S2 Episode 21: A Jolt of Happiness

Is it possible to relieve depression or PTSD using electricity? Kelly Bijanki, PhD, runs a lab at Baylor College of Medicine, where her team is using deep brain stimulation to induce happiness in patients who need it the most. Her fascinating work shows that “emotional” issues are as biologically based as “neurological” ones, and that depression can be treated with the same techniques used for epilepsy or Parkinson’s disease.   Plus … the evolution of the smile.

Phil Stieg: Hello, I want to welcome Dr Kelly Bijanki, a scientist in the departments of neurosurgery, psychiatry and neuroscience at the Baylor College of Medicine. She and her team are leading efforts in an area called functional neurosurgery and, in her case, psychosurgery. How neurosurgeons using electrical impulses can alter the way our minds perceive and respond to specific stimuli. In Dr. Jenckes case, how to bring real happiness and joy into the lives and the possible medical conditions in which these techniques might be useful. Kelly, thank you for being here to discuss happiness and the brain.

Kelly Bijanki: Well, thanks for having me. It’s a pleasure to be with you.

Phil Stieg: OK, since we’re going to be talking about how you’re going to make all of us happy, can you tell me how you define happiness?

Kelly Bijanki: Oh, boy, that’s a really hard question.  I love it. I think it means different things to different people in depression. When we talk about happiness,  happiness is really sort of defined as the absence of all that negative stuff, all of the problems and dysfunction of the depression itself.  

 Phil Stieg: So, Kelly, in your in your introduction, we went through a real mouthful. Can you explain to the listeners what deep brain stimulation really is?

Kelly Bijanki: Deep brain stimulation is a really exciting application where we’re able to see areas of the brain that are not performing as they should be. Perhaps they’re overactive, perhaps they’re underactive. And so we’re able to directly modulate those parts of the brain using an invasive  neurosurgical approach , where we implant a depth electrode into the brain area that needs to be modulated.  And then it is  stimulated from basically a pacemaker battery that runs stimulation to that area of the brain.

Phil Stieg: So you work in a lab called the Translational Neuromodulation Lab that has too many syllables. Can you break that down into what that really is?

Kelly Bijanki: Sure. So the crux of my research actually occurs in patients with epilepsy. So in the case of surgical epilepsy, some subset of patients require intracranial depth electrodes. So this is similar to the DBS wires implanted all over the brain to try to figure out where the patient’s seizures are coming from. And so in that setting, the patients, they’re waiting in the hospital, they’re not in the operating room. They’re just in a comfy, you know, hospital room waiting to have seizures. But they have all these wires in their brain and they want to contribute to our understanding of diseases, whether it be their disease or others.  And so we offer them, you know, to participate in research where we record their brain signals with these intracranial electrodes implanted.  In my case in the translational neuromodulation lab, the experiments that we do are emotional ones that then help us understand the circuitry underlying emotion then can be translated into application for new deep brain stimulation, targets for psychiatric disease patients, non-epilepsy patients.

Phil Stieg: So the psychiatric disorders that you’re most interested in are the affective disorders like depression.

Kelly Bijanki: Yes, Depression, bipolar disorder…yes.

Phil Stieg: When you’re talking to people  and you say that, you know, happiness is happiness is really an electrical impulse, you know, because in some of your materials, you talk about the electricity of the brain and the neural networks of the brain.  What interplay do you see going on there?

Kelly Bijanki: I mean, I think understanding neuroscience and the communication of neurons as I do, I sort of think of everything our brains do in terms of electricity, but that doesn’t make it any less a human phenomenon.  And whether that electricity is chemical energy that’s coming from, you know, the way that your brain typically sends electrical impulses along axons or if it’s electricity that we’re putting into the system from a battery. And we’re still feeding into the same network with the hope of creating the same emergent phenomenon of happiness and wellness.

Phil Stieg: The unique thing for you, though, is this happiness center.   You know, some areas make you happy, but as you said, is more mechanical. And in the area that you’re interested in, it’s true joy. 

