Dr. Casey Halpern: Biology & Treatments for Compulsive Eating & Behaviors

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.880 | I'm Andrew Huberman,

00:00:10.320 | and I'm a professor of neurobiology and ophthalmology

00:00:13.220 | at Stanford School of Medicine.

00:00:15.040 | Today, my guest is Dr. Casey Halpern.

00:00:17.640 | Dr. Halpern is the chief of neurosurgery

00:00:19.640 | at the University of Pennsylvania School of Medicine.

00:00:22.580 | His laboratory focuses on bulimia, binge eating disorder,

00:00:26.560 | and other forms of obsessive compulsive behaviors.

00:00:29.500 | Normally, when we hear about eating disorders

00:00:31.380 | or obsessive compulsive disorders of other kinds,

00:00:33.960 | the conversation quickly migrates

00:00:35.460 | to pharmacologic interventions and serotonin or dopamine

00:00:39.480 | or talk therapy interventions,

00:00:41.160 | many of which can be effective.

00:00:43.300 | The Halpern Laboratory, however,

00:00:44.680 | takes an entirely different approach.

00:00:46.440 | While they embrace pharmacologic and behavioral

00:00:48.600 | and talk therapy interventions,

00:00:50.120 | their main focus is the development and application

00:00:53.120 | of engineered devices to go directly into the brain

00:00:56.000 | and stimulate the neurons, the nerve cells,

00:00:58.200 | that generate compulsions,

00:00:59.920 | that cause people to want to eat more

00:01:02.520 | even when their stomach is full.

00:01:04.720 | In other words, they do brain surgery of various kinds,

00:01:07.960 | sometimes removing small bits of brain,

00:01:09.780 | sometimes stimulating small bits of brain

00:01:12.020 | with electrical current,

00:01:13.140 | and even stimulating the brain through the intact skull,

00:01:16.220 | that is, without having to drill down beneath the skull

00:01:18.520 | in order to alleviate and indeed sometimes cure

00:01:21.240 | these conditions.

00:01:22.160 | Today's discussion with Dr. Halpern

00:01:23.580 | was an absolutely fascinating one for me

00:01:25.900 | because it represents the leading edge

00:01:27.980 | of what's happening in modification of brain circuits

00:01:30.640 | and the treatment of neurologic and psychiatric disease.

00:01:33.820 | For instance, they just recently published a paper

00:01:36.360 | in "Nature Medicine,"

00:01:37.600 | one of the premier journals out there,

00:01:40.120 | entitled "Pilot Study of Responsive Nucleus Accumbens

00:01:43.120 | "Deep Brain Stimulation for Loss of Control Eating."

00:01:45.920 | The nucleus accumbens is an area of our brains

00:01:48.780 | that we all have, in fact, we have two of them,

00:01:50.520 | one on each side of the brain,

00:01:52.180 | that is intimately involved in the release of dopamine

00:01:55.480 | for particular motivated behaviors.

00:01:57.480 | And while most often we think about dopamine

00:01:59.080 | for the release of behaviors that we want to engage in,

00:02:01.720 | in this context, they are using stimulation

00:02:04.820 | and control of neuronal activity in nucleus accumbens

00:02:07.720 | to control loss of control eating,

00:02:10.160 | something that when people suffer from it,

00:02:11.960 | despite knowing that they shouldn't eat,

00:02:13.720 | despite not even wanting to eat,

00:02:15.180 | they find themselves eating.

00:02:16.680 | So again, this represents really the leading edge

00:02:19.120 | of where neuroscience is going,

00:02:20.760 | and it certainly is going to be an area of neuroscience

00:02:22.700 | that's going to expand in the years to come.

00:02:24.600 | And Dr. Halpern and the members of his laboratory

00:02:27.320 | are among a very small group of scientists in the world

00:02:30.280 | that are using the types of approaches

00:02:31.640 | that I described a minute ago,

00:02:33.080 | and that you're going to hear more about in today's episode

00:02:35.320 | in order to resolve some of the most difficult

00:02:37.540 | and debilitating human conditions.

00:02:39.560 | During today's discussion, you will also learn

00:02:41.480 | about the use of deep brain stimulation and other approaches

00:02:44.440 | for the treatment of movement disorders,

00:02:46.480 | such as essential tremor, Parkinson's disease,

00:02:49.120 | and various types of dystonias,

00:02:50.840 | which are challenges in generating

00:02:52.640 | particular types of movement.

00:02:54.240 | So whether or not you or somebody that you know

00:02:56.600 | suffers from an eating disorder,

00:02:58.140 | from obsessive compulsive disorder,

00:02:59.920 | or from a movement disorder,

00:03:01.480 | today's episode is sure to teach you

00:03:03.400 | not only about what's happening in those arenas,

00:03:05.880 | but also in the arenas of neuroscience generally.

00:03:08.720 | In fact, I would say today's episode

00:03:10.160 | is especially important for anyone

00:03:11.640 | that wants to understand how the brain works

00:03:14.280 | and what the future of brain modification

00:03:16.780 | really looks like for all of us.

00:03:19.120 | Before we begin, I'd like to emphasize that this podcast

00:03:21.860 | is separate from my teaching and research roles at Stanford.

00:03:24.640 | It is, however, part of my desire and effort

00:03:26.920 | to bring zero cost to consumer information about science

00:03:29.520 | and science-related tools to the general public.

00:03:32.360 | In keeping with that theme,

00:03:33.420 | I'd like to thank the sponsors of today's podcast.

00:03:36.200 | Our first sponsor is Roca.

00:03:38.200 | Roca makes eyeglasses and sunglasses

00:03:40.240 | that are of the absolute highest quality.

00:03:42.200 | The company was founded by two All-American swimmers

00:03:44.280 | from Stanford, and everything about Roca eyeglasses

00:03:46.880 | and sunglasses were created with performance in mind.

00:03:50.560 | I've spent a lifetime working on the biology

00:03:52.480 | of the visual system, and I can tell you

00:03:53.720 | that your visual system has to contend

00:03:55.260 | with a number of very important challenges

00:03:57.200 | in order for you to be able to see clearly.

00:03:59.180 | For instance, when you go from a sunny area

00:04:01.140 | to a more shaded area and then back out again.

00:04:03.120 | It's a very complex process.

00:04:04.720 | Roca eyeglasses and sunglasses were built,

00:04:07.380 | that is engineered, with that sort of biology in mind.

00:04:10.320 | And as a consequence, no matter where you are wearing them

00:04:13.140 | and where you happen to be,

00:04:14.200 | you always see through them with crystal clarity.

00:04:16.440 | The aesthetic of Roca eyeglasses and sunglasses

00:04:18.600 | is also worth mentioning.

00:04:19.960 | Unlike a lot of performance eyeglasses out there,

00:04:22.200 | which only come in the kind of cyborg variety,

00:04:25.080 | Roca eyeglasses and sunglasses come in those varieties,

00:04:27.280 | but they also come in varieties

00:04:28.760 | that you would feel very comfortable wearing out to dinner

00:04:30.800 | or to work or to school, really anywhere that you go.

00:04:33.540 | If you'd like to try Roca eyeglasses,

00:04:35.120 | you can go to Roca, that's R-O-K-A.com,

00:04:37.680 | and enter the code Huberman to save 20% off

00:04:40.360 | on your first order.

00:04:41.200 | Again, that's Roca, R-O-K-A.com,

00:04:43.480 | and enter the code Huberman at checkout.

00:04:45.840 | Today's episode is also brought to us by Eight Sleep.

00:04:48.440 | Eight Sleep makes mattress covers

00:04:49.800 | with cooling, heating, and sleep tracking ability.

00:04:52.400 | I've talked many times before on this podcast

00:04:54.760 | about the close relationship between temperature

00:04:56.980 | and your ability to stay asleep and emerge from sleep.

00:05:00.040 | The way Eight Sleep mattress covers work

00:05:01.600 | is that they allow you to program the temperature

00:05:03.640 | of your mattress so that you can fall asleep quickly,

00:05:07.320 | get into deep sleep, stay in deep sleep,

00:05:09.480 | and emerge from that sleep feeling especially rested

00:05:12.220 | by dropping the temperature of that surface

00:05:14.320 | by one to three degrees at the beginning of the night,

00:05:16.640 | dropping it a little bit further into the night,

00:05:18.520 | and then raising the temperature towards morning

00:05:20.280 | because waking up requires

00:05:21.280 | that one to three degree re-increase in body temperature.

00:05:24.600 | I've been sleeping on an Eight Sleep mattress cover

00:05:26.440 | for the last six months or so now,

00:05:28.200 | and I can assert that it is the absolute biggest game changer

00:05:32.640 | in the quality and duration of my sleep.

00:05:34.460 | In fact, I don't really like traveling as much as I used to

00:05:36.940 | because the Eight Sleep doesn't go with me

00:05:39.060 | and they don't seem to have them yet in Airbnbs and hotels.

00:05:41.480 | So this is also a call to action.

00:05:42.760 | Airbnbs and hotels, please put Eight Sleep mattresses

00:05:46.120 | on your beds and I'll be more apt to stay in those hotels

00:05:49.600 | and Airbnbs.

00:05:51.020 | With that said,

00:05:51.860 | if you'd like to try an Eight Sleep mattress cover,

00:05:53.720 | you can go to eightsleep.com/huberman,

00:05:56.480 | check out the pod three cover to save $150 at checkout.

00:05:59.700 | Again, that's eightsleep.com/huberman.

00:06:02.700 | And please note that Eight Sleep currently ships

00:06:04.320 | in the USA, Canada, UK,

00:06:06.280 | select countries in the EU and Australia.

00:06:08.520 | Again, eightsleep.com/huberman to save $150 at checkout.

00:06:12.620 | Today's episode is also brought to us by Inside Tracker.

00:06:15.460 | Inside Tracker is a personalized nutrition platform

00:06:17.780 | that analyzes data from your blood and DNA

00:06:20.360 | to help you better understand your body

00:06:21.880 | and help you reach your health goals.

00:06:23.760 | Now I've long been a believer

00:06:24.940 | in getting regular blood work done

00:06:26.300 | for the simple reason that many of the factors

00:06:28.760 | that impact your immediate and long-term health

00:06:31.000 | can only be assessed with a quality blood test.

00:06:33.420 | One of the major issues with the various blood tests

00:06:35.340 | out there is that you get information back

00:06:37.480 | about lipids and hormones and metabolic factors, et cetera,

00:06:40.960 | but you don't know what to do with that information.

00:06:43.120 | With Inside Tracker, they make knowing what to do

00:06:45.080 | with the information you get

00:06:46.080 | about your biological health extremely easy.

00:06:48.880 | They have this very easy to use dashboard,

00:06:51.200 | and that dashboard tells you, for instance,

00:06:53.240 | what to change in your nutrition,

00:06:54.860 | what supplements you may want or may not want to take,

00:06:58.000 | as well as other behavioral and other types of interventions

00:07:00.340 | that can allow you to move those numbers

00:07:02.240 | related to metabolic, hormone, and other factors

00:07:04.880 | into the precise range that's optimal

00:07:06.640 | for your immediate and long-term health.

00:07:08.540 | If you'd like to try Inside Tracker,

00:07:09.920 | you can go to insidetracker.com/huberman

00:07:12.800 | to get 20% off any of Inside Tracker's plans.

00:07:15.240 | Again, that's insidetracker.com/huberman to get 20% off.

00:07:19.600 | On many episodes of the Huberman Lab Podcast,

00:07:21.660 | we talk about supplements.

00:07:23.200 | While supplements aren't necessary for everybody,

00:07:25.320 | many people derive tremendous benefit from them,

00:07:27.840 | things like enhancing sleep and the depth of sleep,

00:07:30.480 | or for enhancing focus and cognitive ability,

00:07:33.200 | or for enhancing energy or adjusting hormone levels

00:07:36.500 | to optimal range for you.

00:07:38.060 | The Huberman Lab Podcast is now partnered

00:07:39.800 | with Momentous Supplements.

00:07:41.160 | We partner with Momentous for a number of important reasons.

00:07:43.820 | First of all, the quality of their ingredients

00:07:46.260 | is exceptional, it's really second to none.

00:07:48.540 | Second of all, they ship internationally,

00:07:50.320 | and that was important to us

00:07:51.400 | because a number of you reside outside of the United States.

00:07:54.120 | Third, we've worked with Momentous very closely

00:07:56.660 | to develop single ingredient formulations.

00:07:59.080 | Now, this turns out to be very important

00:08:01.000 | because if you're going to take supplements,

00:08:03.200 | you want to know what's working for you and what isn't.

00:08:05.600 | And of course, you want to optimize the cost efficiency

00:08:08.780 | and the biological efficiency of those supplements.

00:08:11.840 | To find the supplements we discuss

00:08:13.160 | on the Huberman Lab Podcast,

00:08:14.380 | you can go to Live Momentous, spelled O-U-S,

00:08:17.000 | livemomentous.com/huberman.

00:08:19.340 | And I should just mention that the library

00:08:20.960 | of those supplements is constantly expanding.

00:08:23.140 | Again, that's livemomentous.com/huberman.

00:08:26.220 | And now for my discussion with Dr. Casey Halpern.

00:08:29.400 | Casey, I should say Dr. Halpern for those listening, welcome.

00:08:34.220 | - Thank you, great to be here.

00:08:35.280 | - Yeah, it's been a long time coming.

00:08:37.580 | We were colleagues at Stanford.

00:08:39.740 | And then recently you moved, of course,

00:08:41.600 | to University of Pennsylvania,

00:08:43.120 | also an incredible institution.

00:08:44.760 | We're sorry to lose you.

00:08:46.520 | - It was bittersweet for me too.

00:08:47.720 | - Stanford's loss is UPenn's gain.

00:08:49.920 | But let's talk about your work, past and present.

00:08:54.480 | As I've told the listeners already, you're a neurosurgeon,

00:08:59.080 | which I consider the astronauts of neuroscience

00:09:01.640 | because you're in somewhat uncharted territory

00:09:04.520 | or very uncharted territory.

00:09:05.840 | And yet precision is everything, right?

00:09:08.760 | The margins of error are very, very small.

00:09:12.320 | So for those that aren't familiar with the differences

00:09:14.800 | between neurosurgery, neurology, psychiatry,

00:09:17.760 | you just educate us a bit.

00:09:19.720 | What does a neurosurgeon do?

00:09:21.760 | And what does the fact that you're a neurosurgeon

00:09:26.080 | do for your view of the brain?

00:09:27.820 | How do you think about and conceptualize the brain?

00:09:30.800 | - Yeah, the scope of neurosurgery is quite broad.

00:09:34.480 | When I was in medical school, I was drawn to neurosurgery

00:09:37.320 | because of a procedure known as deep brain stimulation.

00:09:40.620 | When I was at Penn as a college student,

00:09:42.960 | I actually watched my first deep brain stimulation surgery

00:09:45.800 | performed by Gordon Baltuck,

00:09:47.000 | who to date is one of my career mentors.

00:09:50.300 | Deep brain stimulation is one surgery

00:09:53.480 | that neurosurgeons offer,

00:09:55.000 | but it's actually sort of a very small minority

00:09:58.960 | of what neurosurgery does.

00:10:03.240 | You know, we take out brain tumors,

00:10:04.760 | we clip aneurysms in the brain,

00:10:06.820 | we take care of patients

00:10:09.200 | that have had traumatic brain injury,

00:10:11.080 | concussion, spine surgeries,

00:10:14.000 | 90% of what neurosurgeons do around the country,

00:10:17.440 | you know, taking care of herniated discs and lumbar fusions.

00:10:21.020 | So the scope is the entire central nervous system,

00:10:26.020 | including the peripheral nervous system,

00:10:27.960 | we take care of patients with carpal tunnel syndrome

00:10:30.000 | and nerve disorders.

00:10:32.200 | Now over the course of the past two decades or so,

00:10:35.220 | there's been a mission in the field to sub-specialize.

00:10:39.300 | And so historically neurosurgeons

00:10:42.040 | did everything in that domain,

00:10:44.040 | but now we sub-specialize

00:10:46.160 | and I'm lucky to be at Penn Medicine

00:10:48.540 | where we can focus on one of these areas.

00:10:53.540 | So I'm chief of stereotactic functional neurosurgery.

00:10:58.220 | All I do is deep brain stimulation surgery

00:11:00.800 | and a compliment to that is focus ultrasound

00:11:02.880 | or transcranial focus ultrasound,

00:11:05.140 | which is a non-invasive way to do an ablation in the brain,

00:11:08.480 | recently FDA approved,

00:11:10.160 | and it's FDA approved for tremor at the moment.

00:11:12.560 | These two procedures are for me, my everyday,

00:11:18.480 | but still the minority of what neurosurgeons have to offer.

00:11:23.140 | The majority of neurosurgery in my mind

00:11:25.760 | is a bit more structural than it is physiology

00:11:30.520 | or deeply rooted in how the brain functions.

00:11:35.080 | When we take out a brain tumor,

00:11:36.560 | we have to find a safe trajectory to get to the brain tumor

00:11:40.920 | and then we remove it

00:11:42.280 | and we help the patient recover in the ICU.

00:11:45.200 | Similar to a brain aneurysm,

00:11:46.640 | often we don't have to go into the brain

00:11:48.120 | to clip a brain aneurysm,

00:11:49.160 | but we go around the brain or under the brain to get there.

00:11:52.740 | And in my mind, those surgeries are a bit more structural.

00:11:56.440 | Deep brain stimulation, the surgery that I do routinely,

00:12:00.120 | is a procedure where,

00:12:02.720 | yes, there is structure involved, of course.

00:12:05.120 | We have to place a very thin wire that's insulated

00:12:09.540 | deep into a part of the brain

00:12:11.960 | that's involved in Parkinson's disease, for example.

00:12:15.000 | But that's actually not the therapy.

00:12:18.120 | The therapy is delivering electrical stimulation

00:12:21.560 | through the tip of that wire, or one of the tips,

00:12:24.640 | as there actually are multiple contacts

00:12:26.500 | at the bottom of the wire, they're very small.

00:12:29.560 | But that's all done out of the operating room.

00:12:32.920 | This stimulation wire is connected to a battery pack

00:12:36.720 | or a pulse generator that's kind of like a pacemaker.

00:12:39.560 | And so we deliver this therapy and I always tell patients,

00:12:42.720 | it's a bit more like I have to implant a tool

00:12:46.720 | to deliver you a medication,

00:12:48.920 | but that medication is gonna be in the form of electricity

00:12:51.720 | and it's gonna be delivered

00:12:52.600 | into a very small region of the brain.

00:12:55.000 | And it's that procedure that's inspired me

00:12:57.140 | to not just become a neurosurgeon,

00:12:59.040 | but has really defined the focus

00:13:02.600 | of my research laboratory as well.

00:13:04.300 | - Maybe by way of anecdote,

00:13:08.880 | you could tell us one of the more outrageous or surprising,

00:13:13.880 | or who knows, delightful and thrilling things

00:13:17.460 | about the brain that you've observed

00:13:19.640 | as a consequence of stimulating different brain areas.

00:13:22.520 | In textbooks, we always hear about the kind of dark stuff,

00:13:26.920 | stimulate one brain area, somebody goes into a rage,

00:13:29.400 | stimulate another brain area,

00:13:31.080 | person starts laughing uncontrollably.

00:13:33.680 | First of all, given that some of the information,

00:13:36.920 | and let's hope not much,

00:13:37.760 | but some of the information in textbooks is incorrect,

00:13:40.540 | are those sorts of statements true?

00:13:41.900 | Can one observe those in the clinic?

00:13:43.740 | And what are some of the more interesting

00:13:47.180 | and I don't necessarily mean entertaining,

00:13:49.280 | but surprising things that you've seen

00:13:51.460 | when you've poked around in the brain,

00:13:53.880 | deliberately, of course.

00:13:55.040 | And what have you seen?

00:13:57.420 | What have you heard?

00:13:58.920 | - I have to say, I am amazed by these effects every day.

00:14:03.160 | Yeah, I'm very privileged to be able to interact

00:14:05.480 | with the human brain in this way.

00:14:06.720 | It's always with the goal of trying to provide somebody

00:14:10.800 | with a meaningful therapy.

00:14:11.960 | But when we deliver electrical stimulation,

00:14:14.200 | these electrodes, while they might be sitting

00:14:17.920 | in a very small region of the brain,

00:14:19.500 | there are regions within a few millimeters

00:14:22.440 | of where these electrodes are

00:14:23.520 | that if stimulated could cause a temporary,

00:14:26.320 | very brief side effect,

00:14:28.160 | a moment of laughter, like you said,

00:14:29.760 | or a moment of panic.

00:14:31.200 | And of course we can just shut that electrode off.

00:14:33.720 | But often these side effects could be therapeutic.

00:14:37.240 | And actually that's how we have discovered ways

00:14:39.480 | to use deep brain stimulation,

00:14:42.160 | not just for movement disorders like Parkinson's disease,

00:14:44.320 | but for example, patients with Parkinson's disease

00:14:47.000 | that have a psychiatric comorbidity like depression

00:14:52.740 | or obsessive compulsive disorder.

00:14:54.860 | A lot of these patients are highly compulsive and impulsive.

00:14:59.120 | Sometimes these problems actually melt away

00:15:03.580 | and we're trying to help their tremor,

00:15:05.140 | but the patients also tell us that their gambling issue

00:15:07.820 | has gotten better or their mood has improved.

00:15:10.240 | And why is that?

00:15:11.080 | Well, there's probably more than one reason.

00:15:13.760 | You can help somebody's mood

00:15:15.000 | by making their tremor go away, of course,

00:15:17.140 | but we see laughter in the clinic sometimes.

00:15:19.980 | And why is that?

00:15:20.820 | And that's because we're stimulating parts of the brain

00:15:23.560 | that are not just involved in these motor circuits,

00:15:25.960 | but they're also involved in what we call a limbic circuit

00:15:29.080 | or part of the brain involved in emotion.

