SPEAKER: So, Dr. Basu, thank you for joining us, and welcome to Think Research. 

ISHITA BASU: I'm glad to be here, and thank you for inviting me. 

SPEAKER: You're welcome. So you study deep brain stimulation and its effect on cognition. Could you tell us what brain stimulation is and what that means? 

ISHITA BASU: So brain stimulation is an umbrella term used to describe any kind of external stimulation to the brain. It can be through electric current. It can be through magnetically-induced electric current. It can be noninvasive, such as something that's applied on the scalp. Or it could also be invasive, which is deep brain stimulation, as the name suggests, where deeper brain structures are targeted and we use electrical current to induce charge in that area so that we can change the neural dynamics in that area. So that's what is generally meant by brain stimulation. 

SPEAKER: And you talked you mentioned changing the neurodynamics in an area. So what are some of the uses for brain stimulation? And what do you mean by neurodynamics? 

ISHITA BASU: So by neurodynamics I would mean-- brain functioning, the normal brain functioning, is achieved when neurons in the brain fire, they communicate with each other, and that creates a wave kind of activity across our brain. And in a healthy brain, there's a certain pattern of this brain activity or brief brain activity that happens which helps different areas of the brain, such as, let's say, the frontal area, or the back portion, or other deeper structures to communicate. And that's what I mean by dynamics. 

And each region has a particular signature elasticity. And by external stimulation, we can much modulate that. But obviously we wouldn't want to do it in a healthy brain. We apply brain stimulation only when there is a pathologic condition in which the brainwaves might not be in a normal condition, which causes various symptoms. So that's the main purpose of using stimulation to modulate that pathological brain dynamics or activity to restore it to a normal state. 

And normally-- the oldest use of brain stimulation that I can think of is-- old in a modern way-- Parkinson's disease or any kind of movement disorders, such as tremor disorders, movement disorders, such as Parkinson's disease essential tremor. That was where specifically deep brain stimulation started. And then it has been approved for epilepsy now, and it's also being considered for neuropsychiatric disorders, such as depression, obsessive compulsive disorder. In fact, it is approved for obsessive compulsive disorder. That's the only psychiatric indication that it is approved for. 

So yeah, that's where brain stimulation is used. And also, a non-invasive stimulation such as transcranial magnetic stimulation is approved for depression. So these are some of the pathologies that I can think of where brain stimulation is used. 

SPEAKER: And you study movement disorders, correct? 

ISHITA BASU: I used to, but now I'm more interested in the psychiatric domain. 

SPEAKER: OK. And so, yeah, let's step back a little bit. I was looking at your Twitter profile, and your Twitter by a says that you're a neuroengineer. Could you talk a little bit about what that means to you and why you chose to put that as your bio? 

ISHITA BASU: I think I said neural engineer. 

SPEAKER: Neural? OK. Maybe I read it wrong. 

ISHITA BASU: No, that's OK. It's like-- I think of it as using electrical engineering principles in neuroscience. And the engineering aspect of neuroscience-- I mean, it could mean different things to different people. But for me it means how can we, for example, analyze neural signals or model neural signals so that we can design therapies to modulate it. But it could also mean somebody who actually does more of the hardware part and comes up with devices for doing the brain stimulation for example. So that would be neural engineering too. 

So I think it's a pretty broad term. But I think it's more specific than just stating, oh, I'm a biomedical engineer or I'm an electrical engineer. Because I think when people read electrical engineer, they inherently think about the electrical circuits or more of hardware stuff, which has nothing to do with the brain. So that's why I chose to put neural engineer. So it is a bit more specific and says a bit about what kind of applications I'm interested in. 

SPEAKER: And you originally studied electrical engineering. I wonder if you could talk about how that prepared you for your career now and why you became interested or how you became interested in studying the brain and movement disorders. 