Kelly Bijanki: What we’re really hoping for with neuromodulation techniques is not like a euphoria, like a super happy, excited over the top phenomenon, because that’s not real life.  We need to be able to experience the range of positive and negative emotions. That’s how we understand our world. And so we wouldn’t want to, you know, develop a therapy that abolishes all negative emotion. But we do want to sort of unmask the ability to feel positive emotions.

So the things that we can measure to really understand how someone’s feeling typically focuses on facial expression. If the person is smiling, we use computer vision and all these algorithms to figure out like, oh, they started smiling exactly when we stimulated in this area.  So therefore, we have an objective measure. 

Phil Stieg: How else do you measure happiness aside from just their facial expression? Are there other parameters you use as a scientist?

Kelly Bijanki: There are a ton and it’s a very important thing that we think about a lot. The phenomenon of mood, the experience of happiness or joy, can be instantaneous or can be not instantaneous. It depends on how in touch with their emotions a patient is, how willing they are to tell me how they’re feeling.  And so there’s a lot of effort that my lab and my collaborators are putting into developing more objective methods to try to quantify someone’s emotional state without just saying, “So how do you feel now” and then, “how do you feel now” and “how do you feel now”, which is a lot of the programming is.

Phil Stieg: I was kind of hoping you would tell me, some way of being able to recognize whether my staff is happy or unhappy, you know, so they smile.

Kelly Bijanki: So there is a way. So there’s this this property sort of a cognitive property of just humans, that when we’re feeling depressed, we interpret emotional stimuli around us in a way that’s consistent with the way we feel inside. So if you look at a neutral stimulus, this is especially strong in looking at pictures of people’s faces.  And if you look at a neutral face and you’re somebody who has depression, you actually interpret that face a little bit like it’s sad, like it’s aversive or negative. And when you yourself the same depressed person, look at that same face after you take in your very first dose of Antidepressant medication, you interpret it happier. So we show these pictures of faces and then we show them again when the stimulation is on. And if the interpretation, the reading of the face is happier, then you know that the stimulation is having an antidepressant or sort of mood elevating effect. 

Phil Stieg: So as you’re talking about smiling, I don’t know why this came into my mind, but I immediately thought of the evil smile of Hannibal Lecter.

Kelly Bijanki: Oh, dear.

Phil Stieg: And I was wondering, you know, have you had that experience where, you know, you got the oh, it’s a smile, but that’s not a good smile.

Kelly Bijanki: Umm…We do some stuff not with, like the evil smile so much, I can’t say that’s been a focus of my research to date.

Phil Stieg: I wouldn’t it would be.  Let’s face it, you know, a smile can have different meanings.  Right. And Hannibal Lecter had a very distinct meaning.

Kelly Bijanki: Yeah, definitely…


Interstitial

Narrator: The human smile is a surprisingly complicated signal. It’s often warm and welcoming, but it can also be enigmatic, like the Mona Lisa’s, or downright evil, like the aforementioned Hannibal Lecter.

In this episode of This Is Your Brain, the guided tour, we ask the question – why do we smile, anyway? And how do we learn to interpret the smiles of other humans?  

Animal behaviorist Franz de Waal traces the evolutionary roots of the smile back to our primate cousins  –  apes and monkeys.  De Waal says our smiles evolved from a primate’s grin – a sign of deference that lower-ranking monkeys show to the top individuals in their troop. But a monkey’s grin is multi-layered. It’s an intensely social signal that mixes fear with a desire for acceptance.  And even though we humans sometimes signal our subordination by laughing at the boss’s jokes, our smiles are more complicated than that.

De Waal writes,  “Depending on the circumstances, the smile can convey nervousness, a need to please, reassurance to anxious others, a welcoming attitude, submission, amusement, attraction and so on. Are all these feelings captured by calling them “happy”?

Facial expressions like the smile evolved to play an important role maintaining a stable primate community. 

De Waal points out that “…we have far less control over our faces than the rest of our bodies.  We don’t fully control our faces because we don’t fully control our emotions. That this allows others to read our feelings is a bonus. Indeed, the tight link between what goes on inside and what we reveal on the outside may well be the whole reason why facial expressions evolved.”

