Essentials: Compulsive Behaviors & Deep Brain Stimulation | Dr. Casey Halpern

0:00 Welcome to Huberman Lab Essentials, where we revisit past episodes for the most

0:04 potent and actionable science-based tools for mental health,

0:08 physical health, and performance.

0:11 I'm Andrew Huberman and I'm a professor

0:13 of neurobiology and opthalmology at Stanford School of Medicine.

0:17 And now for my discussion with Dr.

0:19 Casey Halpern.

0:20 Casey, I should say Dr.

0:22 Halpern, welcome.

0:24 Thank you.

0:24 Great to be here.

0:25 You're a neurosurgeon, which I consider the astronauts of neuroscience.

0:28 For those that aren't familiar with the differences between neurosurgery,

0:31 neurology, psychiatry, you could just educate us a bit.

0:35 What does a neurosurgeon do and how

0:37 do you think about and conceptualize the brain?

0:40 Yeah, the scope of neurosurgery is quite broad.

0:42 We take out brain tumors.

0:44 We clip aneurysms in the brain.

0:46 We take care of patients that have had traumatic brain injury,

0:48 um concussion, uh spine surgeries,

0:52 90% of what neurosurgeons do around the country.

0:55 uh you know taking care of herniated discs and lumbar fusions.

0:59 So you know the the scope is the entire

1:03 central nervous system including the peripheral nervous system.

1:06 We take care of patients with carpal tunnel syndrome and nerve disorders.

1:09 Historically neurosurgeons did everything in that domain

1:13 but now we subsp specialcialize and I'm

1:15 lucky to be at pen medicine where we can focus on one of these areas.

1:22 So I'm uh chief of stereotactic functional neurosurgery.

1:26 All I do is deep brain stimulation surgery

1:28 and a complement to that is focus ultrasound

1:31 or transcranial focus ultrasound which is a non-invasive

1:34 way to do an ablation in the brain.

1:36 Recently FDA approved and it's FDA approved for tremor at the moment.

1:40 Deep brain stimulation is a procedure where we have to place a a very thin wire

1:47 that's insulated deep into uh a part

1:50 of the brain that's involved in Parkinson's disease for example.

1:54 Uh but that's actually not the therapy.

1:57 The therapy is delivering electrical stimulation through

2:00 the tip of that wire or one

2:02 of the tips as there actually are multiple contacts at the bottom of the wire.

2:06 They're very small.

2:07 It's a bit more like I have to implant a a tool to to deliver you a medication.

2:12 Uh but that medication is going to be in the form of electricity

2:15 and it's going to be delivered into a very small region of the brain.

2:18 I'm very privileged to be able to interact with the human brain in this way.

2:22 It's always in the with the goal

2:24 of trying to provide somebody with a meaningful therapy.

2:27 But when we deliver electrical stimulation, these electrodes,

2:30 while they might be sitting in a very small region of the brain,

2:32 there are regions within a few millimeters

2:35 of where these electrodes are that if stimulated, could cause a temporary,

2:39 very brief side effect, a moment of laughter,

2:42 like you said, or a moment of panic.

2:44 And of course, we can just shut that electrode off.

2:47 But often these side effects could be therapeutic.

2:50 And actually that's how we have discovered ways to use

2:53 deep brain stimulation um not just for movement disorders like

2:56 Parkinson's disease but for example patients with Parkinson's disease that have

3:02 a psychiatric uh uh coorbidity like depression or obsessivempulsive disorder.

3:08 A lot of these patients are highly compulsive uh and impulsive.

3:12 Um, sometimes these problems actually melt away

3:16 and we're trying to help their tremor,

3:18 but the patients also tell us that their gambling

3:21 issue has gotten better or their mood has improved.

3:23 And why is that?

3:24 Well, you know, there's probably more than one reason.

3:26 You know, you can help somebody's mood by making their tremor go away,

3:29 of course, but we see laughter in the clinic sometimes.

3:33 And and why is that?

3:34 And that's because we're stimulating parts of the brain

3:36 that are not just involved in these motor circuits,

3:39 but they're also involved in what we call a liyic

3:42 circuit or or part of the brain involved in emotion.

3:44 And if we learn how to modulate those areas therapeutically, step by step,

3:50 we can actually develop these therapies for other indications like depression.

