Interview: Helen Mayberg

Dr. Mayberg is a professor at Icahn School of Medicine and a neurologist renowned for her research in depression and deep brain stimulation. She's serving as a panelist for a session that's taking place on the second day of the annual meeting, 'Life and Health Decisions with Experimental Brain Implants.'

What is your current position?

I’m a professor at Icahn School of medicine at Mt. Sinai in New York. My primary appointments are in neurology, neurosurgery, psychiatry and neuroscience. I don’t do clinical work, but I’m the founding director of the relatively newly established Center for Advanced Circuit Therapeutics.

I moved to Sinai two years ago to build a multidisciplinary research team embedded on the neuromodulation service. Basically, we have a group of researchers that work hand in hand with the clinical deep brain stimulation (DBS) team. We didn’t just join the functional neurosurgeon philosophically; we actually all work together and have our offices and our labs in the same place. It doesn’t just combine neurosurgery and neuroscience; we use imaging, electrophysiology, and psychology to take care of patients so that the research merges to clinical care through technology and neuroscience innovation. More importantly, psychiatry and neurology uses of DBS are considered together, so that there is no siloing of psychiatry DBS and neurology DBS. All patients are seen by all specialists, and the research considers strategies that can be done across diagnoses.

What are your research interests?

I’m personally interested in depression DBS. We began with hypothesis-driven DBS testing, and when we saw it was successful, we tried to understand how to improve and scale up the delivery of the DBS. This included understanding that we weren’t stimulating a location –– but a node in a network –– and brain imaging had to define that network.

This led to a multimodal imaging-based targeting strategy that then, in turn, led us to ask what happens to the physiology in the cortex. We then leveraged new devices that make recordings of where we’re stimulating to track how people are getting better overtime. The next step was asking how we can have better read-outs of the behavioral impact of DBS so that we can move from patient self-reporting to understanding the psychophysics: How does movement change? How does facial expression change? How do these things that we observe happening in people getting DBS evolve over time? And in the setting of all of that, how can we broaden the use of those tools to other indications? Are they relevant for Obsessive Compulsive Disorder? For the non motor features of Parkinson's disease? Can this multidisciplinary approach be leveraged for developing new treatments? Basically, we always consider that a method used for one disorder might be modified and applied to other indications, or at minimum, to inform our understanding of DBS mechanisms for the disease under study.

What are some advantages to this type of multidisciplinary approach?

Having a holistic team becomes important for clinical management. For instance, even in something like Parkinson's disease, you can improve someone’s motor function, but how do you manage their behavioral health issues, or their psychosocial issues? People may not feel maximum benefit if all aspects of their disease are not considered in context of the particular symptoms we are targeting with DBS. Interestingly, the discussion among specialists seeing a patient leads to recognizing what are ethical issues, what are just psychosocial issues, and what are issues related to the disease itself or the way the brain is being stimulated. It becomes an interestingly complicated question to parse out: Are we doing something to somebody that we don't want to do? Is that the natural history of their illness? Is that idiosyncratic to that individual person? All of that will have bearing on the evolution of the technology and its application.

What are some neuroethical aspects of your work?

I think the neuroethical issues really go back to the very beginning. In my days at Emory with Paul Holzheimer and in collaboration Laura Dunn, we had a neuroethics grant to address attitudes of patient participants in our DBS depression study. What are patients’ motivations for participating in an invasive treatment trial when the outcome is really uncertain? We drew on Paul Applebaum's past studies in order to examine how patients balance altruism to help others along with their own hope to get better.

When you volunteer for an experimental treatment –– whether it’s a sham or placebo controlled study or an open label study –– most people have the expectation that the intervention might help them, even when there is no evidence yet to support that assumption. There’s a disconnect in volunteering for something new when you're desperate because nothing else has worked, which is the definition of why you’re enrolled. How do we understand the nature of misguided altruism? It’s equally not good for someone to say, “Sure, I’m a guinea pig, do whatever you want with me” – that’s disconcerting, versus the therapeutic misconception of how well someone understands that “This is an experiment, it may or may not work, and we really don’t know.”

Those early ethics studies were aimed at understanding patients' attitudes on the front end, at the time of obtaining informed consent. What we learned was that people are very rational in how they weigh potential benefit and potential risk, despite their treatment-resistant status. I think people were surprised –– but shouldn't have been –– about this rationality in depressed patients’ attitudes. Although depressed people may be suffering and they’d certainly like to be better, they also don’t want to be worse.

How have these neuroethical aspects evolved through your work?

There are now new ethical questions to consider as the experiments have progressed, and these questions are no longer a matter of if DBS works or not. I published the first paper on this more than 15 years ago, and the things we had to be mindful of then are very different now.

