- Welcome to Healthy Minds.

I'm Dr. Jeff Borenstein.

Everyone is touched by psychiatric conditions, either themselves or a loved one.

Do not suffer in silence.

With help, there is hope.

Today, on Healthy Minds... - If you're trying to understand why do some people get better?

Why do some people not?

I'm a neurologist.

I'm not a psychiatrist.

I've met depressed people by studying them and trying to understand the mechanisms of treatment and the physiology of depression itself.

But, as you start to see people that don't get better and don't have options, and as a neurologist, you're watching the implementation of this technology deep brain stimulation that is used for people who start to have problems with their medication.

And, I don't think there's been any treatment that can match the idea that with continuous stimulation and refinement of this, we have many people that not only get well, but they stay well.

- That's today on Healthy Minds.

This program is brought to you in part by the American Psychiatric Association Foundation, the Bank of America Charitable Gift Fund, and the John & Polly Sparks Foundation.

Welcome to Healthy Minds.

I'm Dr. Jeff Borenstein.

Today, I speak with Dr. Helen Mayberg about deep brain stimulation, an experimental invasive surgical procedure that has helped a number of people with severe treatment resistant depression.

Helen, thank you for joining us today.

- It's a pleasure, Jeff.

- I want to jump right into deep brain stimulation.

What is it?

- Deep brain stimulation is a generic term for a surgical treatment that's used to treat a variety of neurological and now psychiatric disorders, with the selective and very precise stimulation of a location in the brain continuously.

It involves implantation by what's called a functional neurosurgeon, using advanced kinds of imaging, generally high resolution MRI imaging, that allows the selective targeting of a small area in the brain, the placement of a small wire in that target, the connection of that wire to a small battery pack that can then deliver continuous stimulation to that location in the brain, and effectively tune a circuit that's malfunctioning in that disorder.

- People have referred to it as being similar to being a pacemaker for the brain.

- That's a perfect description.

And, after giving you kind of the more technical terms, so you can do it at home, it really is a technology that's now being used more and more.

It was really introduced many, many years ago, really even in the seventies, but the...

It's a technology that's used to stimulate the spinal cord for pain, but in the contemporary era, really in the last 20, 25 years, it was developed as a reversible and controllable circuit approach to treat predominantly movement disorder.

And, as we've learned more about circuits in the brain, that technology has been leveraged to treat any disorder that one can reduce to actual brain circuits.

And, so deep brain stimulation is deep in the brain, so that you can basically place that wire anywhere in the brain that you can target with the imaging and the delivery of current depending on the question that you have, the problem you're trying to solve, and the neuroscience that supports the approach.

It's now been applied beyond Parkinson's, and tremor, and dystonia, routine use to manage severe movement disorder to actually being applied to psychiatric disorders, including obsessive compulsive disorder and depression as the most common.

- I want to have you explain what a circuit means when we're talking about the brain.

- So, the easy way to think about it is obviously there's billions of neurons in the brain, and gazillions of connections between neurons, and neuroscientists are trying to figure out how those neurons work, how they grow, how they talk to each other.

But, at the end of the day, at the real kind of macro level that clinicians work at, we actually conceptualize the brain as regions talking to each other, and that the brain is organized, not just cell to cell, but region to region.

The brain is literally, regions are wired to each other, they're communication channels, and a vernacular we use is that they're brain circuits.

So, one can have lots of definitions, but I think for thinking about deep brain stimulation, we're not just stimulating a spot, but we're actually stimulating that spot and everything it's connected to, and just like an electrical grid, or just like the communication system across the world, the roadways, we can conceptualize the internet.

We can conceptualize communication between remote areas and the brain works that way too.

- So, you are able to stimulate a specific spot in the brain, and with knowledge of how the brain works, know where that's gonna then go to in terms of stimulating other parts of the brain - In theory, exactly correct.

