Yale Psychiatry Grand Rounds: "From Anxiety to Addiction: New Tools That Leverage Old Brain Technology to Change Habits"

November 01, 2024

November 1, 2024

"From Anxiety to Addiction: New Tools That Leverage Old Brain Technology to Change Habits"

Judson Brewer, MD, PhD, Director of Research and Innovation, Mindfulness Center; Professor of Behavioral and Social Sciences, Professor of Psychiatry and Human Behavior, Brown University School of Public Health

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00:00Dispense with the preliminaries.
00:02So
00:04it's this.
00:09And then this will work.
00:10Yeah? Alright. So as doctor
00:13Moli mentioned,
00:14I'm I've got my labs
00:16have the pleasure of developing
00:18some new digital therapies. Actually,
00:20we started it as a
00:21Yale incubator,
00:23back in the day,
00:24that's now merged with a
00:26company called Sharecare. So I'm
00:27a consultant for them, as
00:29part of the disclosure. All
00:30these disclosures are managed by
00:31Brown University's,
00:33conflict of interest policy. I've
00:35got this as well.
00:37I I wanna start by,
00:40just acknowledging
00:43acknowledging that and, you know,
00:45I just realized this morning
00:46that I started residency here
00:48twenty years ago, so back
00:49in two thousand four.
00:51And,
00:53ten years ago, I left
00:54Yale ten years ago. Ago.
00:55Often, there's if you haven't
00:57heard the joke, I will
00:58say it officially. You know,
01:00I've I've heard from people
01:01say, oh, it's better to
01:02be from Yale than at
01:02Yale.
01:04And I will say, I'm
01:05not I I dispute that
01:06assertion.
01:08And by saying that, I
01:09would just wanna acknowledge some
01:11of the, giants that have
01:13mentored me throughout my career.
01:15And just looking back on
01:16that, how important that mentorship
01:18was. So for all of
01:19you,
01:20that are early in your
01:21careers,
01:22seek out some good mentorship
01:23here. They're such wonderful people.
01:25So Stephanie O'Malley was one
01:26of one of the folks
01:27that mentored me, Izmini Petrakas,
01:30and and some wonderful people
01:32who are no longer with
01:33us. Bob Mallison was the
01:34head of the RTP. Wonderful,
01:36wonderful individual.
01:39Cathy Carroll was one of
01:40my main mentors. And then
01:41I'm mentioning,
01:43so and Mark Mark Battenza,
01:45also one of my primary
01:46mentors. And then also, I
01:48had the great fortune of
01:50working closely with,
01:52this gentleman. Many of you
01:53don't know who this is.
01:54This is Bruce Roundtable.
01:57Wonder and I swear he
01:58he was more excited about
02:00mentorship
02:01than anything else. He did
02:02a bunch of great research,
02:03published a bunch of stuff,
02:04developed some really nice treatments,
02:07and
02:08he was all about mentorship.
02:09So it was a real
02:10loss to us, when when
02:12he died suddenly.
02:13One of the things Bruce
02:14used to I'd sit down
02:15in Bruce's office. This is
02:16over at building thirty six
02:17at the VA, and we'd
02:19sit down with him and,
02:20you know, have a great
02:21something that I thought was
02:22a great idea. And then
02:23he'd give me this big
02:24smile, and he would say,
02:26so what?
02:28And this so what and
02:28I highlight this especially for
02:30for young folks early in
02:32your
02:33careers. He was really trying
02:34to get me to ground
02:35in, like, how is this
02:37practically important for my patients?
02:39And so that's that's really
02:41helped sculpt and shaped my
02:43career over the last, you
02:44know, now twenty years.
02:46In really continuing to ask
02:48that question, I try to
02:49pass this down to my
02:50students. So what? So what?
02:51So what? Smilingly,
02:53kindly. He he did this
02:55with such compassion. It was
02:56it was wonderful and contagious.
02:59So I'm I wanna pass
03:00some of those along today.
03:01And what I'm I thought
03:02I would do instead of
03:03just giving some, you know,
03:04dry talk, I I wanna
03:06kind of do a little
03:06bit of a retrospective.
03:08I but I'll start with,
03:09you know, kind of the
03:10so what question. But I
03:12just wanna
03:13pause and just for all
03:14the folks,
03:15that remember
03:16Bruce,
03:17Kathy,
03:18Bob, and others, just a
03:20a real
03:21moment of gratitude for wonderful
03:23mentorship because that is not
03:25common,
03:26unfortunately. So thank you, Bruce.
03:28Thank you, Cathy. Thank you,
03:29Bob, and thank you, Mark,
03:30and others,
03:31who continued to do great
03:33mentorship today.
03:35So I'll start with a
03:36a clinical case that that
03:38I saw a few years
03:39ago. This is a a
03:40gentleman who was referred to
03:42me for anxiety, chief complaint
03:43anxiety. He came into my
03:44office. He looked anxious, pretty
03:46straightforward.
03:47And as I started taking
03:48his history, I met all
03:50the criteria
03:51for generalized anxiety disorder. He
03:52was forty years of age.
03:54When he came to see
03:54me, he'd had he could
03:56probably trace that back to
03:58about fifth grade where he
03:59had started,
04:00getting panic attacks and, getting
04:02really anxious. And in fact,
04:03he met all the criteria
04:04for generalized anxiety disorder as
04:06well as panic disorder.
04:07On top of that,
04:09he was four hundred pounds.
04:11And so it had some
04:12medical issues related to it
04:14that were contributing to his
04:16medical anxiety. So a lot
04:17of a lot of this
04:18stuff, was really compounding for
04:20him.
04:21So I I use this
04:23cartoon,
04:24because, you know, as as
04:25many of you know or
04:26or learning, even the best
04:28medications we have out there,
04:29for example, SSRIs,
04:31number needed to treat is
04:32five point two. And so
04:34when I walk into clinic,
04:35I'm play basically playing the
04:36medication lottery. You know, which
04:38which one in five of
04:40the next five patients that
04:41I see are gonna show
04:41a significant reduction in symptoms,
04:43and what am I gonna
04:44do with the other four?
04:46On top of that, and
04:47this is now outdated, about
04:48almost ten years old now,
04:50but just looking at our
04:51obesity epidemic. So we can
04:53say, oh, we develop a
04:55lot of treat. This is
04:56all obviously pre,
04:57GLP one drugs, but I'm
04:59not sure that you know,
05:00they certainly have been a
05:01a quantum leap forward, but
05:02I'm not sure that they're
05:03gonna be our saviors.
05:04But we can say, well,
05:05we, you know, we should
05:07be able to help people
05:08with with,
05:09clinically clinical obesity at this
05:11point. But even looking back,
05:13not sure that we've nailed
05:14that either.
05:16So what I'm how I'm
05:17gonna approach this talk today
05:19is I like this quote
05:20attributed to Einstein where he
05:21says no problem can be
05:22solved from the same level
05:24of consciousness that created it.
05:25And, you know, highlighting, Oprah
05:27who said you know, she
05:29said, I've been I realized
05:30I've been blaming myself all
05:32these years for being overweight,
05:33and I've had predisposition predisposition
05:35that no amount of willpower
05:36is going to control. So
05:38I really wanna focus on
05:40a lot
05:41of dogma out there,
05:43that and even some that
05:45was that I learned,
05:47in part of my residency
05:48training,
05:49was, you know, like, we
05:50just need to willpower our
05:52way through whatever it is,
05:53whether it's anxiety, whether it's
05:54an addiction, whether it's with
05:56whether it's eating, you know,
05:57picking the croissants as compared
05:59to the keto friendly,
06:03egg things that were actually
06:04pretty tasty out there.
06:06And one thing I wanna
06:06highlight is that there's a
06:08lot of great neuroscience research
06:10showing that, for example, cognitive
06:12therapies
06:13seem to center around the
06:15prefrontal cortex, whether it's the
06:17dorsal lateral prefrontal cortex or
06:18other parts of the brain
06:20that have
06:21been associated
06:22with cognitive behavioral therapy, this
06:24prefrontal
06:25cortex of ours is the
06:26youngest and the weakest part
06:28of our brain from an
06:29evolutionary perspective.
06:31So, you know, there many
06:32of you have heard the
06:33acronym HALT, hungry, angry, lonely,
06:35tired. This is when people
06:36tend to relapse,
06:38to substance use, etcetera, where
06:40their prefrontal cortex is going
06:42offline. So why are we
06:43spending all this energy trying
06:45to
06:46get people to use the
06:47weakest part of their brain
06:48to change behavior?
06:50So I started asking that
06:52question myself and
06:54opening up and asking, well,
06:55is there anything else that
06:56we can
06:57explore
06:59you know, that might help
07:00as well? And can we
07:00study this? And, you know,
07:02going back to basic principles,
07:04if you look at reinforcement
07:06learning, you know, Eric Kendall
07:07got the Nobel Prize showing
07:08back in two thousand, showing
07:09that this is evolutionarily conserved
07:11all the way back to
07:12the sea slug. We know
07:13a lot about how these,
07:16these habits, these addictions get
07:18set up when I'm just
07:19using smoking and and eating
07:20as examples. But if you
07:22look at some of these
07:22references, this has been known.