Some issues that we’ll discuss in our session may be less theoretical and less interesting, but still incredibly pragmatic and essential. If we have people implanted basically indefinitely –– they are now tied to an experimental device. Upfront, our early experiments had grant funding that paid to implant the device; surgery is expensive. The research team was supported by a time-limited grant, and when the grant ended, the patients continued to receive ongoing care. This wasn’t an insurance-reimbursed procedure then and it’s still not now.

In Canada when we did the initial proof of principle experiments, the implants were reimbursed by the healthcare system. When I moved to the states, not only did I have the FDA to deal with and many more layers of industry and governmental regulation, but we also had to figure out strategies to pay for the surgeries, as private medical insurance has no obligation to pay for something that isn’t an approved procedure.

So, there's a justice argument in which the conversation is more pragmatic. I don't think of it as solely a neuroethics issue – it’s also a medical access discussion that reaches beyond ethics, philosophy or law. I am hopeful to hear potential solutions from others in dealing with these issues outside of the US.

How have you seen these issues playing out in the wider world?

Once a 6-month experiment is completed and a patient is doing well, there is a new issue: who’s going to pay for their ongoing care? Obviously, they’re still in our experiment, so we have the obligation –– happily –– to continue to follow them. What only becomes apparent with time, however, are unanticipated expenses. The battery gets depleted and you have to have another surgery: who should pay for that? If you built your own prototype device, who will support ongoing care and maintenance? Who assumes liability? The investigator? The Institution? The funding agency? When a grant ends, does the intervention end? Should the device be explanted? Who should pay? Should you remove a device if the patient is doing well? What are the potential consequences of these different scenarios?

I think in the session there will be some discussion as to what our [researchers] ethical obligations are in these various situations. It’s not solely a neuroethical discussion, but it’s a principled discussion that we have to think of when we’re doing research: What’s going to be our long game?

Let’s take the more obvious example: We hoped it would work and it really didn't. Why would somebody want to keep a contraption in their brain? The main reason I would want to explant people who didn’t get benefit is the fact that if you have hardware in your brain, you’re going to be ineligible for something new that might come down the pipeline in future. But even then, who should pay for the explantation, particularly if the grant that funded the implant and trial has long ended?

My personal view is that any investigator has to have a plan for managing patients in the long-term and transitioning a patient to active participation in their own care.

There’s no question that for people who didn’t benefit from a study –– or in the event that a study closes down –– you don’t leave patients like tires along the side of the road.

It’s sort of a pedestrian discussion, but you bring it up, and everyone says, “Hold on, I didn't even think about that.” Everyone is very concerned on the front side, asking the question of should we do this at all? We’re past that, and now the questions are: What do we do when it works or it doesn't work?

What’s another topic that might be discussed in your session at the annual meeting, ‘Life and health decisions with experimental brain implants’?

Another layer that we might discuss pertains to the price you pay to be better from the treatment. A lot of the focus in mental illness and these kinds of treatment for neuropsychiatric disorders asks: Does the place you stimulate alter a person's capacity for how they make decisions or for how they see the world? Does it impact their mood and behavior in a way that is a distortion or a side effect? Does it change them?

Of course it changes them, but some interventions may restore you to who you are, and other interventions may put you into a non-ill state, but not restore who you are. What does that mean? Who are you without your illness? I think it depends on where in the brain you're stimulating.

In our studies of treatment resistant depression, patients are disabled by their illness. As many describe: they’ve fallen in a hole and they can’t get out. They know what it’s like to be well, but their treatments have been unable to get them there. As patients improve with DBS, it’s interesting to see all the different ways that patients deal with recovery. As a result of hearing from colleagues who target other brain regions with DBS, it’s my impression that there may be differences that depend on the site of stimulation, the ‘type of depression’, or even the underlying temperament of the person.

It's important to prepare people for the idea that their brain with a device may restore capacities that they haven’t had access to in a while. In other words, people who have been chronically ill need to learn to be well.

What are you looking forward to about the annual meeting?

The annual meeting is always an opportunity to get together with a really eclectic group of scholars who are coming from a perspective that’s very different from my own. I love the informality of senior scholars and young investigators and students. If I just sit back and listen, I get a perspective from philosophers and ethicists that open my eyes to things that I need to keep in mind. I enjoy the breadth of topics and discussants are always insightful. Ultimately, I always leave the meeting inspired and often with pearls to apply to my own work. It’s a meeting I really look forward to every year.

Our Digital Future: Building Networks Across Neuroscience, Technology and Ethics

The 2020 Annual Meeting of the International Neuroethics Society (INS) will convene virtually on Thursday and Friday, October 22-23, 2020. Sessions will address the many areas in which brain technologies and data concerning the brain are developed, deployed, utilized and regulated. We hope you will attend!