And, I think all of this, this whole technology, and really catalyzing its use for really severe psychiatric disorders has been the knowledge that's evolved over the last 20 years to actually map the brain, identify blobs in the brain that are too active, underactive, but more to appreciate that those areas of dysfunction work together, that one area may be abnormal, but it's having influence on its neighbor, both, next door and across town, so to speak in the brain, and that the brain is organized as modules and that things don't happen in just one area of the brain.

They affect remote areas of the brain as well.

So, actually trying to figure out not only what is the map of a particular disorder, where are the neighborhoods, but where one should go if someone needs to understand the problem, the nodes in the network, the possibilities, the potential candidates in which to stimulate, and then develop an approach to actually target the right place, learn whether or not the... How much variation you have in terms of where you target and then utilize and try different kinds of stimulation parameters to see if one can affect how this brain circuit for this given problem might be affected.

- Through your research, you were able to determine specific areas or a specific area of the brain that would be an appropriate target for severe depression.

I'd like you to tell us a little bit about that.

- Sure, I mean, so we're going back to really a long story, because it's easy to talk about now kind of, well, get a surgeon, have a spot, stick a wire in, turn it on, someone gets better.

I mean, this all evolved, because, who knew?

I studied depression, and back when I was training, depression was a combination of stress disorder and chemical imbalance.

But, as a neurologist, I've always been interested in if other kinds of disorders localize in the brain and that they have circuits, what's the mood circuit?

So, what's the depression circuit?

So, only through applications of various kinds of brain imaging, and not just structural brain images, 'cause there is no overt damage to the brain in people who are depressed, unless they have a stroke, or they have Alzheimer's, where you have a clue of where to look, that maps of the brain could be generated with tools such as pet scanning, or functional magnetic residents, imaging scanning, and we and others were able to start to map out what are the abnormalities in the brain.

And, over time, as you look at different treatments, map how treatments affect the abnormalities, a pattern starts to emerge, and the map starts to come into focus.

And, that's where really the idea of brain regions are talking to each other.

It's not arbitrary where the problem is.

And, then, as you develop new tools and new tools become available, you can actually literally map the wiring between areas that aren't working.

And, that literally lays the foundation to even begin to think about a new technology and how you might utilize it.

So, in the early days of mapping the brain, there wasn't deep brain stimulation for movement disorder yet.

And, even though people had tried many years ago to use focal brain stimulation kind of as a outflow of electroconvulsive therapy, but more targeted, that there wasn't enough data on how to go precisely in the brain.

So, it was more theory based than data based.

And, now what evolved in the last 20 years was actually a map.

And, by studying the available treatments for depression, one could map how the brain changed and one could to hone in on what brain areas might be most important to target first.

And, that was our strategy.

So, we were opportunists.

I mean we were studying, how does the brain change?

How do these circuits change on medicine?

How do they change on therapy?

How do they change on placebo?

And, it started to focus in that some regions just kept showing up over, and over, and over again.

- So, you were able to use very basic neuroscience looking at the brain to then take that and develop a method of treatment in these conditions.

- I mean, in our mind, in... You try to go back, it's so long ago, how does one go over your own history of how an idea evolves?

That if you're trying to understand, why does some people get better?

Why do some people not?

Are there differences in the brain that could help us to understand why some people need one treatment over another, make predictions, save people from different treatments?

There's a group of people that just don't get better with anything.

And, in our studies, we not just wanted to know how treatments worked, we wanted to know why treatments didn't work.

And, it started to evolve that there was an area of the brain that if it didn't change its activity, you didn't get better.

And, it didn't matter what treatment you were treated with.

So, we just followed the data.

And, as you start to, and I'm an experimentalist, I mean, I'm a neurologist, I'm not a psychiatrist.

I met depressed people by studying them and trying to understand the mechanisms of treatment and the physiology of depression itself.

But, as you start to see people that don't get better and don't have options, and as a neurologist, you're watching the implementation of this technology, deep brain stimulation that is used for people who start to have problems with their medication.