ISHITA BASU: Oh, sure. Yeah. So although my home department was electrical engineering, I actually started with more of, like in my terms, a neural engineering project. Because my doctoral thesis was designing an algorithm to detect Parkinsonian and essential tremor from muscular signals, such as surface EMG, so that we can use that to design a closed-loop deep brain stimulation. So what would happen is if you detect tremor from the muscular signals, you can signal the device to start stimulating. So that kind of closes the loop. 

So that was my PhD project. So although I don't think there is any department that is neural engineering, the closest we can get to is either biomedical engineering or bioengineering. So a lot of neural engineers are based in either electrical engineering or biomedical engineering. 

So yeah, when I joined my doctoral thesis advisor's lab, she had a collaboration with another professor who was interested in looking at this project. And she asked me if I would be interested in working on it. And it seemed pretty interesting to me, studying the brain, and how can we-- I mean, it seems more application oriented and more in the medical side of things, which was exciting and interesting for me. 

So yeah, there was no particular reason for choosing the project, but it was just presented to me, and I thought it would be a good one. And that's how it started. And then once I was in that field, I remained there, and then I went on for my postdoc at Johns Hopkins, where I studied seizure propagation. And then I went to Mass General Hospital, where I was looking more into deep brain stimulation applications in the psychiatric domain. So that's how it started and evolved. 

SPEAKER: So when you started your PhD in electrical engineering, what did you think you would be doing after your thesis or for your thesis? 

ISHITA BASU: So when I actually joined a lab that was more focused towards power electronics, like making power grids more efficient, and I always thought of electrical engineering as being more either on the power electronics side or building devices or looking at electrical circuits. And that's what I imagined my PhD would be, and then I would go to a company to work for like a semiconductor devices industry or something of that sort. But here, I think you change, and your objectives and goals change, as you go along your PhD. So that's how it evolved. 

SPEAKER: So you have a paper coming out that's going to be published soon based on work you did at MGH that was part of a Defense Advanced Research Project Administration or DARPA project. Can you tell us more about that project? 

ISHITA BASU: Sure. So I would start with the overarching goal of the project, and then I'll talk about my specific role in it. So the big picture of this project was to be able to build a closed-loop deep brain stimulation systems for neuropsychiatric disorders. And this was funded by DARPA, because a lot of veterans are affected by psychiatric disorders, particularly post-traumatic stress disorder, depression, anxiety. 

However, we decided to take more of a functional domain approach, rather than looking at the symptoms of the different disorders. Because in a lot of psychiatric disorders, there's a huge amount of overlap between diagnosis. For example, somebody having major depression might also have a lot of anxiety. However, two patients having depression might not have any overlap in their symptoms or very less overlap. So it's not necessarily the diagnosis that is a good characterization of what's going wrong in their functioning. 

So there is this research domain criteria, and that is in the NIH, where they take a functional domain approach to psychiatric disorders. So that's what we were doing. We had defined five functional domains, and how can we build a simulation system to modulate or improve subjects in those functional domains. And my specific role was in studying the functional domain of cognitive control. Which is basically, how do you flexibly allocate your mental resources for goal-directed behavior, how do you make decisions, how can you resolve conflicts of these executive functioning? 

And in an experimental setting, these studies, these functional domains by using computer games or computer tasks, which a subject can perform, which kind of puts them in a situation that is similar to what a real-life situation might be, but it's way more controlled. Because in a real-life scenario, you might have a situation where you have to make a decision, but that won't be repeated. That will be maybe just one time. 

But in an experimental world, if we just have one situation, it's very difficult to study the brain's response to it, because the signals are so noisy that if you just look at one instance of it it's not very easy to detect that signal. So in an experimental setting, we would have such situations multiple times, so that we can average across those multiple occurrences. And then, in that way, we can better extract the relevant brain signals. 

So in our case, we used a conflict resolution task, where a participant would be encountered with conflicting situation, and he or she has to inhabit a natural response and respond to the conflict. And we measure how long it takes for them to do that. And that is kind of an indication of how good their control or cognitive control is. So that is a surrogate measure of behavior or a measure of how good they are at inhibiting a response and making a decision or making a response. 