00:15:31.080 | And if we learn how to modulate those areas therapeutically,

00:15:35.820 | step-by-step, we can actually develop these therapies

00:15:38.320 | for other indications like depression.

00:15:40.800 | I would say the most impressive and consistent effect

00:15:44.000 | we have when we have a patient with tremor,

00:15:46.160 | who has been tremoring for the past 20 years,

00:15:48.120 | if we can deliver stimulation through that electrode

00:15:50.320 | in the clinic, we have immediate relief of tremor.

00:15:52.880 | And that is the effect that inspired me

00:15:56.000 | to be a neurosurgeon when I was in college.

00:15:57.920 | I've never really wanted to do anything else

00:16:00.360 | except help develop that type of therapeutic

00:16:03.660 | for another kind of symptom.

00:16:06.380 | I'm very interested in obesity and related eating disorders,

00:16:09.920 | compulsive behavior, the urge to have something

00:16:14.600 | that might be delicious, but dangerous, or unhealthy,

00:16:18.880 | or a drug, or a compulsion like we see in OCD,

00:16:23.880 | or obsessive compulsive disorder.

00:16:26.000 | Interestingly, like we see tremor melt away

00:16:30.240 | when we deliver electricity to a certain part of the brain,

00:16:33.960 | we can see these psychiatric, more psychiatric problems,

00:16:37.120 | they're not all psychiatric disorders,

00:16:38.560 | but let's say disorders of the brain,

00:16:42.140 | we can see symptoms of those disorders also improve

00:16:44.600 | and often immediately, just like we do with tremor.

00:16:47.320 | So I see it all the time.

00:16:49.700 | To pick out one would be a challenge

00:16:53.060 | because for me, this is my everyday.

00:16:55.760 | - The speed of the relief that you described for tremor

00:16:59.360 | is really incredible.

00:17:02.460 | Just thinking about drug therapies

00:17:03.940 | and there too, there are side effects,

00:17:05.920 | but there are still a lot of mysteries

00:17:08.880 | as to, for instance, why SSRIs even work when they work.

00:17:13.120 | - Yes, the timing is always a challenge.

00:17:16.640 | Timing, dosage, yes, absolutely.

00:17:18.760 | I'd love to learn more from you about OCD.

00:17:23.300 | I have several reasons for asking this.

00:17:26.140 | First of all, I'm a somewhat obsessive person.

00:17:28.400 | I tend to be very narrowly focused,

00:17:30.960 | although I confess it's not a step function.

00:17:33.160 | It takes me some time to turn off the chatter,

00:17:34.920 | but once I'm into a thought train or a mode of being

00:17:38.800 | and thinking and work,

00:17:40.600 | it's very hard for me to exit that mode.

00:17:42.920 | It's like a deep trench.

00:17:45.000 | Adaptive in some circumstances, less adaptive.

00:17:47.520 | In others, as you know.

00:17:48.640 | The other is that when I was a kid,

00:17:50.280 | I had a little bit of a grunting tic.

00:17:52.600 | I used to, I had this intense, intense desire

00:17:56.620 | to clear my throat to the point where my dad said,

00:18:01.640 | you need to stop that.

00:18:02.600 | He used to squeeze my hand every time I do it.

00:18:04.220 | And I used to hide in the backseat of the car

00:18:05.920 | or in the closet to do it

00:18:07.000 | because it provided so much relief.

00:18:09.460 | And then it eventually passed.

00:18:10.800 | I wasn't medicated.

00:18:11.760 | They never did anything about it.

00:18:13.400 | Every once in a while now,

00:18:14.760 | if I'm very fatigued, if I've been working a lot,

00:18:18.040 | I notice it starts to come back.

00:18:20.000 | I'll do this like kind of grunting.

00:18:21.680 | And so it's been sort of like a pet neurological symptom

00:18:25.880 | for me that reminds me that these circuits exist

00:18:29.280 | in all of us and that sometimes they go haywire

00:18:32.920 | and sometimes they just have subtle, you know,

00:18:35.440 | overexcitation or something of that sort.

00:18:37.840 | And then the third reason is that I get thousands

00:18:40.600 | of questions about OCD.

00:18:42.160 | - Could you perhaps just tell us what is OCD?

00:18:44.940 | - Sure.

00:18:46.120 | - What are some brain areas involved?

00:18:48.160 | What are the current range of treatments?

00:18:50.720 | And what's the difference between someone who is obsessive

00:18:54.800 | and somebody who has true OCD?

00:18:57.840 | - So a brief disclosure, as a neurosurgeon,

00:19:00.600 | I do take care of patients

00:19:01.720 | with severe obsessive compulsive disorder.

00:19:04.280 | But my perspective on OCD may be a little bit different

00:19:08.660 | than a psychiatrist who lives and breathes OCD

00:19:12.200 | and sees patients every single day with OCD.

00:19:15.020 | I probably take care of three to five patients a year

00:19:19.160 | with deep brain stimulation

00:19:20.200 | for obsessive compulsive disorder.

00:19:22.280 | So I don't see these patients as routinely,

00:19:24.120 | but my laboratory is geared as a researcher.

00:19:27.760 | I'm very focused on trying to improve outcomes

00:19:31.120 | of deep brain stimulation for OCD.

00:19:33.760 | So I do feel I have expertise and a perspective to share,

00:19:37.780 | but just a brief disclosure.

00:19:39.440 | I do feel that as a neurosurgeon,

00:19:46.040 | I am obligated to better understand

00:19:49.600 | where the obsessions in the brain come from

00:19:51.840 | and how we can interrupt them to stop the compulsion

00:19:54.560 | that's associated with the obsession,

00:19:57.240 | sort of the intrinsic most feature of OCD,

00:20:01.160 | better than we're actually doing it.

00:20:04.440 | For example, if we were to offer a patient

00:20:07.440 | with tremor deep brain stimulation surgery,

00:20:10.160 | of course there's some risk to the procedure,

00:20:12.000 | but the outcome is so consistent and positive

00:20:15.760 | that many patients are willing to take on that risk.

00:20:18.400 | For obsessive compulsive disorder,

00:20:22.600 | the surgery risk is about the same.

00:20:26.840 | However, the benefit is not quite as robust.

00:20:30.520 | And so a lot of patients and their referring psychiatrists

00:20:33.060 | are reluctant to refer these patients to us,

00:20:35.740 | and it's completely understandable.

00:20:38.160 | I've been leading an endeavor

00:20:40.540 | with a number of collaborators around the country

00:20:42.280 | to try to better understand these circuits in the brain,

00:20:47.280 | study them in humans, both invasively and non-invasively.

00:20:51.540 | That would be with an electrode-based surgery,

00:20:54.180 | sort of like we do in epilepsy

00:20:55.320 | to understand where seizures come from.

00:20:57.140 | We wanna understand better where obsessions come from,

00:20:59.220 | but we're also working with imaging experts and geneticists

00:21:01.800 | to understand OCD at a broader level as well.

00:21:05.460 | I consider OCD to be a spectrum disorder in a way.

00:21:11.960 | And I apologize to those who might feel

00:21:16.140 | that I'm using that term incorrectly.

00:21:17.960 | I'm using it in a way to describe patients

00:21:22.260 | that have obsessions and even some related compulsions

00:21:25.060 | might not meet criteria for OCD.

00:21:28.080 | It may be something, Andrew, that you have.

00:21:30.500 | And as a neurosurgeon, I'm really obsessive about safety

00:21:34.060 | and compulsive about my surgical procedures.

00:21:36.560 | So I think that some aspect of OCD,

00:21:40.020 | which we often joke about, but we should consider seriously,

00:21:43.100 | 'cause people do suffer from this,

00:21:45.560 | some aspect of it helps us.

00:21:47.780 | There are famous CEOs that probably have some level of OCD,

00:21:52.780 | surgeons and scientists alike.

00:21:56.500 | So perhaps if it can be controlled, it's an asset.

00:22:00.540 | But if it goes awry and is uncontrollable,

00:22:05.060 | then it becomes obsessive compulsive disorder.

00:22:07.980 | And I tend to see the patients that are the most severe,

00:22:11.620 | so they have failed medication.

00:22:13.460 | And there are multiple medications

00:22:15.180 | that are worth trying for OCD.

00:22:16.540 | Some can actually be very helpful.

00:22:18.540 | - Which neurotransmitter systems do they tend to poke at?

00:22:21.380 | - Well, SSRIs are sort of the first line for OCD,

00:22:25.480 | but also tricyclics can be helpful.

00:22:27.180 | So this is still the serotonin system.

00:22:29.060 | But as we know, the serotonin system interacts

00:22:32.000 | with the neurodegenergic system and the dopamine system.

00:22:36.140 | So it's hard to be specific to one of these things.

00:22:41.140 | And I think that's also why it's hard for us to predict

00:22:44.580 | how these medications are going to work

00:22:46.740 | for these kinds of patients.

00:22:48.140 | But tricyclics and SSRIs can be very helpful

00:22:51.220 | and are definitely first line.

00:22:52.980 | And there's others, exposure response prevention

00:22:56.880 | is probably the most effective option,

00:22:59.740 | which is kind of like cognitive behavioral therapy,

00:23:01.640 | but these are different and offered by psychologists.

00:23:04.200 | And this is a whole field.

00:23:06.120 | And there's a field, or I should say,

00:23:08.820 | a whole clinic at my institution focused,

00:23:12.680 | it was started by Ed Nafoa at Penn,

00:23:16.280 | who this is what they do for these patients,

00:23:20.180 | is offer these types of cognitive therapies,

00:23:22.980 | exposure to the stressor and to try to get patients

00:23:26.620 | to habituate to whatever it is that stresses them

00:23:28.940 | and causes these compulsions

00:23:31.620 | to help these patients live in every day and function.

00:23:35.140 | These are all fabulously helpful therapies

00:23:39.000 | for a variety of patients,

00:23:40.340 | but there's still about 30% of patients

00:23:42.640 | that still suffer from OCD.

00:23:44.340 | And some of them have severe OCD.

00:23:46.220 | Sometimes it's moderate to severe.

00:23:48.020 | And those are the patients that I'm really motivated

00:23:50.700 | to try to help.

00:23:52.420 | Our therapies for those patients right now,

00:23:54.420 | I would say are worth pursuing, but not optimal.

00:23:59.240 | And so it's one of those things

00:24:00.940 | that we have to balance as a researcher,

00:24:02.420 | because when you see patients like this,

00:24:04.520 | you wanna do everything you can to help them.

00:24:05.780 | And I think it's important to educate patients

00:24:08.060 | on the risks and benefits of them.

00:24:09.640 | This is deep brain stimulation surgery,

00:24:11.560 | but also capsulotomy,

00:24:12.780 | which is more of an ablation approach,

00:24:14.840 | a little bit like deep brain stimulation,

00:24:16.520 | but rather than delivering stimulation through an electrode,

00:24:19.080 | you can actually heat the tissue and even destroy it.

00:24:22.200 | Some would say this part of the brain

00:24:23.660 | is very safe to destroy.

00:24:25.140 | It's kind of like an appendix.

00:24:26.640 | Others would say it's safer to modulate.

00:24:29.480 | I have seen patients do very well with these ablations.

00:24:33.000 | And so, you asked me earlier

00:24:35.240 | what I find so amazing about the brain,

00:24:37.160 | these effects that we can have.

00:24:38.420 | Sometimes the lack of effect is what's so amazing.

00:24:41.680 | You can actually traverse parts of the brain

00:24:44.900 | without having any adverse effects on patients' function,

00:24:48.200 | at least that you can test,

00:24:50.440 | but you can also destroy small parts of the brain.

00:24:52.440 | We're talking three or four millimeters in size.

00:24:54.680 | These little ablations can be really helpful for patients,

00:24:57.440 | but have no obvious side effects that we can tell,

00:25:00.160 | perhaps after a short recovery from surgery.

00:25:03.080 | But nonetheless, despite how safe they might be,

00:25:05.800 | these surgical procedures still are surgical procedures,

00:25:08.080 | and patients are hesitant to proceed,

00:25:10.640 | especially when they know that their chance

00:25:12.320 | of a transformative effect is quite low.

00:25:14.840 | We can generally achieve a responder rate of about 50%.

00:25:19.840 | And responders still have symptomatic OCD.

00:25:24.240 | So I'm really sort of inspired to really find a way

00:25:29.240 | to deliver these therapies in a more disease-specific

00:25:32.900 | or symptom-specific way.

00:25:34.720 | But we're years away probably from that therapy,

00:25:37.720 | since it's all part of a research study at the moment.

00:25:40.620 | - What brain areas should I think about

00:25:43.080 | when I think about OCD?

00:25:44.160 | Years ago, I remember opening a textbook,

00:25:46.640 | I think I was an undergraduate still,

00:25:48.480 | and work from Judith Rappaport

00:25:50.400 | at the National Institutes of Mental Health,

00:25:52.040 | this would be late '80s, early '90s,

00:25:54.120 | had done some neuroimaging, or maybe it was PET,

00:25:59.180 | or some other imaging technique,

00:26:02.040 | and had identified portions of the basal ganglia,

00:26:05.020 | caudate putatum-type structures in OCD,

00:26:09.200 | and maybe some differences in boys versus girls.

00:26:12.680 | So what brain areas?

00:26:14.040 | Are there sex differences in terms of OCD?

00:26:16.440 | And were one to come into your clinic

00:26:20.160 | for this sort of a work of ablations or stimulation,

00:26:25.160 | where would you first start to probe in the brain?

00:26:28.640 | - Yeah, this is a disorder of both cortex and the subcortex.

00:26:33.640 | The cortical control areas,

00:26:40.440 | areas that are involved in inhibitory control,

00:26:42.880 | we have found to not function properly in patients with OCD,

00:26:46.960 | so areas like the overall frontal cortex

00:26:49.120 | and the prefrontal cortex.

00:26:50.920 | If you image these areas,

00:26:52.520 | or study them even in a rodent model of OCD,

00:26:56.000 | which, quite honestly, these models,

00:26:58.000 | they model aspects of OCD, but OCD is a human condition.

00:27:01.920 | You can't really model this whole condition

00:27:04.640 | in a mouse or a rat,

00:27:06.080 | but perhaps you can model compulsive behavior in a rat, sure.

00:27:10.360 | - Pulling out their hair.

00:27:11.440 | - Yeah, exactly.

00:27:12.320 | You know, that's not necessarily obsessive compulsive

00:27:15.200 | disorder, but that is compulsive behavior.

00:27:17.120 | And perhaps if you can ameliorate that in a rat,

00:27:19.640 | that might be helpful for a patient with OCD,

00:27:21.440 | but we have to approach animal modeling of OCD thoughtfully.

00:27:25.920 | And most scientists do, I think.

00:27:28.400 | And when we study OCD in models or in humans with imaging,

00:27:32.800 | and we're trying to do it invasively with electrodes

00:27:35.880 | like we do in epilepsy patients,

00:27:38.000 | we find that areas in the cortex like the prefrontal

00:27:41.160 | and over-frontal cortex are not functioning

00:27:43.440 | the way they would in a non-OCD patient.

00:27:45.360 | They're often hyper-functioning,

00:27:48.400 | such that while you might say,

00:27:50.440 | well, they're hyper-functioning,

00:27:51.360 | so aren't these patients functioning better?

00:27:55.360 | - Hyper-focused.

00:27:56.200 | - Yeah, hyper-focused, exactly.

00:27:58.200 | No, I would say it's not so much an up or a down.

00:28:00.760 | It's more that they're just dysfunctional.

00:28:02.560 | And we need to find a way

00:28:04.120 | to try to restore normal function to these areas.

00:28:06.960 | It's not so much directional, really.

00:28:09.120 | We tend to oversimplify brain function

00:28:11.920 | by thinking about it with directionality too much.

00:28:15.200 | Unfortunately, imaging studies sometimes demonstrate

00:28:17.120 | activation or hypoactivation,

00:28:20.160 | and that's where I think these kinds of things

00:28:21.960 | can be misconstrued.

00:28:23.320 | But what I would call the cortical areas of OCD

00:28:26.200 | is that they're dysregulated,

00:28:27.840 | and we need to find a way

00:28:28.720 | to try to normalize their function.

00:28:30.600 | So the frontal lobe is huge,

00:28:32.600 | but areas of the frontal lobe that are a bit more basal,

00:28:34.840 | like the OFC, or orbital frontal cortex,

00:28:36.800 | and the prefrontal cortex

00:28:38.240 | definitely consistently seem to be implicated

00:28:40.680 | in patients with OCD.

00:28:42.800 | And then there are projections to the subcortex.

00:28:44.800 | This is the basal ganglia, like you were saying.

00:28:46.960 | Caudate putamen, or the dorsal striatum,

00:28:49.120 | and these are interconnected with the ventral striatum.

00:28:51.040 | This is an area of the brain

00:28:51.880 | that I focus a lot of my energy in.

00:28:55.040 | This is the ventral striatum,

00:28:56.080 | which is not limited to,

00:28:57.560 | but includes the nucleus accumbens.

00:28:59.660 | This is an area of the brain

00:29:00.960 | that we know to be involved

00:29:03.120 | in gating reward-seeking behavior.

00:29:05.140 | When it's perturbed,

00:29:05.980 | it seems to gate compulsive behavior,

00:29:07.920 | meaning a rat will pursue a reward despite punishment,

00:29:10.860 | despite foot shock, for example,

00:29:12.860 | and that can be similar to an OCD patient.

00:29:15.780 | They will check their home for safety

00:29:19.400 | until 3 a.m. in the morning and not sleep that night.

00:29:21.980 | In a way, that is similar

00:29:23.960 | to a rat seeking out a food reward despite a foot shock,

00:29:28.420 | doing something because of the urge, but despite the risk.

00:29:32.220 | And perhaps there is some normal judgment there.

00:29:37.220 | We all have to take risks to function in everyday society.

00:29:42.180 | To be successful, we have to take a risk.

00:29:44.280 | To take care of patients with surgery,

00:29:46.840 | there's some risk there.

00:29:48.200 | We make a judgment call,

00:29:50.140 | and that's not a condition.

00:29:53.080 | That's just normal.

00:29:55.080 | But when our judgment consistently sort of puts us at risk,

00:30:00.560 | that's where we have something like OCD.

00:30:03.680 | But OCD is also, you know,

00:30:04.960 | it's one of many conditions

00:30:06.600 | that suffer from these kinds of problems.

00:30:08.100 | We tend to label them

00:30:09.640 | because they tend to present in a consistent way.

00:30:11.880 | So we have patients with OCD

00:30:13.320 | that have hyper-checking behavior

00:30:16.040 | or contamination behavior where if they feel contaminated,

00:30:20.840 | they will wash their hands for hours repeatedly,

00:30:23.080 | or if they drop their toothbrush on the floor,

00:30:25.080 | this will lead to a compulsive behavior

00:30:27.300 | of cleaning a toothbrush

00:30:28.760 | and brushing your teeth consistently.

00:30:30.400 | Very, very common symptoms that we see

00:30:32.480 | or signs that the patients report to us or that we observe.

00:30:35.660 | But, you know, patients with eating disorders,

00:30:39.880 | they tend to, if they have binging disorder,

00:30:42.600 | they'll overeat.

00:30:43.640 | If they have bulimia, they might purge

00:30:45.560 | despite the risk of these things.

00:30:47.400 | And so addiction is similar.

00:30:50.180 | We tend to drug seek if we're addicted.

00:30:52.940 | We'll pay off a dealer in order to get our fix

00:30:57.720 | despite the risk.

00:30:58.840 | And that type of urge, despite the risk,

00:31:01.680 | is something that I've always been really interested in.

00:31:03.780 | And it's a common denominator to all of these problems.

00:31:06.840 | And if you think about these problems,

00:31:08.240 | I mean, these are some of the most common conditions

00:31:10.520 | in our society today.

00:31:12.160 | - I'd like to take a quick break

00:31:13.560 | and acknowledge one of our sponsors, Athletic Greens.

00:31:16.600 | Athletic Greens, now called AG1,

00:31:19.060 | is a vitamin mineral probiotic drink

00:31:21.440 | that covers all of your foundational nutritional needs.

00:31:24.320 | I've been taking Athletic Greens since 2012,

00:31:27.000 | so I'm delighted that they're sponsoring the podcast.

00:31:29.200 | The reason I started taking Athletic Greens

00:31:30.800 | and the reason I still take Athletic Greens

00:31:32.860 | once or usually twice a day

00:31:34.840 | is that it gets me the probiotics

00:31:36.760 | that I need for gut health.

00:31:38.440 | Our gut is very important.

00:31:39.600 | It's populated by gut microbiota

00:31:42.100 | that communicate with the brain, the immune system,

00:31:43.860 | and basically all the biological systems of our body

00:31:46.260 | to strongly impact our immediate and long-term health.

00:31:49.900 | And those probiotics in Athletic Greens

00:31:51.760 | are optimal and vital for microbiota health.

00:31:55.600 | In addition, Athletic Greens contains

00:31:57.160 | a number of adaptogens, vitamins, and minerals

00:31:59.060 | that make sure that all of my foundational

00:32:00.940 | nutritional needs are met, and it tastes great.

00:32:04.400 | If you'd like to try Athletic Greens,

00:32:05.840 | you can go to athleticgreens.com/huberman,

00:32:09.240 | and they'll give you five free travel packs

00:32:11.220 | that make it really easy to mix up Athletic Greens

00:32:13.540 | while you're on the road, in the car, on the plane, et cetera,

00:32:16.120 | and they'll give you a year's supply of vitamin D3K2.

00:32:19.520 | Again, that's athleticgreens.com/huberman

00:32:22.200 | to get the five free travel packs

00:32:23.580 | and the year's supply of vitamin D3K2.

00:32:26.640 | - Yeah, I really appreciate that you're building

00:32:28.840 | this bridge from OCD to nucleus accumbens,

00:32:30.940 | which is, of course, associated with reward in various forms,

00:32:34.240 | and we'll get to that.