3:54 I would say the most impressive and consistent effect we have when we

3:58 have a patient with tremor who has been tremoring for the past 20 years.

4:01 If we can deliver stimulation through that electrode in the clinic,

4:04 we have immediate relief of tremor.

4:06 And that is the effect that inspired me

4:09 to be a neurosurgeon when I was in college.

4:11 I've never really wanted to do anything else except help

4:15 develop that type of therapeutic for another another kind of symptom.

4:19 I'd love to learn more from you about OCD.

4:23 Could you perhaps just tell us what is OCD?

4:26 Um what are some brain areas involved?

4:29 What are the current range of treatments and what's the difference

4:33 between someone who is obsessive and somebody who has true OCD?

4:38 My perspective on OCD may be a little bit different than a psychiatrist

4:41 who who lives and breathes OCD and sees patients every single day with OCD.

4:47 Uh I probably take care of three to five

4:50 patients a year with deep brain stimulation for obsessivempulsive disorder.

4:54 So I don't see these patients as routinely

4:56 but my laboratory is geared as a researcher.

4:59 Uh I'm very focused on trying to improve

5:02 outcomes of deep brain stimulation for for OCD.

5:05 So I I do feel I have expertise and and a perspective to share.

5:09 I do feel that as a neurosurgeon I am obligated

5:13 to better understand where the obsessions in the brain come

5:17 from and how we can interrupt them to stop the compulsion

5:20 that's associated with the obsession better than we're actually doing it.

5:24 I've been uh leading an endeavor with a number

5:27 of collaborators around the country to try

5:28 to better understand these circuits in the brain

5:33 uh study them in humans both invasively and non-invasively.

5:37 That would be with an electrodebased surgery u sort of like

5:40 we do in epilepsy to understand where seizures come from.

5:43 We want to understand better where obsessions come from.

5:45 But we're also working with imaging experts and geneticists

5:47 to understand OCD u at a broader level as well.

5:51 I consider OCD to be a a spectrum disorder in a way.

5:55 Uh and I I I apologize to those who

5:59 who might feel that I'm using that term incorrectly.

6:02 I I'm using it in a way to describe patients that have

6:06 obsessions and even some related compulsions might not meet criteria for OCD.

6:11 As a neurosurgeon, I'm really obsessive about

6:14 safety and compulsive about my surgical procedures.

6:17 So you know I I think that some aspect of OCD

6:20 which we often joke about but we should you know consider seriously

6:23 cuz people do suffer from this u some aspect of it helps

6:27 us u there are you know famous u CEOs that probably have

6:32 some level of OCD uh surgeons and scientists alike so u perhaps

6:39 if it can be controlled it's an asset and uh but if

6:43 it goes ary and is uncontrollable then it becomes obsessivempulsive disorder

6:48 and uh I tend to see the patients that are the most severe.

6:52 So they have failed medication and there are

6:55 multiple medications that are worth trying for OCD.

6:57 Some can actually be very helpful.

6:59 Which which neurotransmitter systems do they tend to poke at?

7:02 Well, SSRIs are sort of the the first uh line for OCD,

7:06 but also tricyclic can be helpful.

7:08 So this is still the serotonin system.

7:10 Um but as we know the serotonin system interacts

7:12 with the you know neurogeneric system and the dopamine system.

7:17 So it's hard to um uh be specific to one of these things.

7:21 And I think that's also why it's hard for us to predict

7:24 how these medications are going to to work for these kinds of patients.

7:28 But tricyclic and SSRIs can be very helpful and are definitely first line.

7:33 And there's others.

7:34 exposure response prevention is probably the most effective option which is kind

7:39 of like cognitive behavioral therapy

7:40 but these are different and offered by psychologists

7:43 and this is a whole field and there's a whole clinic at my institution

7:48 um uh focused was started by Ednafoa um uh at Penn who

7:54 this is what they do for these patients uh is offer these types

7:58 of cognitive therapies exposure to the stressor and to try to get

8:02 patients to habit habituate to whatever it is that stresses them and causes

8:06 these uh compulsions to help these patients live in every day and function.