So what we will do is-- so the population we were studying was subjects with epilepsy. The reason being that these patients have invasive reporting from their brains for detecting a seizure, Because they are being evaluated for surgery. So the surgeon wants to detect the exact brain region that can be resected or that can be stimulated. So we have a recording from different regions of the brain which is not otherwise possible. 

So these subjects would perform a computer task which would mimic a cognitive control domain, and then we would record their brain signals while performing the task. And in some of the experiments, we would also perform some electrical stimulation and see if we can actually change their behavior or change their response times. And what we found in this work was that if we stimulated a certain region of the brain, which is known as the ventral capsule/ventral striatum, we could actually make them faster in the task, in the sense that they would respond faster and still be correct. So that's important, because you can become faster at a task but do it in a less efficient way. 

So the stimulation actually made them faster without reducing accuracy. So that was one of the findings. So we potentially could use such a brain stimulation to change their behavior or to make them better at cognitive control, at least in the experimental setting. 

So this was the main finding of the work, and we also found that there are certain regions of the brain that are more active while performing such cognitive tasks, which is mostly the frontal region-- it's called the prefrontal cortex-- as well as the temporal lobe of the brain. So this also indicates that this would be the brain regions that are involved in these kinds of cognitive control. So these were the basic findings of that study. 

SPEAKER: And so, from what you said, it sounds like-- maybe I'll try and summarize-- basically giving brain stimulation to people with epilepsy can help them control their response. So if they're trying to perform a task. Maybe you could describe a little bit what that task looked like on the computer. I mean, epilepsy is a seizure disorder, and so to be able to-- yeah, let's-- I have a few different questions. 

ISHITA BASU: Right. So it has-- the issue that it will also translate to other populations, specifically psychiatric population, and it would also improve cognitive control in them. But yeah, that needs testing. We just did it in our epilepsy group, because we could access their brain more invasively. 

And regarding the computer task, specifically it shows you three numbers, and two of them are the same. One is a unique number. And the position of the unique number can either match-- so for example, let's say we have 0, 2, 0, and the subject has to respond to the unique number. In this case, it's easier because 2 corresponds to the position two. So it's easy-- 

SPEAKER: Right. It's in the second position, right? 

ISHITA BASU: Exactly. But if I have something like 1, 1, 2, then 2 is in position three, so there is a natural tendency of pressing three3. But the subject actually has to press the key 2. So that creates a conflict. So you have to inhibit your natural tendency to press the third key and press 2. So that's what creates conflict. And what we have seen in general is that such a situation makes you slower by around 300 milliseconds compared to the easier ones. 

So what the simulation did was actually kind of made the subjects faster on both kinds of trials. So not just the harder ones, but also on the easier ones. So it kind of increased your overall responsivity to the decision-making process. 

So what's left to be seen is does this actually translate into the psychiatric domain? And the other important question is, even if it does, even if it improves cognitive control, does it actually translate in the way of their symptomatic view, right? So does making someone functionally better actually alleviate their symptoms of, let's say, mood or anxiety? So that's an important thing that's not established yet. 

SPEAKER: OK. And so for this paper, you said that you chose the epilepsy subjects because you had access to their brainwaves basically. 

ISHITA BASU: Right, exactly. 

SPEAKER: But there wasn't any connection to epilepsy to trying to an alleviate symptoms? 

ISHITA BASU: No, not really. No. So this is when they are not having seizures. We try to avoid, obviously, when they are having seizures. 

SPEAKER: Right. So you were just sort of like-- they had a probe or something that was reading their brain signals, and then you were just [INAUDIBLE], oh, we'll also take a reading, but you're going to use it for something different than what the epilepsy surgeon is looking at. 

ISHITA BASU: Exactly. 

SPEAKER: They're looking at, like you said, where should I take a piece or where should I stimulate. Got it. 

