Mohammed Milad, PhD, discusses recent research into fear conditioning, regulation, and extinction. Dr. Milad is a Professor in the Department of Psychiatry at the NYU Grossman School of Medicine and Director of the Behavioral Neuroscience Program.
Topics covered:
Visit our website for more insights on psychiatry.
Podcast producer: Jon Earle
Mohammed Milad, PhD, discusses recent research into fear conditioning, regulation, and extinction. Dr. Milad is a Professor in the Department of Psychiatry at the NYU Grossman School of Medicine and Director of the Behavioral Neuroscience Program.
Topics covered:
Visit our website for more insights on psychiatry.
Podcast producer: Jon Earle
NOTE: Transcripts of our episodes are made available as soon as possible. They are not fully edited for grammar or spelling.
[00:00:00] DR. THEA GALLAGHER: Welcome to NYU Langone Insights on Psychiatry, a clinician's guide to the latest psychiatric research. I'm Dr. Thea Gallagher. Each episode, I interview a leading psychiatric researcher about how their work translates into clinical practice. Today, I'm speaking with Dr. Mohammed Milad. Dr. Milad is a professor in the department of psychiatry at the NYU Grossman School of Medicine and Director of the Behavioral Neuroscience Program. His research focuses on fear extinction, touching on everything from meditation to estrogen to transcranial magnetic stimulation. Clinicians treating patients with PTSD and anxiety disorders will find his work especially important and interesting. Dr. Milad, thank you so much for being with us today.
[00:00:41] DR. MOHAMMED MILAD: It's a pleasure. Thank you for having me.
[00:00:43] DR. THEA GALLAGHER: We're just gonna start by... We wanna talk a little bit about, um, what you're focusing on currently in your research.
[00:00:49] DR. MOHAMMED MILAD: So my, uh, research is focused on a very simple question, um, that is how do we learn not to fear?
[00:00:56] DR. THEA GALLAGHER: Hm.
[00:00:57] DR. MOHAMMED MILAD: That's just broadly speaking. And, uh, how does the brain form associations that we experience throughout our lifetime to enable us to function, right? And, uh, the key thing is about really fear and fear mechanisms and, and how the brain forms these associations across multiple brain areas. That's just generally speaking.
[00:01:21] DR. THEA GALLAGHER: Gotcha. And why is fear such a problem, or, or again, why are you trying to study it to understand it more?
[00:01:29] DR. MOHAMMED MILAD: Well, fear is... Everyone can relate to. Fear is a, a critical emotion that we all relate to, we all experience. It's just interesting to me, from just a basic science point of view. You know, how, how, where and how in the brain fear is formed and fear is controlled and fear is regulated, 'cause I just, uh, from a, a basic, uh, neuroscience point of view. And I, I was trained as a neuroscientist and that's what I am and that's what I, I'm interested in. So that's just one angle.
The other angle is obviously if fear goes unchecked, if we, uh, are unable to regulate it or control it, then it can lead to some difficulties for some of us to function, and that leads to psychopathology. So, understanding the brain mechanisms of how fear is, uh, formed and interacts with other mechanisms or other systems, like our cognition or our memory or attention, and how, when it goes unchecked, it can lead to disorders like, uh, PTSD, post-traumatic stress disorder, or anxiety disorders and things like that.
So, there are two, like I said, it's, it's two angles. One is just from because it's interesting, because it, I find it cool.
[00:02:48] DR. THEA GALLAGHER: Mm-hmm.
[00:02:48] DR. MOHAMMED MILAD: And, uh, [laughs] the other aspect is how it has a lot of implications to psychopathology.
[00:02:53] DR. THEA GALLAGHER: Can you tell us a little bit about the studies that you're involved in that are ongoing currently and what you're looking at?
[00:02:59] DR. MOHAMMED MILAD: I always get myself into trouble with doing a lot of different studies.
[00:03:02] DR. THEA GALLAGHER: [laughs]
[00:03:02] DR. MOHAMMED MILAD: So we have a lot of ongoing projects here at NYU, all really focused on establishing circuits that learn to fear-
[00:03:11] DR. THEA GALLAGHER: Mm-hmm.
[00:03:11] DR. MOHAMMED MILAD: ... in the brain, and how they are, um, contributing or, or helping us understand psychopathology. So, uh, one project is looking at how the use of estrogen might help women with PTSD as an adjunct to exposure therapy, and we can go more into details about that, but basically trying to find ways in which we can improve clinical outcomes for PTSD treatment, especially in women diagnosed with PTSD.
There's another project that we're doing is involving transcranial magnetic stimulation.
[00:03:46] DR. THEA GALLAGHER: Mm-hmm.
[00:03:46] DR. MOHAMMED MILAD: And we're trying to see how we can use, um, external devices like TMS to manipulate circuits-
[00:03:55] DR. THEA GALLAGHER: Mm-hmm.
[00:03:55] DR. MOHAMMED MILAD: ... in the brain with the objective of trying to enhance the capacity to control or regulate fear in humans, and how that might be, uh, might have future implications to improving treatment outcomes for PTSD. Uh, there are a number of other projects that are using some sort of modulation or another neuromodulation or another to study the, the change in our brain circuits before and after a given treatment-
[00:04:25] DR. THEA GALLAGHER: Hm.
[00:04:26] DR. MOHAMMED MILAD: ... in different populations. So I mentioned PTSD and using estrogen, TMS. There's another project in which we, uh, this is in collaboration with Dr. Naomi Simon at, uh, NYU Psychiatry, in which we're studying patients with anxiety disorders and we're using meditation-
[00:04:43] DR. THEA GALLAGHER: Hm.
[00:04:43] DR. MOHAMMED MILAD: ... and seeing, studying the impact of meditation on the brain circuits, uh, in patients with anxiety disorders. So they, we look at their brains before they start the eight week, um, meditation course. We have them go through a meditation. And then we look at their brain after. So we're always looking at before and after, changes in the brain circuits, as indicates of estrogen, for example. So we're scanning people before, scanning people after. With TMS, we're doing the same thing, and this is another project we're looking at, using meditation to see if we can manipulate brain circuits.