8:11 The these are all fabulously helpful uh therapies for a variety of patients,

8:16 but there's still about 30% of patients that still

8:20 suffer from OCD and some of them have severe OCD.

8:22 Sometimes it's moderate to severe and those are

8:25 the patients that I'm really motivated to try to help.

8:28 um our therapies for those patients right now uh I would say are are

8:32 worth pursuing but not optimal um and so it's it's one of those things

8:37 that we have to balance as a researcher because when you see patients

8:40 like this you want to do everything you can to help them and I

8:42 think it's important to educate patients on the risk and benefits of them

8:46 this is deep brain stimulation surgery but also

8:48 capsulotomy which is more of an ablation approach a little bit like deep

8:52 brain stimulation but rather than delivering stimulation

8:54 through an electrode you can actually heat the tissue and even destroy it.

8:58 Some would say this part of the brain is very safe to destroy.

9:01 It's kind of like an appendix.

9:03 Um, others would say it's safer to modulate.

9:06 I have seen uh patients do very well with these ablations.

9:09 And so, you know, you asked me earlier

9:11 what what I find so amazing about the brain, these effects that we can have.

9:15 Sometimes the lack of effect is what's so amazing.

9:18 You can actually u traverse parts of the brain without having any

9:22 adverse effects on patients um function at least that you can test.

9:26 Um, but you can also destroy small parts of the brain.

9:29 We're talking 3 or 4 millimeters in size.

9:31 These little ablations can be really helpful for patients,

9:34 but have no obvious side effects that we

9:36 can tell perhaps after a short recovery from surgery.

9:39 Uh, but nonetheless, despite how safe they might be, uh,

9:42 these surgical procedures still are surgical

9:44 procedures and patients are hesitant to proceed,

9:47 especially when they know that their chance

9:48 of a transformative effect is quite low.

9:51 we we can generally um uh achieve a responder rate of about 50%.

9:57 Um and responders still have symptomatic OCD.

10:00 So I'm really uh uh sort of inspired to uh really find a way

10:06 to deliver these therapies in a more disease specific or symptom specific way.

10:11 were one to come into your clinic this you know for this sort of a work

10:17 of ablations or stimulation uh where would

10:20 you first start to probe in the brain?

10:23 Yeah, you this is a uh a disorder of both cortex and the sub subcortex.

10:30 We find that areas in the cortex like the prefrontal and orbital frontal

10:34 cortex are are not functioning they the way they would in a nonCD patient.

10:37 They're often hyper functioning and we need to find

10:40 a way to try to normalize their function.

10:42 And then there are projections to the subcortex.

10:44 This is the basil ganglia codeputaman or the dorsal straightum.

10:47 And these are interconnected with the vententral stratum.

10:49 This is an area of the brain that I uh focus a lot of my energy in.

10:53 Um this is the vententral stratum which is

10:55 not limited to but includes the nucleus circumbent.

10:58 Um this is an area of the brain that uh

11:00 we know to be involved in gating reward-seeking behavior.

11:03 When it's perturbed, it seems to gate compulsive behavior,

11:06 meaning a rat will pursue a reward despite punishment,

11:09 despite foot shock, for example.

11:11 And that can be similar to an OCD patient.

11:13 They will check their home for safety until 3:00 a.m.

11:17 in the morning and not sleep that night.

11:18 Doing something because of the urge, but despite the risk.

11:22 when our judgment is consistently uh sort of puts us at risk,

11:27 that's where we have something like OCD,

11:30 contamination behavior where they if they feel contaminated,

11:33 they will wash their hands for hours repeatedly

11:35 or if they drop their toothbrush on the floor.

11:37 This will lead to a compulsive behavior

11:39 of cleaning a toothbrush or brushing your teeth consistently.

11:43 Very very common symptoms that we see uh or signs

11:45 that that patients report to us or or that we observe.

11:48 But you know patients with eating disorders you know they

11:51 tend to if if they have binging disorder they'll overeat.

11:54 If they have bulimia they might purge despite the risk of these things.

11:58 And so um addiction is is similar.

12:01 We we tend to drug seek if we're addicted.

12:04 Um uh we'll we'll pay off a dealer u in order to get our fix despite the risk.

12:10 And and that type of urge despite the risk is something that I I've always

12:14 been really interested in and and it's

12:15 a common denominator to all of these problems.