Some may say “let a smile be your umbrella.”   But — in evolutionary terms — your smile may be more like a yield sign – a way of signaling that you are not a threat, either to the boss or a neighbor we pass on the street. As for the Mona Lisa’s smile… well, that’s still a mystery.

End Interstitial

Phil Stieg: In your experience with deep brain stimulation, have you had an “a-ha” moment all of a sudden like, oh, I’ve found it.  I know what I need to look for now?

Kelly Bijanki: Yes, we did. So in a patient a few years ago, we were stimulating the cingulum bundle, which is one white matter portion of a big network that we know is important for depression.  And this was really sort of the first chance that anyone in the world had had to stimulate only the singulum bundle by itself and in a particular sort of geometry based on the way the electrode was in for this person’s epilepsy.  

When we stimulated it, the patient immediately smiled. She started laughing.  She did it every single time we stimulated her.  The stronger the stimulation was, the stronger her sort of happy response. And when we turned it on long term, she sort of like kind of settled into just a content, relaxed, happy state.  She was smiling.  She was talkative. She was making more eye contact. And we actually then were able to use that stimulation.  Later in her epilepsy treatment course, she required to have an awake brain surgery unrelated to the stimulation. Just that’s what they needed to do for her epilepsy. She was very, very nervous about it. And so we were able to use the stimulation to help keep her calm during that awake brain surgery.

Phil Stieg: Now, I have to ask, having read your stuff, this was not mechanical happiness. This was true happiness and joy, right?

Kelly Bijanki: That’s right. Yep. It really carried some content. I mean, it was hard to be in the room with her and not giggle like we just — the whole team got the giggles. It was just infectious, contagious happiness.

Phil Stieg: Tell me, how do you get your patients ready for,  wrapping their head and having wires coming out?

Kelly Bijanki: So in the case of the epilepsy patients, this is something that’s required for the treatment of of their disease. So it’s not really me trying to talk them into doing anything. It’s that this needs to happen in order to treat their disease. And while they’re waiting for their seizures to occur, do they want to spend some time with the research team? They have this opportunity. I just say, you know, it’s a really a privilege to have the opportunity to work with you.  And it’s also a really special chance that we have for science to work with someone who has these electrodes implanted in the brain.    People try to create meaning from their struggle.   If they can find something positive to contribute some meaning, that’s good coming out of a challenging circumstance. We’re certainly happy to help them with that.

Phil Stieg: Where do you see this going?  Are we going to implant these electrodes in somebody and they have a battery? And are they going to control the battery? Or is the battery going to have like a feedback loop on it so it knows when to fire? What do you envision?

Kelly Bijanki: Yeah, great question. So I think the most immediate and actionable thing we can do is to do the clinical trials of deep brain stimulation to these areas, to elicit happiness in people who are sick, people who have depression, where happiness is the treatment for their for their clinical condition.  From there, then I think the next step is to use what’s called “closed loop stimulation”, where we define a brain state that tells a machine,  “OK, now you need to do something” because we can see that the brain state is moving back toward depression. And so the machine is normally off its monitoring. And if it sees that the brain state starts to get more depressed, then it fires off the happiness signal. And it kind of re-sets you.

Phil Stieg: So this closed loop system, is it like a thermostat in your living room and when it gets too cold the heat comes on?

Kelly Bijanki: Yeah, it’s very similar to that. One of the challenges that we’re hoping to address with these intercranial studies is a lack of the right sensor. And I don’t mean that in the technical sense.  Like we have all the right chips and all the right hardware. We don’t know what we’re measuring. Like, what’s the state like with the thermostat?  It can tell it’s getting too cold in the living room and it’s measuring in degrees and then it fires off its signal to start the furnace.  We don’t know, like how cold is too cold or is it and is that even matters to trigger the “furnace” for depression?

Phil Stieg: Because I was thinking about this in the scenario where the patient controlled the electrode.  You know, they’re starting to feel a little bit sad. Boom, they hit the battery and give themselves a little bit of current. Would you in that scenario find that people abuse it and overuse it because they know they want to feel happy all the time?