[00:05:15] DR. THEA GALLAGHER: Mm-hmm.
[00:05:16] DR. MOHAMMED MILAD: Uh, there's another project that we're trying to see the intersect between avoidance behavior, which we all know about and learn and experience and go through in life, fear, and reward, how the three intersect-
[00:05:31] DR. THEA GALLAGHER: Hm.
[00:05:31] DR. MOHAMMED MILAD: ... in the brain. So an example is if you go through a traumatic experience in a car, you have a serious car accident that, you know, you got severely injured or hurt, you're gonna, after that, try to avoid driving your car. But then, you know, that avoidance subsides after some time, say a week or two weeks or a month, because you have to, say, drive to go to work. And so, there's this thing of, of, of competition between, you know, going over or getting rid of your avoidance response and your fear because of a goal-driven or a goal-directed behavior that we need to do, which is, you know, maintain our jobs, for example.
So that, those are the things we, we're trying to understand in the brain, and we, we study this in, in using functional MRI to basically look at brain circuits. We, we develop paradigms that we have people go through in the scanner, and we, we study that, that dynamic interaction between these three. Um, let's see. We, [laughs] other projects o- and also OCD, obsessive compulsive disorder, and this is in collaboration with, uh, UPenn and Columbia. Also looking at the impact of estrogens on exposure and response prevention in OCD patients.
Um, by the way, the estrogen project n- I forgot to mention that it's also in collaboration with UPenn as well.
[00:06:55] DR. THEA GALLAGHER: Can you tell us a little bit about, I think... Um, so this podcast is really directed to psychiatrists and mental health clinicians.
[00:07:02] DR. MOHAMMED MILAD: Mm-hmm.
[00:07:03] DR. THEA GALLAGHER: And I'm sure people would be interested to know, you know, some of, you know, us out here kind of doing the clinical treatments. Can you tell us a little bit about this relationship between estrogen and fear, and, and what you know about it already and what you're trying to hopefully figure out in the long run, and then we can-
[00:07:16] DR. MOHAMMED MILAD: Yeah.
[00:07:16] DR. THEA GALLAGHER: ... talk about implications for even clinical practice.
[00:07:19] DR. MOHAMMED MILAD: The study of sex differences have not really been carefully done for, for many years in the past. You know, when we would basically, in, in animal models, we would just use... The majority of studies used to look at rats o- male rats only. Female rats were always ignored, or just not included because it's just easier to maintain the reduced variables and because of the estro cycle in the female rat, there's a lot of fluctuations, up and down hormonal changes. So, scientists didn't want that, so they, they left the female rate out.
And in human studies, people would just recruit sample of men and women, and we'd put them together an average. Women, just look at their data that way, averaged. But without necessarily focusing on how men and women may differ.
[00:08:07] DR. THEA GALLAGHER: Mm-hmm.
[00:08:07] DR. MOHAMMED MILAD: And so, we, 20 years ago, I started doing this in human side 'cause my PhD is in the animal models, and I only studied male rats. Um, I'm, I'm guilty of the same.
[00:08:18] DR. THEA GALLAGHER: [laughs]
[00:08:18] DR. MOHAMMED MILAD: But this was... I'm, I'm gonna blame it on my mentor. Uh, [laughs] so when I started to study humans because I start, I'm interested in the human brain and human behavior and the biology of fear in from the human side, my first experiments, I noticed there were some differences between men and women and how they, how they regulate their fears. So I do Pavlovian conditioning.
[00:08:39] DR. THEA GALLAGHER: Mm-hmm.
[00:08:39] DR. MOHAMMED MILAD: In, in, uh, in my lab, that's what I study. That's what I do. I, I show people pictures of blue light and I, I deliver a mild electric stimulus-
[00:08:47] DR. THEA GALLAGHER: Mm-hmm.
[00:08:48] DR. MOHAMMED MILAD: ... call it the shock. Um, and they learn that every time they see a blue light, they get shocked in their fingers.
[00:08:54] DR. THEA GALLAGHER: Mm-hmm.
[00:08:54] DR. MOHAMMED MILAD: And they start not liking blue.
[00:08:56] DR. THEA GALLAGHER: Hm.
[00:08:56] DR. MOHAMMED MILAD: And, uh, then I take away the shock and I just show them blue without shock. And then, they extinguish that fear. Then I send them home, and then the next day, they come back and I s- test their memory. So there's a fear associated state that we study. We call it conditioning. There's the extinction and then there's the extinction memory the day after. Um, th- and we do all of this inside the MRI scanner, the MRI scanner, and we're looking at the brain and we see what lights up and how, how these things form and how are they, h- how these circuits are changing throughout these different phases of learning.
And so, what we found, um, early on is that we noticed differences in how men and women formed these associations or how they expressed them rather.
[00:09:45] DR. THEA GALLAGHER: Hm.
[00:09:45] DR. MOHAMMED MILAD: And so, I was intrigued, and I went to my mentor, Scott Raosch, at the time, and I said, "Scott, there's, you know, something's interesting here. Um, men and women are, are not necessarily be, you know, expressing the same conditioned responses. They're not extinguishing similarly. Now, there may be something to this." And I looked in the literature and there was really not much done.
So, we started looking at it, and what we found is that if we just study a group of men and a group of women, and have them go through this conditioning and extinction training paradigm-
[00:10:19] DR. THEA GALLAGHER: Mm-hmm.
[00:10:19] DR. MOHAMMED MILAD: ... and they learn to condition to form this association between the blue light and the shock just as fine, equal. And they also extinguish their fear similarly. And they also remember that extinction the day after okay. But when we look at women and we evaluate, um, the women by their hormonal state, whether they went through this experience of condition and extinction in a high estrogen state naturally or low estrogen state, so they're near ovulation, for example.