07:24You know, Thor Ed Thorndike,
07:25published the first,
07:27animal study back in the
07:28eighteen hundreds.
07:30This is where,
07:32you know,
07:33all the all the, you
07:34know, famous Skinner became famous
07:37in the fifties. All of
07:38this stuff has really you
07:39know, nothing has has been
07:40disproven here. It's only been
07:42reinforced.
07:43And so I can ask
07:44myself when I'm in clinic
07:46if I have a patient
07:46who's struggling, you know,
07:48mechanistically,
07:49what's going on here? Can
07:50this help me understand,
07:53why they're struggling? And can
07:54we approach things you know,
07:56how are we approaching things?
07:57Is that the best way
07:58to approach things?
07:59So for example, patients with
08:01alcohol use disorder, you know,
08:03there's this saying, I learned
08:04it from one of my
08:05patients, people, places, and things.
08:06And somebody actually corrected me
08:08that that's not an official
08:09AA thing. That was something
08:11that he had learned in
08:12his AA group. But you
08:13can look at this mechanistically
08:15and, you know, it's it
08:16makes, makes sense if we
08:17avoid the bar, if we
08:18avoid the the liquor store,
08:20if we avoid our drinking
08:21buddies, we're less likely to
08:23drink. And so you can
08:24place that mechanistically and say,
08:26okay, if we avoid queues,
08:27we're less likely to get
08:28triggered to do whatever the
08:29behavior is.
08:31If it's smoking, it's a
08:32little more challenging
08:34to avoid. If you smoke
08:35a pack of cigarettes a
08:36day, it's a little more
08:37challenging
08:37to avoid all those twenty
08:39things, you know, time of
08:40day, place, car, you know,
08:43and, and even smoking buddies.
08:45So, you know, there's what
08:46one thing I was taught
08:47was, well, let's provide substitution
08:49strategies. You know, eat some
08:51carrot sticks instead of smoking
08:53a cigarette, do some distraction,
08:54etcetera. And these are just
08:55some, you know, there's been
08:56a lot of great work,
08:57a lot of it grounded
08:58here, you know, in contingency
09:00management and other things. I'm
09:01not gonna speak about those
09:02today.
09:03There can be some really
09:04useful strategies that help,
09:07yet it's unclear
09:08how, you know, if we
09:10bring it back to basic
09:11principles,
09:12how all of these line
09:13up. So for example, with
09:15avoiding cues or substitution behaviors,
09:17you're not actually dismantling this
09:19core loop, whether it's negative
09:20reinforcement or positive reinforcement.
09:23So for those of you
09:24sleep deprive residents here today,
09:26just remember three things, you
09:28know, trigger
09:29a behavior, and a result,
09:30or a reward from a
09:31neuroscience standpoint. That's how all
09:33habits get set up. And
09:34these were set up as
09:36survival strategies. This helped us
09:37remember where food was so
09:38we could go to it
09:39again, get to those food
09:40sources, and also remember where
09:42danger was so we could
09:43avoid it.
09:45So how is this being
09:46used in modern day? Well,
09:48the the food industry certainly
09:49knows how to use these
09:50things. There's a great,
09:53there's a great article,
09:55back over ten years ago
09:56now in the New York
09:57Times just highlighting all the
09:58different ways that food like
10:00objects get engineered
10:01to be addictive. I like
10:02that they use the Doritos
10:03as the cover art for
10:04their article,
10:05because my favorite peer reviewed
10:07journal, The Onion,
10:09they had a, the headline
10:10that says Doritos celebrates its
10:12one millionth ingredient.
10:15And
10:16and I wanna say that
10:18it was actually Chris Pittenger
10:19that taught me that line,
10:20my favorite peer reviewed journal.
10:21He used to say my
10:22favorite peer reviewed journal, The
10:23New York Times, if I
10:24remember. It correctly. So thank
10:26you, Chris, for that.
10:28But we we see this
10:29with food. We see this
10:30with social media.
10:31You know, they're employing literally
10:33thousands of neuroscientists to get
10:35us addicted to these things.
10:36So the question is, well,
10:38if somebody knows how this
10:39process works,
10:41why aren't we in medicine
10:43exploring these same processes and
10:45leveraging them? And this is
10:47where,
10:48I kind of went off
10:50the, the the the straight
10:52and narrow. When I was
10:54first starting my career, I
10:56done a lot of molecular
10:57biology research, during my PhD
10:59years and then wanted to
11:01wanted to actually try something
11:03different.
11:04And I remember Bruce explicit
11:05Bruce Brownsville explicitly saying to
11:07me, you know, he said,
11:08I don't care what you
11:09do as long as you
11:09do it well. You know?
11:10And and he was there
11:11to help guide me to
11:12make sure that that I
11:13was I was doing my
11:15research in a very scientifically
11:16sound way. So I said,
11:17well, I wanna study mindfulness
11:19training. I should have put
11:20this in my disclosure. I
11:21had been meditating starting in
11:23medical school, and so I
11:23was like, well, it was
11:24kinda helpful for me and
11:25taught me some things that
11:26I didn't learn during medical
11:27school. So let's let's study
11:29this. And at the time,
11:30the,
11:32this there was nothing published.
11:34It was, you know, can
11:35candles, unicorns, you know, incense.
11:37That's how people thought of
11:39mindfulness.
11:40And, actually,
11:41somebody in my residency class
11:43here said to me, they
11:44said, you're gonna kill your
11:45career if you study this
11:46stuff because it's so woo
11:47woo. And I I thought,
11:49well,
11:50I'm really interested in this.
11:51I'd rather give this a
11:52go and and risk failing
11:54than, you know, continuing along
11:55the path that that I
11:56could you know, I had
11:57done before and and was
11:59fine.
12:00So studying mindfulness, this is
12:02now much more popular, you
12:03know, twenty years later. But
12:05back in the day, people
12:05didn't even know what it
12:06was. And so John Kabat
12:08Zinn up at at UMass,
12:10medical head coined this term
12:12back in the late nineteen
12:13seventies where he described mindfulness
12:15as paying attention in the
12:16present moment on purpose and
12:17nonjudgmentally.
12:19And if you think of
12:20this mechanistically,
12:21it's not about avoiding things.
12:23It's about bringing awareness to
12:24it. It's not about, you
12:26know, substituting behaviors. The way
12:28that it's often described is
12:30bringing this wedge of awareness
12:31in. So instead of habitually
12:33reacting to something, we can
12:34respond
12:35with awareness.
12:36For example, I had a
12:37patient who'd been smoking forty
12:39years,
12:40and we calculated the number
12:42of times he had reinforced
12:44his smoking habits. For you
12:46mass savants out there, forty
12:47years times roughly three sixty
12:49five days a year times
12:50twenty cigarettes is about two
12:51hundred and ninety three thousand.
12:53And so you could think,
12:54well, let me just, you
12:55know, gird my loins and
12:56use my willpower.
12:58And then our brain's like,
12:58dude, I've got this. Two
12:59hundred and ninety three thousand
13:01times, bring it on. Right?
13:02And so this is where
13:03I'd seen over and over
13:04and over so many patients
13:05failing from trying to just
13:07force themselves to quit smoking.
13:09So instead, we started asking
13:11I asked my patient, well,
13:12let's let's see how much
13:13we understand,
13:14you you understand how your
13:15brain works and how maybe
13:17we could even leverage that.
13:19And so here's here's this
13:20paradox. You know, how is
13:22just paying attention
13:23gonna help somebody change their
13:25behavior?
13:27We we posited
13:29a while ago
13:30that awareness
13:31may be a critical ingredient
13:33in behavior change. We weren't
13:34exactly sure why at the
13:36time and then went on
13:37to try to explore some
13:38of the mechanisms of how
13:39it was helping. Here's a
13:40here's an example from one
13:42of our early studies,
13:43where somebody reported we were
13:45having them pay attention as
13:46they smoked. This person said,
13:48mindful smoking smells like stinky
13:50cheese and tastes like chemicals.
13:52Yuck.
13:53This was a big
13:54not only for this person,
13:55but for me because this
13:56was starting to articulate what
13:58might actually be happening, and
13:59we could start to test
14:00that mechanistically.
14:02So if you look at
14:02this from a reinforcement learning
14:04standpoint,
14:05typically, you know, it's stress
14:06that will trigger somebody's smoke
14:07or withdrawal or something like
14:09that. So something unpleasant triggers
14:10us to do the behavior,
14:11such as smoking. But if
14:13we pay attention to how
14:14rewarding it is, maybe that
14:16helps to change the process.