Kelly Bijanki: I think it’s possible, but I do think we also need to be very careful about the sense of patient’s autonomy and trusting their understanding of what’s too happy and what is sort of a manageable setting for their lives.  For example, the DBS targets that we have now, if they’re overstimulated, it’s not fun. It’s like having way too much coffee. And it’s not quite like “livable”.

Phil Stieg: So there’s a downside to it?

Kelly Bijanki: Yeah. So I think it will be a fairly self-controlled system and then the long term future would really be non-invasive modulation of this where we don’t have to permanently implant somebody.

Phil Stieg: I was wondering if you stimulated somebody enough and they were just you could really see that they’re happy and joyous.  Does their guilt level go down?

Kelly Bijanki: I would hope so. I mean, guilt is a major facet of depression.  And certainly in the case of treatment, resistance for depression.  I think when we’re driving up happiness, it’s not necessarily changing any of the content, you know, of the sad memories or the trauma and things that people have experienced.  So if they feel guilt over a certain, you know, something that happened in their past, no amount of like chemical energy is going to necessarily just erase that.  But we hope that, you know, the stimulation makes it possible that the patient sort of gets “ unstuck” and then they’re able to participate in, you know, cognitive behavioral therapy, talk therapy to really sort of reprocess and try to like form new connections about things they may have experienced in the past or feel guilty about.

Phil Stieg: One of the possibilities you spoke about is post-traumatic stress disorder.  Would you envision this as being, you know, we’re going to temporarily put in some electrodes and strike the happy bone? Or do you envision a more long-term implantable device that’s going to have to stay there for the rest of their lives?

Kelly Bijanki: I think for post-traumatic stress disorder specifically, the goal would really be to help them reprocess their trauma.  One of the patients that we did the stimulation with – we turn the stimulation on and we asked her to think of a sad memory.  And she tried her hardest to keep a straight face.  And she said, I’m trying really hard. And we said, what are you trying to think about?  I’m trying to think about my dog dying. But I – it doesn’t feel sad right now. I know that it’s a sad memory. I know what happened, but it doesn’t feel sad right now.  So, to a scientist hearing this, it sounds to me like she’s keeping the content of the memory, the so-called semantic content, the like knowledge of what happened.  But that emotional trace, the sort of like hyper negativity that gets attached to very sad memories can be sort of turned down maybe by the stimulation, which is exactly the goal of cognitive behavioral therapy for PTSD.

Phil Stieg: Yeah, I could see that being useful for somebody that’s depressed or has PTSD. But on the flip side of it, where is that balance in your mind for the individual?  I think it is an essential part of our life that we do know sadness. You know, my dog died and I’m always sad about that. I always loved my dog and I don’t want to lose that sense of love.

Kelly Bijanki: Yeah. So I think in the case of PTSD, the memory it takes on sort of an outsized role in a person’s life where they’re really sort of living around the history of that trauma.  They’re trying to avoid triggers. They may not go out of their house. They can be on disability. I mean, this can be a really debilitating and serious condition.  And in that case, I think stimulation- whether it be permanent, like just an implanted pacemaker driven chronic stimulation device or temporary, where we implant it, stimulate it during a really intense set of talk therapy sessions where the patient, you know, reexperience as their trauma and sort of unlearn that fearful association and then takes it out.  Despite them being invasive, I think that level of challenge is warranted.

Phil Stieg: What’s your dream?  Where do you want this to go?

Kelly Bijanki: I really want to develop new deep brain stimulation targets for psychiatric diseases that are based on understanding of the neural signals that define the disease state. There’s this idea that psychiatry is, you know, sort of trying to treat problems of the mind or neurology is trying to treat problems of the brain. And people think that psychiatric diseases don’t arise from a brain basis sometimes.  And I think that’s wooey!  And I hope that people stop thinking about it that way.  

Phil Stieg: Kelly Bijanki, thank you so much, you are at the forefront, and in my mind one of the mist interesting areas in neuroscience and neurosurgery.  Thank you so much for doing this work.

Kelly Bijanki: Thank you very much it’s been a pleasure talking to you.