Please Pay attention now (it could change your brain):

mechanisms of mindfulness.

Judson Brewer MD PhDDirector of Research

Center for Mindfulnessjudson.brewer@umassmed.edu

“Money makes people funny”

-Scott Kriens1440 Foundation

Disclosures• There is no money in mindfulness training• There is no money for research

– Write your congressperson!– Formed goBlue labs (Claritas Mindsciences)

• Yale spin-off startup company–Working with social entrepreneurs to

translate research into clinical practice

For our consideration

• Why Facebook (and love) is like crack cocaine

• Why McDonald’s has served over 250 Billion

• How Lolo Jones could have won the Olympic gold medal

• How we can become a Buddha in nine minutes (and quit smoking too!)

Talking about ourselves is rewarding!

Tamir PNAS (2012)

Nucleus Accumbens

Meshi Front Hum (2013)

Facebook Addiction Disorder (FAD)

Lee et al (2012)

POSI = Preference for Online Social Interaction

Bartels, Andreas; Zeki, Semir NeuroReport (2000).

Neural Correlates of Romantic Love

Neural Correlates of Romantic Love

Aron A et al. J Neurophysiol (2005)

©2005 by American Physiological Society

“Love hurts, love scars, love woundsAnd mars, any heart

Not tough or strong enoughTo take a lot of pain, take a lot of pain

Love is like a cloudHolds a lot of rain

Love hurts......ooh, ooh love hurts”

-Nazareth

“In their quest for happiness, people mistake excitement of the mind for real

happiness.’”

-Ven. Sayadaw U. Pandita, In This Very Life

Sensory Information

Changes how we see the world

Sensory Information

Changes how we see

the world

Sensory Information

Cue/Trigger

Pleasant

Unpleasant

CRAVING

Behavior

Memory (“me”)

MIND (evaluation,

interpretation)

(sight, smell, thought, emotion, body sensation)

Habit formation and

reinforcement

Birth (of self-identity)

Brewer, Elwafi and Davis Psych of Addictive Behavior (2012)

Automated

Neutral Cue(get in your car)

Negative Cue(get yelled at by your

boss)

Positive Cue(have a good meal or

sex)

Negative Affect (stressed out)

Positive Affect (happy or relaxed)

AVOIDANCE OF CUES

SUBSTITUTE BEHAVIORS

CRAVINGIncr

ease

da l

ienc

eS

Posi

tive

Rein

forc

emen

t

Increase dal i en ce

S

tveReinforcem

en N

ea

ig

Thorndike 1898, Skinner, 1938, Zinser 1992, Piasecki 1997, Carter 1999, Lazev 1999, Cox 2001, Robinson 2003, Bevins 2004, Baker 2004, Cook 2004, Olausson 2004, Shiffman 2004, Carter 2008, Perkins 2010

SMOKE

Reinforcement of Associative Memory/Habit

(smoking makes you feel better)

Maintain or Increase Positive Affect/Decrease

Negative Affect t

“Just as a tree, though cut down, can grow again and again if its roots are undamaged and strong, in the same way if the roots of

craving are not wholly uprooted sorrows will come again and again.”

-Dhammapada (338)

“I can't get no satisfaction I can't get no satisfaction

'Cause I try and I try and I try and I try

I can't get no, I can't get no…”

-Mick Jaggar

Self-control: competing systems• Affective (self-referential?)/hot processing

– involves self-referential valuation, is automatic and unplanned, and influences behavior through impulses (Weber 2004, Kable 2007).

– fronto-striatal-limbic loop, including the orbitofrontal cortex, ventromedial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), and ventral striatum (McClure 2004; Hare 2009; Kober 2010)

• Deliberative/cold processing– effortful, influences behavior through rules of logic

and involved in inhibitory control (Weber 2004; McClure 2004; Ochsner 2005, Knoch 2007; Hare 2009)

– dorsolateral prefrontal cortex (dlPFC), and posterior parietal cortex etc (McClure 2004; Hare 2009; Kober 2010; Steinbeis 2012)

I WANT!

It’s not

about me

HOT COLD

How to improve the balance between cold and hot processing?

Why study mindfulness?(a Darwinian perspective)

t1/2=?

Ab machineCBTPenicillinPsychoanalysisMindfulness

Overview of MindfulnessTwo Component Definition:1) Self-regulation of attention so that it is

maintained on immediate experience, thereby allowing for increased recognition of mental events in the present moment.