00:32:35.940 | I'll share a personal anecdote as a form of question.

00:32:40.940 | When I was in college and studying a lot,

00:32:44.600 | I relied on caffeine as a stimulant.

00:32:47.800 | I've never really been into drugs or alcohol.

00:32:49.540 | I've been lucky in that sense.

00:32:50.760 | I don't drink, and I care less if alcohol disappeared.

00:32:54.080 | Never really liked recreational drugs,

00:32:55.680 | so I was never drawn to them.

00:32:57.780 | However, when I was in college,

00:33:00.580 | at the time, there were these little epinephrine pills

00:33:04.220 | that were common in a lot of sports supplements.

00:33:07.640 | These were like pre-workout type things.

00:33:10.120 | Not unlike energy drinks now, which I completely avoid.

00:33:13.520 | And I had this experience of taking one of these

00:33:15.500 | and drinking some coffee,

00:33:16.620 | and of course, it gave me a lift in energy.

00:33:18.320 | These are very similar to amphetamine.

00:33:20.160 | They were legal over the counter at the time.

00:33:22.120 | They're now either banned or illegal.

00:33:24.400 | I do not recommend them.

00:33:26.040 | And I had a lot of energy,

00:33:27.280 | but what I noticed is that my grunting came back,

00:33:30.560 | and I had, I made one mistake.

00:33:33.220 | I still think of this as one mistake,

00:33:34.800 | which was I engaged in a superstitious behavior.

00:33:38.040 | I knocked on wood.

00:33:39.600 | And then somehow it felt very rewarding.

00:33:41.740 | Like it gave me some totally irrational,

00:33:44.400 | but internally rational sense of security around.

00:33:48.080 | I forget what I was knocking on wood about.

00:33:49.920 | And I found that I couldn't break

00:33:51.320 | that knock on wood compulsion.

00:33:52.760 | I felt I needed to knock on wood.

00:33:54.680 | And so then I started sneaking knock on woods,

00:33:56.520 | like in mid-exam and studying.

00:33:58.140 | And pretty soon I was knocking on wood often.

00:34:01.760 | I developed a superstition.

00:34:03.760 | And so I'm curious about the role of superstition

00:34:05.760 | and compulsion and the crossover there.

00:34:07.760 | It makes sense logically to me,

00:34:09.000 | but I was equally shocked to learn

00:34:11.580 | that when I stopped taking this stimulant,

00:34:14.320 | which I was quite happy to stop

00:34:16.880 | because it did make me feel too alert,

00:34:18.180 | couldn't sleep well, et cetera,

00:34:20.160 | that the superstition went away as well.

00:34:22.880 | And I'm guessing this has something to do

00:34:24.320 | with some of the reward circuitry,

00:34:27.380 | as it's called, related to stimulants.

00:34:30.460 | Again, I am not encouraging anyone to take stimulants,

00:34:34.780 | although healthy use of caffeine or safe use of caffeine

00:34:37.340 | might be the one universally accepted stimulant.

00:34:40.160 | It was really surprising to me how quickly this came on,

00:34:43.320 | how quickly it engaged my thinking and my behavior,

00:34:47.960 | the obsessions and the compulsions,

00:34:49.920 | and how quickly it turned off

00:34:52.100 | when I stopped taking this sports stimulant

00:34:55.120 | or whatever it was.

00:34:55.960 | I don't even remember.

00:34:56.780 | I think it was some form of epinephrine, ephedrine.

00:34:58.560 | - Sure.

00:34:59.400 | - It's not epinephrine, excuse me, I misspoke, ephedrine.

00:35:01.840 | Does what I described sound totally outside

00:35:06.220 | the bounds of logic or am I imagining it all?

00:35:11.220 | - No. - It did happen.

00:35:12.440 | I'm certain it happened.

00:35:13.400 | - Yeah, no, I don't think you're imagining it at all.

00:35:15.900 | You know, the grunting that you mentioned to me,

00:35:18.940 | first of all, I didn't comment,

00:35:20.900 | but that sort of, not to put a label on it,

00:35:23.900 | but it sounds like a tick,

00:35:25.300 | and ticks in young males, extremely common,

00:35:29.680 | and they do tend to go away.

00:35:31.100 | - Blinking ticks like this. - Exactly.

00:35:31.940 | - I have a good friend who,

00:35:33.300 | actually a famous neuroscientist,

00:35:34.700 | I won't mention who it is,

00:35:35.820 | who's worked very hard to suppress his blinking ticks,

00:35:39.060 | and when he gets fatigued, it comes back,

00:35:41.100 | and he's very high functioning in his personal life

00:35:44.300 | and his professional life.

00:35:45.740 | But when you're talking to him and he starts doing this,

00:35:47.700 | you kind of start wondering what's going on.

00:35:50.740 | - Yeah, and it's unfortunate,

00:35:52.420 | people with these problems,

00:35:53.740 | especially as they get more severe

00:35:55.020 | than you get Tourette syndrome,

00:35:57.200 | it's hard to function in our society.

00:35:59.580 | I have some friends that have Tourette,

00:36:01.420 | and I'll tell you, I'm just so inspired

00:36:03.200 | because they're so confident,

00:36:07.620 | and people obviously notice these problems,

00:36:10.540 | but they just live their life and they're very successful,

00:36:13.640 | and that's not typical.

00:36:16.200 | I have friends that I went to Penn with undergrad

00:36:18.700 | that had these kinds of problems,

00:36:19.860 | and I was always just so happy and inspired by them,

00:36:23.100 | but what's more typical is these problems

00:36:26.740 | cause people to lose their confidence

00:36:30.340 | and not pursue their profession as they may have done

00:36:35.340 | or things of that nature.

00:36:38.360 | So I think it's all related to the fact that we,

00:36:42.020 | our brains are very vulnerable,

00:36:43.480 | and to get back to your question about the stimulant,

00:36:46.540 | you know, I think your brain was very vulnerable to it.

00:36:49.380 | You know, you sort of may have had a predisposition to it.

00:36:53.060 | You mentioned that you're a little obsessive,

00:36:55.660 | and with the tick there, maybe you have this kind of,

00:36:58.260 | you know, on the mild side of the spectrum OCD,

00:37:01.940 | and I probably do as well, by the way,

00:37:03.720 | so I also have avoided drugs for that reason in my life.

00:37:07.620 | I'll drink a little bit of wine here and there,

00:37:09.100 | but that's about it,

00:37:13.380 | but I think most people don't avoid these things,

00:37:15.500 | and we see these problems in relation

00:37:17.540 | to not just taking a stimulant,

00:37:19.620 | but any kind of environmental exposure.

00:37:21.800 | Our own society causes so much stress,

00:37:25.180 | and that's why I think we have these human conditions.

00:37:27.460 | These are human conditions.

00:37:29.200 | We try to model them in animals,

00:37:31.180 | but most animals don't have these kinds of problems.

00:37:34.180 | I've heard that an animal like a monkey in the wild

00:37:38.780 | can have depression, a monkey's version of depression,

00:37:41.580 | but I don't think it's really typical or human depression,

00:37:44.980 | you know, and certainly it's not as prevalent

00:37:46.700 | as depression is in our human society.

00:37:48.260 | I think, you know, we haven't evolved to manage the stresses

00:37:51.640 | that are in this society that we currently have,

00:37:54.220 | and stimulants is probably one of them, you know,

00:37:56.220 | and I suspect you were probably a little bit vulnerable.

00:37:59.160 | It's possible the stimulant led to an overdrive

00:38:02.900 | of your prefrontal and orbital frontal cortex

00:38:04.900 | and even brought out a little OCD behavior

00:38:07.140 | related to this superstition that you had,

00:38:09.960 | so no, I believe that entirely,

00:38:12.360 | and I also think, you know, that's why things like OCD

00:38:15.520 | and other kinds of psychiatric disorders

00:38:17.280 | tend to present themselves in college

00:38:19.080 | when people leave their home and they're in school

00:38:22.540 | and they're stressed and they're getting exposed to things

00:38:25.580 | that they haven't been exposed to before

00:38:27.380 | outside of the home, and, you know,

00:38:29.980 | their brains aren't evolved and sophisticated enough yet

00:38:34.880 | to help them cope with these kinds of stresses

00:38:37.160 | and how it manifests is in these kinds of conditions,

00:38:40.140 | and I don't want to put a label on those conditions,

00:38:42.200 | but certainly it could be a psychiatric disorder,

00:38:43.740 | but it could also just be lots of anxiety.

00:38:45.900 | It could also be the kind of problems that you had as well.

00:38:49.380 | So, and I think the nucleus accumbens

00:38:51.940 | and the cortical areas that we've been discussing

00:38:54.260 | that sort of send projections to these areas

00:38:56.940 | are probably at least one of the main circuits

00:39:00.680 | involved in these kinds of things.

00:39:02.380 | - Well, I'm relieved it's no longer present,

00:39:05.060 | but I confess it, I always feel it close by.

00:39:08.400 | A long run helps.

00:39:09.940 | So, you know, being a slightly fatigued,

00:39:12.200 | not overly fatigued, but slightly fatigued

00:39:14.120 | seems to move out the kind of physical compulsion,

00:39:16.400 | but tried to channel it.

00:39:18.360 | Never taken any medication for it, and here I am,

00:39:20.980 | so I'm still going.

00:39:22.200 | I may call you for a referral at some point,

00:39:24.520 | but at this point I'm feeling okay.

00:39:27.220 | Let's talk about nucleus accumbens and reward circuitry

00:39:31.640 | and the relationship between OCD, reward, addiction,

00:39:36.640 | and to just give you a sense of where I'm headed with this

00:39:39.520 | is into the realm of food-related

00:39:42.220 | and eating-related behaviors and disorders,

00:39:45.640 | because I know you're doing some very important work there.

00:39:49.360 | What is nucleus accumbens?

00:39:50.940 | I know we all have one, or two,

00:39:53.020 | one on each side of the brain.

00:39:55.320 | What is it, what roles does it play

00:39:58.220 | in healthy brain behavior and in pathology?

00:40:01.740 | - Yeah, the nucleus accumbens is a part of the brain,

00:40:05.840 | part of our reward circuits,

00:40:07.800 | the hub of the reward circuits

00:40:09.240 | that I've always been most fascinated in.

00:40:12.120 | There are scientists around the world,

00:40:15.500 | some of the leading,

00:40:16.800 | arguably some of the leading scientists in the world,

00:40:19.200 | the father of addiction neuroscience, I call him,

00:40:22.000 | although he tells me I'm nuts, Rob Malenka,

00:40:24.320 | who has studied the nucleus accumbens

00:40:25.840 | since the beginning of his career

00:40:27.600 | and who I worked with when I was at Stanford.

00:40:30.480 | Fabulous scientist and mentor,

00:40:32.080 | taught me so much, taught the world so much.

00:40:34.920 | - Incredible person, scientist and physician as well.

00:40:38.600 | - Yes, MD, PhD, and brilliant in both ways,

00:40:42.360 | and very fatherly in a lot of ways

00:40:45.960 | in terms of teaching people how to do science

00:40:48.520 | and be good citizens as well.

00:40:50.700 | But the nucleus accumbens is an area

00:40:56.960 | that is also very complicated

00:40:58.560 | because it has a lot of functions.

00:41:01.300 | It interconnects with many parts of the brain.

00:41:05.380 | But there are some things about the nucleus accumbens

00:41:09.160 | that are very consistent.

00:41:10.480 | So when I started getting interested in reward

00:41:15.840 | and what I could do as a surgeon

00:41:18.160 | to try to improve how we manage rewards,

00:41:22.960 | and what I mean by that specifically is

00:41:25.040 | if you have an urge for a reward,

00:41:28.040 | that's a normal phenomenon.

00:41:29.960 | That's not something we're trying to stop.

00:41:31.940 | The issue is if you have an urge for a reward

00:41:34.760 | that either puts you or somebody else at risk,

00:41:37.040 | it's probably a reward we shouldn't have.

00:41:39.420 | I suppose you could say,

00:41:40.260 | well, it depends on the size of the reward

00:41:41.600 | and the size of the risk

00:41:42.560 | and how that fits into your societal norms.

00:41:44.980 | But for example, if you're obese

00:41:49.240 | and you have a doctor who is advising that you lose weight

00:41:53.880 | and try to control your eating habits,

00:41:57.160 | perhaps better food choices is an important way

00:42:00.760 | for you to be healthier.

00:42:01.760 | And not pursuing those better food choices,

00:42:04.160 | that's an urge that we probably need to treat.

00:42:06.940 | If you're a drug addict and you use heroin or opiate,

00:42:13.040 | considering the opiate crisis right now, or cocaine,

00:42:17.220 | which is untreatable at the moment,

00:42:21.400 | that cocaine might make you feel

00:42:26.320 | like you have some more energy that day

00:42:28.220 | to deal with your work,

00:42:29.560 | or that opiate might make you feel better

00:42:31.200 | 'cause life is stressful.

00:42:32.540 | But the risk of doing those things is really high,

00:42:35.760 | in fact, potentially lethal.

00:42:37.460 | So that's an urge that's treatable.

00:42:41.640 | If you have OCD and you can't sleep at night

00:42:46.640 | because you're so nervous that you didn't lock the door

00:42:48.760 | and you've checked 30 times,

00:42:50.440 | that's a reality for some people with severe OCD.

00:42:54.800 | That's an urge we gotta treat.

00:42:57.040 | Eating disorder's the same.

00:42:58.440 | Eating disorders and obesity are obviously linked

00:43:01.880 | because of the relationship of a patient with food,

00:43:04.780 | but they're also quite distinct.

00:43:06.320 | Not everybody with obesity has an eating disorder,

00:43:08.780 | and obviously not everybody

00:43:09.800 | with an eating disorder has obesity.

00:43:12.480 | I'm particularly interested in patients

00:43:14.440 | that have binge eating disorder as well as obesity

00:43:17.160 | because they're so heavily linked.

00:43:18.800 | Not everybody with binge eating disorder has obesity,

00:43:22.280 | but on average, most are overweight.

00:43:25.260 | We are doing a deep brain stimulation trial at Penn

00:43:28.320 | where we're trying to modulate the nucleus accumbens

00:43:31.200 | and understand it better in patients

00:43:32.740 | that have failed gastric bypass surgery,

00:43:34.480 | the most aggressive form of treatment for obesity.

00:43:38.840 | And we believe they failed gastric bypass surgery

00:43:41.760 | because of binge eating disorder,

00:43:43.560 | meaning they just can't control how much they eat.

00:43:45.600 | So their obesity is either related or even due to overeating,

00:43:49.600 | not some predisposition to that body habitus.

00:43:54.360 | You know, obesity is a phenotype, something that we can see.

00:43:57.240 | Not everybody is obese because of the same thing.

00:43:59.180 | So it's very important.

00:44:00.120 | I was taught this by a close mentor and friend, Tom Wadden,

00:44:03.400 | when he was the director of the obesity center at Penn

00:44:07.360 | or the Center for Weight and Eating Disorders.

00:44:09.880 | And he said to me, "You know, Casey,

00:44:12.480 | "be careful with obesity.

00:44:14.080 | "You're interested in addiction,

00:44:15.600 | "and I understand you're interested

00:44:17.160 | "in the addictive tendencies of certain patients

00:44:19.400 | "with obesity and their relationship with food."

00:44:24.400 | But not everybody with obesity has that problem.

00:44:26.840 | And in fact, it's probably present

00:44:28.880 | in about 20% of patients with obesity.

00:44:30.860 | But now taking a step back,

00:44:32.800 | 20% of patients with obesity is still a massive problem

00:44:35.500 | of epidemic proportions.

00:44:37.160 | And perhaps some of these patients

00:44:39.200 | have either some form of binge eating disorder,

00:44:41.760 | or I should say some degree of binge eating disorder,

00:44:44.560 | or at least loss of control eating,

00:44:46.560 | which is common to both.

00:44:48.880 | So that's a feature that I think eating disorder experts,

00:44:52.680 | obesity experts, neurosurgeons,

00:44:55.040 | obesity medicine experts would agree is common

00:45:00.760 | to eating disorders and obesity.

00:45:03.040 | And I also believe is common to addicts

00:45:05.480 | and perhaps patients with OCD

00:45:07.280 | is sort of a loss of control disorder.

00:45:10.340 | It's actually not a disorder known by like the DSM-5,

00:45:14.480 | some diagnostic manual,

00:45:16.140 | but a feature I should say of these conditions

00:45:18.760 | that's common.

00:45:19.640 | And that common denominator I believe can be restored,

00:45:24.640 | or at least this problem can be ameliorated

00:45:26.840 | or improved upon by a better understanding

00:45:30.000 | and a tailored treatment

00:45:32.300 | to the nucleus accumbens specifically.

00:45:34.200 | We have learned in mice that if you expose a mouse,

00:45:38.540 | now this is just a model,

00:45:39.960 | if you expose a mouse to high fat food,

00:45:42.780 | not food that they would normally eat,

00:45:44.320 | food that is like 60% fat, high fat, it's like butter.

00:45:48.520 | We've learned that if you expose them to food like that,

00:45:52.520 | within two weeks, their nucleus accumbens is not functioning

00:45:55.840 | like a mouse that was never exposed to that high fat food.

00:45:58.560 | There's aspects of it that are hyperactive, I could say,

00:46:01.880 | and there's aspects of it that are hypoactive

00:46:03.920 | or decreased activity.

00:46:05.840 | But either way, it's not functioning properly.

00:46:08.360 | And most likely that function

00:46:10.040 | is predisposing continued behavior.

00:46:12.920 | And then probably eventually leads to things like a habit

00:46:16.040 | that gets developed.

00:46:16.900 | And that's a whole nother area of these kinds of problems

00:46:19.440 | that is very complicated and poorly understood.

00:46:22.600 | But in any case, if we just focus on the behavior at hand,

00:46:26.960 | it seems that repeated exposure

00:46:29.000 | to something like high fat food, a drug of abuse,

00:46:32.520 | or any type of reward that is a really strong reward,

00:46:37.520 | in a way it can hijack normal functioning

00:46:40.720 | of the nucleus accumbens.

00:46:41.620 | So the goal of our invasive trial

00:46:44.680 | is to try to restore normal functioning

00:46:46.720 | to that nucleus accumbens.

00:46:48.900 | In mice, there seems to be a signal

00:46:51.160 | that predicts when they're going to lose control.

00:46:54.440 | And we can use that signal to deliver

00:46:56.720 | a sort of a real-time therapy

00:46:58.880 | in the form of deep brain stimulation,

00:47:00.260 | just a brief amount of stimulation.

00:47:02.280 | And that actually blocks the behavior.

00:47:04.480 | And what's interesting is over time,

00:47:05.620 | that signal actually decreases in frequency,

00:47:08.780 | which suggests some level of restoring normal function

00:47:12.560 | to that circuit in a mouse.

00:47:13.680 | And we're trying to do that now in a human trial.

00:47:16.560 | - Fascinating.

00:47:17.640 | Where is the stimulation provided?

00:47:19.320 | Because I would imagine that if one were

00:47:21.040 | to stimulate nucleus accumbens,

00:47:22.560 | you would see a reinforcement

00:47:26.800 | of whatever behavior coincided or preceded the stimulation.

00:47:30.420 | - So the stimulation, it's a brief delivery of stimulation,

00:47:35.160 | anywhere between five and 10 seconds,

00:47:37.320 | that is intended to just disrupt the perturbed signaling

00:47:42.320 | that's happening in the nucleus accumbens.

00:47:45.140 | There are disorders like depression, let's say,

00:47:49.100 | that I would describe as a bit more of a state disorder.

00:47:52.420 | And this is obviously oversimplified

00:47:54.740 | because we know that there's fluctuations

00:47:56.580 | in mood and depression as well.

00:47:57.800 | So don't let me oversimplify it too much.

00:48:00.460 | But for now, let's forgive the oversimplification.

00:48:05.160 | If we accept that depression is a state disorder,

00:48:07.680 | or maybe Parkinson's disease is a state disorder,

00:48:10.240 | recognizing that they do fluctuate,

00:48:12.000 | these types of problems most likely, but not definitely,

00:48:17.120 | most likely need a continuous therapy of some form,

00:48:20.280 | a therapy that's consistent,

00:48:22.480 | perhaps a therapy that fluctuates with the condition,

00:48:24.840 | but nevertheless still consistent.

00:48:26.480 | Binge eating disorder or OCD or addiction,

00:48:35.080 | and binging disorder in the context of obesity.

00:48:37.960 | A lot of these patients are functioning quite normally

00:48:39.920 | every single day.

00:48:40.760 | It's just that intermittently throughout the day,

00:48:43.000 | there's brief interruptions in their normal function,

00:48:45.820 | such that they have thoughts about food

00:48:47.500 | or the drug of abuse that they're really longing to have.

00:48:50.980 | And so we wanna deliver a episodic therapy

00:48:54.620 | delivered at the right time and only at the right time

00:48:59.260 | to try to interrupt the circuit aberration

00:49:04.260 | or the problem at hand

00:49:06.940 | that is gonna lead to that dangerous behavior

00:49:09.060 | and to kind of get the patient back on track

00:49:10.860 | to what they're doing.

00:49:11.960 | I don't necessarily think that it leads to a reinforcement.

00:49:18.580 | It's possible, we have to study that more,

00:49:21.540 | but rather the goal is to just disrupt

00:49:24.900 | perhaps what is kind of habitual

00:49:28.420 | or at least this kind of recurring problem that is happening.

00:49:33.100 | People that have binging disorder,

00:49:34.820 | at least at a severe level,

00:49:35.900 | they tend to binge about once a day,

00:49:37.980 | but they don't binge all day long, of course.

00:49:39.700 | They have a moment perhaps when they get home from work

00:49:42.460 | and they're stressed

00:49:43.740 | where they might have a bout of binge.

00:49:48.260 | - What constitutes a binge?

00:49:49.780 | And I also want to know,

00:49:52.100 | does binge eating disorder come on suddenly,

00:49:55.100 | meaning as an entire disorder?