[00:10:53] DR. THEA GALLAGHER: Mm-hmm.
[00:10:53] DR. MOHAMMED MILAD: Right? Or early in the cycle, in the menstrual cycle. We found differences within women. And then, sex differences emerged, so that women who had, who ran through this paradigm, they came to the lab just when they're high estrogen, near ovulation, for example, or in a luteal phase, they were able to hold on to that extinction mem- memory better.
[00:11:16] DR. THEA GALLAGHER: Hm.
[00:11:16] DR. MOHAMMED MILAD: So that the day after when they came back, their fear and anxiety, as measured by our skin conductance and some brain circuits, had higher activation.
[00:11:25] DR. THEA GALLAGHER: Hm.
[00:11:27] DR. MOHAMMED MILAD: Okay? Compared to the women that went through this training paradigm in a low estrogen state. So that's what gave us that initial hint that there may be something related to estrogens or sex hormones, probably speaking, maybe progesterone, but we're focusing, focused on estrogen and how that might impact the brain circuits that form these memories and store them.
And so, we, we've basically done s- a lot of work the past 15 years, the summary of which is if we manipulate these hormones in women, if we give them estrogen exogenously, if we just give women a pill of estrogen, and have them go through this extinction training, we can actually enhance their capacity to store that extinction memory better.
[00:12:13] DR. THEA GALLAGHER: Hm.
[00:12:14] DR. MOHAMMED MILAD: Which means, translates to having them better regulate and better regulate their emotional response to these condition stimulus, and better, uh, better able to express that safety memory, if you will, the day after. And so, that's what's led us to this clinical trial that we're currently running in which we recruit women with PTSD, diagnosed with PTSD, and then we h- we scan their brains and we have them go through this condition extinction paradigm.
And then when they come into the clinic, they go see the, the, the therapist and they go through prolonged exposure therapy. We give them a pill of... It's a double-blind placebo controlled trial, either estrogen or a, um, a control pill right before they come in to see the therapist. So, they basically, the idea is to try to see if we can elevate estrogen during exposure therapy. Does that make the therapeutic outcome better?
[00:13:12] DR. THEA GALLAGHER: Hm.
[00:13:13] DR. MOHAMMED MILAD: Are they able to go through the therapy session and learn from it more when we're elevating their estrogen?
[00:13:20] DR. THEA GALLAGHER: Mm-hmm.
[00:13:20] DR. MOHAMMED MILAD: And, and instead of doing the, you know, eight to 12 therapy sessions, we're reducing it to six therapy sessions.
[00:13:27] DR. THEA GALLAGHER: Hm.
[00:13:28] DR. MOHAMMED MILAD: So then, can we, instead of having w- you know, the, the clinical trials go for 12 weeks, we can, we're now doing it for three weeks twice a week, and then see, with or without estrogen, and then we're scanning after, and we look at the brain circuits and whether or not that changed because of this estrogen versus a placebo. So that's, that's what we're doing, we're, and we're doing the same clinical trial. We're not really... You know, it, we're studying mechanisms of, of, of, again, the similar patterns of, and how estrogen might impact therapeutic outcomes in patients with OCD. A- And again, that's a, that's in collaboration with, um, Lara Simpson. She's the PI along with, um, NFO as well, s- the PIs.
So we, we're sub here. We're, we're collecting the data from them and we're gonna be analyzing it. But that's probably the, the objective here.
[00:14:19] DR. THEA GALLAGHER: Yeah. And they, you know, your hypothesis and, and things that you expect do happen. What do you think will be the clinical implications for psychiatrists or mental health clinicians?
[00:14:30] DR. MOHAMMED MILAD: There are two folds in my view. One is, is having the patients understand and learn that the brain is plastic, and that when you're going through a therapeutic intervention, y- it's actually impacting your brain. So I think that's really powerful-
[00:14:49] DR. THEA GALLAGHER: Hm.
[00:14:49] DR. MOHAMMED MILAD: ... for a patient, r- you know? If I think I have an infection and I go and I get a blood test, right, and then I, I, I see my white blood cell count is high, and then you are my clinician and you give me this antibiotic and I take that antibiotic, and after a week or 10 days, I, I go back and I do a blood test, I feel better, but I'm not so sure. Right? And if I then do a blood test and I, I convince myself by saying that my, my white blood cell count is down, then I feel assured or reassured.
So, I think the patients' awareness and understanding that the brain is plastic and that therapeutic interventions don't just... They, they don't have an impact on your elbow. You know? W- how is, how is, you know, how does psychotherapy impact you? How does it change you? It, it, it impacts your brain. So that's one thing, what I hope that we show, is that there is different therapeutic interventions, actually do change the brain.
[00:15:43] DR. THEA GALLAGHER: Mm-hmm.
[00:15:43] DR. MOHAMMED MILAD: And we're gonna, we're, we're looking for is to show how and where in the brain these things happen. That's one. The second is that we're trying different interventions, whether it's, you know, device based, neuromodulation, or, you know, different forms of psychotherapies or behavioral therapies or meditation, or, um, or pharmacological agents and things like that.
And, um, again, the objective is to see how they impact the brain, but how we maybe are different. So, maybe meditation works for you but not for me.
[00:16:20] DR. THEA GALLAGHER: Hm.
[00:16:21] DR. MOHAMMED MILAD: Whereas device-based neuromodulation is better for me and not for you. And so, second objective is, as we move forward in this field, is trying to understand which therapies work and which therapies work best for you and not for me and vice versa.
[00:16:39] DR. THEA GALLAGHER: Mm-hmm.
[00:16:39] DR. MOHAMMED MILAD: So try to kind of develop ways to tailor treatments based on who's it gonna work for best, versus not. And the third is, is the obvious, is that we're trying to develop novel interventions to try to improve or accelerate or current interventions, you know. PE works, prolonged exposure therapy works, but not works for everyone, or there's some, you know, stress-induced reinstatement of dramatic experiences, for example, in PTSD.
