at each blue X taped to the floor: a banana across from an extended tape measure, scissors facing blueberries, an orange facing a hammer.

Experiment participant Travis Rouse would have eight minutes to find and remember each pair. Then all the images would be taken down, and he would have to stand at those same spots to try to remember exactly what he had seen there.

But before going off to find the fruits and tools, postdoctoral scholar was equipping Rouse with a backpack and headgear carrying a GPS device, Wi-Fi router, tablet, eye tracker and a scanning wand to gather data from the device implanted in Rouse’s brain that helps manage his epileptic seizures.

While Shankar fidgeted with the headgear, Rouse joked, “There’s so much going on here. Where’s the ?”

It was late March, and 22-year-old Rouse and his stepmother Renay Huntsinger had driven more than two hours from their home near Redding, California, to take part in this experiment led by Dr. , director of the and a core member of the Center for Mind and Brain, a research center in the College of Letters and Science that studies how the human mind works. This kind of research is rare and will take a leap forward in understanding how the brain navigates us through the world from the neurons up. 

“How we go from one place to another is critical for our everyday living, yet we actually don't know a lot about it at the very elemental level,” said Lin. 

What causes an epileptic seizure

Everything we do starts with electrical activity in the brain. Seeing an apple, moving across the room or reading an article like this one all happen via tiny jolts of electricity pulsing through a network of neurons. However, sometimes those networks break down. 

is a condition in which those breakdowns cause seizures. The seizures can range in severity from focal seizures, which can leave a person momentarily confused, to a tonic-clonic seizure, previously called grand mal seizures, which can cause convulsions and a loss of consciousness. Medications can help control epileptic seizures, but not always.

Rouse was diagnosed with epilepsy when he was 12, but the seizures might have begun as early as 6 years old. 

“We started noticing that the seizures were getting more and more frequent and more and more violent,” said Huntsinger. “There were times when he'd fight us coming out of it. He would try and climb the walls. His arms would swing. His legs would swing.”

Since his diagnosis, Rouse experienced a roller coaster of ups and downs. Medication had not worked and neither had any of the treatments recommended by his pediatric doctors.

When Rouse first met Lin, he was scared to have surgery but trusted Lin’s knowledge and team. In the Comprehensive Epilepsy Program clinic, 13 electrical leads implanted into Rouse’s brain showed that the seizures were emanating from the hippocampus, a deep structure that is critical to everyday life. 

The hippocampus has been described as the brain’s storyteller for how it stitches together separate events into a narrative. It’s also where navigational memory is encoded, giving us snapshots of where we have been so we can get where we are going. 

What happens in the hippocampus is hard to study in high detail. It has been possible to capture activity when a person is lying down inside the giant magnet of a fMRI machine. In the Comprehensive Epilepsy Program, implanted electrical leads capture brain activity at even greater resolution — down to small groups of neurons — and with much more freedom. 

This combination of high-resolution observations and relative freedom to move around opens up an incredible potential for studying the brain. However, the experiment with Rouse may not have happened without a completely separate line of research at much lower resolution.

VR as a brain mapping tool

Joy Geng, a professor of psychology at 51�ԹϺ��� Davis and a Center for Mind and Brain affiliate, studies attention. Until relatively recently, her experiments in the involved different colored shapes and dots on a screen. 

“You can imagine our tasks as being similar to the ‘Where’s Waldo?’ games, but even that's way more complicated,” said Geng. 

Participants would look at a screen and click a button as soon as they spotted a target, such as a red square among other red shapes on a screen. Eye trackers showed where their attention shifted while they looked. 

These kinds of experiments seem simple, but they have shown that one of the fundamental principles of attention is competition. Competition is what hinders our ability to find Waldo’s familiar cap in a sea of other objects with red and white stripes. 

However, Geng wanted to study attention in a more realistic environment. With graduate student Shea Duarte, she created a new experiment in immersive virtual reality, or VR, that would involve far more of the brain than the visual system alone. 

This new experiment wouldn’t be just about spotting Waldo. It would be about all the memory, navigation and decision-making that helps us find him in a real place. 

“The ability to do all those things in a coordinated fashion goes beyond just visual attention, which is what I study specifically,” said Geng. “It's a more complete picture of human cognition at once.”

She built a virtual furniture store where research participants were asked to find different types of furniture, such as a sofa or a table of a specific color, while she collected eye-tracking data. 

The results showed that behavior is organized to find objects based on . First comes the type of object that matches the target object, like a collection of lamps on a table, then the quality of that object, like the color blue, that separates it from the others.

Geng also noticed that when someone reached a space where they could choose to go in one direction or another, they stopped and spent a lot of time looking at the different paths. They would then teleport ahead a few steps before stopping to look around again.