ISHITA BASU: Yeah. It has nothing to do with epilepsy. But what is interesting is that a lot of these epilepsy patients actually also have a lot of depression, anxiety. So we can kind of categorize these patients into having anxiety, depression, and a more of normal functioning people. So that's what I'm currently working on, to see if they respond differently based on their mental states. That's something that we did not look at in this earlier project. We were pretty much treating everyone equally and not taking into consideration if they had any previous diagnosis of anxiety or depression. But we were solely looking at the functioning aspect and if we can change the functioning using electrical stimulation. 

So it might turn out that how well the electrical stimulation does might actually depend on their mental state. So for example, if somebody has a poor cognitive control might be more likely to improve than somebody who is already high functioning. Yeah. But that's something that I'm interested in studying now. 

SPEAKER: Yeah. So what other conditions do you think or is brain stimulation possibly useful for? You mentioned some psychiatric conditions, like depression. Is there evidence? And from your work and what you're hoping to study, what do you see as sort of next steps and maybe the future for treatment of some of these psychiatric conditions? 

ISHITA BASU: So do you mean regarding brain stimulation? 

SPEAKER: Yeah. Right, right. 

ISHITA BASU: Yeah. I think this is a promising approach, and there are some other groups who are heavily involved, such as Helen Mayberg, who is in Mount Sinai. She has a big depression trial with invasive brain stimulation. Sameer Sheth in Baylor College of Medicine, he has a similar. So he actually has a trial where he brings in patients with depression to figure out more of like in epilepsy setting, to figure out where the stimulation should be. 

So I think it's a growing field, and there are pockets of places where-- it's not across the country. It's not as advanced as the movement disorders field or the epilepsy field. And of course people have reservations about brain stimulation. But I would think something like maybe transcranial stimulation, which is non-invasive, might actually be the first step. And in that way, TMS or Transcranial Magnetic Stimulation, is something that's approved for depression. And there are trials of transcranial direct current stimulation, which is something that I'm also interested in, because it's very non-invasive, it's easy to do-- there's barely any risk associated with it. 

So those kinds of stimulation might be the first ones that would be the way. But I can foresee a future where we will have more deep brain stimulation for psychiatric indications. There are trials for PTSD. The other thing that I actually forgot to mention is chronic pain. That's something where people have been looking at stimulation, and I think there's center which does DBS for traumatic brain injury. They're looking at disorders of consciousness. 

So various indications people are trying. Because drugs are very less effective in psychiatric disorders. And if you can do anything with neuromodulation, that would be great. I think one of the upcoming ones is ketamine, which also has more of neuromodulatory effect for depression, which is actually an anesthetic. And I think in very low doses, it has been approved for depression. So that's another kind of bridge between, I think, drugs and neuromodulation. 

But I think in the future neuromodulation might be the way to go for psychiatric disorders, as more and more people are realizing that psychiatric disorders ultimately are disorders of the brain. It's the brain networks that are affected. And if we can modulate them, we might be able to restore functioning in these individuals. And I think another aspect would be more awareness in this realm of psychiatric disorders. And I think some form of education would also help bring awareness. 

SPEAKER: Yeah. Talk more about that. What do you mean awareness in this realm? What do you mean specifically? 

ISHITA BASU: I would think there's still a lot of-- I feel like there's still a lot of shame in the world of psychiatric disorders. People don't necessarily want to approach even a medical professional to get help. I know of personal friends who would be, like, no, I mean, I don't think I need anything. But even realizing that maybe you need some help is the first kind of awareness I think. 

And back in the days-- I'm from India-- and I know family members who I suspect have schizophrenia but they never got diagnosed. I mean there's a tendency of people looking down upon somebody with a mental disorder and thinking it as more of a personality trait and not necessarily a condition, a disorder. So I think bringing more awareness in that, getting over that, would be important. 

If someone has epilepsy, they wouldn't think twice before going to see a doctor. But if someone is having depressive episodes or anxiety, they would probably think twice and wouldn't necessarily go to get help. So that's what I mean by bringing more awareness into the problem. 

SPEAKER: Yeah. Well, hopefully, if more effective treatments like what you're talking about are discovered and made available, maybe it'll be easier for people to talk about or easier to reach out. 