W- if we can find ways and we can improve on these current treatments, make them more, you know, solid if you will, if we can try to find ways to enhance the impact of these therapies by adding a pharmacological agent that can sort of cement that therapy better, if you will, in your brain and change neural mechanisms and enhance neuroplasticity in your brain, then that would be a, a very nice thing to show and that's what we're really after.
And obviously, you know, device-based, like I said, trying to develop novel interventions, e- and, and novel approaches for treatment.
[00:17:42] DR. THEA GALLAGHER: Mm-hmm. Yeah. And I think y- you know, one of the themes that we've already seen in this podcast is this concept of personalized medicine, because we know things like PE work and we know that medication works and, but we're trying to now, it seems like, get more granular, and how can we make it even better, and how can we tailor it to the person and understanding what works for which person at the best rate, dose, time, or with an adjunctive? Um, and I think that's one of the really, like, powerful takeaways of how the field is moving. Would you agree?
[00:18:13] DR. MOHAMMED MILAD: Absolutely. And, and again, for me, showing that these therapeutic interventions, that they're skeptics, right?
[00:18:20] DR. THEA GALLAGHER: Mm-hmm.
[00:18:20] DR. MOHAMMED MILAD: And a- about whether or not they work or how they work or where they... You know, a- and I think if we show, from a, a basic neuroscience point of view that they actually do impact your brain-
[00:18:30] DR. THEA GALLAGHER: Mm-hmm.
[00:18:30] DR. MOHAMMED MILAD: ... you know? There are, there are synapses that change when you meditate, and how cool is that? Your, your, the brain, you know, parts of your brain actually... The, the structural changes occur when you do these things, and I think that's, that's an amazing f- achievement that we would, um, would have a, a, a, um, an obligation almost to, to report and show the public and the patients that, look, this is what's happening to you and this is why you should stick to it and this is why it's gonna be good for you if you do it because it actually is changing your brain.
[00:19:00] DR. THEA GALLAGHER: Not just that it works, but how it works.
[00:19:03] DR. MOHAMMED MILAD: Exactly right.
[00:19:03] DR. THEA GALLAGHER: Mm-hmm. Yeah. As an exposure therapist myself, you know, I get to experience the changes, um, but, I, I think it would be, it would really bolster the treatment to explain to patients and to the world and to other, you know, clinicians this is exactly how it's working, and the, um, the real changes that are happening in the brain.
[00:19:22] DR. MOHAMMED MILAD: Exactly. And you know, like, again, we use other, um, analogies of, of, of, you know, h- heart disease and where you, you, your ejection fraction is under 20%, and then you go through a, a triple bypass, and then your ejection fraction goes up to 45%. You have numbers. You have things to look at. Makes it tangible to the patient, and like, it's not just about your breathing is better and your life is better, but you actually s- can see it.
So I think if we can, again, you know, just to [laughs]
[00:19:48] DR. THEA GALLAGHER: Find ways to show it to the patients too? Yeah.
[00:19:50] DR. MOHAMMED MILAD: Find ways to show it to the patient. I think that's something that we're missing. And, and, and so to show, to show your patient, "Look," you know, take a picture of y-
[00:19:57] DR. THEA GALLAGHER: Mm-hmm.
[00:19:57] DR. MOHAMMED MILAD: ... of their brains before therapy, have, go through the therapy, and then show them after.
[00:20:02] DR. THEA GALLAGHER: Mm-hmm.
[00:20:02] DR. MOHAMMED MILAD: Wouldn't that be cool?
[00:20:03] DR. THEA GALLAGHER: Yeah. More, more-
[00:20:03] DR. MOHAMMED MILAD: I, I would want that.
[00:20:04] DR. THEA GALLAGHER: ... objective data, right?
[00:20:05] DR. MOHAMMED MILAD: [laughs]
[00:20:05] DR. THEA GALLAGHER: Yeah. And Dr. Marmar-
[00:20:06] DR. MOHAMMED MILAD: Yeah.
[00:20:06] DR. THEA GALLAGHER: ... and I were talking about that, you know, like if you are diagnosed with cancer, you're, you're not gonna kind of get a one size fits all approach, and you're, and you're gonna wanna see results and levels. And I think, um, that likely will, like, bolster someone's confidence, even in their improvements, and being able to, again, see measurable results that aren't just based on their self-report.
[00:20:25] DR. MOHAMMED MILAD: Absolutely. And it would give you guys, the psychiatrists and the psychologists, an organ-
[00:20:29] DR. THEA GALLAGHER: Mm-hmm.
[00:20:29] DR. MOHAMMED MILAD: ... because, right, [laughs] psychiatry is the only s- branch of medicine without an organ, right?
[00:20:35] DR. THEA GALLAGHER: [laughs]
[00:20:35] DR. MOHAMMED MILAD: It's where, where, where our emotions coming from.
[00:20:37] DR. THEA GALLAGHER: Right.
[00:20:38] DR. MOHAMMED MILAD: Um, they, they don't know. It's, uh, you know-
[00:20:40] DR. THEA GALLAGHER: Yeah. Time for our objective data.
[00:20:41] DR. MOHAMMED MILAD: ... neurology has, neurology has to share.
[00:20:42] DR. THEA GALLAGHER: [laughs] Yeah. Right.
[00:20:43] DR. MOHAMMED MILAD: Yes.
[00:20:43] DR. THEA GALLAGHER: No. Um, so just to go a little bit into meditation, and I don't know if you have this data yet, but do you have a sense of how meditation is working to kind of change the brain?
[00:20:56] DR. MOHAMMED MILAD: Yeah. We, we... So this is, the, the current trial that we're running with Dr. Simon is, is obviously ongoing and it's... I don't have any data to speak to that. But we have been doing some prior work on with, uh, s- a collaborator at MGH, Sara Lazar, uh, and others. And, uh, there are... You know, it's, it's a big field in neuroscience. We're looking at how meditation might impact the brain. And it does so in a number of different ways. Some of these data I'm, I'm talking about have been published, and so it's somewhat, but also somewhat by others.