2) Adopting a particular orientation toward one’s experiences in the present moment, characterized by curiosity, openness, and acceptance.

Bishop 2004

Sensory Information

Mindfulness-based treatmentsEffective for:

–Anxiety (Kabat-Zinn et al 1992, Goldin 2009, others)

–Depression (Teasedale et al 2000; Ma et al 2004, Eisendrath 2008, Segal 2010, others)

–Pain (e.g. Kabat-Zinn et al 1985, Kingston et al 2007, others)

–Addiction (e.g. Brewer 2009, Bowen 2009, Brewer 2011, Carim-Todd 2013)

–Boost immune system function (e.g. Davidson 2003, Pace 2009, others)

–Boost GRE scores! (Mrazek 2013)

The paradox of Mindfulness: less is more

Pay attention, and everything else will take care of itself (really).

Brewer Davis and Goldstein Mindfulness (2013)

End of Treatment 17 week follow-up0

5

10

15

20

25

30

35

40

MT FFS

Po

int

Pre

va

len

ce

Ab

sti

ne

nc

e (

%)

Greater smoking abstinence with MT vs. Freedom from Smoking

*p = .063**p = .012

***

Brewer et al Drug and Alcohol Dependence (2011)

Working hypothesis

• Hypothesis: MT works by decoupling craving and behavior (e.g. smoking)

• Prediction: should see dissociation between craving and smoking BEFORE they both subside– i.e. should still have some craving,

but it is not coupled to smoking

Craving and cigarette use become dissociated during treatment

Baseline(Week 0)

End of Treatment(Week 4)

6-WeekFollow-Up

3-Month Follow-Up

4-MonthFollow-Up

Craving (QSU)X

Cigarette Use

r = 0.582p < 0.001

N = 32

r = 0.126p = 0.491

N=32

r = 0.474p = 0.020N = 25

r = 0.788p < 0.00001

N=28

r = 0.768p < 0.00001

N=29

p = .04

Predictor of Smoking r R2 β p Effect size

Overall ModelBaseline Craving

Baseline Cigarette UseEnd of Treatment Craving

Informal practice (days/wk)Craving*Informal (days/wk)

0.735 0.540 0.266-0.0530.208-1.5220.515

0.0010.5910.53

0.652<0.00010.026

1.17

Mindfulness practice moderates dissociation

Elwafi et al Drug and Alcohol Dependence (2013)

Reduction of craving scores with MT

Baseline End of Trmt 6-Week f/u 3-Month f/u 4-Month f/u0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Abstainers

Non-Abstainers

Cra

vin

g S

co

re (

QS

U)

*

p = 0.03

Elwafi et al Drug and Alcohol Dependence (2013)

Neutral Cue(get in your car)

Negative Cue(get yelled at by your

boss)

Positive Cue(have a good meal or

sex)

Negative Affect (stressed out)

Positive Affect (happy or relaxed)

AVOIDANCE OF CUES

SUBSTITUTE BEHAVIORS

CRAVINGIncr

ease

da l

ienc

eS

Posi

tive

Rein

forc

emen

t

Increase dal i en ce

S

tveReinforcem

en N

ea

ig

Zinser 1992, Piasecki 1997, Carter 1999, Lazev 1999, Cox 2001, Robinson 2003, Bevins 2004, Baker 2004, Cook 2004, Olausson 2004, Shiffman 2004, Carter 2008, Perkins 2010

Reinforcement of Associative Memory/Habit

(smoking makes you feel better)

SMOKE

Maintain or Increase Positive Affect/Decrease

Negative Affect t

“The destruction of craving conquers all suffering.”

-Dhammapada (354)

Craving to Quit(iPhone App)

• 21 day training for smoking cessation

• Daily modules– animations

• In vivo exercises• Experience Sampling

– Test efficacy

Applied mindfulness: RAIN• RECOGNIZE

– “Oh that’s a craving”• ACCEPT/ALLOW

–See if you are resisting the experience• INVESTIGATE

– “what’s happening in my body right now?”• NOTE

–Label or mentally note the body sensations from moment to moment

Mechanisms of Mindfulness?• Improved attentional focus (Jha 2007; Lutz 2009)

• Improved cognitive flexibility (Moore 2009)

• Reduced affective reactivity (Frewen 2008; Farb 2010; Goldin 2010)

• Modification or shifts away from distorted or exaggerated self-view (Teasdale

2002; Ramel 2004; Farb 2007; Goldin 2009) • What’s going on in the brain?