14:18And we'll get into that
14:19in a little bit, but
14:20I just wanted I wanna
14:22see that, with a with
14:23a a question of, like,
14:24how does this actually help?
14:26Hint, this is called reward
14:28based learning or reinforcement learning.
14:31So not to,
14:33I think Yogi Berra put
14:34it nicely. He said you
14:34can deserve a lot just
14:36by watching. So it was
14:37actually my first,
14:39first real randomized controlled trial,
14:42that I did as my
14:44first first study here at
14:45Yale.
14:47We did a randomized controlled
14:48trial just to compare mindfulness
14:50training to the American Lung
14:51Association's freedom from smoking based
14:53on cognitive therapy. And we
14:54did all all the right
14:55things because I'd gotten good
14:56mentorship on how to do
14:58this. I'd you know, this
14:59is my first foray into
15:00smoking cessation work. And we
15:02had actually got, seventeen,
15:04seventeen weeks. That was what
15:05we were funded out to
15:06do. So gold standard's, like,
15:08six months or twelve months.
15:09But we looked, you know,
15:10about four months out, and
15:11we actually got five times
15:12the quit rates of a
15:13gold standard treatment.
15:14So that was interesting. It
15:15was a relatively small trial.
15:17You know, lots of caveats
15:18here, but it was it
15:19was enough of a signal
15:20to start asking, well, what's
15:22going on here?
15:23And so we have this
15:24hypothesis that it would actually
15:26work by decoupling
15:28the urge to smoke with
15:29the behavior of smoking itself.
15:30And we could test this
15:32mechanistically,
15:34where, you know, at baseline,
15:35we saw this really strong
15:36correlation between the urge to
15:37smoke and smoking makes a
15:38lot of sense. But it
15:40by the end of treatment,
15:41this is in the mindfulness
15:42training group, we saw a,
15:44complete dissociation of that correlation.
15:46And when we when we
15:47did the moderation
15:48analyses, we found that the
15:50the primary driver here was
15:52not about number of cigarettes
15:54that people are smoking or
15:55they're craving, but it was
15:56really about these mindfulness practices
15:58that people are doing. So
15:59this this,
16:00being able to work with
16:02the urge, when it came
16:03up.
16:04Going back to the
16:06the mechanism,
16:08the idea here seems to
16:09be supporting that this wedge
16:11of awareness is helping people
16:12have that urge but not
16:14act on it and maybe
16:15starting to break this loop
16:16at its core.
16:17So at the time, I
16:18was working at the VA,
16:20in West Haven and, you
16:21know, look out my window,
16:23see all my patients smoking
16:25in the parking lot because
16:26it's a smoke free campus.
16:27And so actually building on
16:29inspiration from Cathy Carroll, who
16:31was starting to develop CBT
16:33for CBT at the time.
16:35I had it was actually
16:37with a,
16:38a young entrepreneur that had
16:40just come out of this
16:40Yale School of Management, who
16:42was actually a documentary filmmaker.
16:44We'd had these, these positive
16:47results in person with mindfulness
16:48training. We said, well, can
16:49we digitize this? If people
16:51you know, if they've got
16:52their phone in one hand
16:53and a cigarette in another,
16:54let's you know, instead of
16:55this being their social media,
16:57their news news feed, let's
16:58let's actually teach them stuff.
17:00So we started playing with
17:01this idea. This is back
17:02in two thousand twelve. It
17:03was
17:05some of you might not
17:06have even been born back
17:07then. But anyway, way back
17:08in two thousand twelve,
17:10there were the Android phone
17:11actually looked like a huge
17:12clunky Texas instrument calculator for
17:14those of you that remember.
17:15So this is early days
17:17for smartphones. Now we we,
17:18you know, we walk out
17:19of our bedroom in the
17:20morning and our smoke smartphone's
17:22gone and we panic because
17:23we were like, oh my
17:23god. My light there's something
17:24wrong with you know, there's
17:26something missing in me. So
17:27it's very different now, especially
17:29for digital natives. But back
17:30then, this was this was
17:31very different territory. So we
17:33started exploring, can we actually
17:34digitize these things and deliver
17:36evidence based trainings,
17:38through an app? And, you
17:40know, it seems like, you
17:41know, that's pretty straightforward. But
17:42back then, it was it
17:43was uncharted territory. So we
17:45started with smoking,
17:46then even explored eating.
17:48I I won't go into
17:49a lot of the details
17:50with the eating program,
17:51but I I'd like to
17:52I'm very proud that the,
17:54the eating program is now
17:55the first, CDC recognized diabetes
17:58prevention program that's based in
17:59mindfulness, that's not based in
18:01cognitive therapy.
18:03And then even exploring anxiety
18:05as a habit.
18:06And for for you residents,
18:08I must have slept through
18:09that class where they talk
18:10about Borca Beck and and
18:12anxiety being a habit. If
18:13you slept through that class
18:14too, here's the one liner
18:16that you need to know,
18:17because I didn't know this
18:18back then, that Borkovec, back
18:20in the nineteen eighties, back
18:21when Prozac was introduced, you
18:23know, and and overshadowed
18:24this this really seminal
18:27idea, in my opinion. He
18:28was saying, you know what?
18:29Anxiety could be driven, through
18:31negative reinforcement like a habit.
18:32And he was saying that
18:33worry thinking isn't is reinforcing
18:35enough where it makes us
18:36feel like we're in control
18:37or avoid things or at
18:38least doing something.
18:39I recently heard from a
18:40patient the, you said that,
18:42you know, my grandmother used
18:43to say that that worrying
18:44is like being in a
18:45rocking chair. It gives you
18:46something to do, but you're
18:47not going anywhere.
18:48And so I think that
18:49really touches on this. But
18:51the problem also is you're
18:53not going anywhere, but you're
18:54actually
18:55feeding more anxiety. Because when
18:56we worry, it tends to
18:57feed forward and drive these
18:59anxiety habit loops.
19:00So we started developing these
19:02digital therapeutics just to see
19:04if they would work, where
19:05we could cut the training
19:06into bite sized pieces,
19:09help people understand how their
19:10minds work,
19:11give them, you know, things
19:13that are accessible instead of
19:14patients having to, you know,
19:15take a bus, come to
19:16my clinic, spend fifteen minutes
19:18with me, and then take
19:19a bus home, get childcare,
19:20all those things. We could
19:21just see if we can
19:22deliver it through their phone,
19:25drive some key points, come
19:26through animations and in the
19:27moment exercises. But as a
19:28researcher,
19:29really wanted to see how
19:31we could study this stuff
19:32to see if it actually
19:33worked, because we had we
19:34had no idea if and
19:35how it would work. We
19:36could also pair this with
19:38online communities,
19:39to have people support each
19:41other, etcetera.
19:42Just to give you an
19:42example,
19:44of how how this might
19:45work,
19:47even with eating, I had
19:48a patient with binge eating
19:49disorder,
19:50who who was, she was
19:51about thirty years of age
19:53when she came to see
19:54me
19:54and had been binging on
19:56entire large pizzas twenty out
19:58of thirty days a month.
19:59And the way she described
20:00it was
20:01the details are actually not
20:02that important here, where her
20:04mom had been starting to
20:05emotionally abuse her when she
20:06was eight.
20:07And the way that she
20:08coped
20:09was to eat, because that's
20:11something that she had control
20:12over. And so you can
20:13you know, if we map
20:14this out mechanistically,
20:16the negative emotion that
20:18that that started then, and
20:19then she would
20:20broaden this to, you know,
20:21any negative emotion she would
20:23eat, she would binge, and
20:24it would give her some
20:25temporary relief. And again,
20:26just like my patients who
20:28struggle with smoking or other
20:29addictive behaviors, she had no
20:30idea how her mind worked.
20:32So how do we actually,
20:34you know, how do we
20:35actually
20:36target this? So mechanistically,
20:39you know, building on what
20:40we'd done in our early
20:41work with smoking,
20:42this is in a study
20:44in collaboration with Ashley Mason.
20:46Ashley Mason actually, led this
20:48at at UCSF.
20:49She asked the question, well,
20:50can we target we use
20:51this, digital mindfulness training
20:54to help people
20:56decouple
20:57that urge to eat and
20:58eating,
20:59from, you know, from just
21:01habitually going through the behavior.
21:02And, again,
21:03caveat, this is a this
21:05is a single arm mechanistic
21:06study, where she was really
21:08focused on looking to see
21:10if you can decouple that
21:11relationship, and she used experience
21:13sampling to study
21:14this. So a lot of
21:15caveats here, but she, in
21:17fact, found a forty percent
21:18reduction in craving related eating.
21:20And importantly,
21:21going back to this, you
21:23know, if you go back
21:23to the mechanism that, or,
21:25you know, that something unpleasant
21:26causes that urge to eat,
21:28she found a thirty five
21:29percent reduction in eating to
21:30cope with negative emotions. So
21:31not a hundred percent, but
21:33some signal there that, suggested,
21:35you know, that mechanistically,
21:37it could be, it could
21:38be affecting that as well.