Uh, Richard Davidson's another name in, in, um, in Wisconsin, Madison, Wisconsin, that basically... The way we have data showing the way it works is that it causes or induces structural changes in your brain. It makes some parts of your brain bigger, thicker, uh, which is sort of, you know, crazy to think that it's possible, but it is actually. It does happen.
And particularly, brain areas like the hippocampus and some areas in the parietal lobe that change, and those areas are important in memory-
[00:22:09] DR. THEA GALLAGHER: Hm.
[00:22:10] DR. MOHAMMED MILAD: ... and important in attention, and also some sensory brain areas. So, there's a, a change in the structure that is, uh, associated with ch- with meditations or people that, that meditate, and also change in function and functional connectivity. Basically, how brain, how brain areas are, are wiring together. And people who meditate tend to have sort of better communication between nodes in the brain that are-
[00:22:36] DR. THEA GALLAGHER: Hm.
[00:22:36] DR. MOHAMMED MILAD: ... important in attention and in sensory processing and in, in memory. What that suggests is that it, you know, what meditation is supposed to do is it makes you aware of the present moment, of yourself, of your surroundings. And the, the data so far suggests that, that there's support for that, that th- it changes brain areas both structurally and functionally so that they are better able to communicate with one another.
[00:23:08] DR. THEA GALLAGHER: And so, in doing so, the goal is that... Do you need to practice this kind of for ongoing in order to have these changes be long-lasting, or do you think that the changes might happen and then it carries with them, like, for the long-term?
[00:23:23] DR. MOHAMMED MILAD: Well yeah. It's ch- you know, practice is essential. It's sort of like you're, you're practicing to be a better, uh, basketball player or a, or, um, football player, or, or... You need to practice. So, uh, the way the brain works is, in, you know, it causes neuroplasticity, that that have to happen, and there are changes in connections. And the structural changes and the functional changes don't just happen overnight. So it just takes some time for the brain to change those things, and not only change, but to make those changes permanent. And the way that happens is you have to basically go through that meditation practice, and, and homeworks and so on for that to, again, to be maintained in the brain.
[00:24:06] DR. THEA GALLAGHER: Mm-hmm.
[00:24:07] DR. MOHAMMED MILAD: And that, then you're able to utilize that not just in your meditation, but across different modalities of your life, different aspects of your life.
[00:24:16] DR. THEA GALLAGHER: Mm-hmm. Yeah. And I think it, it's s- it's something that many therapists would suggest to patients, but again, having some more measurable data on how it works and that there are these changes that happen, again, can bolster the treatment moving forward.
[00:24:31] DR. MOHAMMED MILAD: Absolutely. Yeah. N- this idea that, you know, again, I hear it a lot from, from when I talked to people, that, you know, there's something about neuroscience, but then there's something about psychology that they're different, and I, I always get confused by that 'cause I don't know psychology, where is psychology, you know. It, it has to be coming from an action potential.
[00:24:51] DR. THEA GALLAGHER: Mm-hmm.
[00:24:52] DR. MOHAMMED MILAD: Otherwise, I don't know where would that be coming from.
[00:24:54] DR. THEA GALLAGHER: And so for people that are listening, you know, psychiatrists, uh, and psychologists, therapists who are listening, from your work, what is a takeaway that you would like people to focus on, in, you know, kind of, in their clinical work? From everything, I don't know, y- from these studies that you're working on, but maybe studies in the past or things that you know about the brain, um, it sounds like helping people to realize, okay, the brain's plastic, ch- real changes can be made. Anything else that you think, again, someone can take with them today and have incorporated into their clinical work?
[00:25:27] DR. MOHAMMED MILAD: I, I think, at least the way I see it here, in, in how, how psychiatry is being practiced at NYU and, and how it's, how it's being taught in the residency programs is that th- I, I feel that clinicians are becoming more and more aware of what neuroscience is doing, and there's more dialogue between psychiatry and neuroscience-
[00:25:51] DR. THEA GALLAGHER: Hm.
[00:25:51] DR. MOHAMMED MILAD: ... and psychology and neuroscience. And I think that dialogue is very important in learning about each other's language, if you will, and I'm better understanding, for example, what is PTSD and what is anxiety, because I was trained as a neuroscientist. I don't, I didn't learn about any of these things. And psychiatry and psychology in the past, I g- my, you know, from my understanding, um, had m- m- minimal training in neuroscience-
[00:26:19] DR. THEA GALLAGHER: Mm-hmm.
[00:26:19] DR. MOHAMMED MILAD: ... and neuromodulations and things like that. And I think the takeaway for, you know, my, my fellow clinicians, you know, my wife is a psychiatrist, and so we, we talk a lot about these things, is that when we talk, we better understand each other, and I think that better understanding between the two is gonna ultimately help the patient-
[00:26:37] DR. THEA GALLAGHER: Mm-hmm.
[00:26:38] DR. MOHAMMED MILAD: ... because your improved understanding of not just your feeling, your training as a clinician, whether you're a psychologist or a psychiatrist, and all of the inpatient and outpatient, uh, amazing work that is done th- that you acquire, but I think some better understanding of neuroscience can also help you help your patients-
[00:26:59] DR. THEA GALLAGHER: Mm-hmm.
[00:26:59] DR. MOHAMMED MILAD: ... in that you can maybe... There's more of the psycho education to teach and tell your, your patients that what you're doing isn't just talk therapy. It's, it's-
[00:27:08] DR. THEA GALLAGHER: Hm.
[00:27:08] DR. MOHAMMED MILAD: ... talk therapy that impacts their brain.
[00:27:11] DR. THEA GALLAGHER: Mm-hmm.
[00:27:11] DR. MOHAMMED MILAD: And you can, you can say that, and you can say that with confidence, you can say that with knowledge, you can say that with, you know, with a base-
[00:27:20] DR. THEA GALLAGHER: Mm-hmm.
