Imagine your life as a coloring book. The pages are filled with scenes that make you who you are—moments, memories, and experiences—and the colors you use to fill those pages are the emotions that provide meaning and significance.

Now, imagine your coloring book has no color at all. And that you’ve never been given the crayons to color the pages in front of you.

That’s how Tom describes the first 40 years of his life. For almost as long as he can remember, Tom, who asked us to omit his last name, has navigated life with severe depression by his side. A depression that cratered his self-worth and prevented him from experiencing the full spectrum of emotions that make us all human.

He was first hospitalized for depression as a teenager. Over the years, more hospitalizations followed. Twice, he tried to take his own life.

“I just didn’t care,” he recalls. “I wasn’t ever really planning for a future. Everything was just kind of painful. I was always adding up reasons why suicide was the best option.”

Various medications provided respite, but their efficacy would wane, and the depression would inevitably rear its head once again. That pattern of ups and downs—“living in pudding,” as Tom calls it—became a way of life. “I remember thinking, ‘I can’t live like this anymore,’” he says.

One day in 2022, Tom visited the federal government’s clinical trial registry website, looking for something, anything, that might help. A study at the University of Minnesota caught his eye. It aimed to explore whether a new, personalized approach that uses brain stimulation to address depression could help people like him finally find relief from their symptoms.

The brain’s fingerprint

Brain stimulation—which involves sending electrical currents to the brain via electrodes—has been used to treat movement disorders like Parkinson’s disease since the early 2000s. Evidence has suggested it might be useful in treating depression, too, but previous clinical trials to evaluate that idea have proved futile.

The reason why, explains Ziad Nahas, MD, the principal investigator leading the U of M trial, is that these studies have taken too narrow a view of the brain and of depression itself.

Depression is actually a catch-all term that encompasses a whole host of symptoms, he says. Some people with depression may have trouble planning their day, others may feel sad or empty, while others still are unable to find joy in activities or have trouble sleeping.

Many people experience multiple symptoms at once. These symptoms arise from different networks across the brain—and look different in every person.

So it should come as no surprise that a one-size-fits-all approach to brain stimulation to treat depression wouldn’t work. And yet, that’s exactly what previous trials have done, Nahas says.

Nahas and his collaborators at the U had a different idea. What if, instead of targeting just one area in the brain for stimulation, they targeted several to account for depression’s many symptoms and targeted areas based on each person’s unique brain structure?

“Instead of saying there’s one sweet spot in the brain we need to stimulate, our approach is to individually identify these locations based on each person,” says Nahas, an M Health Fairview psychiatrist and professor in the Medical School’s Department of Psychiatry and Behavioral Sciences.

Visualizing a person’s individual brain networks requires a specialized MRI technique known as precision functional mapping. That’s how Damien Fair, PhD, PA-C, the Redleaf Endowed Director of the U’s Masonic Institute for the Developing Brain and one of the world’s leading precision functional mapping experts, got involved.

As Fair explains it, this technique allows scientists to create finely tuned images of a person’s brain, including details about how their neural networks are organized and how their brains respond to certain stimuli.

“It’s a personalized map,” he says. “Like a fingerprint of the brain.”

Creating such a map requires individuals to spend upward of a few hours inside the MRI scanner. And, a few months after finding the trial online, that’s exactly where Tom found himself.

“I knew it was a research study, and I knew there were no guarantees of success,” Tom says. “But every day that I was a part of the study was another day I had hope. And that kept me going.”

Black and white no more

After meeting with Tom and creating his “brain fingerprint,” the research team identified the specific spots in Tom’s brain where electrodes would be placed during surgery.

Next, David Darrow, MD, MPH—an M Health Fairview neurosurgeon and one of the trial’s collaborators—carefully implanted the electrodes at four locations on the outermost layer of Tom’s brain, the cortex.

After Tom woke up from the surgery, the research team asked if he was ready for the electrodes to turn on. He agreed. A video recording captured that moment.

“I can just sense the waves,” Tom says. “It’s like a wash.” He closes his eyes and smiles.

“Look at that smile,” Nahas says. Tom begins to cry. “It’s emotional, huh?” Nahas asks calmly. Tom takes a deep breath, and after a few moments, he says, “It feels good. … I don’t know what to do with it.” Another member of the team offers to turn the stimulation down to give Tom time to adjust.

“No,” Tom says quickly with another smile and a laugh. “Let’s stay here for a second.”

Looking back on it, Tom says that was the moment his life went from black and white to full color. He had spent his entire existence coloring in shades of gray, and suddenly he had every color crayon imaginable at his fingertips. It was simultaneously overwhelming and incredible.

“It was like something had just opened, or a wall had come down, and I just had access to all these emotions,” he says.

Fine tuning

The four electrodes on Tom’s cortex can be tuned to an almost infinite number of settings. After surgery, it was up to the research team to find the setting that suited Tom best, one that would allow him, in time, to healthily experience all of life’s emotions.

To do that, Tay Netoff, PhD, a professor in the U of M College of Science and Engineering, called on Tom to be his partner in research, asking him to try different settings at home and report back.

When they found a setting that Tom enjoyed, Netoff would explore similar settings to see if one nearby was even better. When they tried a setting that Tom didn’t like, Netoff knew to stay away from that part of the setting map. It was a bit like a game of Battleship, Netoff says.

“We tried about 17 different settings,” Netoff says. “And the very last one we tried, he said, ‘This is the one.’”

Setting No. 17 gave Tom a feeling of calmness, of being at ease. “Like after you take a few deep breaths,” he says.

His treatment has given him the ability to understand, process, and feel all the emotions he lived without for decades. It’s not easy, he says, and it’s not to say he doesn’t get sad or feel down some days. But it’s different.

“It’s a healthy sadness,” he says. “It’s a richer sadness. Having this extra color palette to experience life, it makes a difference.”

It’s been nearly two years since his surgery, and Tom considers himself in remission from depression. The research team is overjoyed about Tom’s progress and hopeful that this treatment could help others like him.

They plan to enroll more people in the trial soon. Tom says he empathizes deeply with anyone else who might participate in the clinical trial, because it means they’ve endured some of the same challenges he has. But he wants those people to know that there is life on the other side of depression, and that he’s here waiting for them—with a box of crayons and open arms.

“I just want to be there for them,” he says, “to give them a hug, when they cross that finish line.”

To find out how your gift can support mental health research and care, contact Peter Hubbard of the University of Minnesota Foundation at hubbardp@umn.edu or 612-625-0497.