12:18 And if you think about these problems, I mean,

12:19 these are some of the most common conditions in our society today.

12:22 And I think the nucleus ccumbent and the cortical

12:25 areas that we've been discussing that that sort of send

12:27 projections to these areas are are probably at least one

12:31 of the main circuits involved in these kinds of things.

12:34 What is nucleus?

12:35 What roles does it play in healthy brain behavior and in pathology?

12:39 Yeah, the nuclear circumbent is a part of the brain,

12:43 part of our reward circuits.

12:45 It has a lot of functions.

12:47 Uh, it interconnects with many parts of the brain.

12:51 So, when I started getting interested in reward and what a what I

12:56 could do as a surgeon to try to improve how we manage rewards.

13:01 And what I mean by that specifically is if you have an urge for a reward,

13:06 that that's a normal phenomenon.

13:08 That that's not something we're trying to stop.

13:10 The the issue is if you have an urge

13:12 for a reward that either puts you or somebody else at risk,

13:15 it's probably a reward we shouldn't have.

13:17 If you're a drug addict and you uh use heroin or opiate,

13:22 that opiate might make you feel better cuz life is stressful.

13:25 But the risk of doing those things is really high.

13:28 in fact potentially lethal.

13:30 If you have OCD and you can't sleep at night because you're

13:36 so nervous that you didn't lock the door and you've checked 30 times,

13:39 that's an urge we got to treat.

13:40 Eating disorder is the same.

13:42 This problem can be ailarated or improved upon

13:45 by a better understanding and a tailored treatment to the nucleus.

13:50 Specifically, it seems that repeated exposure to something like

13:54 a drug of abuse or any type of reward that is a really strong reward in a way

14:01 it can hijack normal functioning of the nucleus cumbent.

14:04 So, the goal is to just disrupt perhaps what is kind of habitual

14:09 um or or at least this kind of recurring problem that is happening.

14:15 You know, people that have binge disorder at least at a severe level,

14:18 they tend to about once a day.

14:20 So what we decided to do in the operating room was to actually try to leverage

14:26 a tool that we use all the time when we take care of patients with Parkinson's.

14:30 So with Parkinson's, these a lot of these patients, not all, have tremor.

14:33 And so when we place an electrode into this motor

14:37 structure to try to improve their movement disorder,

14:40 uh we often can hear tremor cells and they

14:44 sound we convert their electrical signal to an audible signal.

14:48 So we can actually hear it and it sounds kind of like the tremor

14:50 looks like the frequency of the signal is the same as the hand shaking.

14:56 So exactly and you're poking around in a dedicated

14:58 careful way of course one poke at a time.

15:00 One poke at a time with a very fine

15:02 wire a set of wires listening to the electrical

15:05 activity until you you encounter some cells that are

15:10 sending out electrical activity at a similar frequency.

15:13 Exactly.

15:13 And then you can stimulate them or quiet them and see if the tremor goes away.

15:17 So we we are very confident that when we stimulate that area of in this case

15:22 the subthalamic nucleus we will disrupt that tremor

15:25 circuit and that tremor will dissolve and it does.

15:28 So what is the um analog to tremor in terms of appetite and desire to binge?

15:35 Craving.

15:35 So craving is a term that you know there's probably other terms we could use

15:40 by the way but that that's the term we've chosen to use for a number of reasons.

15:44 One because people relate with that term.

15:46 People that have binge eating disorder or obesity they if you

15:50 ask them if they crave the answer will often be yes.

15:52 Um if you ask them if they lose control or binge they might not know

15:56 what you mean or they might not actually feel out of control even when they are.

16:00 Um so uh but the word craving is relatable and so

16:05 we set out to see if we could identify craving cells.

16:09 Um in a patient with OCD which is related in fact we target a very similar part

16:15 of the brain uh we tried to identify cells

16:20 related to obsessions and we believe we did do that.

16:23 It was a single case study uh where

16:26 we tried to optimize where our electrode was placed.

16:28 So we had some proof of concept that we would be able to elicit

16:32 a sort of disease-specific symptom in the operating

16:35 room assuming the patient could tolerate being awake.