[00:27:21] DR. MOHAMMED MILAD: ... a f- you know, a, a neuroscience base. And these are the brain areas, and that's how they talk, and that's how, when we do this therapy over time, this is what it's going to do to your brain.
[00:27:30] DR. THEA GALLAGHER: Mm-hmm.
[00:27:30] DR. MOHAMMED MILAD: And so, I think that's something that I see d- done here, and I think there's more to be done as well to just help us b- all better educate one another and communicate with one another so that we can ultimately impact the patient.
[00:27:47] DR. THEA GALLAGHER: Mm-hmm.
[00:27:48] DR. MOHAMMED MILAD: And help the patient.
[00:27:49] DR. THEA GALLAGHER: Yeah. And, and kind of more synergy there, and it sounds more of a both and approach, rather than an either or, you know, being less siloed and more collaborative in how we understand and how we approach.
[00:28:03] DR. MOHAMMED MILAD: Absolutely.
[00:28:03] DR. THEA GALLAGHER: Yeah. And I, I did wanna go into, just briefly I guess, can you explain to us a little bit about TMS and your work with TMS and, and fear, and what your understanding there?
[00:28:15] DR. MOHAMMED MILAD: Yes. So, y- you know, I mentioned action potentials, of how just the, the brain is just a bunch of neurons that talk to each other and I, and so, more than 20 years ago now, I d- did these experiments with rats in which I recorded from a brain area, prefrontal region, when the rat is learning not to fear and found s- increase in brain activation. And the higher the increase in this activation in this brain area, the less fear that animal expressed, or less threat responses the animal expressed.
You know, we got excited about that. And my mentor, Greg Kork, said, "Hm, what if we tried to manipulate the behavior of the animal by putting electrodes deep in that same area and deliver an artificial stimulation to that brain region. Would the animal's behavior change?" And he said, "Okay, let's try it." So we did that, and we artificially implanted a safety memory in the animal's brain, and we conditioned the animals. The animals were afraid. They were showing threat, threat responses, conditioned threat responses. Then we delivered these micro-stimulation, very, very brief stimulations, artificially.
I turned the switch on, put the electrodes in there, turned the switch on, and the animal wasn't showing fear. Wasn't showing these threat responses.
[00:29:34] DR. THEA GALLAGHER: Hm.
[00:29:34] DR. MOHAMMED MILAD: So we got really excited with the idea that if you do some stimulation in the brain, if you artificially manipulate neural activation, you can actually impact behavior. Now, that's a crazy thing that some people might not like or might not feel comfortable with, but that's the reality, that if you put devices on someone's hand or if you put deep brain stimulation in, in patients, and that's already been done and a lot of work has been done on this, uh, DBS and, and so on, you can change human behavior.
And so, our objective for the TMS, and I don't wanna go into, into that territory, but our objective with the TMS is, if we identify the brain areas and the brain circuits that are critical to inhibit fear, can we put an electrode on the surface? Can we put this coil, TMS coil, on the surface and turn the stimulator on, when you see that blue light, for example, that I told you about earlier?
[00:30:38] DR. THEA GALLAGHER: Mm-hmm.
[00:30:39] DR. MOHAMMED MILAD: That I conditioned you. You see blue light, you're like, uh oh, shock is coming. Well, can I turn the stimulator on and hit a specific target at a specific time, target in your brain? And can I be... Would I be able to manipulate or change your expression, your conditioned responses to that? And we actually did that study a few years ago and showed that, in a small sample of participants, that that is in fact possible.
[00:31:09] DR. THEA GALLAGHER: Hm.
[00:31:10] DR. MOHAMMED MILAD: And so, now we're, we're trying to do this at a much larger scale, and we're trying to fine tune the stimulation parameters and the location of the stimulation across different targets in the brain to see if we can... This is from a mechanistic point of view.
[00:31:28] DR. THEA GALLAGHER: Mm-hmm.
[00:31:28] DR. MOHAMMED MILAD: To see if we can modulate brain responses to stimulate that have been conditioned.
[00:31:35] DR. THEA GALLAGHER: Hm.
[00:31:36] DR. MOHAMMED MILAD: With exogenous or, you know, with the TMS. And how we can manipulate not only the circuits and how they interact, but how they also, how we can potentially manipulate behavioral expressions, [inaudible 00:31:52] expressions of those conditioned responses in humans. And the objective is that we would use this as a, a form of therapeutic intervention, for, for example, PTSD patients.
[00:32:04] DR. THEA GALLAGHER: Mm-hmm. It seems like the timing is really... The timing and the specificity is really important. So as you look down the pipeline, how... Like, getting this research into, you know, the hands of people who could do something about it, you know, we know that there's like a pretty big lag between, you know, research to practice.
Um, it sounds like there should be though some collaboration across providers, 'cause there is like, it seems like there is some specificity to what you're doing, uh, both with timing and, and a focus.
[00:32:35] DR. MOHAMMED MILAD: Yes. So example, if you, if you think about... Absolutely right, because, you know, TMS is, is used for, for treatment of depression. It's FDA approved, and it's also now being used for PTSD treatment.
[00:32:47] DR. THEA GALLAGHER: Mm-hmm.
[00:32:47] DR. MOHAMMED MILAD: And but the way it's done is you put the coil at some particular location in the l- left prefrontal cortex, and, and you turn the stimulator on, and you know, for a certain amount of time. Uh, and you do that repeatedly for X number of days, and then that's it. It's done. And it's effective. It's, it's, it's, it's useful and, and a lot of patients get better, which is wonderful.
But can we do better? And instead of having it on for a long time and, and like with PEs, uh, can we reduce the sessions and can we make it very, very specific? You know, can we help people with specific phobias, for example? Spiders or snakes or heights-
[00:33:28] DR. THEA GALLAGHER: Mm-hmm.