21:41So, you know, smoking may
21:43be a signal there. Eating
21:44may be a signal there.
21:45A lot of caveats,
21:46with these studies, small
21:48studies.
21:49You know, this one, for
21:50example, didn't have a comparison
21:51group, but that gave us
21:53I actually had a a
21:54patient who was who was
21:56using this this program
21:57and saying, you know what?
21:58As I map out these
21:59habit loops around eating, I
22:01realized that anxiety is driving
22:03my my eating behavior. So
22:05can you develop an a
22:06program for for anxiety? And
22:08I was thinking, I I
22:09I prescribe medications for anxiety.
22:11I hadn't really thought about
22:12that. But then I went
22:13back and looked at the
22:14literature, especially as I would,
22:15you know, have four out
22:17of patient, five patients struggle
22:19with, with the medications I
22:21was prescribing for them. I
22:22started I found Borkubeck's work
22:24and said, Hey, could we
22:26actually target anxiety like I
22:27have it as well?
22:28So we,
22:31we did a study
22:32starting,
22:33I was like, What's the
22:35most challenging population to work
22:36with? It's like, who are
22:38who who really don't take
22:39care of themselves and, you
22:40know, and this and that.
22:41And this is long story
22:42short, I was like, oh,
22:42yeah. Physicians. We are not
22:44good patients.
22:46So we did our first
22:47study. This was just a,
22:48you know, a signal finding
22:50study to say, okay, can
22:51we work with challenging populations
22:53who are anxious to see
22:54if there's a reduction in
22:55anxiety
22:56with this, with this anxiety
22:58program?
22:59Long story short,
23:01the details are are in
23:02the published papers, but we
23:03actually got a fifty seven
23:05percent reduction in anxiety at
23:06our primary endpoint
23:08at at three months. And
23:09so you can see most
23:10of these folks started,
23:11with GAD seven scores of
23:13above ten, so they were
23:14all within that, you know,
23:15that presumptive diagnosis of generalized
23:17anxiety disorder. And here, they
23:19were getting close to remission,
23:20which is below five.
23:22So that was that was
23:23an interesting signal, and that
23:24gave us enough,
23:26pilot data to go to
23:27the NIH and,
23:29get funding for randomized controlled
23:31trials. So here we started
23:32doing randomized controlled trials with
23:33people with generalized anxiety disorder.
23:35And I won't bore you
23:36with the details.
23:38Again, this was published a
23:39couple of years ago,
23:40but we just we did
23:41a real world study where
23:42we said, okay, let's take
23:44clinical care and then just
23:45add in you know, if
23:46you prescribe a medication, how
23:47about just prescribing an app?
23:49And so we had people,
23:51you know, randomized to one
23:52of these two conditions. And
23:53you can see
23:55the,
23:55in in green, the treatment
23:57as usual, which actually fourteen
23:59percent is right on par
24:00with the number needed to
24:01treat a five point two.
24:02About, you know, about one
24:03in five people were showing
24:05a a some, you know,
24:06significant reduction. It wasn't a
24:08a
24:09remission, but it was some
24:10reduction. Yet when you added
24:11in mindfulness training,
24:14we're getting sixty four percent
24:15remission, which was pretty interesting
24:17with the number needed to
24:17treat calculated at one point
24:19six.
24:20So we're seeing some signal
24:22there, and we wanted to
24:23understand mechanistically what was going
24:25on.
24:26So here we looked at,
24:28some standard measures like, well,
24:30are they worrying? Does the
24:31worry change?
24:32MAIA is the multidimensional
24:34assessment of interoceptive awareness. So
24:36we wanted to see if
24:36they were becoming more interoceptively
24:38aware. That's what mindfulness training
24:39is about. And, also, we
24:41wanted to see if were
24:42people less emotionally reactive? So
24:44we took this five facet
24:45mindfulness questionnaire, one of the
24:47subunits
24:48It's called the non reactivity
24:49subscale, and we we could
24:50see shifts in all three
24:52of those. And we could
24:53plug those into mechanistic equations
24:55and see a mediation effect.
24:57So we were finding that
24:58mindfulness training was increasing non
24:59reactivity, emotional non reactivity,
25:01which was leading to a
25:02reduction in worry, and that
25:04reduction in worry was mediating
25:05a reduction in anxiety. So
25:08mechanistically,
25:09it was acting as theorized.
25:10You know, mindfulness is helping
25:12people be with these unpleasant
25:13emotions, but not react to
25:15them.
25:16We then asked, well, is
25:17everybody benefiting
25:19from this or are there
25:20subgroups? So we could actually
25:21split out our split our
25:23questionnaires into single items and
25:24do cluster analyses
25:26to see if there were
25:26phenotypic clusters at baseline that
25:28would predict outcomes.
25:30You can see that they
25:31self organized into roughly equal
25:33clusters of three.
25:35And, you know, let's call
25:37them cluster one, two, and
25:38three, it doesn't matter. You
25:39can see how they these
25:40are z scores, so these
25:41are all relative to each
25:42other. You can see some,
25:45had more
25:46were scored higher on worry,
25:47some scored lower on interoceptive
25:49awareness, and some scored higher,
25:51for example, on interoceptive awareness.
25:53So why am I telling
25:53you this? Because it matters.
25:55So if you look at
25:56cluster one, two, and three,
25:57there were actually differential treatment
25:59effects. So in this randomized
26:01controlled trial, we actually found
26:02that group one started with
26:03the highest amount of anxiety
26:05and did the best. Cluster
26:06three was somewhere in the
26:08middle. Again,
26:09significant reductions, but cluster two
26:11didn't seem to move much.
26:13And here, we haven't
26:15we we need to take
26:16this to the next step,
26:17which is to ask, you
26:18know, what is it about
26:19being low in interoceptive awareness,
26:21for example? You can see
26:22these blue markers here. These
26:24are the that was the
26:25biggest differentiator.
26:26You know, are these folks
26:27that are are avoidant of
26:29unpleasant sensations? Are they, you
26:31know, do they have,
26:32anxiety? Are are their anxiety
26:34sensitivities higher, etcetera?
26:36We need to explore this
26:37more, but it suggests that
26:38it is worth exploring
26:40because, you know, at baseline,
26:41we actually,
26:42got this down to about
26:43nineteen questions when you when
26:45you ask what's the minimum
26:46number you could ask. So
26:47you could imagine in clinic
26:49giving somebody a questionnaire
26:51at on a tablet as
26:52they're in the waiting room.
26:53And in three minutes, you
26:54can get you can get
26:55a baseline,
26:56phenotype, let's say, where you
26:58could guess, but and that
26:59can get beamed to your
27:00your epic or or or
27:02whatever your medical record is,
27:03where it could say, okay,
27:04there's a prediction that this
27:05person's gonna do well with
27:07this mindfulness training, or this
27:08person's not gonna do well.
27:10They might need a a
27:10booster before you,
27:12before you start, or they
27:13might need something else entirely.
27:14So we can start to
27:15even get it personalized medicine
27:17in a way that is
27:18dirt cheap. Like, this this
27:19would take pennies,
27:21to develop and deploy.
27:24I won't belabor this, but
27:25just, just to show we
27:26did, you know, the hallmark
27:27of science is replication. So
27:29we got some more NIH
27:30funding to look at worry
27:31and sleep. Many of you
27:33probably seen this. I see
27:34this all the time where,
27:35you know, patients try to
27:37go to sleep, their head
27:38hits the pillow, and then
27:39their brain says, it's my
27:39turn, and they start worrying.
27:41And so we started asking
27:43and this is so common
27:44that,
27:45NIH has standardized questionnaires in
27:47the promised battery that are
27:49specifically aimed at worry and
27:50sleep. So we said, well,
27:52can we actually affect,
27:54you know, without saying anything
27:55about sleep, can we treat
27:56their anxiety and their worry
27:58and see if that helps
27:59with their sleep?
28:00So we brought in people
28:02who scored high on these
28:03measures where worry was affecting
28:05their sleep,
28:06And we asked we or
28:07two months was our primary
28:08endpoint, another randomized controlled trial,
28:11and we found
28:12that,
28:14that GAD seven scores were
28:15going down at two months.
28:17And, you know, that was
28:18that was nice to see.
28:19It wasn't quite the same
28:21reduction that we were seeing
28:22in generalized anxiety disorder. But
28:24at four months, you see
28:24that the control group catches
28:26up. Well, here we did
28:27a trial within a trial
28:28where we could, at two
28:29months, give the people in
28:31the control group the active
28:32intervention
28:33so that we could answer
28:34two questions. One, is there
28:35a
28:36is there duration? Is there
28:37durability of the effect in
28:39the people,
28:40who had primarily got the
28:41treatment? And how you know,
28:42can the control group catch
28:43up? Does this give us
28:44a replication within a trial?