00:49:57.820 | One day, people wake up,

00:49:59.560 | suddenly they have binging disorder,

00:50:00.940 | or is this a few too many buffets?

00:50:03.580 | And I'm being entirely serious here,

00:50:05.260 | you know, unlimited food and a circuit gets flipped

00:50:10.100 | or kind of starts moving into the high RPMs, so to speak.

00:50:13.860 | So how does it come on?

00:50:15.700 | And I'm actually surprised to hear that it's once a day.

00:50:20.320 | I would think just hearing binging disorder,

00:50:22.460 | I assumed it's like OCD,

00:50:23.700 | which it probably fluctuates across the day as well.

00:50:26.420 | But I would have thought anytime people around food,

00:50:29.100 | they just simply can't control their intake of food.

00:50:31.020 | - Yes.

00:50:31.980 | - So what does this look like

00:50:33.060 | in terms of the onset of the disorder?

00:50:35.340 | And then what do you think underlies this

00:50:37.440 | once a day type of phenomenon?

00:50:38.980 | That's pretty interesting.

00:50:40.140 | - Yeah, so severe binging disorder,

00:50:43.420 | these patients will binge about once a day.

00:50:45.540 | It could be a couple of times a day,

00:50:46.600 | but in general, it's not more than that.

00:50:48.300 | Moderate is about three to four times a week, for example.

00:50:51.140 | The reason I think that that seems surprising to you

00:50:56.300 | and if you think about it, it is surprising.

00:50:59.980 | But, and I agree with you,

00:51:02.220 | but the reason for that

00:51:03.500 | is actually just in the definitions of the word.

00:51:06.420 | And as a neurosurgeon in full disclosure, as I mentioned,

00:51:09.920 | I don't see these patients clinically.

00:51:12.020 | I see them for research trial purposes

00:51:14.500 | and I try to understand the literature

00:51:17.060 | around eating disorders.

00:51:18.180 | And I obviously collaborate

00:51:19.580 | with fabulous eating disorders in these problems

00:51:23.120 | that are highly innovative people.

00:51:25.840 | But the word binge is a definition.

00:51:29.240 | There's a definition to that word

00:51:30.800 | and you can't necessarily binge all day

00:51:34.640 | because our stomachs are not big enough.

00:51:36.640 | And so there's a limit to how much one can eat.

00:51:40.880 | And to meet criteria for a binge,

00:51:42.440 | you have to have a sense of loss of control.

00:51:45.600 | You have to eat an enormous amount of food

00:51:47.740 | in a brief period of time.

00:51:49.920 | And yes, generally that doesn't happen

00:51:52.120 | more than about once a day

00:51:53.800 | in a patient with severe binge eating disorder.

00:51:56.100 | However, they can lose control quite often.

00:52:00.480 | And in fact, perhaps even at every meal,

00:52:02.640 | they might meet criteria for a bout of loss of control

00:52:05.600 | where they, yes, they may have lost control,

00:52:07.280 | but they might not have eaten enough

00:52:09.360 | to constitute what we would define as a binge.

00:52:13.200 | And that would be,

00:52:14.800 | there's no specific number to that by the way.

00:52:16.920 | It's really just compared to their normal meal.

00:52:20.320 | Perhaps it's 50% of their daily calories

00:52:23.320 | in that one brief moment.

00:52:25.300 | So that's why I think it seems surprising

00:52:29.280 | that binges aren't happening more often than that.

00:52:32.360 | What I would say is if we replace the term binge

00:52:35.480 | with loss of control eating,

00:52:37.080 | loss of control eating could happen dozens of times a week.

00:52:40.700 | And in fact, the patients that we're studying,

00:52:43.560 | we've seen patients that lose control 20, 30 times a week.

00:52:47.240 | And that's probably the term you have in mind

00:52:49.400 | when you're surprised that it's just one time a day.

00:52:51.880 | And it's specifically related to the fact

00:52:53.340 | that these patients have to eat such a large amount of food

00:52:56.040 | in such a brief period of time.

00:52:58.480 | So it's hard to do that more than once a day.

00:53:00.200 | - I see.

00:53:01.040 | You mentioned that some preexisting anxiety

00:53:05.620 | might bias somebody to have a binge.

00:53:08.840 | I'm also fascinated by something I've observed before,

00:53:11.800 | which is when I was in college,

00:53:12.880 | my girlfriend had a roommate who we were aware was bulimic

00:53:17.040 | and would binge and then purge.

00:53:20.480 | And often when she ingested alcohol,

00:53:24.180 | that would lead to a binge.

00:53:25.480 | - Sure.

00:53:26.320 | - Which is kind of the opposite of anxiety

00:53:28.460 | when I think about alcohol as something

00:53:30.020 | that slightly reduces prefrontal activity,

00:53:32.960 | somewhat of a sedative

00:53:34.080 | or certainly a set of higher dosages.

00:53:36.680 | So this brings to something that you said,

00:53:39.860 | I'm just going to, I won't say it as eloquently

00:53:42.580 | as you did that.

00:53:43.440 | It seems like it's neither the case

00:53:45.560 | that anxiety leads to binging

00:53:48.040 | nor that hypo reduced activation of the forebrain

00:53:51.840 | and lower anxiety leads to binging.

00:53:54.120 | It's this dysregulation of circuitry

00:53:56.520 | that the seesaw could go either way

00:53:58.520 | and it can throw things off.

00:54:00.140 | It's off balance in both cases.

00:54:02.040 | - Yes.

00:54:02.880 | - And that seems to be, that seems to pose a problem.

00:54:08.240 | It seems like it's a particularly tricky problem

00:54:11.040 | and kind of explains to me in my nonclinical awareness

00:54:15.200 | why medication might be really hard to use

00:54:18.180 | as a way to treat this,

00:54:19.020 | but that being able to poke around in the brain

00:54:20.960 | and assay in real time, you know, how do you feel?

00:54:23.640 | Do you feel like binging now

00:54:24.620 | or do you feel further from the binge impulse?

00:54:28.500 | Is that what you do with these patients?

00:54:30.840 | Are they awake while you're stimulating the brain?

00:54:32.880 | 'Cause it's one thing to say,

00:54:33.780 | I stimulate a brain area and the binging goes away

00:54:36.400 | or partial relief or complete relief,

00:54:38.800 | but how do you know?

00:54:39.860 | Are they in there with a donut and you're tempting them?

00:54:44.100 | So how do you actually know if a bleeding of brain area

00:54:47.300 | is going to lead to a relief or exacerbation

00:54:50.760 | or no impact on this disorder?

00:54:54.260 | - Yeah, so there's a lot to unpack there.

00:54:57.840 | I'll try to go one step at a time.

00:54:59.480 | And if I miss something, please remind me.

00:55:00.320 | - No, and I tend to ask these three-part questions

00:55:02.960 | specifically of neurosurgeons

00:55:04.100 | because I like to challenge you guys.

00:55:06.140 | 'Cause again, you are the astronauts of neuroscience.

00:55:08.220 | Also, I'm just going to take a moment to poke at neurosurgeons

00:55:10.500 | 'cause I have a couple close friends who are neurosurgeons

00:55:13.660 | and I consider Casey a friend.

00:55:14.920 | I don't know if he considers me a friend,

00:55:16.080 | but I consider him a friend.

00:55:17.520 | I'm teasing there too, which is, first of all,

00:55:19.400 | they all have incredible hands, right?

00:55:21.700 | They have, I'm not, they all guard their hands

00:55:24.280 | with the kind of protection that you would guard,

00:55:28.960 | the tools of, the most important tools of your trade.

00:55:31.680 | So they're very careful with their hands.

00:55:33.040 | You're not going to see them doing heavy deadlifts.

00:55:35.500 | You're not because of the way that impacts the motor neurons.

00:55:39.060 | It's all about fine control.

00:55:40.940 | So if your neurosurgeon does heavy deadlifts,

00:55:42.840 | you might want to consider getting a different neurosurgeon.

00:55:45.740 | Hope I didn't put anyone out of work there.

00:55:47.220 | And then the other thing is that you all

00:55:52.220 | tend to be very calm people, at least on the exterior.

00:55:55.100 | We'll return to this later.

00:55:56.440 | But I do throw three or four questions out at once.

00:55:59.500 | So elevated autonomic arousal and alertness,

00:56:03.340 | as well as decreased autonomic arousal and alertness,

00:56:05.700 | both seem to be able to lead to binging.

00:56:07.500 | And then there's this question of how do you know

00:56:09.980 | whether or not to stimulate or to ablate

00:56:12.920 | or whether or not to leave a structure alone?

00:56:14.720 | In other words, what does one of these experiments

00:56:16.160 | look like in the laboratory?

00:56:17.280 | - Yeah, sort of a-

00:56:18.480 | - Clinic, excuse me.

00:56:19.380 | - Yeah, of course.

00:56:20.220 | Yeah, these are questions I think about all the time.

00:56:23.340 | And I do want to come back to the deadlifting comment,

00:56:29.160 | but regarding, and you referred to this earlier as well,

00:56:34.160 | and I don't know if I addressed it sufficiently either,

00:56:38.120 | is sort of like what comes first here

00:56:40.020 | or how does this develop?

00:56:41.400 | I think, first of all,

00:56:43.860 | I like to understand these kinds of problems

00:56:48.700 | in sort of the construct of what I consider to be

00:56:52.740 | a bit of a two-hit hypothesis.

00:56:54.700 | So you sort of need, like in the concussion literature,

00:56:57.620 | you need, the second hit can be devastating.

00:56:59.840 | So if you have a concussion, you wanna only return to play

00:57:02.880 | when your symptoms are gone and cleared by a physician.

00:57:07.800 | So in the context of eating disorders,

00:57:10.600 | or let's say binge eating disorder,

00:57:11.880 | and first of all, I didn't mention earlier,

00:57:13.500 | but this is the most common eating disorder,

00:57:15.280 | affects anywhere between three and 5% of the population.

00:57:18.000 | - Wow.

00:57:19.400 | - And is probably under-diagnosed in obesity, by the way.

00:57:23.200 | And if obesity affects 35% of our population,

00:57:25.920 | most likely binge eating disorder

00:57:27.160 | affects more than three to 5%,

00:57:28.880 | but that's the current literature estimate

00:57:32.560 | on the prevalence.

00:57:33.740 | So how do we develop binge eating disorder

00:57:37.120 | and is it related to this anxiety question?

00:57:39.440 | I think that there is a predisposition,

00:57:43.280 | that's the first hit.

00:57:44.340 | I actually think all humans have this predisposition,

00:57:48.080 | just some have it more than others.

00:57:50.000 | I don't think that we've evolved to live in a society

00:57:52.580 | where foods are so readily available

00:57:55.420 | and enormously delicious and have so much sugar

00:57:58.360 | and fat in them.

00:57:59.300 | Not that there's any particular problem

00:58:01.180 | with either of these macronutrients,

00:58:03.080 | it's just the excess of it and how they're refined

00:58:07.000 | that I think is the problem.

00:58:08.360 | There's high fructose corn syrup

00:58:11.480 | in almost everything we eat, it's in bread.

00:58:13.840 | I don't even know why it's in bread sometimes.

00:58:15.480 | It's just kind of crazy.

00:58:17.040 | So I don't think we're evolved to live in a society

00:58:21.280 | that has food that's so readily available like that,

00:58:25.880 | and cheap, by the way.

00:58:27.440 | In fact, the cheaper the foods are,

00:58:29.160 | sort of the more refined and palatable

00:58:32.480 | and I would argue, dangerous to eat.

00:58:34.400 | I think they change our reward circuits for the worse

00:58:37.040 | and put us at risk for wanting more.

00:58:39.920 | I tend to get a headache when I eat food like that

00:58:43.440 | and perhaps that's an evolutionary advantage

00:58:46.800 | because I don't want to eat those foods

00:58:48.400 | 'cause they actually do make me sick.

00:58:50.200 | So in a lot of ways, I kind of wish that headache

00:58:54.000 | on everybody because perhaps we wouldn't have

00:58:56.040 | all these problems or some of them would go away.

00:58:59.200 | So I think that's the first issue

00:59:00.800 | is a predisposition to, or a vulnerability

00:59:05.760 | to these types of foods, which we undoubtedly all have

00:59:10.760 | to a certain extent, but some more than others.

00:59:13.080 | And then, so that's the first hit,

00:59:16.200 | is this predisposition in the context

00:59:18.280 | of this sort of food-focused society.

00:59:21.480 | And then the second hit is probably a stressful event

00:59:26.680 | or a stressful life and probably a recurring stressful event.

00:59:31.520 | I'm not sure this is published.

00:59:33.180 | I've never sat down with like a eating disorder expert

00:59:36.080 | and had this question about how this develops

00:59:38.480 | and I'm not sure it's actually well known.

00:59:40.740 | But in a lot of ways, I think that that answer,

00:59:45.140 | anybody would agree with, that we need sort of

00:59:47.400 | a predisposition in the exposure,

00:59:48.960 | the environmental exposure and the genetic predisposition,

00:59:53.720 | but also a stressor and that stressor is probably one

00:59:57.200 | that's recurring and it's obvious in our society,

01:00:00.480 | these stressors are everywhere and how we can manage them

01:00:03.120 | is often poor and I think we can all relate with that.

01:00:07.400 | And then there's something else in the background

01:00:09.140 | that I think is really important to mention

01:00:10.780 | is that patients with these kinds of problems

01:00:12.680 | are embarrassed because our society doesn't think fondly

01:00:17.680 | of these kinds of patients.

01:00:19.520 | Binging disorder patients, they do tend to be overweight.

01:00:22.380 | That's obviously a stigma.

01:00:24.720 | Obesity is another stigma.

01:00:27.660 | Then there's the opposite, in a way it's an opposite

01:00:30.320 | by the way, from a phenotype standpoint, that's anorexia.

01:00:33.140 | I mean, that's another stigma and you know, gosh,

01:00:37.440 | not to make this about one sex over another,

01:00:41.760 | but when girls are told they're pretty

01:00:45.160 | because they're thin, it just reinforces this problem

01:00:48.520 | and of course you want to compliment people

01:00:51.000 | and make them feel good about themselves,

01:00:52.800 | but the problem is that in this vulnerable society,

01:00:56.440 | that that can lead to problems because people start thinking,

01:00:59.080 | oh, I should be thin or thinner.

01:01:00.680 | So I think that it's a little bit of a societal understanding

01:01:07.040 | that our brains are very vulnerable

01:01:09.520 | and I think that will really help changing society, it's hard

01:01:12.880 | and most of society is not, you know, ill meaning.

01:01:16.640 | It's all done by accident,

01:01:18.780 | but that is the society that we live in.

01:01:20.400 | So if we can try to improve that stigma

01:01:24.600 | and be kinder to people in that way,

01:01:28.160 | I think a lot of these problems would get better.

01:01:29.640 | People that are obese that feel embarrassed

01:01:32.440 | by their obesity, it doesn't help.

01:01:34.800 | It only makes it worse because they give up.

01:01:37.320 | Same thing might be true for anorexics.

01:01:39.300 | So I really think it's important

01:01:42.240 | to consider all of these things

01:01:43.720 | and that's why it's so complicated

01:01:45.240 | and it would be so hard to do a well-controlled study

01:01:47.880 | to understand it better because there's so many

01:01:49.800 | of these variables to control for

01:01:51.240 | that you really can't control for.

01:01:53.240 | You might be able to control for them

01:01:54.120 | in a mouse's home cage,

01:01:55.720 | but not in the society that we live in.

01:01:58.000 | So that's kind of my brief sort of summary

01:02:03.000 | of how I would answer your first question.

01:02:05.520 | Then I think, you know, your second question,

01:02:08.140 | I sort of take that as, well,

01:02:09.440 | how do you study such a complicated problem

01:02:13.480 | in the operating room and in the clinic?

01:02:15.640 | Because I mentioned the operating room

01:02:17.760 | because that's sort of the first step here.

01:02:20.420 | First, we have, just to clarify,

01:02:23.060 | we have a NIH-funded trial approved by the FDA

01:02:27.760 | for research to do this first in human study.

01:02:30.920 | We've treated two patients.

01:02:33.580 | We have four more to come at Penn.

01:02:35.340 | And in this study, it's something I've been working

01:02:39.880 | towards my entire career.

01:02:41.440 | What we don't know is where in the nucleus

01:02:47.640 | accumbens will we identify cells or regions

01:02:52.640 | that seem to be involved

01:02:59.200 | in this sort of reward-seeking behavior.

01:03:02.400 | I would call it appetitive.

01:03:04.280 | It's kind of like appetite,

01:03:06.280 | but the word appetitive is, I think, a good word to use.

01:03:09.520 | What part of the nucleus accumbens is appetitive?

01:03:11.680 | Is the whole thing appetitive?

01:03:12.960 | Probably not.

01:03:13.800 | It's huge.

01:03:14.620 | In my world, it's huge.

01:03:15.580 | As a neurosurgeon, you know,

01:03:16.600 | I target parts of the brain

01:03:17.840 | that are three or four millimeters in size.

01:03:19.960 | The nucleus accumbens is almost a centimeter in size.

01:03:22.360 | - Wow, I didn't realize it was that large.

01:03:24.300 | - Yeah.

01:03:25.140 | - This sort of reminds me of discussions

01:03:26.380 | around the amygdala.

01:03:27.220 | Everyone thinks amygdala fear,

01:03:28.800 | but amygdala has got a lot of different sub-regions

01:03:31.260 | and stimulation of certain areas of the amygdala

01:03:33.880 | makes people feel great.

01:03:34.840 | - That's right.

01:03:35.680 | - And stimulation of other areas

01:03:36.840 | makes them feel terribly afraid.

01:03:38.420 | - Exactly.

01:03:39.260 | And that shouldn't surprise us

01:03:40.320 | because when we treat patients with Parkinson's disease,

01:03:43.580 | for tremor, if we're in one part

01:03:45.420 | of the subthalamic nucleus, we'll help their tremor.

01:03:47.500 | If we're in another part of the subthalamic nucleus,

01:03:49.580 | the neurologist is looking at me like,

01:03:50.960 | why isn't this working?

01:03:52.460 | And that shouldn't surprise us.

01:03:53.580 | We already know that, you know,

01:03:54.820 | two or three millimeters deviation

01:03:57.300 | or two or three millimeters away from where we wanna be

01:03:59.580 | and you might not have the result you want.

01:04:01.220 | And that's probably also true

01:04:02.420 | for these more limbic structures

01:04:04.120 | like the amygdala and the nucleus accumbens.

01:04:07.060 | So, you know, regarding the nucleus accumbens,

01:04:09.580 | we traverse some of the nucleus accumbens, not all of it,

01:04:13.300 | in order to place the electrode that we want to use

01:04:16.460 | to detect when cravings are happening, for example,

01:04:21.040 | and to try to block the cravings

01:04:23.540 | from leading to the behavior related to the reward seeking,

01:04:27.100 | which is the overeating in this case.

01:04:29.000 | So what we decided to do in the operating room

01:04:34.180 | was to actually try to leverage a tool

01:04:38.400 | that we use all the time

01:04:39.460 | when we take care of patients with Parkinson's.

01:04:41.420 | So with Parkinson's, a lot of these patients,

01:04:43.260 | not all, have tremor.

01:04:45.080 | And so when we place an electrode

01:04:47.080 | into this motor structure

01:04:49.880 | to try to improve their movement disorder,

01:04:52.600 | we often can hear tremor cells

01:04:55.300 | and they sound, we convert their electrical signal

01:04:58.460 | to an audible signal so we can actually hear it.

01:05:00.780 | And it sounds kind of like the tremor looks,

01:05:04.000 | like the frequency of the signal

01:05:05.540 | is the same as the hand shaking.

01:05:07.500 | - So like zzz, zzz, zzz. - Exactly.

01:05:09.620 | - And so the patient with Parkinson's is trembling,

01:05:13.620 | they're awake, and you're poking around

01:05:15.920 | in a dedicated, careful way, of course.

01:05:19.580 | - One poke at a time. - One poke at a time

01:05:21.540 | with a very fine wire, a set of wires,

01:05:23.780 | listening to the electrical activity

01:05:25.740 | until you encounter some cells

01:05:29.020 | that are sending out electrical activity

01:05:31.860 | at a similar frequency. - Exactly.

01:05:33.720 | - And then you can stimulate them or quiet them

01:05:36.220 | and see if the tremor goes away.

01:05:37.580 | So we are very confident that when we stimulate that area

01:05:41.060 | of, in this case, the subthalamic nucleus,

01:05:43.700 | we will make that tremor,

01:05:46.820 | we will disrupt that tremor circuit

01:05:48.860 | and that tremor will dissolve, and it does.

01:05:51.540 | That's why Parkinson's is so beautiful and inspiring

01:05:54.140 | and from a surgical-- - And tractable.

01:05:55.940 | - Yeah, exactly. - Yeah, but what is the--

01:05:57.740 | - It makes us feel we understand the brain,

01:05:59.720 | at least in that limited way.

01:06:01.060 | - So what is the analog to tremor

01:06:04.980 | in terms of appetite and desire to binge?

01:06:07.260 | - Craving.

01:06:08.340 | So craving is a term that,

01:06:11.900 | there's probably other terms we could use, by the way,

01:06:13.500 | but that's the term we've chosen to use

01:06:15.500 | for a number of reasons.

01:06:16.820 | One, because people relate with that term.

01:06:19.020 | People that have binge eating disorder or obesity,

01:06:22.480 | if you ask them if they crave, the answer will often be yes.

01:06:25.900 | If you ask them if they lose control or binge,

01:06:28.460 | they might not know what you mean

01:06:29.820 | or they might not actually feel out of control,

01:06:31.700 | even when they are.

01:06:35.300 | But the word craving is relatable,

01:06:37.340 | and so we set out to see if we could identify craving cells.

01:06:41.760 | In a patient with OCD, which is related,

01:06:46.540 | in fact, we target a very similar part of the brain,

01:06:49.140 | we tried to identify cells related to obsessions,

01:06:54.620 | and we believe we did do that.