[00:33:28] DR. MOHAMMED MILAD: ... or things like that so that we, we don't just turn on the stimulator while they're just looking at the white wall or, or thinking about their grandmother. Y- It's basically, you show them the stimuli that are causing the, the discomfort, the anxiety, and things like that, and you deliver the stimulation at that time, and so that you make it more precise, you make it mechanistic, and you... It's targeted.
And also, better location of where we're gonna be delivering those stimulations, and potentially also maybe reducing any unwanted effects or side effects or things like that. N- Th- that's the, that's the idea. That's the future, um, is to try to have these TMS sessions be more precise timing wise, and also location wise.
[00:34:18] DR. THEA GALLAGHER: Mm-hmm. Yeah. And it s- it sounds like, again, getting into that personalized medicine approach, which will be better for both clinicians and patients. And the, the last kind of area I wanna get into a little bit is, how do these findings in the, the things that you're researching, how do they fit together, or maybe they don't yet, um, with research into psychedelic assisted psychotherapy for PTSD?
[00:34:45] DR. MOHAMMED MILAD: I don't know the answer to that yet. I'm not sure that there is an intersect at this point.
[00:34:50] DR. THEA GALLAGHER: Mm-hmm.
[00:34:50] DR. MOHAMMED MILAD: Uh, I think research in the psychedelic domain is just beginning.
[00:34:55] DR. THEA GALLAGHER: Mm-hmm.
[00:34:56] DR. MOHAMMED MILAD: I think that, in the end, what we will probably find is that it's just a different venue to impact the same circuits. So, I, I, you know, whether it's e- meditation or whether it's TMS or whether it's estrogen or psychedelics, I, you know, we have one set of brain areas, right?
[00:35:19] DR. THEA GALLAGHER: [laughs]
[00:35:19] DR. MOHAMMED MILAD: You know? We're not, we're not gonna... I know, discover a new, um, brain region behind your left ear. It, it's, we, we have what we have.
[00:35:29] DR. THEA GALLAGHER: Mm-hmm.
[00:35:29] DR. MOHAMMED MILAD: So I think it's just a different way. I, I think it's gonna be maybe different mechanisms that psychedelics are impacting, or having their, their impact. Um, there could be a broader impact at, um, different networks. I'm not so sure. I don't know. The answer is I don't know. But I think it's still, it, it's probably gonna... What we'll end up finding is, it's, it's a different way to modulate the same or similar circuits, but th- with different mechanisms.
[00:36:01] DR. THEA GALLAGHER: Yeah. Um, and I think it, in some ways, it's good that there, like you said, there is only, you know, the, the brain has boundaries, [laughs] so it's not endless in that part of the discovery. But I guess when you're thinking about, you know, in, in your career, is there kind of... Is your million dollar question kind of always like, why do we fear, and is that what you kind of are continuing to try to understand?
[00:36:24] DR. MOHAMMED MILAD: No. I, my, I like fear.
[00:36:27] DR. THEA GALLAGHER: Mm-hmm.
[00:36:27] DR. MOHAMMED MILAD: I don't know if I mentioned this at the beginning or not. [laughs]
[00:36:30] DR. THEA GALLAGHER: No.
[00:36:30] DR. MOHAMMED MILAD: I th- [laughs] I think fear is good. I mean, it's too much fear. It, it's a the continuum.
[00:36:35] DR. THEA GALLAGHER: Hm.
[00:36:35] DR. MOHAMMED MILAD: Yeah. I, I think of it as, um, in a spectrum of like colors of lights. I, I think fear is okay. Um, and fear is useful for us.
[00:36:46] DR. THEA GALLAGHER: Mm-hmm.
[00:36:46] DR. MOHAMMED MILAD: If you're not afraid you're crossing the street at, you know, Park Ave., you're, you're, you'll die or you'll get hurt.
[00:36:51] DR. THEA GALLAGHER: Mm-hmm.
[00:36:51] DR. MOHAMMED MILAD: And I think fear is important. I think that too much fear, we're unable to regulate it or contextualize it, you know, there's no, there's no reason to fear a snake when it's behind a thick glass-
[00:37:02] DR. THEA GALLAGHER: Hm.
[00:37:02] DR. MOHAMMED MILAD: ... in, in the Bronx Zoo.
[00:37:03] DR. THEA GALLAGHER: Mm-hmm.
[00:37:03] DR. MOHAMMED MILAD: But you better run if you're [laughs] hiking in Colorado-
[00:37:06] DR. THEA GALLAGHER: Mm-hmm.
[00:37:07] DR. MOHAMMED MILAD: ... and, or somewhere and you see a snake coming after you, you go.
[00:37:10] DR. THEA GALLAGHER: Mm-hmm.
[00:37:11] DR. MOHAMMED MILAD: You know? Like no. I don't wanna be afraid of snakes. No. You'll, you'll, you'll die. So, I think maybe the million-dollar question for me is, why do we differ in, in how we regulate fear? I, I'm interested in, in individual differences in our abilities to control fear and what happens when we're unable to regulate it.
[00:37:37] DR. THEA GALLAGHER: Hm.
[00:37:37] DR. MOHAMMED MILAD: That's what I'm interested in.
[00:37:38] DR. THEA GALLAGHER: Mm-hmm.
[00:37:39] DR. MOHAMMED MILAD: That's what I, I'm continuously curious about.
[00:37:42] DR. THEA GALLAGHER: Yeah. And if, um, I don't know if you have any suggestions, but for, you know, again, many of us as clinicians, you know, utilize meditation in the work that we're doing and personally, are there certain resources for meditation that you like over others, or that you found in your research, um, are more effective than others?
[00:38:02] DR. MOHAMMED MILAD: So I don't meditate. [laughs]
[00:38:05] DR. THEA GALLAGHER: [laughs]
[00:38:06] DR. MOHAMMED MILAD: I don't. I am not... I, I, I can't meditate. I tried.
[00:38:09] DR. THEA GALLAGHER: [laughs]
[00:38:10] DR. MOHAMMED MILAD: Um, I fly. So I, I think that the, the key thing is to engage your sensory processes in one way or another, and I think one of the aspects of meditation is just refocusing and reshifting your attention.