16:38 Not everybody needs to be awake for this procedure

16:40 but at least for these first in human

16:42 trials where um we're trying we're trying to establish

16:45 where in the brain we need to be.

16:47 Uh I think this type of approach is really critical.

16:50 What is the status of non-invasive brain

16:52 stimulation ablation and blocking activity in the brain?

16:56 My understanding is that transcranial magnetic

16:58 stimulation is being used to treat

16:59 depression and a number of other um brain syndromes uh non-invasively.

17:04 So no no drilling through the skull.

17:05 My understanding is that the spatial precision isn't that great.

17:09 Um ultrasound is something I hear a lot about these days.

17:13 Um and my understanding is that ultrasound can

17:15 allow researchers and clinicians to stimulate specific brain areas.

17:19 What are your thoughts on these forms of non-invasive meaning no flipping open

17:24 of a piece of the skull type brain stimulation and blockade of brain activity?

17:30 We need to embrace non-invasive approaches.

17:32 Some of them are a little fluffy in that we don't understand how they work.

17:36 We don't necessarily understand how deep brain stimulation works by the way.

17:38 So, but because we don't know exactly how they work,

17:41 they're not as precise as we would like them to be.

17:43 So, we have work to do there.

17:44 And I actually think that work is doable and actually underway.

17:47 TMS transpanomagnetic stimulation.

17:50 It is FDA approved for depression.

17:52 By the way, it's also FDA approved for OCD and for nicotine addiction.

17:55 We believe we can use TMS to to define

17:57 a circuit that if modulated improves OCD, albeit temporarily.

18:04 And in those patients, if it's temporary,

18:06 they would be appropriate for an invasive study.

18:08 So, um something we're actively working on.

18:11 I've always believed that neurosurgeons need to be

18:13 part of the discussion with these non-invasive approaches.

18:16 we don't need to do them.

18:17 Um but um I think we can help make

18:20 them more precise and to probe non-invasively with purpose.

18:25 Perhaps one day there will be a TMS target for anorexia and obesity.

18:30 Uh if we are scratching the surface with invasive approaches to these problems,

18:36 we we're even doing less with the brain stimulation.

18:40 Um so we have so much work to do there.

18:42 eating disorders and TMS have been so um sort

18:46 of scarcely studied or or there have been such little

18:50 research done in that space and so it it is an area that we need to to work on.

18:54 So ultrasound right now transcranial magnetic

18:58 guide magnetic resonance guided focus ultrasound.

19:02 So um uh this this is an FDA approved

19:06 method to deliver an ablation to the brain non-invasively.

19:13 There are uh researchers myself included that are trying to use

19:17 transranial magnetic guided magnetic resonance guided

19:19 focus ultrasound or MRI guided focus

19:22 ultrasound u to use it in a modulatory way not just

19:25 as an ablation but to drive neuronal activity or inhibit it perhaps.

19:30 We're still learning how to do that.

19:31 Um there are trials u that are trying to understand

19:34 if you can use ultrasound to open the bloodb brain barrier

19:37 so you can deliver a medication to that specific uh

19:40 area uh perhaps for a brain tumor or something like that.

19:44 So um it's a very exciting field um and it

19:47 is FDA approved for tremor right now and so I actually

19:50 do it routinely um for patients with uh tremor with Parkinson's

19:55 or essential tremor and so um I I love doing it.

19:59 It's uh often just kind of a miracle because there's no incision.

20:03 I don't have to place an electrode into the brain to achieve a similar result.

20:06 It's fabulously effective for these patients.

20:08 It treats patients on one side, usually their dominant hand or their worse hand.

20:12 And it um it really speaks to the fact that wow,

20:15 you can deliver non-invasively an ablation to the brain in a hypothesized

20:20 zone that we think is related to the problem at hand.

20:23 And at least with tremor, it works really well.

20:26 Could this be effective for psychiatric disease, obesity, eating disorders?

20:31 Uh well um perhaps uh actually that would be the ideal.

20:36 The problem is we don't know where to do the ablation.

20:40 Um there is a trial that we would like to do

20:42 for OCD where we would deliver an ablation to the same

20:45 area of the brain that we've been delivering ablations

20:47 to for years for patients with OCD and it helps a bit.

20:50 That's called a capsulotomy.