01:06:56.380 | It was a single case study where we tried to optimize

01:06:59.620 | where our electrode was placed.

01:07:01.260 | So we had some proof of concept

01:07:03.600 | that we would be able to elicit

01:07:05.260 | a sort of disease-specific symptom in the operating room,

01:07:08.860 | assuming the patient could tolerate being awake.

01:07:11.360 | Not everybody needs to be awake for this procedure,

01:07:13.540 | but at least for these first in human trials

01:07:15.400 | where we're trying to establish

01:07:18.600 | where in the brain we need to be,

01:07:20.180 | I think this type of approach is really critical.

01:07:22.680 | And by the way, none of this has been published,

01:07:27.460 | but I think it's so important for people to know this,

01:07:30.620 | so I am willing to share some aspects

01:07:32.600 | of what we're trying to do.

01:07:33.900 | But that's really the first goal of this trial

01:07:38.860 | is to identify where in the nucleus accumbens

01:07:43.060 | we can detect these craving cells.

01:07:44.700 | So we have to provoke food craving in the operating room.

01:07:47.140 | That's the first thing.

01:07:48.100 | - How do you do that?

01:07:49.500 | - Ah, well, there are some somewhat validated ways

01:07:53.860 | to do that.

01:07:55.420 | So for example, we asked patients to provide pictures

01:07:59.040 | of food that they rate very highly

01:08:01.300 | as something that they would typically crave.

01:08:03.620 | And depending on the patient,

01:08:05.660 | it might be something that's very salty.

01:08:07.260 | It could be very sweet, like a donut.

01:08:09.100 | - Donuts are good.

01:08:11.120 | - I love donuts.

01:08:11.960 | - Right, donuts are great.

01:08:13.200 | - You should try the Cronut when you're here

01:08:14.460 | in New York City.

01:08:15.300 | - I just might, I try not to eat that sort of thing.

01:08:17.920 | For all the reasons they change your brain,

01:08:19.860 | worth one bite. - It's worth one bite.

01:08:21.340 | Just try to stop yourself after that one bite.

01:08:22.940 | - So if I were one of these patients,

01:08:24.260 | given the fact that the binges come on pretty seldom

01:08:29.340 | once a day, do you, I imagine you have them come

01:08:31.940 | to the operating room fasted or semi-fasted?

01:08:35.220 | - They're fasted, yep.

01:08:36.060 | - Okay, they're fasted, which probably,

01:08:37.340 | there are probably surgical reasons for wanting that too.

01:08:39.660 | - Yes, they kind of have to be.

01:08:40.900 | - Right, and then you've done the craniotomy,

01:08:44.180 | you've removed a patch of skull, lowered the wire

01:08:46.740 | into the nucleus accumbens, and then they are viewing

01:08:50.500 | pictures of food that they crave and thinking about it.

01:08:52.820 | Do they have olfactory cues, smells of Cronuts and donuts?

01:08:55.980 | - Yeah, I would love to do the olfactory cues.

01:08:57.460 | We haven't implemented that, but that is a great,

01:09:00.160 | thank you, and I'll give you full credit when we do.

01:09:02.020 | - Sure, I didn't review the grant, but it sounds,

01:09:04.140 | I'm so glad this work is funded because I mean,

01:09:06.300 | this is what I, I'll make, this time it's not a joke.

01:09:09.220 | When I referred to you all, you neurosurgeons

01:09:13.180 | as the astronauts of the brain, you know,

01:09:16.220 | this is out on the extreme edge of what we don't know

01:09:21.220 | about how the brain functions.

01:09:23.340 | And this is so far and away different

01:09:25.220 | than giving a mouse access to a high fat food.

01:09:28.240 | Not that that, I'm not being disparaging of the mouse work,

01:09:30.420 | but so the person says, well, I'm the patient in this case,

01:09:34.660 | so I might say, you know, I'm hungry,

01:09:36.380 | a donut sounds really good right now,

01:09:38.620 | but craving to me is like, I, you know,

01:09:41.700 | I'll cross the street, cross town, be late for my meeting,

01:09:46.340 | eat three of these, maybe even hide that from somebody

01:09:50.740 | that cares about me, that doesn't want me doing this,

01:09:52.860 | this kind of thing, hide it from myself.

01:09:54.580 | - Yes.

01:09:55.620 | - These kinds of behaviors I'm projecting,

01:09:57.260 | I'm fortunate that I have cravings for things in life,

01:10:01.220 | but donuts are not among the more extreme of them.

01:10:03.980 | So, so this is all happening in real time

01:10:07.380 | and you're listening to the cells the same way

01:10:09.220 | you would listen to it and search for tremor cells.

01:10:11.700 | - Exactly, same exact tools.

01:10:13.080 | - And you're doing that by recording

01:10:15.460 | from a small population of cells in the area?

01:10:18.100 | - Yeah, in fact, we do get multi-unit activity,

01:10:21.340 | which is multiple cells, but we really try to find one.

01:10:24.540 | A single unit to listen to.

01:10:26.860 | - One neuron.

01:10:27.700 | - Yeah, because it's just much easier to understand

01:10:30.460 | what that one neuron is doing

01:10:32.300 | versus trying to listen to multiple.

01:10:33.960 | And we also measure local field potential recordings,

01:10:37.220 | but those are analyzed,

01:10:38.680 | which is more of a population response, thousands of cells.

01:10:41.620 | - Kind of a chorus of cells.

01:10:43.180 | - Exactly, that we measure offline.

01:10:45.940 | The device that we use to sort of treat these patients

01:10:52.220 | or intervene that we're studying,

01:10:55.060 | it can't do single unit recordings.

01:10:57.040 | It's only doing these more population responses.

01:10:59.300 | So, we correlate what we see in the operating room

01:11:01.900 | at the single unit level to the population response,

01:11:04.580 | but we do that all offline.

01:11:06.980 | I can explain that in a moment.

01:11:08.840 | But yeah, so we try to identify these craving cells

01:11:14.300 | and because this is a feasibility study

01:11:19.220 | and we can't be in the operating room searching

01:11:22.340 | for hours and hours and hours,

01:11:23.900 | we do have some sort of,

01:11:25.520 | we have guidelines that we've set for ourselves,

01:11:27.780 | that we've developed with the NIH or the FDA

01:11:31.540 | to make sure that what we're doing

01:11:33.580 | is feasible and safe as well.

01:11:35.900 | So, we will spend a limited time

01:11:38.100 | trying to identify these craving cells.

01:11:40.340 | But another sort of strategy

01:11:44.200 | that we think is really important

01:11:45.840 | is the effect of the stimulation.

01:11:48.940 | So, a lot of patients,

01:11:50.220 | and this gets to sort of your question earlier

01:11:51.860 | about what kind of, what comes first.

01:11:54.040 | A lot of people when they binge

01:11:58.220 | or they lose control over food or seek drugs,

01:12:03.080 | that moment of vulnerability is preceded

01:12:06.520 | by what we call a moment of sort of pre-meal negative effect

01:12:11.520 | which basically means right before they binge,

01:12:15.100 | they're feeling down or they feel stressed or anxious

01:12:18.560 | and they compensate for that momentary symptom

01:12:23.560 | by binging or losing control over food.

01:12:27.340 | Not everybody meets criteria for a binge,

01:12:28.940 | so I try to specify that we are looking

01:12:31.980 | at loss of control eating specifically

01:12:33.540 | just because the criterion of a binge

01:12:36.200 | is not as critical for us.

01:12:37.820 | So, what we wanna be able to do is trigger stimulation

01:12:44.240 | when this craving is detected by the device.

01:12:48.420 | But we trigger it only when the craving is there

01:12:51.820 | and we believe that if we can sort of

01:12:54.760 | temporarily elevate their mood ever so briefly,

01:12:58.480 | again, this is about five to 10 seconds of stimulation only,

01:13:01.680 | that perhaps that elevation in mood

01:13:04.020 | could actually sort of disrupt the craving to binge cycle.

01:13:09.020 | Maybe that's a habit, maybe it's not,

01:13:12.860 | but if you crave and then you binge,

01:13:15.100 | if we can interrupt that with this moment

01:13:17.780 | of feeling good, that might be a really good therapy

01:13:21.380 | for a patient.

01:13:22.500 | And in fact, when we do deep brain stimulation

01:13:25.880 | for obsessive compulsive disorder,

01:13:28.060 | we can fairly reliably induce a positive effect.

01:13:32.680 | The problem is that it's not sustained

01:13:35.100 | and the reason it's likely not sustained

01:13:37.100 | is because with obsessive compulsive disorder,

01:13:39.760 | we treat that condition with continuous stimulation

01:13:44.000 | and it's not surprising that over time,

01:13:46.160 | the effect kind of goes away.

01:13:47.740 | So when they're in the clinic and we turn the device on,

01:13:49.700 | our patients feel great

01:13:51.260 | and we feel like we've solved the problem,

01:13:54.300 | but they call us the next day

01:13:55.500 | and they're like, you know, my depression came back

01:13:57.620 | or my OCD hasn't gotten better

01:14:00.120 | and my mood's back to where it was.

01:14:02.180 | Can you get it back to where it was yesterday?

01:14:03.940 | 'Cause that felt great.

01:14:05.140 | - The brain loves homeostatic regulation.

01:14:07.020 | - It does.

01:14:07.860 | - And it does not like to shift patterns.

01:14:10.020 | - Regression to the norm.

01:14:11.020 | - Right.

01:14:12.020 | - And I think there's sort of a tolerance effect there

01:14:15.180 | that is limiting the effect of continuous stimulation

01:14:19.620 | and actually in a mouse, if you do continuous stimulation,

01:14:22.420 | the sort of blockade of binge eating goes away.

01:14:27.300 | So actually in a mouse, we've actually demonstrated,

01:14:30.940 | we published this not too long ago in PNAS,

01:14:33.460 | that if you deliver stimulation intermittently

01:14:37.300 | and only when sort of a craving signal is detected,

01:14:40.200 | so to speak, that effect will be the most robust

01:14:44.920 | and durable.

01:14:46.520 | But if you deliver it continuously,

01:14:48.380 | actually the benefit goes away over time.

01:14:50.100 | So I've always encouraged my colleagues

01:14:52.380 | to consider more of an episodic stimulation approach

01:14:55.440 | rather than continuous deep brain stimulation.

01:14:57.280 | But of course that's for these more episodic conditions,

01:15:00.380 | whereas these more quote unquote state disorders,

01:15:02.900 | as I oversimplified earlier,

01:15:04.300 | they might need more of a continuous therapy.

01:15:06.060 | So that's definitely subject for a lot of research

01:15:08.600 | in the future.

01:15:09.440 | So in any case, the goal in the operating room

01:15:12.940 | was to identify a craving cell,

01:15:15.940 | deliver stimulation safely,

01:15:20.020 | but also to capture a moment of elevated mood.

01:15:23.240 | We were able to do that as we are in our OCD patients

01:15:27.060 | as well.

01:15:28.340 | And also to get an intraoperative CAT scan.

01:15:31.540 | We have devices now in the operating room

01:15:33.760 | that allow us to get imaging in real time.

01:15:35.900 | They're fabulous tools that we didn't have 10 years ago.

01:15:39.500 | So we can confirm accuracy.

01:15:42.700 | - So you can see where the electrode is precisely.

01:15:45.100 | - Exactly, with 0.5 millimeters of error.

01:15:48.500 | So super precise or as precise as we think we need to be.

01:15:52.220 | And we use connectomics.

01:15:55.980 | So there's a tool in brain imaging called tractography,

01:16:00.980 | where we can actually measure circuit connections.

01:16:04.020 | It's an indirect assay, but we believe it's powerful.

01:16:07.460 | It has its assumptions,

01:16:10.340 | but like anything in science.

01:16:13.340 | But we can actually map out

01:16:16.980 | where the nucleus accumbens connects

01:16:18.980 | to the prefrontal cortex,

01:16:21.520 | sort of the cortical control and inhibitory control pathway

01:16:25.060 | and where that pathway intersects

01:16:26.700 | with the nucleus accumbens.

01:16:27.940 | And we can target that area structurally.

01:16:31.620 | So those three goals of the surgery,

01:16:34.360 | we aim to set out to accomplish.

01:16:37.100 | And we believed if we achieved two of those three,

01:16:39.900 | that we would have a successful result in our early trial.

01:16:43.940 | - Amazing.

01:16:44.780 | Given that at least to me, the non-clinician,

01:16:49.060 | that anorexia is the mirror image of binge eating disorder.

01:16:54.060 | And at least from what I learned,

01:16:57.520 | one of the more deadly psychiatric conditions,

01:17:00.340 | but also quite common.

01:17:02.980 | - Yes.

01:17:03.820 | - Is it possible that nucleus accumbens,

01:17:07.540 | this so-called reward circuit is also involved in anorexia,

01:17:12.540 | but somehow it is the resistance to eating,

01:17:16.100 | the craving of the fasted state or something like that

01:17:19.300 | that's being reinforced.

01:17:20.940 | And I asked this for two reasons.

01:17:22.460 | One, because I'm genuinely curious about anorexia.

01:17:25.640 | I've observed anorexia in a number of people I know,

01:17:27.780 | and it's a striking thing to see somebody just resist food,

01:17:32.780 | despite all better knowledge of the fact

01:17:36.920 | that they're getting quite ill, maybe even at risk of death.

01:17:40.580 | But the other reason is that if in fact nucleus accumbens

01:17:45.580 | is the site which can harbor cells to promote craving

01:17:50.620 | and craving of fasted states, so to speak,

01:17:55.940 | then that I think might tell us something fundamental

01:17:58.260 | about how the brain works,

01:17:59.140 | which is that structures don't control functions per se,

01:18:02.500 | structures control dynamics of interactions.

01:18:05.980 | Sort of like a orchestra conductor

01:18:09.940 | has a certain number of operations that they perform,

01:18:12.140 | but really their main function is to coordinate the actions

01:18:14.840 | of a lot of things,

01:18:16.100 | not to make sure that the violins always play

01:18:18.420 | in a certain way alongside the oboes.

01:18:21.500 | You can tell I'm not a musician here.

01:18:23.200 | [laughing]

01:18:24.420 | - I actually have an appreciation for the oboes.

01:18:26.040 | Those usually get left out.

01:18:27.020 | - What's that, the oboes?

01:18:27.860 | - Yeah, they usually get ignored.

01:18:29.820 | - My partner plays the oboes.

01:18:31.040 | - Oh, wow.

01:18:31.880 | - Yeah, so.

01:18:32.700 | - I think it's a great analogy, by the way.

01:18:35.940 | I make this statement, it's a little controversial,

01:18:38.780 | but I actually think people would understand

01:18:40.940 | where I'm coming from across all of these

01:18:43.980 | sort of subspecialties of medicine.

01:18:46.820 | But I actually think, especially with obesity,

01:18:49.420 | remember it's a phenotype that's reflective often,

01:18:52.340 | but not always of a behavior.

01:18:54.660 | But if you consider patients that have obesity

01:18:57.660 | and they exhibit some sort of compulsion towards food,

01:19:00.620 | so they overeat despite the risk of it,

01:19:03.300 | I think those kinds of patients are more similar

01:19:06.020 | to anorexics than they are different.

01:19:08.340 | Anorexia and obesity are both phenotypes that are,

01:19:11.620 | at least in this specific case of obesity and anorexia,

01:19:15.180 | a result of a compulsion to either over or under eat

01:19:18.300 | despite the risk.

01:19:20.380 | These types of compulsions are driven by societal pressures,

01:19:24.940 | brain vulnerabilities that are probably more similar

01:19:28.180 | than they are different.

01:19:29.580 | They just happen to manifest differently.

01:19:32.740 | Why they manifest differently is probably related

01:19:34.860 | to each patient's predisposition or perhaps preference.

01:19:39.300 | That's hard to know.

01:19:41.100 | Like you, I have a personal connection

01:19:43.220 | to these eating disorders, anorexia included,

01:19:45.580 | and yeah, I think it's very scary.

01:19:49.940 | And it's a condition that often instills fear

01:19:55.900 | in psychiatrists because I think,

01:19:59.700 | not everybody, by the way,

01:20:01.740 | I mean, I have some phenomenal psychiatrists

01:20:04.260 | that I work with both at Stanford and at Penn.

01:20:07.380 | They're also involved in my obesity study

01:20:09.020 | that take care of these patients.

01:20:10.180 | I mean, these are heroes,

01:20:11.140 | but there's a lot of psychiatrists that are not

01:20:13.380 | in this domain that find anorexia scary

01:20:15.660 | for the reason you said.

01:20:16.500 | It has the highest mortality of all psychiatric conditions.

01:20:19.940 | That includes depression

01:20:21.940 | because not only can these patients die of suicide,

01:20:24.020 | but they die of metabolic complications

01:20:25.900 | of being underweight.

01:20:28.260 | So it is a scary condition.

01:20:31.820 | I relate with that.

01:20:33.820 | I am trying over time to bridge what I'm doing

01:20:37.660 | in obesity and binging disorder to anorexia

01:20:40.300 | for two reasons.

01:20:41.140 | One, because I think these problems are more similar

01:20:43.260 | than they are different, and two, because of the need.

01:20:46.340 | And I think we're well positioned

01:20:48.620 | to sort of tackle anorexia using similar approaches,

01:20:53.620 | not identical, but similar approaches.

01:20:56.840 | The nucleus accumbens has been studied

01:20:58.700 | in patients with anorexia in China.

01:21:01.460 | Actually, my postdoc, my first postdoc,

01:21:03.980 | who I had the honor to train when I was at Stanford

01:21:07.100 | as a neurosurgeon in China when, before he came to me,

01:21:10.160 | actually was involved in a trial of anorexia

01:21:12.300 | that had some benefits.

01:21:13.460 | And there's studies in Europe

01:21:18.020 | and elsewhere that have examined preliminarily

01:21:23.500 | the effects of deep brain stimulation

01:21:24.920 | targeting the nucleus accumbens.

01:21:27.540 | Four anorexia colleagues of mine in Canada,

01:21:30.900 | Andres Lizados, a wonderful neurosurgeon scientist,

01:21:34.640 | has been studying the effects of going after area 25,

01:21:37.420 | which is directly connected to the nucleus accumbens by,

01:21:40.560 | it's a monosynaptic connection, so in a lot of ways,

01:21:45.000 | perhaps delivering stimulation there could be very similar

01:21:48.260 | to delivering stimulation to the nucleus accumbens.

01:21:50.100 | It's all part of one critical inhibitory control circuit.

01:21:53.260 | He's seen benefits as well.

01:21:55.280 | So I definitely think there's some evidence

01:21:59.520 | that this is an area that we need to be studying.

01:22:02.920 | I think our more episodic approach

01:22:04.520 | with responsive stimulation going after sort of a signal

01:22:07.560 | in the nucleus accumbens that seems to be related

01:22:10.020 | to the compulsion to withhold from eating,

01:22:13.300 | I think is what we will be trying to accomplish

01:22:16.100 | in our study.

01:22:16.940 | It's right now just being conceived, though.

01:22:21.180 | These studies, they move so slowly

01:22:23.340 | because you have to get a grant.

01:22:25.140 | That grant gets reviewed by the NIH six months

01:22:27.500 | after you submit it, often gets rejected

01:22:30.000 | because it's too innovative and too high risk,

01:22:33.220 | so then you have to edit it and decrease the risk.

01:22:36.220 | So it takes, my obesity study took two years to get funded.

01:22:39.980 | And I worry about that timeframe

01:22:41.780 | because that's a lot of time for patients

01:22:43.500 | with anorexia to suffer that I might be able to help,

01:22:45.860 | at least in a small sample of patients.

01:22:47.460 | So, but that is the nature of how these things go.

01:22:50.980 | You also have to get FDA approval

01:22:52.320 | to do these kinds of things.

01:22:53.540 | We try to do all of this in parallel.

01:22:54.940 | It's an enormous undertaking.

01:22:56.740 | And in a lot of ways, we're starting from scratch,

01:22:58.660 | but in some ways, we have some preliminary data

01:23:00.860 | to go after this.

01:23:01.900 | So my hope is in about a year,

01:23:03.700 | we'll have a similar trial for anorexia at Penn,

01:23:06.100 | so more to come on that.

01:23:08.540 | And we're not the only lab that's trying to go after it

01:23:11.620 | because of the clear need, so.

01:23:14.300 | - What is the status of non-invasive brain stimulation,

01:23:17.540 | ablation, and blocking activity in the brain?

01:23:20.420 | - I get a lot of questions

01:23:21.340 | about transcranial magnetic stimulation.

01:23:23.620 | I've actually had that done as a research subject.

01:23:26.460 | And I was at Berkeley, Rich Ivory's lab,

01:23:27.940 | put a coil on my head.

01:23:29.180 | I was tapping my finger in concert to a drum beat.

01:23:33.100 | And then all of a sudden, because of the stimulation,

01:23:35.860 | it was impossible for me to keep time with the drum beat.

01:23:40.020 | It's a pretty wild experience to not have motor control

01:23:44.220 | and then to have motor control returned

01:23:47.860 | at the flip of a switch when someone else is controlling

01:23:50.740 | the switch makes it especially eerie.

01:23:52.780 | So my understanding is that transcranial magnetic stimulation

01:23:56.700 | is being used to treat depression

01:23:57.940 | and a number of other brain syndromes non-invasively,

01:24:02.380 | so no drilling through the skull.

01:24:03.960 | Surgeons don't like that.

01:24:04.940 | Surgeons love to cut and drill with purpose, but they do.

01:24:08.100 | - With purpose, yes.

01:24:09.340 | - But my understanding is that the spatial precision

01:24:13.540 | isn't that great.

01:24:15.700 | Ultrasound is something I hear a lot about these days.

01:24:19.660 | And my understanding is that ultrasound can allow

01:24:22.420 | researchers and clinicians to stimulate specific brain areas,

01:24:25.460 | perhaps with more precision.

