Sanders: Amanda’s experience with ECT is a reminder that the treatments for depression can be as difficult as the disease itself. And for some people, like Jon and Amanda, these treatments just don’t work. That’s where deep brain stimulation comes in. This experimental treatment involves permanent brain implants that send electrical signals into the brain to regulate mood. It’s a last resort for people like Jon and Amanda, who have tried everything else.
The history of deep brain stimulation is fascinating. In the early days, researchers experimented with animals, like rats and monkeys. They found that stimulating certain areas of the brain could affect mood and behavior. This led to the first human trials in the 1960s, but those early attempts were crude and ineffective. It wasn’t until the 1990s that deep brain stimulation began to show promise as a treatment for depression.
One of the pioneers in this field is Dr. Helen Mayberg, a neurologist who has been studying depression for decades. She’s the one who developed the specific brain targets for deep brain stimulation in people with treatment-resistant depression. Her work has shown that these implants can have a profound effect on mood and behavior.
Mayberg: The brain is a very complex organ, and we’re just beginning to scratch the surface of how it works. Deep brain stimulation is a powerful tool that allows us to modulate the brain’s activity in ways that were previously impossible. It’s not a cure for depression, but it can provide significant relief for people who have tried everything else.
Sanders: Jon and Amanda are two of those people. They volunteered for the deep brain stimulation experiments as a last resort. They knew the risks, but they were willing to try anything to find relief from their suffering. And for Jon, at least, it worked.
Jon: After the surgery, it was like a cloud had been lifted. I could see the world in a whole new light. I still have bad days, but they’re nothing like they used to be. I can finally live my life again.
Sanders: Amanda’s story is still unfolding. She’s still adjusting to life with the implants, but she’s hopeful that they will bring her the relief she’s been searching for. And for both of them, the future is looking brighter than it has in a long time.
Depression is a complex and debilitating disease, but thanks to researchers like Dr. Mayberg and brave volunteers like Jon and Amanda, we’re making progress in understanding and treating it. The road ahead may be long and difficult, but there is hope for a brighter future for those who suffer from this silent epidemic.
And that’s it for this episode of The Deep End. Thanks for listening, and remember, you’re not alone.
But it wasn’t until 2005 that the first study was done using DBS to treat depression. And that study showed, for the first time, that DBS could be effective in treating depression. Since then, more studies have been done, and the results have been promising. DBS has been shown to be effective in treating treatment-resistant depression, like what Amanda and Jon have.
One of the key areas of the brain that researchers target with DBS is called the subcallosal cingulate. This area is known to be involved in mood regulation, and it is often overactive in people with depression. By delivering electrical pulses to this area, researchers hope to help regulate mood and alleviate symptoms of depression.
For Amanda, the decision to undergo DBS was not an easy one. She knew the risks, she knew the potential benefits, and she knew that it was her last hope. And so, in 2016, Amanda underwent surgery to have electrodes implanted in her brain. The surgery went well, and Amanda was hopeful that this could finally be the answer she had been searching for.
After the surgery, Amanda had to go through a period of adjustment. She had to work with her doctors to fine-tune the settings on the stimulator to get the best results. It took some time, but eventually, Amanda started to notice a difference. She started to feel better, to have more energy, to be able to do things that she hadn’t been able to do in years.
And now, four years later, Amanda is doing well. She still has bad days, of course, but overall, she is much better than she was before DBS. She is able to work on her art, to spend time with her friends, to enjoy life again.
For Amanda, DBS was a lifesaver. It was the last hope that she had, and it worked. And she is grateful every day for the researchers and doctors who made it possible. She knows that she is one of the lucky ones, that not everyone with treatment-resistant depression is able to find relief with DBS.
But for those who can, like Amanda and Jon, DBS is a game-changer. It offers hope where there was none before, and it gives people a chance to live their lives again. And for that, Amanda is forever grateful.
Mayberg: It was, in some ways, pretty straightforward to say, do you think you can put the electrode here instead of in this other place you use for Parkinson’s. So if you can implant safely, the principle was the same.
Sanders: In 2003, Mayberg and her colleagues were ready to try. This first step wasn’t to see if her idea actually worked, it was to see if it was safe. You heard about Mayberg’s first volunteer in the previous episode. Here’s the full story.