28:46And here you can see
28:47that both answers were were
28:48seemed to be true.
28:50And and so when we
28:51looked at our the big
28:52question was, well, how is
28:53it affecting their sleep? You
28:54can see significant reductions in
28:56sleep again in our primary
28:57endpoint. And at that four
28:59months, the control group, you
29:00know, caught up. They were
29:01almost identical.
29:02So what this suggests
29:04is that if we actually,
29:05you know, target the core
29:08mechanisms you know, here we
29:09were targeting reinforcement learning.
29:11And I'll say, you know,
29:12it it's important for any
29:14type of treatment developments, whether
29:15it's in person, whether it's
29:17digital.
29:18And also this will now
29:19start applying to AI based
29:21methodologies,
29:22it's really important that we
29:24start first with mechanism.
29:26And I think
29:27mechanism can help drive efficiency
29:30and efficacy,
29:31when we when we target
29:33the treatments to that as
29:34compared to starting with, you
29:35know, the kitchen sink approach
29:36and then trying to do
29:37dismantling studies to see what
29:39what the effect is.
29:40So now I'm gonna spend
29:42a few minutes,
29:43just to talk a little
29:44bit about some of the
29:46neuro mechanisms, and then we'll
29:47get into some pragmatic stuff
29:49that hopefully will be clinically
29:50useful, for anybody.
29:52I I like this. There's
29:55some many of you may
29:56not recognize this person. This
29:57is Lolo Jones, a picture
29:59of her from a little
30:00while ago. She's,
30:02she was actually a three
30:03time Olympian. Back in two
30:04thousand eight, she was favored
30:05to win the hurdles at
30:06the Beijing Olympics. And I
30:08use her as a story
30:09because she had made it
30:10all the way through the
30:11preliminary. She was favored to
30:12win. She was in the
30:13finals at the ninth of
30:14ten hurdles.
30:16And then I'll read a
30:17quote from, that she gave
30:18to Time magazine where she
30:19said, you know,
30:21I was just in an
30:22amazing rhythm, and then I
30:23knew at one point I
30:23was winning the race. It
30:25wasn't like, oh, I'm winning
30:26the Olympic gold medal. It
30:27just seemed like another race.
30:28And then I was telling
30:30myself,
30:32to make sure that my
30:33legs were snapping out, so
30:35I over tried.
30:37That's when I hit the
30:38hurdle. So she clipped the
30:39ninth of ten hurdles. She
30:40finished seventh. It was devastating
30:41for her career, hard to
30:43recover from that.
30:44But the highlight here is
30:46not that not that this
30:47is
30:48a a tragedy, it certainly
30:50was for her,
30:51but it highlights something where
30:53if we if we rely
30:54too much on this thinking
30:56part of our brain, we
30:57kinda get in our way
30:58or as this, as teacher
31:00put it, your me is
31:01in the way.
31:02And so we can start
31:03asking,
31:04well, how often does the
31:05me get in the way?
31:06Back in two thousand ten,
31:08there was a famous study,
31:09that came out of Harvard,
31:10one of the first, ecological
31:12momentary assessment
31:13studies using an an iPhone,
31:16where they just probe people,
31:18and and they found that
31:19forty percent of waking life
31:20people are daydreaming. They're thinking
31:21caught in the past, the
31:23future,
31:24rarely present. So you can
31:25think of getting caught up
31:26in daydreaming
31:27about half the you know,
31:28if you pay attention for
31:29forty eight percent of this
31:31lecture, then you're you're beating
31:32the averages.
31:34But you can think of
31:34that as getting caught up
31:35in our experience. On top
31:37of that, when we get
31:37stressed out, a little harder
31:39to get you know, to
31:40tell our you know, to
31:41snap out of that and
31:41say, oh, pay attention, you
31:43know, stop being stressed.
31:45So when we're stressed, we're
31:45a little more caught up.
31:46And I like to think
31:48of this as a continuum
31:49where with addiction, we're at
31:50the far end of the
31:51spectrum. We could be fully
31:52aware of what's happening, but
31:53completely out of control. You
31:55know, continued use despite adverse
31:56consequences. I think that was
31:58one of the definitions
31:59of addiction that I still
32:01carry forward that I I
32:02I might have learned that
32:03from Mark Bettenzer or somebody
32:04in residency. Really simple.
32:07It it it's still it's
32:08still used today. So
32:11so caught up that we
32:12can't get out.
32:13So what does that actually
32:14look like? What's that feel
32:15like in our direct experience?
32:17About ten years ago, a
32:18research group in in,
32:21Europe started asking us questions,
32:23then they started doing these
32:24body maps of emotions. And
32:26so if you think of
32:27a time recently when you
32:29were afraid or anxious,
32:31sure that never happens to
32:32the residents here, but just
32:34imagine, you know, being anxious,
32:36and and just feel where
32:38you feel that in your
32:39body. And if you, you
32:40do that for a second,
32:41you might notice
32:42whether it's fear or anxiety,
32:44we kind of feel that
32:44in our chest, that, that,
32:46that closed down contracted feeling.
32:48And so that contraction, you
32:50know, it's, you can think
32:51of it as a protective
32:51mechanism. We're, we're closing down
32:53to protect our vital organs.
32:55So if that's happening, even,
32:57you know, fifty, fifty percent
32:58of waking life when, you
32:59know, that little contraction that
33:00comes with daydreaming, we can
33:02start to map this out.
33:03And I'm sure all of
33:05you,
33:06are familiar with this default
33:07one network,
33:09discovered back in year two
33:10thousand, Mark Raeckel's group at
33:12WashU. In fact, he sat
33:13on his data for several
33:14years because he wasn't sure
33:15what to make of it.
33:16Because he had given people
33:17the simple task, which is
33:18lay still in the scanner
33:20and don't do anything in
33:21particular. And, you know, he
33:22got this consistent finding over
33:23and over and over and
33:24wasn't sure what to do.
33:26So he published it as
33:26his inaugural
33:28paper in in, when he
33:29was inaugurated into the National
33:31Academy of Sciences because they
33:32kinda lightly review, you know,
33:33your inaugural paper. And it
33:35turns out to be one
33:35of the most cited and
33:36reproducible findings in all of
33:38neuroscience.
33:39So without going into all
33:41of that history,
33:42there's this network
33:43that seems to be self
33:44referential. Didn't even he didn't
33:46even know nobody knew what
33:47was actually happening at that
33:48time, but over the span
33:49of the next decade and
33:51and still continuing, people are
33:52starting to get into that
33:54more.
33:55So for example, and I'm
33:56gonna highlight these two hubs
33:58of the default mode network
33:59here, the the medial prefrontal
34:01cortex and the posterior cingulate
34:02cortex. So for example,
34:04a study in twenty sixteen
34:06showing the only manipulation in
34:07this study, this is in
34:08adolescence,
34:09shown their own Instagram feeds.
34:11They manipulated how many likes
34:13each picture got. And, what
34:15they found was that they
34:16were activating these reward pathways,
34:18like the nucleus accumbens was
34:20activated,
34:20but also they were activating
34:22these self referential networks, like
34:23the posterior singlet shown here
34:25in the in the red
34:26circle.
34:27Well, it's not just adolescents
34:29who get excited about, you
34:30know, that their picture's got
34:31a bunch of likes,
34:32even though it's arbitrary in
34:34an fMRI scanner. Hugh Gerevan,
34:36for example, showed that these
34:38these regions get activated in
34:39people who are addicted to
34:40cocaine or shown pictures of
34:42people,
34:42smoking crack cocaine.
34:45Amy Jane's developed this great
34:46paradigm,
34:47in people who are addicted
34:48to cigarettes, showing that posterior
34:50cingulate and medial prefrontal cortex
34:52light up like Christmas like
34:53a Christmas tree when you
34:54show them cues. We see
34:56the same thing in gambling,
34:58you know, etcetera, etcetera, etcetera.
35:00And also
35:01it's not just about craving,
35:03but,
35:04this was a study,
35:07published back in two thousand
35:08and seven showing that when
35:09people
35:10resist
35:12cravings, when they resist a
35:13craving, they're also activating this
35:15default mode network. And if
35:16you compare just the the
35:18resists,
35:19you know, even to accepting
35:20a craving that that
35:22really seems to localize
35:24to the posterior cingulate, maybe
35:26a little bit of the
35:27medial prefrontal cortex as well.
35:29So keep this in mind,
35:30this resistance, this contraction. And
35:32when we resist something, we
35:33tend to grit grit our
35:34teeth and resist, which can
35:36also sound familiar. I'm gonna
35:37resist
35:38smoking a cigarette. I'm gonna
35:39resist eating the croissant as
35:41compared to the, healthier egg
35:43thing.
35:44So what's that like? And
35:45also, I'll just add into
35:47this. This isn't just about
35:48addiction.