ISHITA BASU: Yeah. Or even introducing in education or in science education in school or college. I think that would also help. 

SPEAKER: Great. Well, Dr. Basu, thank you very much for speaking with us. I really appreciate your time. Thank you very much. 

ISHITA BASU: It was a great pleasure. 

SPEAKER: Thank you. 

ISHITA BASU: Thank you. 

SPEAKER: Great. Cool. So was there anything about the paper that we didn't go over or you felt like we should add? 

ISHITA BASU: No, nothing that I can think of. Do you think it was clear enough? I can clarify if you have some things that-- 

SPEAKER: I thought it was-- yeah, I thought it was clear. I think-- 

ISHITA BASU: I mean, you can cut out some of the portions if I need to. 

SPEAKER: There was-- yeah. I tried to clarify a little bit, and I think I got what we need. But there was-- I was interested in-- I don't know if you had anything to add about how the brain-- I was thinking towards the end, the brain runs on electricity, but there's also neurochemicals and sort of how you think about that. Because, coming from electrical engineering, you're thinking about brainwaves, but then I don't know if there's-- 

ISHITA BASU: There are transmitters. 

SPEAKER: Yeah. Like in psychiatry, if you're talking about chemicals and drugs, and how those kind of work together. 

ISHITA BASU: Right. I mean, there are the neurotransmitters, which are chemicals. But I think the output of that is still the neuronal firing. You can change the neurotransmitter concentration, you can change the firing. So it's basically chemical energy gets converted into electrical energy is what I'm thinking about. And the drugs actually affect the neurotransmitters. So it kind-- but thing is I don't think the drugs can be that target specific is what my thinking is. 

So I think of external neuromodulation can be more targeted. So what we try to study is which are the networks that are affected, and how can we target that through external stimulation? But if we provide a drug, it will probably affects all the regions that have a similar-- I don't know if it can be that specific. 

SPEAKER: Right. Yeah. Because if you're taking a drug, it's going through your bloodstream, it's going through your entire brain. 

ISHITA BASU: Exactly. Yeah. So I would say it's more of a generic versus personalized in a way. 

SPEAKER: Well, I don't want to get-- but at some point, you do have to consider the balance there and what effects the other. 

ISHITA BASU: Yeah. And I'm not even saying that electrical stimulation would entirely replace drugs. They would just supplement it. So even in epilepsy and movement disorders, it's not like people who have DBS would completely get rid of their drugs. They would still take some, but it reduces the amount that they take. And there's a time that the drugs stop acting-- they might even be getting side effects. So that's what neuromodulation helps with. 

Neuromodulation or electrical stimulation, they don't have any side effects. And if you stop it, the effect is gone, kind of. 

SPEAKER: Right, right. 

ISHITA BASU: It's reversible. So that's why, in a way, it's better than cutting out a portion of your brain like is done in a lot of settings. 

SPEAKER: Right, because that's not reversible. 

ISHITA BASU: Yeah. 

SPEAKER: Yeah. 

ISHITA BASU: And they used to do it for movement disorders to-- 

SPEAKER: Oh, yeah. 

ISHITA BASU: --just cauterize the subthalamic nucleus, which would stop seizures-- sorry, stop the tremor. But with stimulation, you can-- it's reversible. And also, you're not worried that, oh, if I take this part out, that other functions might be compromised. Because it's all connected. So if one thing is gone, other networks might be destroyed. 

SPEAKER: Yeah. And not everybody's brain is exactly-- the regions are kind of in the same area, but the shape, the density, the size is all different. 

ISHITA BASU: Yeah. 

SPEAKER: Yeah. 

ISHITA BASU: So I think the positive thing about DBS is it's targeted, it's reversible, there's no side effect. But the challenge is getting the right target, the right stimulation, and how do you even know if the response to stimulation is not always obvious. It might be a gradual process, especially in psychiatric disorders. It might take months to actually see the effects. So how do you like optimize the stimulation. So those are all problems that we study or we attempt to solve.