20:52 Um but really the outcome is probably going to be about the same.

20:55 It's a nice method because it's it's noninvasive,

20:57 but we need to find a new target for these for these conditions and because

21:01 of the common denominator of the urge despite the risk sort of that compulsion.

21:07 Um yeah, perhaps it could be the same target.

21:10 I don't know.

21:10 Um but I would argue we need to do

21:13 these modulatory experiments either with a device or with uh invasive

21:17 recordings uh to better understand where these problems are coming

21:21 from to define where we should do an ultrasound treatment.

21:24 There has been a revolution in America.

21:27 It was in Europe before it was in America where we would do stereo

21:30 encphilography which is basically like doing an EEG

21:34 of patients with epilepsy but with invasive

21:37 electrodes and we would place tiny little

21:39 wires less than a millimeter in diameter

21:41 all throughout the brain into parts of the brain that we believe are

21:43 involved in seizures and we would admit the patients to the hospital and figure

21:48 out where the seizures were starting and propagating and then um you know we

21:52 could stimulate these electrodes to see if

21:53 there was a symptom that was important and try to identify by a region

21:57 that we thought we could either remove surgically,

22:01 ablate with a laser or put a stimulator in it perhaps.

22:04 Um, that's common place now for epilepsy.

22:07 Um, and it works extremely well and it's very safe.

22:11 Of course, it's still a brain procedure.

22:13 Um, but the u the complication rate is surprisingly low quite honestly

22:18 for the amount of electrodes that we place and it's extremely well tolerated.

22:21 Most of these patients leave the hospital

22:22 and they don't even feel like they've had surgery.

22:25 So uh there's actually a lot of interest

22:27 in using that procedure to study mental health disorders.

22:31 We are trying to do it for patients with obsessivecomp compulsive disorder.

22:34 We're awaiting an FDA decision on that.

22:36 Uh but actually I credit uh uh our colleagues

22:39 at Baylor and at UCSF for for studying this uh

22:43 already bringing together the epilepsy technique and the psychiatry expertise

22:48 to study how we could better target electrodes in depression.

22:52 And I'll tell you if they have

22:53 a consistent target perhaps there becomes an ultrasound target.

22:58 Um but right now the approach is a bit

23:01 more reversible because you can always shut that electrode

23:04 off or even remove the electrode if perhaps it's

23:07 not in the optimal location to treat the depression.

23:10 Uh but actually after a large volume of uh cases perhaps they

23:15 could pull that data to develop a a new ultrasound target for depression.

23:20 I think that would be fabulous.

23:22 probably is their long-term goal.

23:23 Not to speak for them, uh,

23:25 but that would be something that I I'm sure is on their radar.

23:28 You might ask, well,

23:28 why aren't you doing this for obesity right now in uh in our in our study?

23:32 And the reason is that um we've developed a target for obesity uh

23:36 and binge eating disorder uh developed out of mice that we believe um

23:41 is relevant for the human state because you can model this problem

23:45 in a mouse a bit better than than you can model depression or OCD.

23:49 So, we feel like we can rely on the pre-clinical studies more.

23:53 Whereas with these perhaps more I don't want to say more complicated,

23:57 but more human mental health conditions that are hard to model in a mouse,

24:02 you really have to study it in the human.

24:05 And you can perhaps start in an epileptic patient,

24:07 a patient that has electrodes and try to provoke a depressed

24:09 state or study epileptics that have comorbid depression, for example.

24:14 Uh, and that can really validate this approach as well.

24:16 But in the end it's it's getting into the human

24:18 brain that we need to do in the disease

24:21 specifically u that will eventually lead to a non-invasive

24:26 approach uh either a lesion or modulatory approach.

24:29 Modulatory would be like TMS or lesion approach would be with ultrasound.

24:33 If people can be made to feel or make themselves feel just a little bit better,

24:39 a little less anxious just prior to a craving episode or a binge episode.

24:44 Maybe even if people can become better at detecting

24:47 their own internal states and when they're kind

24:49 of veering toward a binge or veering toward using

24:52 a drug or maybe even veering towards suicidal thinking.

24:58 Seems like that awareness seems like maybe

25:01 among the best tools that people could develop.