01:24:27.460 | Maybe you could just give us a brief coverage

01:24:29.420 | of what those are being used for.

01:24:31.040 | What are your thoughts on these forms of non-invasive,

01:24:36.040 | meaning no flipping open of a piece of the skull

01:24:39.920 | type brain stimulation and blockade of brain activity?

01:24:44.380 | - Sure, yeah, I wanted to clarify also.

01:24:46.500 | These surgeries generally don't, by the way,

01:24:49.820 | require a full craniotomy.

01:24:51.980 | It's usually just a small opening about the size of a dime

01:24:54.420 | in the bone, so just to clarify.

01:24:56.300 | - But painless too, right?

01:24:58.380 | - Usually without pain.

01:24:59.420 | - Yeah, a little bit of scalp numbing.

01:25:01.260 | - We give a scalp block and the patients are getting

01:25:03.660 | IV sedations, so they in general don't feel anything.

01:25:06.580 | And if they do, they tell me and we give them

01:25:08.180 | more local anesthetic, but they're usually asleep

01:25:10.500 | during that part.

01:25:11.660 | So it's minimally invasive, but in a lot of ways,

01:25:14.040 | there's no such thing as a minimally invasive procedure

01:25:16.280 | in the brain, you know?

01:25:17.300 | It's kind of a misnomer. - I'm so glad

01:25:18.700 | to hear you say that.

01:25:19.680 | - Oh no, I am not one of those neurosurgeons

01:25:22.780 | that you've probably encountered,

01:25:24.040 | and we have mutual friends that,

01:25:26.120 | and these mutual friends are some of my favorite people

01:25:29.260 | in neurosurgery, and they probably actually think

01:25:30.820 | more like me than not, but there are neurosurgeons

01:25:34.040 | that you're absolutely right.

01:25:34.880 | And this is true for all surgeries.

01:25:36.140 | They really, in a lot of ways, they think what they do

01:25:39.180 | is sort of the ground truth, or closer to the ground truth.

01:25:42.220 | And I get that, you know, probing with purpose.

01:25:47.020 | I actually really like that.

01:25:48.960 | I'm gonna use that if you don't mind.

01:25:51.540 | - It's just describing what you do, so the, yeah.

01:25:54.160 | - But I actually have, I've always said this.

01:25:57.580 | I've said it publicly.

01:25:58.480 | I've said it to my boss.

01:25:59.720 | I've said this to my team.

01:26:02.200 | We need to embrace noninvasive approaches.

01:26:04.460 | Some of them are a little fluffy, fluffy in that

01:26:10.020 | we don't understand how they work.

01:26:12.300 | We don't necessarily understand how deep brain stimulation

01:26:13.940 | works, by the way, so.

01:26:15.180 | But because we don't know exactly how they work,

01:26:18.760 | they're not as precise as we would like them to be,

01:26:20.620 | so we have work to do there, and I actually think

01:26:22.400 | that work is doable, and actually underway.

01:26:25.600 | You know, at Stanford, we have great collaborators

01:26:28.980 | that I think are doing this, people like Nolan Williams,

01:26:31.820 | and Connor Liston at Cornell, and others.

01:26:35.800 | So we, I think that TMS, trans-cranial magnetic stimulation,

01:26:40.800 | it is FDA approved for depression, by the way.

01:26:43.240 | It's also FDA approved for OCD and for nicotine addiction.

01:26:46.460 | - Where do they put the coil for those three,

01:26:49.040 | or more or less?

01:26:49.880 | - Yeah, so they put it over, well, it's always on the scalp

01:26:52.460 | and over the frontal lobe, and there's different parts

01:26:55.760 | of the frontal lobe that have been demonstrated

01:26:58.240 | to be a little better or a little bit worse,

01:27:00.760 | but what the FDA has approved for depression,

01:27:04.800 | I believe is similar to what's been approved for OCD,

01:27:08.960 | but for addiction, I believe it is a different target,

01:27:11.380 | but we'd have to ask our TMS experts on that.

01:27:14.080 | - Can they direct the trans-cranial magnetic stimulation

01:27:16.440 | deep below the cortex?

01:27:17.520 | - They try, and we're actually studying this

01:27:20.560 | in OCD patients now.

01:27:22.240 | As a part of our invasive trial,

01:27:26.440 | we are trying to pull patients from a TMS trial

01:27:29.360 | that's in parallel to what we're doing,

01:27:31.920 | all funded by the Foundation for OCD Research,

01:27:35.480 | where we believe we can use TMS to define a circuit

01:27:40.240 | that, if modulated, improves OCD, albeit temporarily,

01:27:45.240 | and in those patients, if it's temporary,

01:27:47.460 | they would be appropriate for an invasive study,

01:27:49.640 | so something we're actively working on.

01:27:52.760 | I've always believed that neurosurgeons need to be part

01:27:55.440 | of the discussion with these non-invasive approaches.

01:27:57.920 | We don't need to do them,

01:27:59.720 | but I think we can help make them more precise

01:28:03.840 | and to probe non-invasively with purpose

01:28:07.200 | rather than this more kind of, I don't know,

01:28:13.120 | a non-invasive blast effect kind of, you know,

01:28:16.960 | I just can't imagine how that is gonna be as effective

01:28:19.760 | as probing with purpose,

01:28:21.720 | but you can do that non-invasively as well,

01:28:23.400 | and I think we need to do better in that way.

01:28:26.080 | I do believe that's possible,

01:28:27.160 | and I think people are actively trying to do it.

01:28:30.040 | Getting deep in the brain with TMS,

01:28:31.400 | I think, will always be hard,

01:28:32.560 | but you can get there indirectly

01:28:34.520 | by using connectivity assays

01:28:36.480 | and targeting superficial structures

01:28:38.760 | that have high connectivity to deep structures.

01:28:42.720 | So, for example, perhaps one day,

01:28:46.200 | there will be a TMS target for anorexia and obesity.

01:28:50.080 | If we are scratching the surface

01:28:53.320 | with invasive approaches to these problems,

01:28:56.920 | we're even doing less with the brain stimulation.

01:28:59.920 | So we have so much work to do there.

01:29:01.640 | Eating disorders and TMS have been so sort of scarcely studied

01:29:06.640 | or there have been such little research done in that space.

01:29:12.360 | So it is an area that we need to work on.

01:29:14.920 | For the obvious reason, for example,

01:29:17.480 | in a patient with anorexia, just thinking practically,

01:29:20.000 | you know, placing a device in a patient

01:29:21.760 | who is significantly underweight

01:29:23.640 | might not be the best approach.

01:29:25.360 | You know, wound erosion and issues like that could come up.

01:29:28.480 | So developing a non-invasive approach, I think, is critical.

01:29:31.360 | The problem is where do we target?

01:29:34.720 | And so the only way to answer that, I think, reliably

01:29:37.880 | is to accept that we have to get into the brain

01:29:40.680 | before we're out of the brain.

01:29:42.560 | And with these kinds of conditions,

01:29:43.760 | we're only just starting to get into the brain, you know?

01:29:46.200 | So I worry that we're a long way away

01:29:49.360 | from a non-invasive approach that really works consistently.

01:29:54.240 | - Sorry to interrupt.

01:29:55.920 | I want to make sure we touch on ultrasound 'cause-

01:29:58.080 | - Yes, sure, no, I love that.

01:29:59.040 | - But historically, it seemed that there was

01:30:03.120 | a bit more permission for people to probe around

01:30:05.800 | in the human brain.

01:30:06.640 | I sometimes refer the podcast to some of these papers

01:30:11.200 | that were done allowing patients

01:30:14.320 | to self-stimulate in the brain.

01:30:16.080 | These are work done in the '60s

01:30:18.480 | and now his name escapes me, Robert.

01:30:21.160 | Anyway, there's a couple of papers published in Science

01:30:22.880 | allowing patients to stimulate

01:30:24.520 | a couple different brain areas,

01:30:25.520 | asking which ones they preferred.

01:30:26.920 | And I was always shocked and slightly intrigued

01:30:29.920 | by the fact that the brain area

01:30:31.840 | that all three of these patients,

01:30:33.480 | who I don't think had any syndromes,

01:30:34.880 | I think they volunteered for these experiments.

01:30:37.160 | I don't think you could do this anymore.

01:30:38.560 | - Yes, regulatory was not the same as it is now.

01:30:43.080 | - Things have changed, fortunately.

01:30:45.400 | But they, all three of them seem to like

01:30:49.160 | some midline thalamic structure,

01:30:50.880 | which for those listening,

01:30:51.700 | is just an area kind of in the dead center of the brain,

01:30:55.080 | more or less,

01:30:56.400 | that evoked a sense of kind of frustration and anger,

01:30:59.680 | which surprised me because I would have thought,

01:31:01.700 | oh, it's Robert Heath, these experiments,

01:31:03.760 | rather than patients preferring to stimulate areas

01:31:05.920 | that evoke laughter or joy

01:31:07.440 | or a feeling of drunkenness or delight.

01:31:10.680 | It also explains a lot of what I observe in social media,

01:31:13.520 | the sort of kind of people repeatedly engaging in battles

01:31:17.880 | that are kind of trivial.

01:31:19.080 | It seems like frustration and anger

01:31:20.540 | might have its own reward circuitry.

01:31:23.120 | Anyway, I don't want to go too far down that rabbit hole,

01:31:25.240 | but it-

01:31:27.000 | - It's a deep one.

01:31:27.840 | - It's a deep one.

01:31:28.660 | And kind of gets to our nature as humans

01:31:32.260 | and what we find interesting or rewarding.

01:31:34.820 | But the inability to probe around the brain in a safe way

01:31:39.820 | without the need for somebody to be very sick would be,

01:31:46.640 | I think it would be enormously powerful.

01:31:48.080 | And at least to my mind, if I were in charge,

01:31:50.360 | which I'm not, would offer the opportunity

01:31:53.480 | to really come to an understanding

01:31:55.800 | about how the human brain works without all these issues

01:31:58.780 | of how to translate for mouse studies.

01:32:00.560 | And again, there's huge value to animal studies

01:32:02.700 | as we both agree,

01:32:03.540 | but so many of the things that we want to know

01:32:06.980 | about the human brain involve asking the person,

01:32:09.780 | hey, what do you feel when that set of neurons

01:32:12.180 | is stimulated and what don't you feel?

01:32:14.820 | And a mouse, we can ask and ask,

01:32:16.920 | but they're not going to tell us them.

01:32:17.760 | They do tell us, they're not going to tell us in English.

01:32:19.740 | So how do we overcome this challenge?

01:32:23.040 | But first ultrasound, or if you prefer after ultrasound,

01:32:27.380 | is ultrasound going to be really useful

01:32:28.780 | toward solving these clinical issues and these basic issues?

01:32:31.480 | - Yeah, so I think, let's start with ultrasound

01:32:35.400 | and then we'll come back to it.

01:32:37.000 | So ultrasound right now,

01:32:39.020 | transcranial magnetic resonance guided focus ultrasound.

01:32:44.020 | So this is an FDA approved method.

01:32:50.060 | To deliver an ablation to the brain non-invasively.

01:32:55.060 | There are researchers, myself included,

01:32:57.940 | that are trying to use transcranial magnetic guided,

01:33:01.100 | magnetic resonance guided focus ultrasound

01:33:03.140 | or MRI guided focus ultrasound.

01:33:05.120 | To use it in a modulatory way, not just as an ablation,

01:33:08.980 | but to drive neuronal activity or inhibit it perhaps.

01:33:12.540 | We're still learning how to do that.

01:33:14.760 | There are trials that are trying to understand

01:33:17.380 | if you can use ultrasound to open the blood-brain barrier

01:33:19.540 | so you can deliver a medication to that specific area,

01:33:23.940 | perhaps for a brain tumor or something like that.

01:33:26.680 | So it's a very exciting field.

01:33:29.780 | And it is FDA approved for tremor right now.

01:33:32.020 | And so I actually do it routinely

01:33:34.460 | for patients with tremor with Parkinson's

01:33:37.880 | or a central tremor.

01:33:39.380 | And so I love doing it.

01:33:41.580 | It's often just kind of a miracle

01:33:44.420 | because there's no incision.

01:33:45.580 | I don't have to place an electrode into the brain

01:33:47.160 | to achieve a similar result.

01:33:49.120 | - How early into the pathology of Parkinson's

01:33:52.540 | can someone think about approaching this?

01:33:54.260 | So for instance, if somebody has a parent or a sibling

01:33:57.560 | and they're developing some resting tremor,

01:33:59.780 | obviously they should talk to a neurologist,

01:34:01.400 | but a neurosurgeon, but this non-invasive approach

01:34:05.060 | could be incredible for them,

01:34:06.800 | as opposed to just only taking drugs

01:34:09.720 | to increase dopamine levels.

01:34:11.180 | - Yeah, so depending on the reason you have tremor

01:34:13.900 | would dictate the kind of medication you would use.

01:34:15.960 | It could be Parkinson's, but if it's not,

01:34:17.420 | it might be a central tremor.

01:34:18.420 | By the way, central tremor is 10 times

01:34:20.220 | as common as Parkinson's.

01:34:22.140 | Central tremor is the most common neurologic condition

01:34:24.780 | in patients over the age of 70.

01:34:27.060 | We often aren't aware of that.

01:34:29.520 | People with a central tremor feel

01:34:30.620 | they have their forgotten disease

01:34:31.860 | because there's no Michael J. Fox for a central tremor.

01:34:34.940 | I sent a letter to Bill-

01:34:36.260 | - Sorry, is it essential tremor or essential tremor?

01:34:39.700 | - Yeah, E-S-S-E-N-T-I-A-L.

01:34:44.100 | I actually sent a letter to Bill Clinton.

01:34:46.160 | I've observed tremor in him,

01:34:48.700 | and I think he's actually disclosed that he has it,

01:34:50.560 | and I hoped he'd become a champion

01:34:52.740 | for patients with a central tremor.

01:34:55.160 | Sandra Day O'Connor does as well.

01:34:56.580 | She's also public about it,

01:34:57.740 | but I was not able to get them eager

01:35:00.160 | to become the champion for this condition,

01:35:01.880 | but like Michael J. Fox,

01:35:03.440 | these patients need a champion like that,

01:35:05.620 | but unfortunately, it's a bit of a forgotten disease.

01:35:10.080 | Nevertheless, because of the FDA approval

01:35:12.420 | of Focus Ultrasound for tremor,

01:35:14.320 | they're starting to get some attention for sure,

01:35:17.700 | and it's fabulously effective for these patients.

01:35:20.580 | It treats patients on one side,

01:35:21.820 | usually their dominant hand or their worse hand,

01:35:24.240 | and it really speaks to the fact that, wow,

01:35:27.360 | you can deliver noninvasively an ablation to the brain

01:35:31.060 | in a hypothesized zone that we think is related

01:35:34.580 | to the problem at hand,

01:35:35.880 | and at least with tremor, it works really well.

01:35:38.620 | Could this be effective for psychiatric disease,

01:35:41.340 | obesity, eating disorders?

01:35:44.080 | Well, perhaps.

01:35:46.860 | Actually, that would be the ideal.

01:35:48.660 | The problem is we don't know where to do the ablation.

01:35:51.620 | There is a trial that we would like to do for OCD

01:35:55.300 | where we would deliver an ablation

01:35:56.980 | to the same area of the brain

01:35:58.260 | that we've been delivering ablations to for years

01:36:00.460 | for patients with OCD, and it helps a bit.

01:36:02.220 | That's called a capsulotomy,

01:36:03.620 | but really, the outcome is probably gonna be about the same.

01:36:07.100 | It's a nice method because it's noninvasive,

01:36:09.860 | but we need to find a new target for these conditions,

01:36:13.260 | and because of the common denominator of the urge

01:36:17.340 | despite the risk, sort of that compulsion,

01:36:20.160 | perhaps it could be the same target.

01:36:22.580 | I don't know, but I would argue we need

01:36:25.440 | to do these modulatory experiments either with a device

01:36:28.700 | or with invasive recordings to better understand

01:36:32.480 | where these problems are coming from

01:36:34.360 | to define where we should do an ultrasound treatment.

01:36:37.880 | So you're right.

01:36:39.880 | Historically, without much regulation,

01:36:43.560 | we've probed the brain.

01:36:45.160 | The problem, we can't learn a lot

01:36:49.000 | from those experiments now, well, in this way at least.

01:36:52.760 | We don't know exactly where those electrodes were.

01:36:54.800 | We didn't have MRI scanning or high-quality CAT scanning

01:36:57.920 | to know where those electrodes were with certainty,

01:37:01.200 | and we know two or three millimeters matters,

01:37:03.640 | and we also didn't have the tools

01:37:05.040 | to place electrodes in a precise way back then.

01:37:08.840 | So unfortunately, we can't learn a lot

01:37:10.720 | from those experiments right now.

01:37:12.760 | So we're sort of redesigning them,

01:37:14.640 | and there is a way to do it now.

01:37:17.240 | Patients with epilepsy benefit from this all the time.

01:37:19.840 | There has been a revolution in America.

01:37:22.120 | It was in Europe before it was in America

01:37:24.240 | where we would do stereoencephalography,

01:37:26.860 | which is basically like doing an EEG

01:37:29.440 | of patients with epilepsy but with invasive electrodes,

01:37:32.760 | and we would place tiny little wires,

01:37:34.480 | less than a millimeter in diameter,

01:37:36.160 | all throughout the brain into parts of the brain

01:37:38.020 | that we believe are involved in seizures,

01:37:40.280 | and we would admit the patients to the hospital

01:37:42.380 | and figure out where the seizures

01:37:43.760 | were starting and propagating,

01:37:45.640 | and then we could stimulate these electrodes

01:37:48.280 | to see if there was a symptom that was important,

01:37:50.500 | and try to identify a region

01:37:52.760 | that we thought we could either remove surgically,

01:37:55.920 | ablate with a laser, or put a stimulator in it perhaps.

01:37:59.520 | That's commonplace now for epilepsy,

01:38:03.780 | and it works extremely well, and it's very safe.

01:38:06.340 | Of course, it's still a brain procedure,

01:38:08.680 | but the complication rate is surprisingly low,

01:38:12.540 | quite honestly, for the amount of electrodes that we place,

01:38:15.440 | and it's extremely well tolerated.

01:38:17.620 | Most of these patients leave the hospital,

01:38:18.920 | and they don't even feel like they've had surgery,

01:38:21.160 | so there's actually a lot of interest

01:38:23.280 | in using that procedure to study mental health disorders.

01:38:27.480 | We are trying to do it for patients

01:38:30.640 | with obsessive-compulsive disorder.

01:38:32.500 | We're awaiting an FDA decision on that,

01:38:35.160 | but actually, I credit our colleagues at Baylor

01:38:38.720 | and at UCSF for studying this already.

01:38:42.380 | We have fabulous colleagues at UCSF

01:38:45.920 | that have studied depression using this type of approach.

01:38:49.080 | A mutual friend of ours, Eddie Chang,

01:38:52.760 | who's a wonderful friend and colleague,

01:38:55.360 | somebody I've emulated for many years as well,

01:38:58.240 | and the psychiatry team at UCSF

01:39:00.520 | have worked together on this, sort of bringing together

01:39:03.760 | the epilepsy technique and the psychiatry expertise

01:39:06.680 | to study how we could better target electrodes

01:39:10.080 | in depression, and I'll tell you,

01:39:12.000 | if they have a consistent target,

01:39:14.520 | perhaps there becomes an ultrasound target,

01:39:18.240 | but right now, the approach is a bit more reversible

01:39:21.220 | 'cause you can always shut that electrode off

01:39:23.360 | or even remove the electrode if perhaps it's not

01:39:26.360 | in the optimal location to treat the depression,

01:39:29.920 | but actually, after a large volume of cases,

01:39:32.960 | perhaps they could pool that data

01:39:35.640 | to develop a new ultrasound target for depression.

01:39:39.440 | I think that would be fabulous,

01:39:40.600 | and probably is their long-term goal,

01:39:43.440 | not to speak for them, but that would be something

01:39:45.520 | that I'm sure is on their radar,

01:39:47.560 | and Baylor's trying to do the same thing for depression.

01:39:51.120 | Their approaches are a little bit different,

01:39:52.720 | but a similar tool to try to understand depression,

01:39:55.520 | and we're working with all of these types of colleagues,

01:39:59.680 | some of these are our friends,

01:40:00.720 | to try to bring this to OCD as well,

01:40:03.320 | and it makes sense to try to do this for addiction

01:40:06.200 | and obesity and anorexia.

01:40:08.500 | You might ask, well, why aren't you doing this

01:40:10.000 | for obesity right now in our study,

01:40:13.000 | and the reason is that we've developed a target

01:40:15.960 | for obesity and binge eating disorder developed out of mice

01:40:20.440 | that we believe is relevant for the human state

01:40:23.760 | because you can model this problem in a mouse

01:40:26.360 | a bit better than you can model depression or OCD,

01:40:30.060 | so we feel like we can rely on the preclinical studies more,

01:40:34.080 | whereas with these perhaps more,

01:40:36.280 | I don't wanna say more complicated,

01:40:37.480 | but more human mental health conditions

01:40:39.920 | that are hard to model in a mouse,

01:40:42.720 | you really have to study it in the human,

01:40:45.620 | and you can perhaps start in an epileptic patient,

01:40:47.660 | a patient that has electrodes

01:40:49.000 | and try to provoke a depressed state or study epileptics

01:40:52.000 | like Dr. Chang has done that have comorbid depression,

01:40:55.280 | for example, and that can really validate

01:40:57.720 | this approach as well, but in the end,

01:40:59.820 | it's getting into the human brain

01:41:01.360 | that we need to do in the disease specifically

01:41:04.680 | that will eventually lead to a non-invasive approach,

01:41:09.600 | either a lesion or a modulatory approach.

01:41:11.680 | Modulatory would be like TMS,

01:41:13.200 | or lesion approach would be with ultrasound.