How the human brain navigates the real world

Both Geng and Lin have labs at the Center for Mind and Brain, and one day Geng casually shared how her research participants would stop to look around in her virtual furniture store. This reminded Lin of an earlier study by three European neuroscientists that explained how the brain maps the body in space. Those results would win the researchers the 2014 .

But that research used rats. The researchers implanted electrodes in the rats’ brains, and the experiments identified in the hippocampus what they described as “place cells” that made up a map of the rat’s environment.

Rodents have a particular way of getting around. They have poor eyesight and navigate partly by dragging their whiskers along anything nearby. 

Humans are very different. Instead of constantly monitoring where we are through any of our senses, we take snapshots that let us think ahead to the buildings and streets we expect to see next. 

“It’s almost like time travel,” Lin said. 

Lin partnered with Geng to conduct her virtual furniture store experiment with some of his patients in for seizure monitoring at the Comprehensive Epilepsy Program. Shankar, Lin’s postdoctoral researcher, tracked the patients’ brain activity while they moved through the virtual space on a laptop with a joystick from their hospital beds. 

The study is still under review, but preliminary results suggest that some neurons fired when recognizing an object by its category, such as “sofa.” Completely different neurons fired when recognizing a shelf they were asked to find. 

This result confirmed what Geng found with eye tracking data but now to the level of neurons. It also showed how the target information stayed in memory while people navigated the virtual space.

The next step would be to test these ideas in the real world. If it was possible.

“The brain actually codes virtual space really differently from real space,” said Lin. “The only way to really get in real space is if somebody has these electrodes inside the brain to treat epilepsy and they're walking around.”

A rare opportunity to observe neurons in action

Rouse has always been active, maybe more than made his parents comfortable. He rode a dirtbike. He played football for two years in junior high and two more in high school. He taught himself to play the drums, and in a middle school talent show played them blindfolded.

Today, he rides an electric skateboard. His friends have been trained on how to help if he has a seizure. 

In 2023, Dr. , chief of pediatric epilepsy at 51�ԹϺ��� Davis, implanted two leads in Rouse’s hippocampus and connected them to a permanent , or RNS, that collects data on electrical activity there. If the device senses an oncoming seizure, it sends electrical signals that either blunt it or stop the seizure entirely. 

“They were much stronger before I got the RNS implanted,” said Rouse. “It's just been a lot better. The grand mals, those are once in a blue moon. I've noticed that I have them in my sleep, which is a little odd, but that's about it. I just wake up from it and realize I had one, and go back to bed.”

Rouse downloads data from his RNS device daily and sends it to Lin every week. Every few months they have a visit when Lin tunes the device. 

“We love Dr. Lin,” said Huntsinger. “He’s been upfront with us. He will answer all of our questions. And he even said, ‘You can call my cell phone if you want.’ I go, ‘I'm not bothering you, no, I will send you a message. You can get back to me later unless it's important.’ And he goes, ‘No, everything's important.’”

Rouse’s RNS device means he can take those leads walking, creating a rare opportunity to observe neurons in the real world. In the Center for Mind and Brain hallway, he stood wearing the backpack and headgear produced by the to Shankar’s specifications. He listened carefully to Lin’s instructions:

• Eight minutes to walk the halls and find each image on the wall. 
• Ten seconds to stare at each image to remember it.
• Then return through the hallways with the images gone and try and remember what was there.

Lin stood at the corner where two hallways met while Rouse started toward the X on the floor near the first pair of images on the wall. Maria Tangalos, who helped design and run the experiment, held a laptop showing the data streaming in from Rouse’s RNS device as he navigated from image to image.

Analysis of the brain signals recorded by Rouse’s RNS device will show electrical activity in his hippocampus when he locates each image.

Besides expanding our basic understanding of navigation and memory, this research could be the foundation of future treatments for debilitating conditions like dementia or Alzheimer’s. Both conditions leave people both forgetting and getting lost.

“This opportunity to record directly from the human brain allows us to investigate the full basis of cognition,” said Lin. “There’s no other way of doing that with a human.” 

When the eight minutes were up, Rouse had a short break before he would be asked to recall what he had seen. This was actually his second try with the experiment. Lin said he did really well the first time, both in following the experiment’s detailed instructions and in remembering where each image had been. 

Rouse said doing well made him feel proud, but the research had interested him from the start.

“When he first told me, I thought that it was just a really neat thing that would possibly help others and help him,” said Rouse. “It would be wonderful. That's what I thought. I was kind of excited about it, honestly, and I still am.”

This research was funded by the National Institutes of Health.