35:49We also see similar things,
35:51in
35:52anxiety. So this was a
35:54a study where they found
35:55that the more people worried
35:56this is the if we
35:58focus on the orange
35:59regions of activation here,
36:01the more people worried, the
36:02more they were activating their
36:03posterior cingulate and medial prefrontal
36:05cortex. So in work that
36:07we did with in collaboration
36:08with, Sue Whitfield Gabrielli,
36:11now back ten years ago,
36:13we started asking this question,
36:15well, what's common here? You
36:16know, we see all these
36:17different findings. It wasn't just
36:18an addiction. It was in
36:19all these different things.
36:21Could it be that we're
36:22getting caught up in our
36:23experience? Could that be the
36:24marker? And we could actually
36:26test this directly
36:27because mindfulness training, you could
36:29say, you know, in a
36:30nutshell, is is about not
36:31getting caught up in our
36:32experience, getting out of our
36:33own way.
36:35So this was a study,
36:37so we did a study
36:38back when I was first
36:39cutting my teeth on neuroimaging,
36:42and it was actually a
36:43suggestion of Mark Potenza
36:44where, you know, people were
36:46just starting to publish studies
36:47of of experienced meditator. And
36:49he said, why don't you
36:50do a study like that?
36:50I'm like, oh,
36:51I don't and he's like,
36:53yeah. Just think about it.
36:54And so I thought about
36:54it. I was like, oh,
36:55that's actually a great idea.
36:56So long story short,
36:58we did a study where
36:59we looked at experienced versus
37:00novice meditators. We looked across
37:02three different types of meditation,
37:04looking to see what was
37:05common, not what was different,
37:06not which was better or
37:08anything else. And we actually
37:09found across the entire brain,
37:11only four brain regions that
37:12were different in activation and
37:14experience versus novice meditators. And
37:16in fact, we at first,
37:17we thought this was a
37:18failed study because we were
37:19just, at first, just looked
37:20at increased activation
37:23in the brain. We didn't
37:23find a single brain region
37:25that was increasing activity. And
37:26it was a kind of
37:27a confound for me because
37:27I'm like, boy, I feel
37:28like I'm working hard when
37:29I'm meditating.
37:30At the time, I didn't
37:31realize that that effort was
37:33actually problematic.
37:34But then we said, well,
37:35what if we flip the
37:36script and say, are there
37:37changes in the deactivation,
37:39side of things? And that's
37:41exactly what we found was
37:42experienced meditators were not activating
37:44their default mode network as
37:45much as novices were. And
37:46we found some differences in
37:48functional connectivity and other things
37:49as well. And we'll go
37:50into the details in in
37:51the interest of time,
37:53but that was it was
37:54a really interesting finding for
37:55us. We and it helped
37:56us kind of shape how
37:57we were thinking about
37:59what meditation and what mindfulness
38:01were actually about.
38:03So this was a relatively
38:04small study. It took us
38:05several years to actually collect.
38:07Back then, you could actually
38:09publish with twelve subjects in
38:10each group.
38:12But so we said, well,
38:14let's let's make sure we
38:15replicate this first. And and
38:16I was fortunate enough to
38:17have now one of your,
38:19faculty members, Katie Garrison, join
38:21my lab at the time.
38:22And I have to say
38:23she's one of the most,
38:24productive, wonderful postdocs that I've
38:26ever had. And so she
38:28actually let us study where
38:29we did a replication,
38:31where we doubled the sample
38:32size. And you can see
38:33here, there's if you look
38:35at the posterior cingulate reticular
38:37oops.
38:38Supposed to be somewhere. Well,
38:40ignore that.
38:42I guess, hopefully, here, but
38:44maybe I got the time
38:45wrong.
38:47You can see that the
38:48posterior cingulate is showing that
38:50replication. We're seeing other brain
38:51regions. We won't go into
38:52those now, because it's, you
38:54know, it's it's a little
38:54messier. It's hard to hard
38:56to tell definitively,
38:58but it seems like we
38:58could actually replicate the results.
39:00And that gave us enough,
39:02it gave us enough confidence
39:03to say, okay. Let's go
39:04to the NIH and and
39:05try to get some funding
39:06to do a randomized controlled
39:07trial, not just in experienced
39:09meditators, but in people who've
39:10never meditated before.
39:12So in collaboration
39:14with Amy Janes, who had
39:16this wonderful smoking cue reactivity
39:17paradigm, she was at Harvard
39:18at the time, she's now
39:19at NIMH,
39:21we brought people in who
39:22wanted to quit smoking, and
39:23we asked you know, we
39:25scanned their brains at baseline
39:26to see how active their
39:27posterior cingulate was, as well
39:29as the rest of their
39:30brain. But we our region
39:31of interest was the posterior
39:32cingulate. Then we randomized them
39:34to get mindfulness training or
39:35the National Cancer Institute's quick
39:37guide app. A month later,
39:38we scanned them again,
39:39to see if changes in
39:41brain activity predicted outcomes.
39:43Now just for those of
39:44you earlier in your careers,
39:46you know, this this constitutes,
39:47you know, years of trying
39:49to get funding, years of
39:50doing studies, etcetera, etcetera, and
39:52it all culminates in one
39:53slide. So here it is,
39:55the the, you know, multimillion
39:57dollar slide, where we actually
39:58found that reductions in posterior
40:00cingulate cortex activity
40:02predicted or correlated
40:04with reductions in cigarette smoking.
40:05And you can see that
40:06that was actually specific
40:08to mindfulness training. So people
40:10that got mindfulness training, they
40:11showed a correlation of point
40:13three nine, whereas there was
40:14no correlation
40:15in the, cognitive therapy group.
40:17And the we as a
40:19surrogate of a dose response,
40:20we actually found that the
40:21number of modules that people
40:23completed
40:24also predicted reductions
40:26in,
40:27in activity.
40:28Now this is in contrast
40:30to people completed about the
40:32same number of modules in
40:33the National Cancer Institute's app,
40:35but we didn't see that
40:37prediction based on that. So
40:38that was an interesting finding
40:40and was kind of the,
40:41you know, the culmination where,
40:42you know, we're we're seeing
40:43theory, like mindfulness training supposed
40:45to help people be with
40:46a craving and not get
40:47caught up in it. We're
40:48lining that up with neural
40:49mechanism
40:50where, you know, here's a
40:51brain network that's that's activated
40:53when people are caught up
40:54in their experience. And then
40:55this predicts clinical outcomes, which
40:57goes back to Bruce Ransville's
40:59so what question. Right?
41:01Who cares unless it actually,
41:03directly aligns with clinical outcomes?
41:04And so this was this
41:05was nice to see that
41:06they were lining up.
41:08So around that time that
41:09we were doing some of
41:10these replication studies,
41:13that I was working,
41:15Zenios Papadimatris
41:17and, he at the time,
41:18his graduate student, who's now,
41:19I think, an associate professor
41:20here, Dustin Shinos,
41:22were playing with these, gaming
41:24chips, these, these I don't
41:26know what maybe they're even
41:27I don't know remember what
41:28chips they were, but they
41:29were there were some computer
41:30chips that they were saying,
41:31hey. Can we use this
41:32to increase processing speed
41:34in fMRI analysis? And so
41:36they developed some of the
41:37first real time neurofeedback paradigms,
41:39right here at Yale. And
41:40we said, hey, can we
41:41actually use that to line
41:43up people's brain activity
41:45with their, subjective experience? Because
41:47we wanted to be very
41:48careful about the reverse inference
41:50problem, which is
41:52was huge then and is
41:53still huge now where you
41:54say, oh, this brain region's
41:55deactivated and reactivating, and therefore,
41:57this must be happening in
41:58somebody's experience. Well, you've gotta
42:00check their experience to see
42:01if the two line up.
42:02I'm not gonna go into
42:03the the details we published.
42:05This is, again, a lot
42:06of work that Katie Garrison
42:07did and led,
42:09but I I'll just show
42:10you the paradigm
42:11and then, you know, some
42:13some nuggets. And if you're
42:14interested, I can send you
42:15some of the papers. But,
42:16basically,
42:17we could have people meditate
42:18while they're giving them feedback
42:20from their, their posterior singlet.
42:22And in fact, we had
42:22to work out a paradigm
42:24for a long time to
42:25to minimize the interference that
42:27that would have with their,
42:28with collecting the data because,
42:30you know, rarely does anybody
42:31get to meditate while they
42:32watch their brain activity change.
42:34And so that could actually
42:35be, you know, get be
42:36exciting in itself.
42:38I'll and we actually,
42:40replicated some of our findings,
42:42in with EEG. I'll show
42:43you, actually, what this looks
42:45like. We were fortunate enough
42:46to have Anderson Cooper come
42:47in and try this out,
42:48for a piece he did
42:49on sixty minutes.
42:50This is just the next
42:51generation of exercise. We've got
42:53the physical,
42:54you know, exercise components,
42:56down, and now it's about
42:57working out how can we
42:58actually train our minds. Doctor
43:00Brewer is trying to understand
43:02how mindfulness can alter the
43:04functioning of the brain.