01:41:15.740 | - I couldn't agree more.

01:41:19.520 | Meanwhile, because there are many, many millions

01:41:22.960 | of people suffering from depression, eating disorders,

01:41:25.900 | Parkinson's and essential tremor, et cetera.

01:41:29.760 | Well, first of all, I should say,

01:41:32.440 | based on everything you've told me thus far,

01:41:34.960 | it's amazing to me that any pharmacologic treatments work

01:41:39.440 | because of how systemic they are

01:41:41.400 | and impacting serotonergic neurons over here

01:41:44.480 | and dopaminergic neurons over there

01:41:46.000 | and not targeting any specific batch of cells.

01:41:47.980 | It makes perfect sense

01:41:49.000 | as to why all the side effects exist,

01:41:51.240 | but earlier you said something

01:41:52.440 | that really grabbed my attention I want to come back to,

01:41:54.780 | which is that if people can be made to feel

01:41:59.040 | or make themselves feel just a little bit better,

01:42:02.320 | a little less anxious just prior to a craving episode

01:42:05.560 | or a binge episode,

01:42:06.720 | maybe even if people can become better

01:42:09.800 | at detecting their own internal states

01:42:12.160 | and when they're kind of veering toward a binge

01:42:14.520 | or veering toward using a drug

01:42:16.320 | or maybe even veering towards suicidal thinking,

01:42:22.000 | based on what you said earlier,

01:42:23.800 | that those kind of pre-behavioral states

01:42:28.560 | on the kind of drift on the steering,

01:42:31.200 | those sound like powerful levels of awareness,

01:42:37.360 | at least for now,

01:42:38.960 | until we have specific sites in the brain

01:42:40.960 | that we can target non-invasive methods

01:42:42.680 | that could be deployed to millions and millions of people.

01:42:44.880 | It seems like that awareness seems like

01:42:47.840 | maybe among the best tools that people could develop.

01:42:50.760 | - Yes, I 100% agree with you.

01:42:52.560 | - So for the person with OCD

01:42:54.160 | or who suffers from anorexia or binge eating disorder

01:42:58.040 | and to their clinicians,

01:42:59.800 | I just want to highlight that you said that.

01:43:01.680 | I mean, again, I'm not a clinician.

01:43:03.560 | I always say this, I don't prescribe anything.

01:43:05.080 | I profess things.

01:43:06.340 | But awareness of one's thinking

01:43:11.840 | seems immensely powerful in this context.

01:43:14.600 | And after all, it is the clinical probe that you use

01:43:20.680 | because let's say the patient were to lie to you

01:43:23.200 | about their experience of what happens in their mind

01:43:27.360 | when you stimulate,

01:43:28.440 | basically the whole thing, the whole surgery,

01:43:31.760 | the whole procedure could go badly wrong.

01:43:34.600 | So it's up to the patient to be, of course,

01:43:37.120 | honest with you and they're incentivized to do that.

01:43:40.120 | But to be honest with themselves about,

01:43:42.960 | ah, you know, I've gone all day without a binge,

01:43:45.800 | but you know, the smell of a donut

01:43:48.480 | or the thought of a donut

01:43:49.440 | is starting to have a particular allure,

01:43:51.640 | that awareness seems like an incredibly powerful thing

01:43:54.520 | to own and to build and cultivate.

01:43:57.080 | - Yes.

01:43:57.960 | I've always thought that if we could improve awareness,

01:44:00.320 | we can improve outcomes.

01:44:01.760 | I think that's probably true for many of these patients.

01:44:04.560 | The problem I think comes down to the fact

01:44:06.720 | that some of these patients are so resistant to treatment.

01:44:10.600 | And the patients that we see as a surgeon, for example,

01:44:14.160 | are the patients that they've tried

01:44:16.480 | cognitive behavioral therapy,

01:44:18.160 | certainly have tried medications,

01:44:19.480 | they've tried behavioral management.

01:44:21.600 | They are aware of their problem.

01:44:23.880 | And they've shown that to us.

01:44:24.960 | They can tell us when they're craving,

01:44:27.520 | but despite the craving and despite being involved

01:44:29.800 | in this invasive brain surgical trial,

01:44:32.520 | highly, you know, first in human novel study,

01:44:36.160 | which I think will have a positive effect,

01:44:38.520 | but it's still experimental.

01:44:40.040 | They still can't stop themselves.

01:44:42.800 | So they're sort of as made aware as could possibly be.

01:44:47.880 | Did I use grammar there correctly?

01:44:49.280 | I think so.

01:44:50.120 | They're as aware as they could possibly be

01:44:53.760 | and they still lose control.

01:44:55.920 | We've had this studied in the lab.

01:44:57.880 | So we will bring patients to the laboratory

01:44:59.880 | with this implanted device

01:45:02.040 | to try to provoke this electrographic electrical signal

01:45:05.840 | that can be detected by the actual device

01:45:08.880 | that will stimulate them when they're at home.

01:45:11.960 | But before we actually initiate stimulation,

01:45:13.760 | we want to see can this device detect this craving cell

01:45:18.200 | signal, which is gonna be different

01:45:20.120 | than what we saw in the operating room

01:45:21.080 | because that's a single cell.

01:45:22.240 | But these devices, these electrodes are about a millimeter

01:45:24.920 | in diameter instead of like a 10th of a millimeter,

01:45:27.560 | which is what we use in the operating room.

01:45:30.320 | So they're only hearing or detecting, I should say,

01:45:34.160 | thousands of cells responses.

01:45:36.560 | And we actually have a way to provoke binges.

01:45:41.560 | It's called a mood provocation.

01:45:43.440 | It's very well validated.

01:45:46.040 | It's a little bit like provoking seizures

01:45:47.640 | in the epilepsy monitoring unit.

01:45:49.000 | But here in the sort of psychiatric monitoring unit

01:45:53.520 | or the food monitoring unit,

01:45:55.360 | we actually have a psychiatrist

01:45:58.400 | and eating disorder specialists come and induce a mood

01:46:02.600 | that is related to each patient's

01:46:05.880 | sort of self-described binge episode.

01:46:09.440 | - So the psychiatrist comes in and provokes

01:46:12.720 | a feeling that can evoke the negative behavior.

01:46:17.440 | - That's exactly right.

01:46:18.280 | So that we can video and synchronize the video

01:46:21.200 | to the brain signal recordings.

01:46:23.480 | The patients all wear an eye tracker

01:46:25.840 | so we can see what they're eating at all times

01:46:28.240 | and what they're looking at specifically.

01:46:30.400 | And that allows us to have the best temporal resolution

01:46:35.400 | possible to understand what is happening

01:46:38.280 | right before the bite.

01:46:39.960 | And even under video surveillance through a one-way mirror

01:46:43.400 | in a laboratory setting when patients are very well aware

01:46:48.400 | that they're there to be studied if they're going to binge.

01:46:53.080 | They still do.

01:46:54.400 | And we believe they do because they just can't control it

01:46:57.600 | as aware as they are of it.

01:47:00.360 | And it's probably because they're the most severe.

01:47:03.040 | So I think if we can improve awareness,

01:47:05.800 | not just the societal awareness

01:47:07.160 | that I was talking about earlier,

01:47:08.160 | but the patient awareness around their problem,

01:47:11.440 | I think that could be a powerful way

01:47:13.160 | to help so many of these patients.

01:47:14.560 | And that's sort of the role of cognitive behavioral therapy.

01:47:18.160 | The problem with cognitive behavioral therapy,

01:47:19.840 | or I should say the limitation of it,

01:47:21.200 | I actually don't have any problem with it,

01:47:22.560 | I think it's a wonderful treatment,

01:47:24.200 | is that if you stop it,

01:47:27.600 | many of these patients go back to their old behaviors.

01:47:30.800 | I don't want to say old habits, but it might be a habit,

01:47:32.760 | but the old behaviors.

01:47:34.600 | And so that's the problem

01:47:37.200 | is that it's not necessarily lasting

01:47:38.400 | in the absence of continued cognitive behavioral therapy.

01:47:40.640 | Some people can benefit from it long-term, but some can't.

01:47:43.480 | But I think in the less severe patients,

01:47:48.360 | improving awareness is key.

01:47:50.160 | But in these really refractory patients,

01:47:51.680 | this is kind of like, this is the disease.

01:47:54.240 | Despite the awareness, they can't control themselves.

01:47:56.960 | And that's what we're trying to restore

01:47:58.400 | is that improved ability to control their behavior.

01:48:01.840 | - Do you think there's a role for machines

01:48:03.880 | and artificial intelligence here?

01:48:07.320 | - There are a couple laboratories

01:48:08.280 | up at the University of Washington

01:48:10.040 | that are using particular signature patterns within voice

01:48:15.040 | to try and help people who are suicidally depressed

01:48:22.240 | know when they're headed towards an episode

01:48:24.840 | before they even can consciously know.

01:48:26.760 | So this gets right down to issues of free will

01:48:28.280 | and whether or not machines can be smarter than we are.

01:48:30.400 | But one could argue that some of the search algorithms

01:48:33.440 | on Google and other search engines

01:48:35.080 | are actually more aware of our preferences than we are.

01:48:37.960 | Basically what these are,

01:48:40.880 | these are devices that are listening to people talk all day.

01:48:43.420 | They're also paying attention to patterns of breathing

01:48:45.480 | and how well people slept, et cetera.

01:48:46.880 | Integrating a huge number of cues

01:48:49.600 | and then signaling somebody with a yellow light.

01:48:53.200 | Like, you're headed into a depressive episode

01:48:55.320 | and the person might say, "Oh, I feel fine,"

01:48:57.000 | or, "I feel pretty good.

01:48:58.060 | This is kind of baseline state for me."

01:48:59.880 | And they'll say, "Uh-uh, this is where you were

01:49:03.520 | preceding the last episode that took you down

01:49:05.600 | a deep dark trench and it took months to get out of."

01:49:09.000 | I wonder whether or not some of these devices

01:49:11.320 | could help with the sorts of things

01:49:13.160 | that we're talking about today.

01:49:14.400 | - Yeah, I think so.

01:49:16.700 | I've always said we have to get in the brain

01:49:19.040 | before we get out of it.

01:49:20.280 | And if we get in the brain and understand

01:49:21.960 | what these signals look like,

01:49:23.720 | we'll know what those non-invasive signals are.

01:49:26.520 | I think it's possible that we are

01:49:30.320 | scientifically sophisticated enough to

01:49:33.960 | use machine learning and sort of this kind of bot technique

01:49:38.960 | to anticipate when somebody is going to be highly impulsive.

01:49:43.040 | Suicide is the most dangerous impulse.

01:49:44.560 | It's something that is

01:49:45.760 | immensely a focus of the lab is impulsivity.

01:49:50.860 | We've talked mostly about compulsion.

01:49:53.120 | Compulsion being going after a reward

01:49:56.320 | or the urge despite the risk.

01:49:59.480 | Impulsivity is similar but different.

01:50:01.520 | It's kind of going after something a little bit.

01:50:05.640 | If you model impulsivity in a mouse,

01:50:08.240 | it's related to going after a food reward

01:50:13.240 | without the sort of paired tone

01:50:16.180 | that the mouse is supposed to wait for.

01:50:18.180 | The mouse doesn't want to wait anymore.

01:50:19.400 | They just go after the food.

01:50:21.440 | - I've been that mouse.

01:50:22.360 | - Yeah, we all have been.

01:50:24.520 | We can all relate with this to a certain extent.

01:50:26.920 | Again, it's the spectrum.

01:50:29.200 | So in any case, non sequitur.

01:50:33.120 | But I certainly think that there is a way

01:50:36.960 | to use our own body's physiology

01:50:40.620 | to anticipate when these impulses are coming online.

01:50:45.360 | How best to do that,

01:50:46.940 | I think we're just scratching the surface.

01:50:48.640 | But these are the kinds of solutions we need.

01:50:52.280 | Some of these problems are of epidemic proportions.

01:50:57.440 | The largest public health problems in this country,

01:50:59.680 | in this world, obesity, opiate crisis, depression,

01:51:03.080 | suicidality, I mean, that's like a third of our country,

01:51:05.560 | maybe more, probably more.

01:51:07.920 | And think about it.

01:51:08.760 | - And a colleague of ours at Stanford Psychiatry

01:51:10.720 | told me something that still just blows my mind,

01:51:13.180 | which is that something like 75% of the antidepressant

01:51:18.180 | and anti-anxiety medication that exists in the world

01:51:21.480 | is consumed in the United States.

01:51:23.480 | - That's amazing.

01:51:24.300 | - Which is, I mean, that's an outrageous number.

01:51:26.500 | - Yeah, we do have an obsession in this country for pharmacy.

01:51:29.680 | And the pharmaceutical industry is very powerful here

01:51:32.940 | and probably related to some aspect of capitalism.

01:51:35.760 | I'm capitalistic and just like everybody else,

01:51:38.640 | but I do worry about that a little bit.

01:51:41.160 | But we tend to over-prescribe

01:51:44.740 | and I think we, as patients, tend to over-want medication.

01:51:49.660 | We like quick solutions

01:51:50.940 | and sometimes medications provide it, sometimes not,

01:51:53.060 | or they're often just a band-aid.

01:51:54.460 | It depends on the problem, of course.

01:51:57.120 | So, but I agree that we need scalable solutions.

01:52:02.120 | I'm a neurosurgeon.

01:52:03.840 | I'm only gonna be able to treat the most severe of patients

01:52:07.040 | with these problems.

01:52:08.220 | We've only done about 200,000

01:52:12.200 | deep brain stimulation surgeries ever.

01:52:15.440 | So, I mean, the problem we're talking about here

01:52:18.220 | is 50 million Americans.

01:52:20.880 | There's no possibility that surgeons can address that problem

01:52:24.580 | but we could help inspire an initiative

01:52:28.060 | to go after that kind of problem

01:52:29.520 | or help make it more rigorous

01:52:31.360 | because the last thing we need is some sort of wearable,

01:52:34.680 | fancy tool that wastes people's money and time.

01:52:39.680 | We need real therapies for these things.

01:52:42.240 | Not that these devices that we're discussing are not.

01:52:44.840 | I think actually there's lots of promise.

01:52:47.000 | We use machine learning in the lab all the time.

01:52:48.980 | I'm not an electrical engineer

01:52:51.520 | or the computational neuroscientist doing this type of work.

01:52:54.080 | I just helped develop the hypotheses around it

01:52:56.360 | but, and help fundraise around it.

01:52:58.340 | But I definitely think there's a future for it.

01:53:01.120 | I just, I suspect we're scratching the surface

01:53:03.460 | on how best to do it.

01:53:05.360 | - Let's talk about your hands.

01:53:07.100 | - Yeah, sure.

01:53:08.460 | - All the neurosurgeons I know are, you know,

01:53:10.820 | very faithfully protect their hands.

01:53:13.500 | And let's talk about--

01:53:14.340 | - It's 'cause hand insurance is too expensive.

01:53:16.080 | - That's right.

01:53:17.680 | But I'm guessing that you all are not the ones

01:53:20.720 | to reach into the garbage disposal,

01:53:23.040 | even if your eye is on the switch

01:53:24.520 | to make sure that it isn't gonna get turned on.

01:53:26.440 | They're just too precious.

01:53:27.360 | They are your livelihood.

01:53:28.660 | And earlier we talked about deadlifts.

01:53:31.920 | There are other forms of exercise.

01:53:34.240 | There are things like tennis.

01:53:35.980 | They're drawing and painting a full range of things

01:53:38.880 | that one can do with their hands.

01:53:40.040 | Use your imagination, folks.

01:53:42.800 | - Is it true that neurosurgeons don't do any

01:53:47.760 | really like heavy grip activity

01:53:49.400 | because it can refine the motor circuits

01:53:54.320 | in the brain and elsewhere

01:53:55.920 | that can throw off their neurosurgery game?

01:53:59.640 | - I would say that many neurosurgeons

01:54:03.320 | avoid activities that put their hands at risk.

01:54:07.960 | Another one, by the way, you know,

01:54:09.120 | there's an annual softball tournament

01:54:13.080 | that neurosurgeons come to in New York City,

01:54:17.160 | in Central Park, and play. - With a very softball.

01:54:19.220 | No, I'm just kidding.

01:54:20.060 | - Well, actually, it's actually a very, you know,

01:54:23.000 | typical hard softball.

01:54:24.360 | I don't know why they call it softball.

01:54:25.800 | And actually, two close colleagues of mine

01:54:29.120 | have gotten injured at that tournament.

01:54:30.960 | - Maybe this is, it's also, I must say,

01:54:32.840 | and here I'm poking fun,

01:54:34.280 | but for those of you who are going

01:54:35.280 | to the medical profession, it's also one of the more,

01:54:38.620 | how should I say this?

01:54:39.460 | Well, I'm just going to say it.

01:54:40.680 | There's a steep hierarchy of training in neurosurgery.

01:54:43.740 | - Yes.

01:54:44.580 | - There's a certain harshness that's been conveyed to me

01:54:47.180 | about the training, much like astronaut training,

01:54:50.180 | to be totally fair.

01:54:51.540 | And so maybe this is a tactic to weed out

01:54:54.740 | either the younger or the older generation.

01:54:57.700 | - This is evolution, right?

01:54:58.740 | We have to evolve.

01:55:00.060 | - We need medical training. - We have the week, I guess.

01:55:02.960 | Well, I could say that one of the individuals

01:55:04.960 | that got injured is one of the more senior surgeons

01:55:07.080 | that I work with now and is one of the best athletes

01:55:09.740 | that I know, and he's definitely not weak,

01:55:11.520 | but you can get injured playing these sports.

01:55:13.660 | And that being said, I can tell you briefly is,

01:55:17.220 | I think that, you know, it's funny,

01:55:20.060 | my mother came to me recently.

01:55:21.700 | She has osteopenia, and she told me,

01:55:24.700 | her doctor told her she's not allowed to do deadlifts.

01:55:26.700 | And I was like, okay, that's fine.

01:55:30.460 | I'm not telling you you should do deadlifts.

01:55:31.940 | I just don't exactly understand the relationship.

01:55:34.440 | But I can say that I do think,

01:55:38.360 | I'll give you a little story here.

01:55:40.780 | The reason why I'm being a little hesitant

01:55:42.580 | to confirm that I agree with you on the deadlifts is,

01:55:45.220 | when I was operating,

01:55:48.260 | this was when I was at Stanford University operating,

01:55:50.820 | and as I mentioned earlier,

01:55:53.300 | we get an intraoperative CAT scan

01:55:54.940 | to confirm accuracy of our lectures.

01:55:56.140 | I do this for all of my surgeries.

01:55:57.900 | When I was reviewing that CAT scan,

01:55:59.460 | the X-ray technician looked at me and said,

01:56:02.580 | whispered into my ear, he's like,

01:56:03.940 | "Your posture is really bad, it's embarrassing."

01:56:08.020 | - Your physical posture while doing your surgeries?

01:56:09.960 | - Yeah. - Uh-huh.

01:56:10.940 | - And I looked at him,

01:56:11.780 | and I kind of wanted to say I won't curse,

01:56:13.480 | but I, yeah, exactly.

01:56:15.380 | I've been doing it intermittently during our conversation,

01:56:17.600 | 'cause he made me realize

01:56:19.000 | that I really did have bad posture.

01:56:20.780 | And we kind of had a little brief aside,

01:56:23.800 | and I learned he was a personal trainer,

01:56:26.080 | and his name was Zach.

01:56:27.860 | And he said to me, "Your posture is weak because,

01:56:32.100 | "or your posture is poor because you're weak.

01:56:34.220 | "You need to strengthen your body and strengthen your core."

01:56:37.780 | I was like, "How?"

01:56:39.140 | He's like, "Powerlifting."

01:56:41.500 | And I'm like, "I'm a little hesitant to do this."

01:56:43.800 | And I'll tell you, I started very slowly,

01:56:46.100 | and I can't prescribe powerlifting to everybody

01:56:48.060 | for the exact reason you said,

01:56:49.680 | and I've gotten hurt doing it, by the way.

01:56:52.360 | But I do think, I wish I started a little younger,

01:56:56.540 | and I would argue that with close supervision

01:56:59.940 | and very well, if you have a very experienced trainer,

01:57:04.940 | which I would argue if you're a neurosurgeon or an astronaut,

01:57:09.140 | or have a highly specialized profession

01:57:11.260 | where you need your limbs to function,

01:57:15.060 | dentist, things like that,

01:57:16.300 | if you're gonna take something on like this,

01:57:18.420 | it really needs to be extremely carefully supervised.

01:57:20.980 | And I can tell you that my trainer had a profound impact

01:57:24.300 | on my life and my posture and my physical health.

01:57:27.660 | And so we did deadlift, I'll admit.

01:57:30.820 | So when you brought it up, I kind of chuckled to myself.

01:57:33.140 | But yes, I have gotten mildly hurt deadlifting,

01:57:37.100 | but it was when I was doing it by myself

01:57:38.460 | and I was kind of cocky and I wasn't paying attention.

01:57:41.100 | But when I was with him and he was all over my technique,

01:57:45.180 | it actually was the most efficient way

01:57:46.780 | for me to feel stronger,

01:57:48.320 | and it improved my posture significantly.

01:57:51.620 | And I miss him since I left California.

01:57:54.060 | I have a new trainer in Philadelphia who's great,

01:57:56.140 | but, and I still deadlift occasionally with him,

01:57:59.500 | but I can say I am opposed to deadlifting callously.

01:58:04.380 | But if you're extremely well monitored

01:58:07.580 | by an experienced personal trainer or weightlifter,

01:58:11.180 | I think it could be a great exercise.

01:58:13.500 | - Great, I'd love to be wrong in this case,

01:58:16.500 | because I'm a huge proponent,

01:58:18.660 | and on the podcast I go on and on.

