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Deep Brain Stimulation for Treatment Resistant Depression Part 2

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Posted on November 28, 2016 - 4:03pm

Written by Colton Smith

In April 2016 I attended the Symposium on Neuroethics hosted by the State University of New York Downstate Medical Center. Here Neurologists and Neuroscientists discussed emerging neurotechnology and how it’s being implemented. While at this conference I had the pleasure to speak with Dr. Helen Mayberg. She is a professor of psychiatry, neurology, and radiology and the Dorothy Fuqua Chair in Psychiatric Neuroimaging and Therapautics at Emory University. Her research takes an interdisciplinary-approach to integrate cutting-edge imaging strategies, quantitative behavioral and psychophysiological metrics, and experimental treatment trials to define brain-based biomarkers that can optimize treatment selection for individual patients. This is the second half of the interview.

Deep brain stimulation probes. Courtesy of Wikimedia Commons.

Deep brain stimulation probes. Courtesy of Wikimedia Commons.

Colton Smith- I think a lot of people don’t understand that while we as humans may have the same brain structures, we can be mapped differently and depression can arise in many different ways.

When it comes to deep brain stimulation what would you like the public to know about it? Also, do you think this new technology has the potential to solve everything or is this something that really needs to get hashed out?

Dr. Helen Mayberg- The first experiments were to test if it was safe to stimulate in the subcallosal cingulate region.  We had mapped the putative circuits required for antidepressant response with other treatments and designed an experiment to test the hypothesis that this same circuit could be modulated with DBS in people who were not helped by other treatments.  Once it was shown to be safe and seemingly effective in a subset of patients, the goal has been to define the subtypes most suitable and to characterize how it is working.   It might be that subcallosal cingulate DBS, works well in people who have a particular kind of depression, but not for others. On the other hand, there’s no reason to operate on someone if we could get them better in another way, particularly a non-invasive approach. You should do the most that you need to do to get someone well and not more.

Smith – So deep brain stimulation can be a bit too much?

Mayberg- Not if you need it. This is brain surgery.  You make a hole in the skull and insert an electrode into the brain that is used to deliver a small pulse of current continuously.  Nobody should want a brain implant if there are alternatives that are effective to treat their illness.  On the other hand, if one has failed available options, then this might be a reasonable next step if one is eligible for the research studies.    With such studies we are learning about the mechanisms of recovery and about treatment-resistant depression more generally.  To me, performing experiments, mapping the brain, understanding what changes in the brain as you go from sick to well, how we are stimulating, what the phenomenology is, and what the patients experience are all very important to understand. It’s also important that the patients understand that DBS may not work for them. We need to be able to understand why it doesn’t work for some patients because that might teach us what we need to do differently with the device or what we might do for them if we were to develop something new. So every opportunity like this is both an experimental trial but also an opportunity to learn from when it does work and when it doesn't work.

Smith- I like that perspective, I think a lot of people think that neuroscientists understand everything about the brain, but in reality, the further we venture into the brain the more we realize how complicated it really is.

Mayberg- Let me tell you, when I started out as a neurologist wanting to study depression I thought we could make significant progress with our straightforward metabolic maps. Now what I realize is that we have to think differently about what abnormal brain functioning means.  We are starting to think not just about specific regions but the communication between regions including brain rhythms. Such is the focus of ongoing research studies.   

Smith- So we need to be able to put the brain back into its normal homeostasis as opposed its new homeostasis?

Mayberg-  Perhaps.  It isn’t clear if we are correcting an abnormal rhythm and returning it to a former normal state or modulating it so it assumes a new but stable state.  Clinically, what we observe is that once the brain seems to be back in working order, the hard work begins. The rehabilitation process actually takes more work than performing the surgery and figuring out the right circuits to stimulate.

Smith- So the hard part is keeping patients from relapsing?

Mayberg- Not exactly. It is training patients to work with a newly responsive brain.  They actually have to get used to being unstuck and learn to reprogram their lives without ongoing severe depression symptoms. They need to learn to trust feeling better. Actually, once the stimulation parameters are established, which is now pretty straight forward, we maintain the same settings chronically without changes.  We have found if you turn it off, the depression will return over several weeks. The bigger issue is having a patient get used to NOT relapsing since that has been their typical course prior to the DBS implant. We also have learned and now teach the patients that the brain implant can’t do all the heavy lifting for them. While the initial turn on is often associated with sudden behavioral changes that many patients describe as a switch, with chronic stimulation that sensation is no longer present and patients learn that they need to work on rebuilding their lives.  That can be easier said than done when a patient has been severely disabled by their depression over many years.   

Smith- So depression is like going down a hill and then having to climb your way back up again. You don’t just immediately go back to being happy again?

Mayberg- Exactly. They have to learn to be happy again just as they have to learn what it is to have a bad day. You have to relearn these emotions and recondition yourself through experiences. People without depression don’t even think about the ups and downs of everyday life, but if you haven’t had normal variation in your mood for a long time then you’re going to have to relearn what having a bad day or a good day is. These people’s brains need to relearn what it’s like to not be stuck in a negative state and what the excursions of highs and lows feelings are. They need to recalibrate what bad feelings are, what good feelings are, and what the world is like with them in it as opposed to not being in it. The road to recovery is a process.

Smith- It sounds like deep brain stimulation has a lot of work to go through, but I’m glad that there are researchers out there such as yourself working on this. It does sound fascinating that you are not only using this technology to try and help people with depression but also using it to learn more about how the brain connects in all these intricate ways. Thank you for allowing me to talk with you.

Mayberg- My pleasure.

This blog post is in connection with the closed scientific workshop in partnership with the National Institutes of Health that was held to spark discussions of big, unanswered questions on how the brain and machines process patterns, aimed at understanding consciousness, intelligence, and madness. Also related is the Origins Dialogue with Johnny Depp and Lawrence Krauss on Finding the Creativity in Madness.

Read part 1 of this blog series, Deep Brain Stimulation for the Minimally Conscious Part 1

Read part 2 of this blog series, Deep Brain Stimulation for the Minimally Conscious Part 2

Read part 3 of this blog seriesDeep Brain Stimulation for Treatment-Resistant Depression Part 1