25:04 Yes, I've always thought that if we can improve awareness,

25:07 we can improve outcomes.

25:08 I think that's probably true for many of these patients.

25:11 The problem I think comes down to the fact that some of these patients are

25:14 so resistant to treatment and the patients that we see as a surgeon for example

25:20 are the patients that they've tried cognitive

25:23 behavioral therapy certainly have tried medications they've tried

25:26 behavioral management they're as aware as they

25:29 could possibly be and they still lose control.

25:32 We've had this studied in the lab.

25:34 So we will bring patients to the laboratory

25:36 with this implanted device to to try to provoke this electrographic

25:41 electrical signal u that can be detected by the actual

25:45 device that will stimulate them when they're at home.

25:48 But before we actually initiate stimulation,

25:50 we want to to see can this device detect this craving cell signal which is going

25:56 to be different than what we saw

25:57 in the operating room because that's a single cell.

25:59 But these devices, these electrodes are about a millimeter

26:01 in diameter instead of like a tenth of a millimeter,

26:04 which is what we use in the operating room.

26:06 Um, so they're they're only hearing or or detecting,

26:10 I should say, thousands of cells responses.

26:13 And we actually have a way to provoke binges.

26:18 It's called a mood provocation.

26:20 It's very well, very well validated.

26:22 It's a little bit like provoking seizures in the epilepsy monitoring unit,

26:25 but here in the sort of uh psychiatric

26:29 monitoring unit or the the food monitoring unit,

26:32 uh we we actually have a psychiatrist

26:35 and eating disorder specialist come and induce

26:38 a mood that is related to each patient's sort of selfdescribed binge episode.

26:46 So the psychiatrist comes in and provokes Yes.

26:49 a feeling that can evoke the negative behavior.

26:54 That's exactly right.

26:55 So that we can video and synchronize the video to the brain signal recordings.

27:00 Um the patients all wear an eye tracker so we can see

27:03 what they're eating at all times and what they're looking at specifically.

27:07 And that allows us to have the best temporal resolution

27:12 possible to understand what is happening right before the bite.

27:16 And even under video surveillance through a one

27:18 day one-way mirror in a laboratory setting when

27:22 patients are very well aware that they're there

27:26 to be studied if they're going to binge.

27:29 They still do and we believe they do because they

27:33 just can't control it as aware as they are of it.

27:37 And it's probably because they're the most severe.

27:39 So I think if we can improve awareness,

27:42 not just the societal awareness that I was talking about earlier,

27:44 but the patient awareness uh around their problem,

27:48 I think that could be a powerful way to help so many of these patients.

27:51 And that's sort of the role of cognitive behavioral therapy.

27:54 Um the problem with cognitive behavioral therapy

27:56 or I should say the limitation of it, I actually don't have any problem with it.

27:59 I think it's a wonderful treatment.

28:01 Um is that if you stop it,

28:04 many of these patients go back to their old behaviors.

28:07 I don't want to say old habits, but it might be a habit, but the old behaviors.

28:11 And so, um, that's the problem is it's not

28:14 necessarily lasting in the absence of continued cognitive behavioral therapy.

28:17 Some people can benefit from it long term, but some can't.

28:20 Uh, but I think in in in in the less severe patients, improving awareness key,

28:26 but in these really refractory patients,

28:28 this is this is kind of like this is the disease.

28:31 Despite the awareness, they can't control themselves.

28:33 And that's what we're trying to restore

28:35 is that improved ability to control their behavior.

28:38 Do you think there's a role for machines and uh artificial intelligence here?

28:43 Uh there are a couple laboratories up at the University of Washington

28:46 that are using particular signature patterns of within voice to try

28:54 and help suicidal uh people who are suicidally depressed know when

29:00 they're headed towards an episode before they even can consciously know.

29:03 So this gets right down to issues of free will

29:05 and whether or not machines can be smarter than we are.

29:07 But you know, one could argue that some of the search algorithms on Google

29:10 and other search engines are actually more aware of our preferences than we are.

29:16 Um, basically what these are,

29:17 these are devices that are listening to people talk all day.

29:20 They're also paying attention to patterns

29:21 of breathing and how well people slept, etc.

