I study the relationship between brain circuits and brain stimulation therapies. This involves analyzing complex brain imaging data and pairing that up with brain stimulation data. A patient lying in a scanner may have their brain activity measured over about a thousand time points at about a million different spots in the brain. You end up with billion data points for every patient and it ends up becoming a data science challenge. The question then becomes how to integrate that with information about where a patient was incidentally stimulated and how they got better. Based on all that information, I develop models to try to figure out better ways to target our therapies.



How did you become interested in brain stimulation?
When I first went to med school, I wanted to be either a radiologist or a pathologist. At the time, those seemed more like detective work; you had to think a bit outside the box about what’s actually going on in a patient’s body. However, at the end of the day, fortunately, I fell in love with psychiatry. I just loved it more than anything else. I loved the fact that there was ambiguity to it. Every other specialty seemed to have a formula for what the next best step is.

Once I actually went into psychiatry, however, I realized that we know practically nothing about our specialty. I knew that there was a lot of ambiguity, but I didn’t realize just how much there was. And I think the reason for that is because we haven’t been able to study causality in the brain. We have no idea what actually happens in the human brain when you causally modulate anything because everything we’ve done has been sort of nonspecific.

Brain stimulation and brain imaging give us a unique window into that. We can map and stimulate specific circuits and study the effects of stimulating one circuit versus stimulating another circuit. I think that’s the closest thing we have to causal inference. I liked the idea of actually being able to study cause and effect in the brain.

Your passion comes through. It seems like you really wanted to do something investigative.
I wanted to do something where the answer was not always clear, and I had to think about what’s going on. And the nice thing about psychiatry is you do that in context of a real human and develop a relationship with somebody. I like being in a room with somebody who shares things with me that they wouldn’t share with anybody else. And then think about how that impacts their brain, line that up with my knowledge of brain circuits, brain anatomy, brain chemistry, and then turn that into a plan for the real patient.

Where in your training did you get interested in TMS (transcranial magnetic stimulation)?
Around the time of my first or second year in residency. About several months into my residency, I started to understand how little we know about the brain. That’s when I started to realize this cause and effect thing that I’m talking about and started developing an interest in this because I realized this was a solution to that.

I don’t know how much you’re allowed to share, but do you have any stories about times you saw TMS making an amazing transformation in your patients?
In my last year of residency, I ran a clinical trial of functional connectivity-targeted TMS for depression after a traumatic brain injury. A lot of these patients are military veterans who come back with bad injuries along with PTSD. We developed this new treatment targeting algorithm that we thought was going to be optimal for them. The first patient that I enrolled in the study was a really friendly good guy, who endured a life-changing brain injury while serving in Iraq. His condition hadn’t really improved after eight different medications and something like five different courses of psychotherapy. He got remarkably better after we tried targeted TMS treatment. The way he described it was, “it’s like when you have a splinter in your finger and you finally get that splinter out,” that’s how much things improved – like all of a sudden, a feeling that the thing that was wrong is now fixed.

This was a double-blind trial, so I wasn’t personally administering the treatment because I was blinded. I did the assessments before and after treatment and we saw remarkable changes in that one month. When I first saw him, I was ready to say, “You’re too severe and too treatment resistant. I don’t think this treatment’s going to work for you.” I was on the verge of saying that, but I was like, “You know what? I don’t want to do that. I’ll just try it anyway.”

What aspect of your work do you find the most challenging?
The most challenging thing for me is looking at what I’m doing in an objective way instead of trying to get excited about what I want to show. It’s very easy to be biased in research, especially data-driven research, which is what I do. For example, there was a recent paper in Nature that showed they used the same neuroimaging dataset and gave it to 70 different neuroimaging analysis teams and got 70 different results. I find myself doing that a lot, or I used to find myself doing that a lot at least. I’ve learned how to get a lot better at that from my mentor, Michael Fox, who is known for that sort of thing in data-driven research. I didn’t get that kind of training as a medical doctor, so it was important for me to learn that as fellow.  I’ve got all these big data sets that I’m always analyzing.

What is the balance between your research time and the time you spend seeing patients?
I probably spend about 90% of time on research now, mainly because, as a physician-scientist 10% is  the minimum you need to do in order to keep your clinical skills sharp. And there’s a certain clinical intuition that needs to happen if you’re doing clinical research.

Who inspires you?
I don’t know if there’s anybody in particular who inspired me as a person. I think I’ve always been inspired by the work itself more than by individual people. It might be cliché, but my wife helped me more than anybody else. Like I said before, I have trouble restraining my own enthusiasm and it is hard to actually get anything done because I’m too excited about 15 different things at once. So that’s my weakness. Her strength on the other hand is focusing and getting things done effectively and in an organized way. I think ever since I met her, I’ve been publishing fewer papers, but better papers, you might say.

What are your hopes for the future? What are you most excited about?
At the end of the day, the goal of everything we do is to develop new treatments and better diagnoses, to figure out how to take better care of patients. What I’m really excited about in the short term is a new clinical trial which will hopefully translate into real world treatments. But broadly speaking, what I’m excited about is taking all this neuroscience and translating it into the clinic. And that’s the goal of this new center that we’re starting at Brigham and Women’s Hospital, the Center for Brain Circuit Therapeutics. To take these sort of cutting-edge, circuit-based findings and turn them into real treatments and see how well they work.