That one can bring the neuroscience and this available clinical strategy together, and test a hypothesis about how do we alter the activity or tune the activity in this brain area that doesn't respond to medicine, doesn't respond to therapy, doesn't respond to shock.

And, can we use the focal stimulation to decrease its activity?

So, it was totally driven by everything we had learned from all the studies of studying other kinds of treatment.

- So, one important message for people watching is this treatment is not yet ready for prime time.

It's still very much experimental.

That being said, there are people who had severe depression, that was treatment resistant, that nothing else worked, multiple other types of treatment didn't work, who, with this treatment, actually were able to get better.

And, I'd like you to speak about what it's like to see a person who had been so severely depressed without any improvement, then get better with this type of treatment.

- I've been doing this a while now, and I'm of two minds, there was the original opportunity to test this hypothesis that you could tune this circuit with this approach and see what happened.

Of the other side, as a physician, it's terrifying.

Is it safe?

What if it doesn't work?

What if it makes people worse?

But, you have something that's reversible.

So, even though, yes, it does require an implant in the brain, if it didn't work, we could take it out.

And, so, when you start something, who do you operate on?

You're basically recruiting people who have absolutely no options, who in their own mind are, something new?

Yeah, maybe, nothing else has worked, why should this work?

And, so everybody comes to the table with hope, but really kind of a neutral starting point.

You really have to be agnostic experimentally to do this while, at the same time, be hopeful that your idea is not totally lame, but that to see patients, not just the first patient, which was a total revelation to see someone, and, again, depression recovery is generally slow.

This was well before ketamine was done.

- The rapid acting forms of treatment.

- Exactly, rapid acting forms of treatment, we now have treatments that do work fast, but that they don't last, unless you repeat them, that we had no expectation of anything happening quickly, that we'd get this in, we'd turn it on, we'd use parameters that have been used for Parkinson's and we'd see what happened.

And, we'd expect something to happen slowly.

And, not only were we surprised that many of the early patients and now every patient can reliably have a very rapid effect in the operating room to see people who had pretty much given up, who were off the grid, who really did nothing, couldn't do nothing, 'cause they were in such dead pain, that they virtually didn't move, to watch them emerge to trust a recovery over weeks to months.

But, I now have patients, the first one implanted in 2003, and many from that original cohort are still doing well, 15 years later - People who have their lives back.

- Totally have their lives back.

To watch people just be able to get outta bed, make a cup of coffee, go to get a paper, wash their hair, basic stuff, to trusting that it isn't just gonna be a couple months since they... Until they relapse again as had been the case over the last number of years if they did respond to anything, to actually trust recovery.

And, I don't think there's been any treatment that can match the idea that, with continuous stimulation and refinement of this, we have many people that not only get well, but they stay well.

And, they may have ups and downs, but they've never gone back to where they started and that just begs you to continue it even though it remains experimental, to try to figure out what it is we did, because there isn't any other treatment that can actually make that claim.

- Where do you see this going over the next period of time?

'Cause, I think part of this work is to better understand the brain and come up with other approaches that maybe would be less invasive, that could be just as effective.

So, what do you see happening moving forward?

- So, again, no crystal ball, but wishful crystal ball that...

When you do something invasive, that is expensive, has its risk, it is surgery, it does have a device that lives in you, that one wants to understand it deeply, particularly when it isn't kind of a ambivalent response when it works.

That, one wants to understand not just mechanism, but can one substitute what one does with this implant with something that doesn't require an implant.

So, with transcranial magnetic stimulation, it uses magnetic stimulation rather than electrical stimulation.

It's delivered outside the head as opposed to along a wire deep in the brain, but it uses, in some ways, the principle of circuit modulation, and that, can you stimulate anywhere in this multi node network and change the dynamics of this brain circuit in a way that tunes the circuit and the person gets well?

So, the more we understand the components of the circuit, the changes in either nodes or the dynamics of how regions in the brain talk to each other, we can have a very evidence based approach to where we might test external stimulation, and look to see, is it the same?

Is it complimentary?