29:23 integrating a a huge number of cues

29:26 and then signaling somebody with a, you know, a yellow light, you know,

29:30 you're headed into a depressive episode and the person might say,

29:32 "I feel fine or I feel pretty good.

29:34 This is kind of baseline state for me." and they say, "Uh-uh,

29:38 this is where you were preceding the last episode that took you down a deep,

29:42 dark trench and it took months to get out of."

29:45 Um, I wonder whether or not some of these devices could

29:48 help with the sorts of things that we're talking about today.

29:51 Yeah, I think so.

29:52 Um, I've always said we have to get in the brain before we get out of it.

29:57 And if we get in the brain and understand what these signals look like,

30:00 we'll know what those non-invasive signals are.

30:03 I think it's possible that we are uh

30:07 scientifically sophisticated enough to use machine learning and sort

30:12 of this kind of bot tech technique to anticipate

30:16 when somebody is going to be highly impulsive.

30:18 You know, suicide is the most dangerous impulse.

30:20 It's something that is immensely a focus of the lab is impulsivity.

30:26 We've talked mostly about compulsion.

30:29 Compulsion being, you know,

30:30 going after a reward or or the urge despite the risk.

30:34 Um, impulsivity is is similar but different.

30:37 It's it's kind of going after something um a little bit if

30:42 you if you model impulsivity in a in a mouse, it's, you know,

30:45 related to, you know, going after a food reward without the sort of paired

30:51 tone that you're the mouse is supposed to wait for.

30:54 The mouse doesn't want to wait anymore.

30:55 They they just go after the food.

30:57 Um, I've been that mouse.

30:58 Yeah, we've all been we can all relate with this uh to a certain extent.

31:03 Again, it's a spectrum.

31:05 So, um so in any case, I nonsequiter,

31:09 but I I I certainly think that there is a way to use

31:14 our own body's physiology to anticipate when these impulses are coming online.

31:21 How best to do that?

31:23 I think we're just scratching the surface,

31:24 but um these are the kinds of solutions we need.

31:28 Some of these problems are of epidemic proportions.

31:31 Largest public health problems in this country,

31:33 in this world, obesity, opiate crisis, depression, suicidality.

31:37 I mean, that's like a third of our country, maybe more.

31:40 We need scalable solutions.

31:41 But, you know, I'm I'm a neurosurgeon.

31:43 I'm only going to be able to treat

31:44 the most severe of patients with these problems.

31:47 you know h you know we've only

31:49 done about 200,000 deep brain stimulation surgeries ever.

31:55 So I mean the problem we're talking about here is 50 million Americans.

32:00 There's no possibility that surgeons can address that problem.

32:04 But we could help inspire an initiative to go after that kind

32:08 of problem or help make it more rigorous because the last thing we need

32:12 is a you know some sort of wearable fancy tool that you know

32:18 wastes people's money and time you know we need real therapies for these things.

32:21 Not that these devices that we're discussing are not uh I think actually there's

32:25 lots of promise and we use machine learning in the lab all the time.

32:28 I'm not a an electrical engineer

32:30 or the computational neuroscientist doing this type of work.

32:33 I I just help develop the hypothesis around it,

32:35 but um and help fund raise around it.

32:38 But I I definitely think there's a future for it.

32:40 I just I I suspect we're we're scratching the surface on how best to do it.

32:44 I really appreciate you sharing uh those tools,

32:46 a number of people uh I'm guessing out there might want to become neurosurgeons.

32:50 I really believe that in hearing today's conversation

32:53 that you will spark an interest in medicine andor neurosurgery.

32:57 I hope so.

32:57 Um well, certainly you need to be

32:58 a physician before you can become a neurosurgeon.

33:00 end neurosurgery in some cases and that would be beautiful and I

33:04 predict that will be happen that will happen excuse me as a consequence

33:07 of what you've shared today really want to thank you for taking time

33:10 out out of your not just immensely busy but very important schedule because

33:14 again the work that you're doing is really out there on that cutting

33:18 I don't want to say bleeding edge because in this context it's not

33:21 going to sound right but on that extreme cutting edge of what we

33:24 understand about how the human brain works and how it can be repaired.

33:28 on behalf of everybody and myself as well.

33:30 Thank you so so very much.

33:32 I'm honored.

33:33 Thank you so much for having me.