43:05He uses a cap lined
43:07with a hundred and twenty
43:08eight electrodes.
43:09We're gonna start filling each
43:11of these hundred and twenty
43:12eight wells with conduction gel.
43:14The electrodes are able to
43:16pick up signals from the
43:17posterior cingulate,
43:18part of a brain network
43:20linked to memory and emotion.
43:22This is all just picking
43:23up electrical signal from the
43:25top of your head.
43:26Since attending the mindfulness retreat,
43:28I've been meditating daily and
43:30was curious to see if
43:31it had an impact on
43:32my brain.
43:33We're gonna have you start
43:34with thinking of something that
43:36was very anxiety provoking for
43:38you. Okay.
43:40When I thought about something
43:41stressful, the cells in my
43:42brain's posterior cingulate immediately started
43:45firing, shown by the red
43:47lines that went off the
43:48chart on the computer screen.
43:49Just drop into meditation.
43:51Okay. When I let go
43:53of those stressful thoughts and
43:54refocused on my breath, within
43:56seconds, the brain cells that
43:57had been firing quieted down,
44:00shown by the blue lines
44:01on the computer.
44:02That's really fascinating to see
44:03like that.
44:04Doctor Brewer believes everyone can
44:06train their brains to reach
44:08that blue mindfulness zone, but
44:10he says all the technology
44:11we're surrounded by makes it
44:13difficult.
44:15So I wanna skip ahead
44:17and
44:18you know, so some interesting
44:20findings from neuroimaging.
44:21We'd
44:22it it was actually,
44:24some of the some of
44:25the work here at Yale
44:27where we were exploring, could
44:28you actually turn this into
44:29a neurofeedback device?
44:31The hardware actually wasn't nearly
44:34in place to be able
44:35to do that from a
44:36scalability
44:37perspective. So I I think
44:39people are still exploring those
44:40types of things. And, you
44:42know, it goes back to
44:43mechanism. If we can find
44:44some of these neural mechanisms,
44:45line them up, how can
44:47we actually use these for
44:48for clinical use? So that's
44:50still an open question, that
44:51that we and others are
44:52exploring. But I just wanna
44:54end, because I I know
44:54that we're getting short on
44:56time, with some something that's
44:57actually clinically useful that we
44:59all can take home and
45:00even play with if it's
45:02if it's helpful in our
45:03clinical practice. So over the
45:05years,
45:05we've been doing you know,
45:07we've been collecting some data,
45:08and I had a great
45:09graduate student, Ariel Bechia, who
45:11was a qualitative researcher.
45:13And so we started doing
45:14interviews and and checking to
45:16see if there was a
45:17stepwise process that people were
45:18following as they were changing,
45:20some of their habitual behaviors.
45:22And I'll just lay out
45:23what we found and then
45:24go through some examples quickly.
45:26So it seems to be
45:27a a three step process.
45:28I don't know why lots
45:29of things fall into threes.
45:30This one happens too.
45:33Probably a coincidence, but interesting
45:35nonetheless.
45:36So first we have to
45:37be aware of being caught
45:38up in a habit loop
45:39that none we have to
45:40explore
45:41how rewarding it is, which
45:42is actually critical and counterintuitive.
45:45And then we can use
45:46practices to, step out of
45:47these habit loops. So what
45:49does this look like? Here's
45:50an example from somebody, who's
45:52struggling with eating said, I
45:54understand why I go to
45:55food to avoid or cover
45:56up or distract from uncomfortable
45:57feelings, such as anger, sadness,
45:59or restlessness. Who wants to
46:00feel those things? Trigger, uncomfortable
46:02feeling. Behavior, eat something that
46:03temporarily diminishes the feeling. Rewards,
46:06still have to deal with
46:07the unpleasant feelings plus the
46:08sugar headache. I can clearly
46:10see how I got caught
46:10in this habit loop trying
46:11to escape difficult feelings with
46:13food, but that ultimately it
46:14doesn't work. So I wanna
46:16highlight this because this takes
46:17literally takes thirty seconds to
46:19just do some psychoeducation.
46:21Hey. This is this is
46:22how habits form. And then
46:24send patients home to start
46:26mapping out their habit loops.
46:27And that's what I've been
46:28doing, for years now, which
46:29is, you know, listening as
46:31I take a history to
46:32see, you know, what habitual
46:33pay behaviors are people caught
46:35in, and are these important
46:36enough? You know, are these
46:37problems that they wanna that
46:39they wanna change?
46:41For example, my patient who
46:42was referred to me for
46:43anxiety,
46:44I pulled out a sticky
46:45note. She actually sent me
46:48a picture of it so
46:49that he kept it over
46:50the years. I don't think
46:51I have it in this
46:52presentation, but it was literally
46:53you can't read my handwriting
46:54anyway, but, you know, the
46:55trigger behavior result. And we
46:57went through that, and I
46:58sent him home and said,
46:59hey. Just start mapping out
47:00your anxiety habit loops. And
47:02we set a follow-up for
47:03two weeks later. So it
47:04doesn't take long, but the
47:05psychoeducation piece can really
47:07possibly be helpful. So I
47:10think that the next step
47:11is the beginning of the
47:11end,
47:12because once we get into
47:13this step, we can't go
47:14back. And so many of
47:16you may be familiar with
47:17the orbital frontal cortex. I
47:18know some people are in
47:19particular.
47:20This part of the simplistically,
47:22hopefully not over simplistically, the
47:24orbital frontal cortex kind of
47:25determines and stores reward value,
47:27And this helps us make
47:28decisions quickly. So for example,
47:30if I eat some milk
47:31chocolate and some broccoli, my
47:32brain's gonna determine, you know,
47:33which one's more calorically dense
47:35from a survival standpoint. And
47:36generally, I'll prefer milk chocolate.
47:38If you give me some
47:39dark chocolate, I'm gonna prefer
47:40dark chocolate. We can get
47:41into sea salt and cayenne
47:42and all of that. But
47:43I set up this reward
47:44hierarchy in my brain so
47:45that I can make decisions.
47:46You know, I'm at the
47:47store. I see some chocolate
47:49bars. Okay. I want the
47:50dark chocolate with a little
47:51cayenne and sea salt.
47:53So this goes back to
47:54the 1970s
47:55where Skorla and Wagner actually
47:56worked out the math behind
47:58how reinforcement learning works, and
48:00it's actually a relatively simple
48:01equation. These equations are still
48:02used today.
48:04So,
48:04and they're important for both
48:06learning and unlearning behaviors.
48:10One thing I'll highlight here
48:11is that willpower is not
48:12part of this equation, but
48:13what is critical is awareness.
48:16So there's this error term
48:18that is,
48:19you know, the prediction error,
48:21basically. So So if we
48:22have a certain value, let's
48:23use chocolate. I've if I
48:25have a certain value of,
48:26like, mango habanero truffles, just
48:29as a hypothetical
48:30illustration, and I go into
48:31a new bakery and they've,
48:32like, the best mango habanero
48:33truffles I've ever had, I
48:34get a positive prediction error.
48:36It's better than expected. And
48:37I learned, Hey, this is
48:38good bakery. On the other
48:39hand, if they taste like
48:40cardboard, I'm like, you guys
48:41got to work on your
48:41formula. I get a negative
48:43prediction error where my brain
48:44says, not so good. And
48:46I learn
48:47right? Both, both sides of
48:49the equation I'm learning and
48:50learn, oh, this isn't such
48:51a good place. Well, we
48:52can actually apply this clinically
48:54where we can say, pay
48:55attention,
48:56see if something is actually
48:57rewarding
48:58and then see what happens
48:59next. Don't force yourself not
49:01to do it. Just see
49:02how rewarding it is. So
49:03we can do the studies
49:05and actually measure change in
49:06reward value. And Long story
49:08short, it doesn't take that
49:10long for somebody to pay
49:11attention when they're overeating to
49:12see that see and importantly
49:14feel that overeating doesn't feel
49:16very good and they start
49:17to shift that behavior. This
49:18was a small study, led
49:20by one of my undergraduates.
49:22But then we replicate this
49:23in a community sample. And
49:24you can see that that
49:26shift happens relatively quickly, or
49:28as people put it, dear
49:30sneaky habit loop that says
49:31eating junk food is fun.
49:32I'm on to you. Right?
49:33So that reward value shifts.
49:34We see the same thing
49:35in smoking. Interestingly, this happens
49:37less quickly,
49:39probably because,
49:40you can smoke twenty cigarettes
49:41a day, but you don't
49:42overeat twenty times a day.
49:43Most people don't.
49:45But you can still see
49:45that the general trend holds
49:47true. Or similar to what
49:48I showed earlier, one person
49:49said, today, all the cigarettes
49:51I smoked were disgusting. So
49:52this is something that we
49:53can apply clinically. You don't
49:54need an app. You don't
49:55need a formal training. You
49:56can say, hey. Pay attention
49:57as you smoke a cigarette.