01:58:20.080 | I mean, there's so much data now pointing to the fact

01:58:23.220 | that 180 to 200 minutes of zone two cardio

01:58:27.860 | kind of jogging, cycling, swimming type behavior

01:58:30.200 | is very healthy for everybody,

01:58:31.740 | and we should all be doing that, at least that.

01:58:33.700 | - Yes, I need to as well.

01:58:34.940 | - And that resistance training on the order of,

01:58:37.860 | you know, six hard sets per muscle group per week

01:58:40.620 | is really important just to offset deterioration of muscles.

01:58:43.820 | - I'm learning as we go here.

01:58:44.740 | - Skeletal function and tendon strength,

01:58:47.060 | and that's just to maintain.

01:58:48.540 | We're not talking about all outsets to absolute failure,

01:58:51.020 | but as you point out with proper form.

01:58:53.880 | So even the neurosurgeons are doing this,

01:58:56.920 | which I think is wonderful.

01:58:59.600 | As a final question, but one that I think really,

01:59:04.600 | or maybe second to final question,

01:59:06.780 | earlier I commented on the remarkable calm,

01:59:10.060 | at least perceived calm of neurosurgeons.

01:59:13.580 | It could be cause or could be effect of the training,

01:59:16.700 | but it's obvious to me why one would want that trait

01:59:20.900 | in their neurosurgeon.

01:59:22.340 | I wouldn't want a hyperactive,

01:59:25.020 | certainly not an impulsive neurosurgeon,

01:59:26.940 | given that the margins of error are so, so tiny,

01:59:30.860 | the spatial scale, and probably on the temporal scale too.

01:59:33.820 | You don't want people doing things in time

01:59:35.860 | that are being spontaneous at all.

01:59:38.300 | Do you think that this branch of medicine that you're in

01:59:43.060 | selects for people that at least can know how to control

01:59:47.720 | any kind of fluctuations in autonomic arousal,

01:59:50.060 | they can calm themselves in real time?

01:59:52.020 | And here's a specific question,

01:59:53.420 | when I've never operated on the human brain,

01:59:55.700 | although I've had the privilege of being

01:59:57.080 | in the operating room and seeing this

01:59:58.660 | with some of our experiments with people in VR,

02:00:01.220 | it's a remarkable thing.

02:00:02.780 | I wish for everybody that would get this experience

02:00:04.820 | at some point, not hopefully as a patient,

02:00:06.700 | unless they have a need, but to observe it.

02:00:09.220 | But what was just striking to me is

02:00:13.580 | the various stereotype behaviors of the surgeon.

02:00:17.940 | And when I did surgeries as a graduate student,

02:00:19.920 | as a postdoc in the brains of other types of animals,

02:00:22.600 | I would find, for instance,

02:00:23.440 | that if I started to tremble a little bit,

02:00:24.880 | if I tapped my left foot,

02:00:26.820 | that my hand would stabilize a bit,

02:00:28.760 | that there's this kind of need to move the body,

02:00:30.580 | or one feels the impulse.

02:00:31.540 | Maybe that's my Tourette's-like compulsions again.

02:00:35.180 | But that one can kind of siphon off some of that energy

02:00:39.600 | into another limb so that you could remain precise.

02:00:42.640 | So are these sorts of things that I'm talking about are,

02:00:46.100 | maybe it's entirely my imagination,

02:00:47.920 | but are these the sorts of things that one learns

02:00:50.340 | as a neurosurgeon how to still the body and still the mind?

02:00:54.180 | Do you have a meditative practice?

02:00:55.760 | When you go into the operating room,

02:00:57.500 | if you had a particularly challenging morning

02:00:59.780 | or a poor night's sleep,

02:01:01.580 | do you have tools that you use to calibrate yourself

02:01:04.780 | and get yourself into the zone?

02:01:06.700 | I think this would be very interesting

02:01:08.220 | for people to get some insight into,

02:01:09.940 | even if they don't want to be a neurosurgeon.

02:01:11.740 | - Yeah, I completely agree.

02:01:13.220 | And I appreciate the earlier reference to neurosurgeons

02:01:17.300 | as astronauts, 'cause I've also heard us

02:01:20.740 | compared to cowboys before,

02:01:22.060 | and it's a little bit less flattering.

02:01:23.920 | Some of what we do surgically really does require

02:01:30.480 | a substantial amount of confidence.

02:01:32.180 | And that confidence hopefully comes from

02:01:36.500 | years of training and experience.

02:01:39.060 | You always worry that the confidence is sort of misplaced,

02:01:43.660 | and that is problematic.

02:01:45.600 | Luckily, you so rarely see that,

02:01:47.580 | because our training is so rigorous.

02:01:50.240 | We have a board of,

02:01:53.080 | American Board of Neurological Surgeons

02:01:54.680 | that sort of allows and assesses surgeons

02:01:59.680 | to continue practice and holds us to a really high bar.

02:02:04.140 | I do think it tends to attract a certain personality.

02:02:08.660 | In my subspecialty, as a deep brain stimulation surgeon,

02:02:12.820 | we call it stereotactic and functional neurosurgery.

02:02:15.620 | Some people have likened us

02:02:16.800 | to the neurologists with a scalpel.

02:02:19.700 | We tend to be a bit more intellectual.

02:02:21.660 | Maybe bedside manner is a little bit friendlier.

02:02:27.700 | And then there's the vascular neurosurgeon

02:02:29.660 | who doesn't sleep, and so they're not as friendly.

02:02:32.060 | There's the spine surgeons who operate the most,

02:02:34.900 | and so they're busy, busy, busy.

02:02:37.280 | There are some of these kind of reputations going around,

02:02:40.460 | but I agree with you.

02:02:41.460 | There's a sort of a common feature of a calmness

02:02:44.660 | across neurosurgeons, and there's some of my,

02:02:47.840 | obviously my favorite people, my closest friends,

02:02:50.920 | and I can relate with them probably because of that.

02:02:55.020 | Sort of a big picture.

02:02:56.540 | They don't get sort of flustered.

02:02:59.540 | They tend to be really good at figuring out

02:03:05.940 | how to have quality time, because we work really hard.

02:03:08.380 | Our hours are significant,

02:03:10.820 | and so the time with our families, our friends,

02:03:13.940 | is less than we would like it to be.

02:03:16.260 | Obviously, that's true for people who work hard

02:03:19.180 | across any profession,

02:03:20.180 | but definitely true for neurosurgeons.

02:03:22.260 | And I think that we're very good at figuring out

02:03:24.340 | how to make that time high quality.

02:03:26.160 | Even just texting with some of my friends

02:03:30.780 | that are neurosurgeons, a great friend of mine

02:03:32.640 | just became chairman at Duke,

02:03:34.380 | and just connecting with him by text, which takes seconds.

02:03:38.300 | We feel connected.

02:03:41.260 | I think that's a trait amongst neurosurgeons.

02:03:43.900 | We sort of know how to cut to the chase, in a way,

02:03:46.380 | and prioritize our time.

02:03:48.580 | It's a skill that we probably have innately,

02:03:52.100 | but it's also part of the training.

02:03:53.780 | When we are interns now, there's a lot of work hour

02:03:57.040 | regulations that is probably quite appropriate, by the way.

02:04:00.420 | I think our hours before were bordering on not necessarily,

02:04:05.420 | let's just say they were not ideal for mental health,

02:04:10.220 | and sleep, which we know are very important components.

02:04:13.900 | Certainly, we had no time for meditation.

02:04:15.740 | I definitely did not.

02:04:16.740 | I wish I did.

02:04:17.840 | Now, knowing what I know about meditation,

02:04:21.540 | my wife's a health coach.

02:04:22.580 | I get it, I see it, I practice it myself with her.

02:04:27.000 | I see the value.

02:04:28.780 | I wish I had that tool when I was in training,

02:04:30.760 | because it's stressful.

02:04:31.960 | Even with the work hour restrictions,

02:04:35.140 | we still don't sleep very much.

02:04:36.260 | We're still at work a lot, about 80 hours a week.

02:04:39.700 | - Throughout the entire career?

02:04:41.900 | - There are times when it's more,

02:04:43.180 | because after training, there's no work hour restrictions.

02:04:47.340 | So sometimes I feel like as faculty, we get abused,

02:04:51.100 | and the trainees are a little bit more protected now.

02:04:53.440 | It definitely was the reverse at one point.

02:04:55.540 | That's also a huge problem, probably more of a problem.

02:04:58.580 | And I'm joking a little bit.

02:04:59.500 | I don't necessarily think we're abused,

02:05:01.180 | but certainly our hours are significant.

02:05:03.900 | But they come a bit more here and there.

02:05:08.900 | On my OR days when I'm operating, those are long days,

02:05:11.740 | but on the days that I'm lucky enough to be a researcher,

02:05:15.020 | like you, those days tend to be a bit gentler,

02:05:17.940 | unless I'm grant writing, those days can be long,

02:05:19.980 | as you know.

02:05:20.820 | So to answer your question,

02:05:23.940 | I do think we're sort of self-selected for it,

02:05:26.140 | but I also think it's part of the training.

02:05:28.520 | Because of the long hours that we're in the hospital,

02:05:30.820 | we're taking care of sick patients,

02:05:33.060 | and we have sort of a type A mentor approach,

02:05:36.840 | where our mentors are hard on us.

02:05:39.360 | We learn to cope with our stress and be efficient

02:05:43.040 | and prioritize things despite the stress of it all.

02:05:47.440 | And I think we take from that this sort of calm demeanor.

02:05:51.760 | And perhaps it just amplifies what we're probably drawn to,

02:05:56.760 | because before we come to neurosurgery,

02:05:59.580 | we might rotate in neurosurgery.

02:06:01.280 | We might spend a month pretending to be a neurosurgeon,

02:06:05.240 | learning from residents and faculty

02:06:08.280 | that are practicing the specialty.

02:06:10.120 | But prior to actually starting your training,

02:06:13.360 | you never experience anything

02:06:14.940 | like being a resident in neurosurgery.

02:06:17.840 | The stress and the volume of patients

02:06:20.440 | that you have to take care of and the long nights.

02:06:23.080 | It can be quite lonely, by the way.

02:06:25.360 | You develop friends in the hospital,

02:06:26.800 | but sometimes you're on your own when you're on call,

02:06:29.540 | and you have backup.

02:06:30.380 | You can call your chief resident or your attending,

02:06:32.920 | but you really have to learn how to take care of patients

02:06:35.340 | yourself.

02:06:36.180 | You obviously form teams with nurses and staff

02:06:38.400 | and things like that and other residents,

02:06:39.920 | but it can be lonely.

02:06:41.360 | It can be really challenging.

02:06:42.820 | And I think because of those experiences

02:06:45.240 | that all neurosurgeons go through,

02:06:47.320 | we tend to have this sort of unflappable personality

02:06:54.720 | that perhaps we started with a bit

02:06:56.740 | compared to the average person,

02:06:58.820 | but the training definitely amplifies it.

02:07:01.120 | And do you have tools that you implement

02:07:04.580 | if you ever feel that you're getting slightly off center?

02:07:07.760 | - I do now.

02:07:08.660 | When I was in training,

02:07:13.880 | I actually remember in my second year,

02:07:17.900 | so most neurosurgery programs when you're a junior resident,

02:07:21.840 | in some ways that's your toughest year, not in every way.

02:07:24.820 | It is your toughest year because you're young

02:07:29.040 | and you're inexperienced and you don't know

02:07:31.320 | what you don't know.

02:07:32.420 | And that's why it's such a tough year

02:07:34.240 | 'cause you have to learn a lot very quickly

02:07:36.320 | for patient safety reasons, for self survival.

02:07:39.920 | You just have to learn a lot

02:07:41.320 | and you're on call by yourself in the hospital.

02:07:44.640 | And it's a real challenge.

02:07:46.760 | And I think that I personally,

02:07:49.260 | I gained a lot of weight during that year.

02:07:51.280 | The only exercise I did consciously was taking the stairs.

02:07:54.560 | I refused to take the elevator.

02:07:56.160 | And I was at Penn at HUP where I currently practice now.

02:08:00.240 | And I remember I would see patients

02:08:02.400 | anywhere from sort of the ground floor

02:08:04.200 | where the trauma bay was or the ER

02:08:06.200 | all the way up to Founders 12th floor.

02:08:08.280 | And I would never take an elevator.

02:08:09.700 | That was my rule for the year

02:08:10.880 | 'cause I knew I would not have time to exercise,

02:08:13.360 | but I would just take the stairs.

02:08:14.680 | And in the beginning of the year,

02:08:15.920 | I would be a little winded when I got to the 12th floor.

02:08:18.480 | But by the end of the year,

02:08:19.320 | actually it didn't really faze me

02:08:20.760 | and it became a great habit to have.

02:08:22.800 | The problem with that though,

02:08:25.120 | is I paired that unfortunately with a lot of sleepless nights

02:08:29.280 | or not enough sleep let's say.

02:08:31.400 | And I had this terrible habit

02:08:33.760 | of drinking coffee late at night

02:08:36.620 | and I would put a lot of sugar in it.

02:08:38.140 | And it was sort of the only way for me to get a quick,

02:08:40.760 | a quick bout of energy

02:08:43.800 | that for some reason I prioritized at that time,

02:08:46.600 | obviously knowing that I would crash, which I always did.

02:08:49.020 | And I always kind of regretted it, but I still did it anyway.

02:08:51.320 | And I attribute that to poor decision-making, inexperience,

02:08:56.320 | and perhaps being a little vulnerable,

02:08:59.160 | like I think we all are.

02:09:00.160 | That's why I relate with a lot of the research that I do.

02:09:02.960 | And I remember I got married in my third year,

02:09:05.400 | the year after my second year.

02:09:07.000 | And my wife and I, or my fiance at the time,

02:09:09.600 | we started going to the gym together in the morning

02:09:11.880 | and my hours were a little better.

02:09:13.700 | So I would actually be able to exercise

02:09:15.180 | before I operated that day.

02:09:16.920 | And I operated almost every day as a third year resident.

02:09:19.420 | So I remember I'd get to the gym really early

02:09:21.120 | and in three months I lost like 20 pounds

02:09:23.240 | and I wasn't trying to lose weight.

02:09:24.360 | I just was sleeping better and taking care of myself.

02:09:27.300 | And I remember when we got married,

02:09:28.860 | I fit into a tuxedo that I had in college,

02:09:32.660 | or it would have fit me in college.

02:09:33.720 | It actually was a new tuxedo admittedly,

02:09:35.240 | but it was the same size as my tuxedo from college.

02:09:37.440 | So I think that I've always related with the problems

02:09:41.360 | that our patients have to a certain extent.

02:09:43.840 | And when I've been most vulnerable,

02:09:47.200 | which is when I was working the hardest

02:09:49.200 | with the least amount of sleep,

02:09:50.260 | I related with it the most.

02:09:51.760 | And yes, exercise for me has always been my tool.

02:09:55.680 | More recently, exercise, some strength training

02:10:00.820 | I think is important compared with cardio.

02:10:03.560 | I don't do enough of either,

02:10:05.360 | but I definitely do some and that helps.

02:10:07.820 | Meditation helps me a bit.

02:10:09.160 | I do that every night before I go to sleep.

02:10:11.260 | I use an app for it.

02:10:14.260 | It's probably not the best way to do meditation, but-

02:10:16.440 | - If it keeps you doing it regularly,

02:10:17.820 | it's the best way to do it.

02:10:19.400 | - Andrew, I couldn't agree with you more.

02:10:21.000 | It's one of those things

02:10:21.840 | where I look forward to it every night.

02:10:23.300 | And sometimes my wife falls asleep

02:10:26.840 | and I come to bed a little later and I whisper,

02:10:28.840 | I'm like, "Are you okay if I turn the app on?"

02:10:30.540 | So she does the same to me 'cause I think we both value it.

02:10:34.000 | And I think that's been very helpful.

02:10:35.720 | And I didn't have that tool probably when I needed it most,

02:10:38.960 | but I have it now and it's very helpful.

02:10:41.720 | - I really appreciate you sharing those tools.

02:10:44.360 | A number of people I'm guessing out there

02:10:46.860 | might want to become neurosurgeons.

02:10:48.240 | I really believe that in hearing today's conversation

02:10:50.880 | that you will spark an interest in medicine

02:10:53.360 | and or neurosurgery. - I hope so.

02:10:55.500 | - Well, certainly you need to be a physician

02:10:57.660 | before you can become a neurosurgeon.

02:10:58.860 | So end neurosurgery in some cases,

02:11:00.840 | and that would be beautiful.

02:11:02.120 | And I predict that will happen, excuse me,

02:11:04.640 | as a consequence of what you've shared today.

02:11:07.960 | I really appreciate your mentioning of the emphasis

02:11:12.320 | and appreciation on quality time.

02:11:15.720 | I very much see this as quality time.

02:11:17.720 | I know that our listeners will as well.

02:11:20.700 | Really want to thank you for taking time out of your,

02:11:22.640 | not just immensely busy, but very important schedule

02:11:25.160 | because again, the work that you're doing

02:11:27.440 | is really out there on that cutting,

02:11:30.920 | I don't want to say bleeding edge,

02:11:31.920 | 'cause in this context it's not going to sound right,

02:11:33.720 | but on that extreme cutting edge of what we understand

02:11:37.000 | about how the human brain works and how it can be repaired.

02:11:40.000 | They're doing marvelous work.

02:11:41.540 | We will point people to various places

02:11:44.120 | they can find you online.

02:11:45.680 | And should they need the help of your clinic,

02:11:49.600 | to your clinic and your laboratory as well.

02:11:52.200 | So on behalf of everybody and myself as well,

02:11:55.240 | thank you so, so very much.

02:11:57.120 | - I'm honored.

02:11:57.960 | Thank you so much for having me.

02:11:59.120 | - Thank you for joining me today

02:12:00.160 | for my discussion with Dr. Casey Halpern

02:12:02.340 | about the use of deep brain stimulation

02:12:04.440 | and novel technologies for the treatment

02:12:06.220 | of eating disorders and movement disorders of various kinds.

02:12:09.460 | For those of you that are interested

02:12:10.560 | in learning more about Dr. Halpern's research,

02:12:12.880 | please see the links in our show note captions

02:12:14.680 | that include links to his laboratory website

02:12:17.400 | and to his clinic as well as various research publications

02:12:20.840 | that are available in complete form as downloadable PDFs.

02:12:24.340 | If you're learning from and or enjoying this podcast,

02:12:26.800 | please subscribe to our YouTube channel.

02:12:28.560 | That's a terrific zero cost way to support us.

02:12:31.040 | In addition, please subscribe to the podcast

02:12:33.080 | on both Spotify and Apple.

02:12:34.800 | And on both Spotify and Apple,

02:12:36.440 | you can leave us up to a five-star review.

02:12:38.920 | If you have questions for us or comments

02:12:40.760 | or feedback of any kind,

02:12:42.000 | please put that in the comment section on YouTube.

02:12:44.700 | We do read all the comments.

02:12:46.760 | Please also check out the sponsors mentioned

02:12:48.440 | at the beginning of today's episode.

02:12:49.960 | That's the best way to support this podcast.

02:12:52.160 | Not so much today, but in many previous episodes

02:12:54.320 | of the Huberman Lab podcast, we talk about supplements.

02:12:56.720 | While supplements aren't necessary for everybody,

02:12:58.920 | many people derive tremendous benefit from them

02:13:00.920 | for things like enhancing sleep and focus

02:13:02.900 | and hormone optimization.

02:13:04.580 | The Huberman Lab podcast has partnered

02:13:06.040 | with Momentous Supplements.

02:13:07.240 | If you'd like to see the supplements

02:13:08.320 | that the Huberman Lab podcast has partnered

02:13:09.800 | with Momentous on, you can go to Live Momentous,

02:13:12.280 | spelled O-U-S, so livemomentous.com/huberman.

02:13:15.760 | And there you'll see a number of the supplements

02:13:17.680 | that we talk about regularly on the podcast.

02:13:19.640 | I should just mention that that catalog of supplements

02:13:21.580 | is constantly being updated.

02:13:23.060 | If you haven't already signed up

02:13:24.000 | for the Neural Network newsletter,

02:13:25.200 | this is a monthly Huberman Lab podcast newsletter

02:13:27.960 | in which you get some brief show notes summaries,

02:13:31.000 | as well as a lot of actionable tools in summary form.

02:13:33.940 | Many people find these very useful for distilling out

02:13:36.880 | the vast amount of information that we cover on the podcast.

02:13:39.560 | So for instance, if you go to HubermanLab.com,

02:13:41.880 | you can click on the menu,

02:13:43.640 | click to Neural Network newsletter or simply newsletter,

02:13:47.040 | and you can sign up, just give us your email.

02:13:49.000 | We do not share your email with anybody.

02:13:50.880 | And again, it's completely zero cost.

02:13:53.180 | We also have examples of previous newsletters

02:13:55.320 | that you can download immediately

02:13:56.480 | without having to sign up for anything

02:13:57.840 | and decide whether or not you want to sign up.

02:13:59.520 | Again, that's the Neural Network newsletter

02:14:01.080 | at HubermanLab.com.

02:14:02.840 | If you're not already following us on social media,

02:14:04.920 | we are Huberman Lab on Instagram, on Twitter,

02:14:07.360 | on Facebook, and on LinkedIn, and especially on Instagram

02:14:11.020 | and on Twitter, I cover many of the tools

02:14:13.660 | that are discussed on the Huberman Lab podcast,

02:14:15.360 | but also a lot of science and science-based tools

02:14:17.200 | not covered on the Huberman Lab podcast.

02:14:19.360 | Again, it's Huberman Lab on all platforms.

02:14:21.600 | Once again, thank you for joining me today

02:14:23.280 | for my discussion with Dr. Casey Halpern.

02:14:25.260 | I hope you learned as much as I did.

02:14:27.360 | And as always, thank you for your interest in science.

02:14:30.180 | (upbeat music)

02:14:32.760 | (upbeat music)

Dr. Casey Halpern: Biology & Treatments for Compulsive Eating & Behaviors | Huberman Lab Podcast #91

Chapters