Basilis Zikopoulos uses an electron microscope to magnify cross sections of the human brain up to 500,000 times, revealing connections between axons and neurons. Photo by Jackie Ricciardi

If you can concentrate on the words you’re reading now without getting distracted, one Sargent researcher wants to know your secret.

Basilis Zikopoulos, an assistant professor of health sciences, is studying the attention filter of the human brain, which is at the heart of why we can focus—or why we can’t. And the impact of his work extends well beyond your ability to read this story.

With a team of researchers in his lab, Zikopoulos is looking at how autism, schizophrenia, depression, anxiety, and sleep disorders are linked to disruptions or miswiring between the thalamic reticular nucleus (TRN), amygdala, and prefrontal cortex. He’s already at the forefront of this research as one of the first people to plot the path of TRN networks in monkey brains.

THE BRAIN’S FILTER

“Any kind of information that reaches your brain has to pass through a structure called the thalamus,” says Zikopoulos. “It will either be routed into the cortex so that you become conscious about the information, or it will be filtered out.”

So how does the brain determine what goes where? Inside the thalamus is the TRN, a smaller bit of brain orchestrating this process, and that’s the piece that Zikopoulos is fascinated by. “The TRN acts like a filter. It’s so important—it sorts out what we need to pay attention to and what we don’t,” he says. It also plays a central role in determining if we are awake or sleeping.

Which is why it makes sense that it can be hard to sleep when you’re consumed by thoughts about a new love interest or a family member’s illness. In that case, the TRN is taking its cues from the amygdala, the emotion regulation center of our brain. The amygdala is so strongly connected to the TRN, Zikopoulos says, “it’s practically yelling at it.”

Zikopoulos uses an electron microscope to magnify cross sections of the human brain up to 500,000 times, revealing connections between axons and neurons.
Photo by Jackie Ricciardi

Despite how hard it is to think of anything else, nature gave your brain an override mechanism that can (hopefully) direct your attention elsewhere. The ability to drive your attention toward a specific task, Zikopoulos says, depends largely on the executive functioning part of the brain, the prefrontal cortex, which has evolved and expanded the most in humans compared to other animals. It determines our individual personalities and cognitive skills, and it can control the TRN. But our ability to control our own attention and behavior comes at a high cost.

“As far as we know, animals do not display the full spectrum of symptoms seen in autism or schizophrenia,” Zikopoulos says. “But humans are more vulnerable because we have more complex brain networks that take longer to develop. Therefore more things can go wrong.” That idea is at the core of his working hypothesis that emotional and psychiatric disorders stem, in many cases, from abnormal links between the TRN and other parts of the brain.

“In autism, for example, one of the things we see is extremely focused attention on one thing, with difficulty switching to another task. In schizophrenia, we have the exact opposite,” he says. “At the core of all these disorders, we have a problem with attentional networks.”

A NEW FRONTIER

The TRN is such a new topic of interest for scientists that Zikopoulos, with the support of the National Institutes of Mental Health, is trailblazing the first map of how it works in humans. With his research on TRN networks in monkey brains, he has a good head start.

Zikopoulos and Helen Barbas, a professor of health sciences, used neural “tracers” to chart the TRN networks in the brains of macaques. Through careful dissection and high-resolution imaging, they precisely mapped the three-dimensional networks of TRN connections zig-zagging toward other areas of the monkeys’ brains.

“Having done these studies in monkeys, we have identified specific features of the TRN network and how it connects to other areas of the brain,” like the amygdala and the prefrontal cortex, Zikopoulos says. “We think that defining these features in humans could allow us to distinguish between the brains of neurotypical individuals and of people with attention-related disorders.”

WORK OF A LIFETIME

Zikopoulos once dreamed of being a marine biologist, inspired by undersea explorer Jacques Cousteau. But he found that the marine ecosystem wasn’t as exciting as questions he wanted to answer about the brains of marine animals. “I went into a neurobiology lab as a second-year undergraduate student and I’ve been there ever since,” he says. Now, he focuses on the questions he finds most interesting, like: How are we different from other animals? Why do we have enormous behavioral flexibility?

To find out those answers, Zikopoulos doesn’t plan on putting the neural tracers to work in living humans (who would then need to donate their brains after death). Combining the monkey data with their observations of human brain specimens, his team will collaborate with computational neuroscientist Arash Yazdanbakhsh, a BU College of Arts & Sciences research assistant professor of psychological and brain sciences. They will enter all the information into a computer model and create a digital brain, where they can simulate TRN network connections.

“Once we can look at all the data in a computer simulation of a human brain, then we will be able to start disrupting the model and seeing how it responds in comparison to people who we know have sleep disorders, autism, schizophrenia, depression, etc.,” he says.

Zikopoulos says there are enough questions about the TRN to keep him busy for the rest of his career. He’s been working on unraveling its mysteries for the last 15 years, and only now feels as though he’s amassed enough data to start seeing the total picture. “There’s a lot of information and we have no idea what we will eventually find. But we now have some pretty good guesses.”

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