Mayberg: So when we were ready to do this, actually this was, the first patient was a psychiatric nurse. And her attitude was, “Whatever. It’s unlikely to work, but why not try, because maybe I can help you learn something.”
Sanders: The surgery went as planned. Mayberg wasn’t the surgeon. Her role there was to observe any change that resulted from the stimulation during the operation. She wanted the patient to feel calm and stay observant.
Mayberg: And I’m not a particularly good poker player myself, so I remember being nervous because again, not my hands in her brain. I, all I can do is watch, and observe, and react. So the instructions were, look, we are going to turn it on, and we’re going to turn it up slowly, and your job is to tell us if you notice anything.
Sanders: They began running through all the different electrodes, stimulating one at a time.
Mayberg: And so we started at the bottom contact. There’s an electrode in each side of the brain. We started on the left side, we started at the lowest one. We turned it on at low current. We turned it up, you know, relatively quickly, you know, increased the dose to kind of the, not the maximum, but kind of higher, twice the dose that you would ever use in Parkinson’s, waiting to see if she noticed anything. And she didn’t notice anything. So then we moved to the second contact and tried it again, and she didn’t notice anything.
Look, depression, when you get better on a medicine, it takes a while, you know. It’s not a rapid-acting effect. That, we really were doing a safety experiment in the OR to make sure that, I wasn’t expecting anything to happen, so turning it on and turning it up and having nothing happen was just exactly what I wanted.
Sanders: No response was a good response as far as Mayberg was concerned, but that’s not what happened.
Mayberg: And so it was pretty surprising when we get to the third contact and we start to turn it up and we get to about five volts. It’s like it goes from zero to 10. And all of a sudden, patient goes, “Oh, that’s interesting. The void is gone.”
Sanders: That got the researcher’s attention.
Mayberg: We went with it. What’s a void? What’s it feel like? What are you talking about? Explain it. And she goes, and then it was actually, she got a little testy, because somehow I was supposed to know what that was, which was kind of funny.
I don’t know how to describe it. She goes, “You’re, there’s a lightness. It’s, it’s a clearing.” And you can see her struggling for a word, to the point of being sort of annoyed. And she kind of, she kind of, well, you can’t, like, flip your head around because she’s like bolted into the machine. But she kind of lifts her hand and like she’s kind of flipping you away, and she kind of goes, “Look, it’s like you’re trying to ask me the difference between a laugh and a smile.”
Sanders: Those early results from this patient and others were promising. So in 2008, Mayberg and her collaborators began enrolling people for a large DBS clinical trial. Called the Broaden trial, the six-month study followed 90 people with severe depression. All 90 got brain implants, but the scientists wanted to know if the electricity flowing through those implants helped. So some people had electrical stimulation on, and some had the stimulation off. Neither the patients nor the scientists knew which people were getting stimulation. This is what’s called a double-blind trial. Researchers kept track of how everyone felt over the months that followed.
The results were not good. In fact, they were so bad that the experiment was stopped early.
By six months, the people with their stimulation on were no better off than those who didn’t have it on. The sponsor and maker of the DBS device, Saint Jude Medical, determined that the trial wasn’t likely to hit its goals. Around the same time, there was another unsuccessful trial.
This one had 30 people who received stimulation in a different part of the brain. These disappointing results were a real setback. Those failures led to criticism of DBS as a treatment for depression. Some critics thought the research was being driven by financial interests. Mayberg, for instance, receives fees for consulting and licensing intellectual property from Abbott Laboratories. That’s the company that bought Saint Jude Medical. These sorts of financial relationships aren’t necessarily problematic, but they do exist. Despite setbacks and despite criticism, the research didn’t stop. It matured. Advances began to slowly accumulate.
Mayberg: There’s been a lot of progress. It’s not helpful when people say a company failed, ergo, it doesn’t work. When the reality is, that is not true. It just didn’t scale properly. That means you need to understand what went wrong and make adjustments. But it’s gotta scale.
Sanders: Scientists kept going, focusing on imaging and longer-term follow up. They got better at understanding their method and better at grappling with the variance, with the uncertainty and the mysteries. Those changes brought the treatment to where it is today, with small studies happening and the science still improving.
Mayberg: We can’t make science go any faster than it goes, but we can be aware of the need to go as fast as possible.