And, then ask the same questions we ask of drug or therapy.

Are there patterns or are there ways in which these circuits are malfunctioning that are best approached with one treatment over the other?

The goal in all of this is to get people the treatment that's best for them.

That's like Einstein said, things should be as simple as possible, but not simpler.

And, so if you need, because the brain and these circuits are so dysfunctional, that you need to go to a deep area, because the connections are bad.

You may, if you can be at one end of a telephone, and if the cable is cut, you can scream as loud as you want.

You're still not gonna get your message through.

So, we have to understand the integrity of the circuit, structurally.

We have to understand how these structural connections, where they are, whether or not they're intact, whether or not they're important.

And, then we can explore through these newly evolving and really exciting multiple kinds of non-invasive forms of stimulation or different patterns of stimulation.

Can we substitute totally, these invasive methods for non-invasive methods?

And, if we can, what's the way to best optimize those with the same goal to get people well and keep them well.

- If somebody's watching right now and they or a loved one has experienced severe depression, that's resistant to treatment, what do you say to them?

- I think the first thing is you never give up, because A, like everything, always get another opinion.

And, we as physicians look at what may be the same problem in different ways, not just me, but you, I mean, the community.

And, I think it's because there are many ways to skin a cat, and there are many kinds of treatment available.

And, even our definitions of depression is varied.

We don't agree.

It's not like when you have a broken bone, four radiologists can look and we can all agree on the name of the bone, the kind of break, there's a vernacular we use that we agree on.

And, we still struggle with that I think in psychiatry, because we don't have pathology in the same way.

But, back to the really important question for patients is everyone should always have hope, because the approaches that are now ongoing to treat depression are more than we've ever had, because our knowledge has grown considerably.

We made guesses 50 years ago, we had drugs, and we worked backwards to try to figure out what was wrong by how a drug worked.

Now, we have maps.

Now, we can be systematic.

But, I think that it's important that people are evaluated carefully, if people have responded in the past to a treatment and they've stopped responding, there may be another problem involved.

There may be a misdiagnosis.

As people are older, I think if they have depression, we need to always look that there isn't an another neurological problem that could be presenting with depression.

And, it may not be responsive to our conventional treatments.

I think that the availability in most large cities of various experimental trials is an option for people, but one needs to be seen, evaluated, tested, and never give up, and look for options.

There's no one option that's best for everyone.

I think that's one of the most important kind of demands we have on us as scientists is not just to come up with a new mouse trap, but to understand who it's best for, and who it isn't best for.

And, I think that's part of this mix that we all work on every day, even as we're trying to go deep on any one problem or any one treatment that we might be working on.

- So, never give up, get another opinion, and keep on trying, because, as you've seen in the research you've done, people who may have lost all hope actually are able to get better.

- Absolutely, and the other thing, when you are recruiting for these small very demanding experimental studies, I mean, we're very hard on our patients.

We demand a lot, because in order to figure out what we're doing, we require them to help us.

We have devices now that allow us to measure all the time, the neural signature of the how the area we implant is changing.

We're learning what the recovery signal is over time by basically monitoring it.

Patients have to help us.

And, that what we've learned, as you recruit patients for studies, is you learn through your own lens that you see a problem that maybe wasn't recognized as being a contributor.

And, so someone doesn't necessarily even come into your study, you identify that they might be better for another study.

And, that's why centers that run different kinds of studies, and not just one, can be really a valuable resource in any community, and many medical centers, medical schools, departments of psychiatry.

- Helen, I want to thank you for joining us today.

Thank you for the work that you've done and continue to do which offers so much hope to so many people, thank you.

- Oh, was a pleasure being with you, Jeff.

- [Dr. Jeff] Until next time, I'm Dr. Jeff Borenstein.

Do not suffer in silence.

With help, there is hope.

This program is brought to you in part by the American Psychiatric Association Foundation, the Bank of America Charitable Gift Fund, and the John & Polly Sparks Foundation.

Remember, with help, there is hope.

(gentle piano)