49:58But importantly, keep that mechanism
50:00in mind. If somebody does
50:02this out of context, they're
50:03gonna be like, I don't
50:04know why I'm doing this.
50:05So a little bit of
50:06psychoeducation first and then helping
50:08people ask the simple question,
50:09what am I getting from
50:10this? Right? And feeling into
50:12their direct experience
50:13can have a lot of
50:14effects.
50:15Last step here is, finding
50:18what I think of as
50:18rewards that are more rewarding.
50:20So what can we find
50:21that's intrinsically rewarding
50:22that we can tap into,
50:24maybe even use it as
50:25a superpower? And here, I'm
50:27going to highlight another quote
50:29attributed to Einstein. You know,
50:30I'm, I'm of no special
50:31talents. I'm only passionately curious.
50:33So what if we substituted
50:35curiosity
50:36for these other behaviors? So
50:38when we have, when we're
50:39worrying that, oh, no of
50:40worry, what if we go,
50:41oh,
50:42what does this feel like
50:43in my body? And we
50:44turn our experience
50:45toward ourselves instead of running
50:47away from it or doing
50:48something to distract ourselves. Here,
50:50I love the quote, you
50:51know, the only way out
50:53is through. So instead of
50:54being afraid
50:55of our sensations, of our
50:57thoughts, we get curious. Oh,
50:59what does that feel like?
51:00That might seem a little
51:01far fetched, but we've actually
51:03seen cases where, you know,
51:05this person said, I didn't
51:06quite buy into the benefits
51:07of curiosity. Today, I felt
51:09a wave of panic. And
51:10instead of immediate dread or
51:11fear, my automatic response was,
51:13that's interesting. So that
51:15helps us open to our
51:17experience.
51:18And they said, you know,
51:18took the wind right out
51:19of the sails. I'm just
51:20saying it was interesting. I
51:21actually felt it. So I
51:23won't go into the details,
51:24but this suggests that that,
51:25you know, just take mindfulness
51:27training
51:27as a way to train
51:28curiosity
51:30instead of, you know, getting
51:31caught up in our habitual
51:32behaviors. It's path a in
51:34this diagram, or trying to
51:35force ourselves
51:36to not do the thing,
51:37whether it's smoke or eat
51:39or worry.
51:40What if we actually brought
51:41that curiosity in so that
51:43we could have this unforced
51:45and and our patients described
51:47it this way as this
51:47third step is this unforced
51:49freedom of choice that emerges
51:50from embodied awareness. That's their
51:52words, their definition
51:53that came from these focus
51:54groups. These these can be
51:56both aligned with our goals,
51:57but also not feel like
51:59a lot of work.
52:00So I'm gonna I'm gonna
52:01end there and just say,
52:03we're starting to bring this
52:04into physician burnout,
52:07because there are a lot
52:08of, misconceptions and misnomers around,
52:11you know, how, you know,
52:12we're supposed to learn to
52:13be empathetic with our patients.
52:14Well, if our patients are
52:15suffering, we might be suffering
52:16as well. We might be
52:17burning out. So can we
52:18actually start to apply some
52:20of these principles,
52:21to helping,
52:23people like ourselves and develop
52:25resilience and reduce burnout?
52:27I'm not gonna go into
52:29the
52:29the data, but just to
52:31give you a hint of
52:32some of the work,
52:33that that we've,
52:35that we're moving forward with,
52:37it you you can start
52:38to see some signal here.
52:39Again, pilot work,
52:40when we actually just deliver
52:42this through a podcast, it's
52:43like, what will physicians do?
52:45They'll listen to podcasts. They'll
52:46drive to work for fifteen
52:47minutes a day. So can
52:48we give them seven short
52:49segments, you you know, through
52:50a podcast and see if
52:51we can get an effect?
52:52And we can you know,
52:53we're starting to see some
52:54signal there.
52:55So I'll just end, you
52:57know, of course, I'm only
52:58gonna share examples of patients
53:00who do well,
53:01but plenty of patients that
53:03struggle. But how about my
53:04patient who came in with
53:05binge eating disorder, that she'd
53:06been doing for about twenty
53:07years? Well, as she started
53:09to learn to be aware
53:11and and importantly kind to
53:12herself, we didn't get a
53:13chance to talk about kindness
53:14as another side of the
53:15coin of of curiosity, but
53:17really critical as well.
53:19She came back about four
53:20months, later and said, you
53:22know,
53:23I I feel like I
53:24have my life back. I
53:25can eat actually eat a
53:26single piece of pizza and
53:27enjoy it. And I like
53:29that because she's highlighting it's
53:30not about avoiding whatever it
53:32is. It's about changing our
53:33relationship to it. And in
53:34fact, just a couple of
53:36months ago, this was, I
53:37saw, eight or nine years
53:39ago, she sent me a
53:40email. I it took me
53:41a while to even register
53:42who this person was. And
53:44she said, hey. I just
53:45wanna send you an email.
53:46I've now, you know, lost
53:48over a hundred pounds.
53:49I've checked off a bunch
53:51of things on my bucket
53:52list, including,
53:53hiking to base camp of
53:54Mount Everest. And just said,
53:56you know, these these techniques
53:57have really helped me,
53:59discover a lot about myself.
54:00She's even talking about writing
54:01a book about her experience.
54:02So this highlights, you know,
54:04when we learn a little
54:05bit about ourselves, this can
54:07gain the strength of curiosity
54:09and kindness. These can go
54:10a long way.
54:11How about my patient with
54:13anxiety? Well, I'd send him
54:15home to map out his
54:16anxiety habit loops. He comes
54:17back two weeks later. And
54:18the first thing he says
54:19to me is, Hey doc,
54:20I lost fourteen pounds. I
54:21looked at him like, I
54:22didn't even think we talked
54:23about weight loss yet, because
54:24that was going to be
54:25lower on the list. And
54:25he said, I realized that
54:27I was eating,
54:28fast food in particular, as
54:30he's described it as his
54:31addiction,
54:32and that it wasn't actually
54:33serving me, you know, it's
54:34and so I've become disenchanted.
54:35He also went on to
54:36lose over a hundred pounds.
54:38But about six months into
54:39treatment, I'm walking out of
54:40our school of public health
54:41For any of you that
54:42have been in Providence, the
54:43school of public health on
54:44main street, pretty busy, narrow
54:46well, all the streets in
54:46Providence are narrow, but a
54:48busy, narrow street, this guy
54:50pulls up, rolls down his
54:51window, my patient. I'm like,
54:52great. He's driving. Gives me
54:53this big grin. He goes,
54:55Hey doc, I'm an Uber
54:56driver now. I'm headed to
54:57the airport to pick somebody
54:58up. So I just wanna
55:00again, these are extreme cases
55:02that that highlight points. But
55:04maybe I'll just I'll just
55:05bring this to a close
55:07by highlighting how this is
55:08different than a lot of
55:09other things. It's not about,
55:10you know, if I do
55:12x, then I'm happy. It's
55:13about the the journey as
55:15compared to the, the destinations.
55:17This person said what's most
55:18interesting to me is how
55:20we define the rewards. In
55:21the past, the reward of
55:22eating right has been weight
55:23loss, but it's more often
55:25than not short lived because
55:26I hadn't made the real
55:27process changes in my daily
55:28life. Here, it feels like
55:29the reward is defined differently,
55:31and weight loss is a
55:32side effect.
55:33The reward is here, for
55:34lack of better expression, a
55:35more balanced life or inner
55:37peace.
55:38So I'll just end there.
55:40I just wanna say, you
55:41know, I get to stand
55:42up here and talk about
55:43all this work, but we've
55:44had
55:45tons of great people starting
55:46with the folks that that,
55:49donated their time and their
55:50their brains to be scanned
55:51for this work. But as
55:52you can see here, a
55:53lot of collaborators,
55:55many of whom,
55:57are or were here at
55:59Yale. And so I'll just
56:01end there and say,
56:03we are gonna be recruiting
56:04for physicians for a for
56:06a study, coming shortly. So
56:08if you know folks that
56:08are interested, you can send
56:10them my way. And also,
56:11we've started a nonprofit,
56:13to see how we can
56:14bring together digital therapeutics with
56:16peer mentorship,
56:18to help people who are
56:20who are in recovery or
56:21struggling,
56:22with addiction. So if you're
56:23interested in that work, you
56:24can just check out mind
56:25shift recovery dot org. But
56:26if you remember nothing else,
56:27remember this curiosity piece, or
56:29as as Mary Oliver puts
56:30it, pay attention, be astonished,
56:32and tell about it. So
56:34with that,
56:35I wanna say I I
56:36personally went over so you
56:37couldn't ask tough questions, but
56:39I we might have a
56:40few few minutes for questions.
56:41Sorry, Stephanie, if I went
56:42over a little bit.