[00:38:24] DR. THEA GALLAGHER: Hm.
[00:38:25] DR. MOHAMMED MILAD: And so, in terms of resources, I don't know r- the resources because I don't meditate.
[00:38:28] DR. THEA GALLAGHER: Right. [laughs]
[00:38:29] DR. MOHAMMED MILAD: Um, but I, when I, when I, when I get tense or anxious, I, I fly for fun.
[00:38:35] DR. THEA GALLAGHER: Mm-hmm.
[00:38:36] DR. MOHAMMED MILAD: Actually, going to fly makes me relaxed.
[00:38:39] DR. THEA GALLAGHER: Hm.
[00:38:39] DR. MOHAMMED MILAD: And that may be crazy to say-
[00:38:41] DR. THEA GALLAGHER: Mm-hmm.
[00:38:41] DR. MOHAMMED MILAD: ... or hear, or people understand that, but to me, it just disconnects me from everything else.
[00:38:46] DR. THEA GALLAGHER: Mm-hmm.
[00:38:46] DR. MOHAMMED MILAD: When I'm up in the plane and I'm talking to tower and I'm, I'm, I'm controlling the [inaudible 00:38:51] power and writing down and changing s- frequencies on the radio-
[00:38:54] DR. THEA GALLAGHER: Mm-hmm.
[00:38:55] DR. MOHAMMED MILAD: ... I, you know, if I'm anxious about anything outside or if anything is bothering me, I don't think about that because I can't.
[00:39:03] DR. THEA GALLAGHER: Mm-hmm.
[00:39:04] DR. MOHAMMED MILAD: Um, because I'm forced to focus on the present moment, and the present moment is flying the plane.
[00:39:08] DR. THEA GALLAGHER: Yeah.
[00:39:09] DR. MOHAMMED MILAD: And to me, that's meditation.
[00:39:11] DR. THEA GALLAGHER: Mm-hmm.
[00:39:12] DR. MOHAMMED MILAD: It's just a different form.
[00:39:14] DR. THEA GALLAGHER: Yeah. Yeah. But it's the, it's a different form, and yet it sounds like some of the core ingredients of being able to be fully present in one place and focused on, again, what is happening in the here and now, which could be, you know, maybe some interesting future research in understanding what is a, what is a meditative space for, um, an individual.
[00:39:34] DR. MOHAMMED MILAD: Yeah. I think, I really think there's a, there's a key element of the, an interrupt signal, if you will.
[00:39:38] DR. THEA GALLAGHER: Hm.
[00:39:39] DR. MOHAMMED MILAD: That you c- if you're continually, continuously perseverating onto your thoughts of anxiety and fear and so on, if there's a way in which you're able to interrupt that-
[00:39:48] DR. THEA GALLAGHER: Mm-hmm.
[00:39:49] DR. MOHAMMED MILAD: ... and meditation's a form, and for me, flying is, is my form. And I- then it breaks that cycle.
[00:39:55] DR. THEA GALLAGHER: Mm-hmm. Mm-hmm.
[00:39:56] DR. MOHAMMED MILAD: And then when, you know, if I'm really upset or something, I just go fly, and when I come down, I just feel really exhausted.
[00:40:02] DR. THEA GALLAGHER: Hm.
[00:40:03] DR. MOHAMMED MILAD: And a- again, it's, it's a- almost like going through that state of meditation, and I think maybe that's another aspect that we haven't really been paying attention to, is all these different ways, whether it's therapeutics or things like that, is just trying to give the patient a power to find a way to put a stop sign, you know, and then, and then say, "Okay, anxious feelings and, you know, perseverative thoughts, stop."
[00:40:30] DR. THEA GALLAGHER: Mm-hmm.
[00:40:30] DR. MOHAMMED MILAD: And if there's a way you're able to do that, then that gives you an ability to control.
[00:40:35] DR. THEA GALLAGHER: Mm-hmm.
[00:40:36] DR. MOHAMMED MILAD: And if you're able to control, then some anxiety and fear and so on will subside in my opinion.
[00:40:42] DR. THEA GALLAGHER: Mm-hmm. Yeah.
[00:40:42] DR. MOHAMMED MILAD: I'm not a clinician, so-
[00:40:44] DR. THEA GALLAGHER: Yeah.
[00:40:44] DR. MOHAMMED MILAD: ... just make sure I'm, I'm a basic neuroscientist.
[00:40:47] DR. THEA GALLAGHER: Yeah. But I, like, again, I think we're coming back to this point of it's not a one size fits all, um. I did a, a media story recently on how they found a correlation between, you know, managing anxiety and birdwatching, and [laughs] uh, I, I bet that's not for everyone. But as we're talking about it, kind of being focused, being meditative in the sense that it brings you to the moment, you're able to like interrupt-
[00:41:07] DR. MOHAMMED MILAD: Right.
[00:41:07] DR. THEA GALLAGHER: ... that cycle and be engaged with what's in front of you, like you said, helping patients maybe to figure out what that is for them from trial and error, and then ultimately from, you know, further study of what's happening in the brain will be really powerful for our field moving forward.
[00:41:23] DR. MOHAMMED MILAD: Absolutely.
[00:41:25] DR. THEA GALLAGHER: Well, thank you so much for being with us, Dr. Milad, and we'll definitely have you on in the future.
[00:41:30] DR. MOHAMMED MILAD: Look forward to it. Thank you.
[00:41:32] DR. THEA GALLAGHER: Thanks so much again, Dr. Milad, for that conversation. If you enjoyed this episode, be sure to rate and subscribe to NYU Langone Insights on Psychiatry on your podcast app. On the next episode, I'll be speaking with Dr. Naomi Simon about her research into using yoga and mindfulness to address anxiety disorders. I hope you'll join us for that. From the Department of Psychiatry at NYU Langone, I'm Dr. Thea Gallagher. See you next time.