Sanders: This history, full of promising ups and crushing downs, ultimately delivered the experiment that Amanda, Jon, and others encountered in 2022.
Amanda: So the day of the surgery, I remember not being very nervous. But as soon as they wheeled me into the operating room, I started to feel anxious. The doctors and nurses were all very kind and reassuring, which helped calm my nerves a bit.
As I laid on the operating table, I couldn’t help but feel a sense of hope mixed with fear. The idea of having electrodes implanted in my brain was both exciting and terrifying. But I knew that I had come this far and had to see it through.
The surgery itself was a blur. I remember the sound of machines beeping, the voices of the medical team discussing the procedure, and the feeling of being surrounded by sterile white walls. I tried to focus on my breathing and stay as calm as possible.
When it was time for the stimulation to be turned on, I felt a surge of anticipation. Would this be the moment that changed everything for me? Would I finally find relief from the heavy weight of depression that had been crushing me for so long?
As the voltage increased, I closed my eyes and waited for something, anything, to happen. And then, suddenly, I felt it. A lightness, a clearing, a sense of peace that I hadn’t felt in years. Tears pricked at the corners of my eyes as I realized that this could be the breakthrough I had been praying for.
Over the coming weeks and months, I noticed gradual changes in my mood and outlook. The void that had plagued me for so long seemed to be receding, replaced by a newfound sense of hope and possibility. I knew that the road ahead wouldn’t be easy, but for the first time in a long time, I felt like I had a fighting chance.
As I reflect on my journey, I am grateful for the courage and determination that led me to that operating table. I am thankful for the researchers and scientists who never gave up on the quest to find new treatments for depression. And most of all, I am hopeful for the future, knowing that there are still so many possibilities waiting to be explored.
Depression may be a formidable opponent, but with the power of science and the resilience of the human spirit, we can face it head-on and emerge stronger on the other side.
When Jon first walked into the operating room (OR), he felt a wave of fear wash over him. The sight of the machine, similar to a CAT scan but smaller, used for surgery, and the vast operating room made the reality of what was about to happen sink in. It was the first and only time he truly felt scared.
Sanders, a close friend, recalls how Jon remained calm and collected leading up to his surgery. The only thing that seemed to bother him was shaving his head. Jon, who had always been self-conscious about his big head, found it emotionally challenging to part with his hair. However, the prospect of the 8-hour brain surgery didn’t faze him at all. He approached it with the same nonchalance as going for a routine dental check-up.
On the other hand, Jon’s wife, Barbara, was overwhelmed with fear and anxiety. She couldn’t shake off the worry of something going wrong during the surgery, such as a slip or a sneeze that could affect Jon’s brain. Her biggest concern, though, was the uncertainty of what lay ahead after the surgery. What if it didn’t work? What if it did? The unknown outcomes kept her up at night.
As Jon underwent the experimental treatment and had electrodes pulsing electricity into his brain, Barbara’s concerns only grew. She hoped for a positive change in Jon’s condition but couldn’t shake off the fear of the unknown.
In the next episode, listeners will get to hear about Jon’s surgery, his recovery in the following days and weeks, and the experience of having electricity stimulating his brain. Barbara will also share her perspective on the process and the hope she held onto throughout.
If you or someone you know is in emotional distress or facing a crisis, reach out to the 988 Suicide and Crisis Lifeline for support. This is The Deep End, a podcast by Science News, hosted by Laura Sanders. Share your feedback and questions with us at podcasts@sciencenews.org and don’t forget to leave us a review if you enjoyed the show.
The Deep End is made possible by the support of the Alfred P. Sloan Foundation, the John S. James L. Knight Foundation, and the Burroughs Wellcome Fund, with assistance from PRX. The music for the podcast is by Blue Dot Sessions, and production credits for Episode 2 include Laura Sanders as the host, reporter, and writer, Helen Thompson as the producer, Ella Rowen as the mixer, and Ashley Yeager as the project manager.
For any inquiries or feedback on this episode, feel free to email us at podcasts@sciencenews.org. Thank you for tuning in to The Deep End, where we dive into the depths of scientific exploration and discovery. In today’s fast-paced world, it can be easy to overlook the importance of self-care. With so many responsibilities and commitments pulling us in different directions, taking time for ourselves often falls to the wayside. However, self-care is essential for maintaining our physical, emotional, and mental well-being.
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