DAYDREAMING STRESS ADDICTION

The Underperformance Continuum

Default Mode Network (DMN)

Andrews-Hanna Neuron (2010)

Overlap between DMN and Self-referential processing

Whitfield-Gabrieli Neuroimage (2011)

Resting state anti-coupling between monitoring (dACC) and

default mode network

Castellanos et al Biological Psychiatry (2008)

default mode network

self/conflict

monitoring

Mindfulness meditation practicesConcentration Loving-

kindnessChoiceless Awareness

In the next period, please pay attention to the physical sensation of the breath wherever you feel it most strongly in the body. Follow the natural and spontaneous movement of the breath, not trying to change it in any way. Just pay attention to it. If you find that your attention has wandered to something else, gently but firmly bring it back to the physical sensation of the breath.

Please think of a time when you genuinely wished someone well (pause). Using this feeling as a focus, silently wish all beings well, by repeating a few short phrases of your choosing over and over (for example: May all beings be happy, may all beings be healthy, may all beings be safe from harm.)

In the next period please pay attention to whatever comes into your awareness, whether it is a thought, emotion, or body sensation. Just follow it until something else comes into your awareness, not trying to hold onto it or change it in any way. When something else comes into your awareness, just pay attention to it until the next thing comes along.

Attention directed at single (physical) object

Attention directed at physical and mental objects

Attention focused, but not directed to specific object

Task of MT?

• The “task” common to all of these meditation techniques is the training of attention away from self-reference and mind-wandering and toward one’s immediate experience.

• (Don’t feed the self!)

Experienced meditator study (n=12)

Meditation hours  Mindfulness 7748.3+4250.5Loving Kindness 1060.1+958.9Other 1756.8+2476.6Total 10565.2+5148.9

2 min

baseline

Trial Time Course

30 sec

Instructions

4.5 min

Choiceless Awareness Meditation

Concentration Meditation

Loving Kindness Meditation

2x Trial (randomized between conditions)

Decreased DMN activity during meditation in experienced

meditators

z = 21

(all meditations, Experienced > Novice)

x = -6

Brewer et al PNAS (2011)

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Meditators Controls

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Garrison et al (under review)

Meditation > Resting Baseline (eyes open)

Meditation > Active Baseline (‘does the word describe you?’ ‘is the word in upper

case?’)

Decreased DMN activity during meditation as compared to both resting and active baselines

(n = 20 expert, 26 novice meditators)

“For people whoHave agitated thoughtsAnd intense passion,And who are focused on what’s pleasant,

Craving grows more and more.Indeed, they strengthen their bonds”

-Dhammapada (349)

“Romantic love is one of the most addictive substances on earth.”

-Helen Fisher

Neural substrate of loving kindness meditationReduced BOLD signal in meditators (n=20) v. novices (n=26)

Garrison et al (2014) Brain and Behavior

Hold the door for someone

“Whatever joy there is in this world All comes from desiring others to be happy, And whatever suffering there is in this world

All comes from desiring myself to be happy.”

-Shantideva

Does practice make perfect?

• Relatively specific deactivation of DMN during meditation– Common to all 3 meditation types– Reproducible

• Do state changes during meditation correlate with changes in default brain activation patterns after (a lot of) practice?

• Functional connectivity – Seed-based using DMN (Andrews-Hanna 2010)

– Helps to control for control state (i.e. what if experienced meditators are meditating during baseline)

meditator > control

x = 0 -1

-0.5

0

0.5

1

1.5

2

Con

nect

ivity

z-s

core

Meditators Controls

Altered DMN connectivity in experienced meditators

(PCC seed region)

Brewer et al PNAS (2011)

Seed region

-1

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Meditators Controls

Brewer et al PNAS (2011)

z = 24z = 15

meditator > controlB

asel

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z = 24

meditator > control

z = 15

Med

itatio

n(PCC seed region)

State to trait?

Meditators have a different Default Mode!

Relation between Granger causal influences and behavioral performance during visual spatial

attention task.

Wen X et al. J. Neurosci. 2013©2013 by Society for Neuroscience

“Science is a way of trying not to fool yourself. The first

principle is that you must not fool yourself, and you are the

easiest person to fool.”

-Richard Feynman

1 min

baseline

Real-time meditation feedback

3 min

meditate“active” feedback“dummy” feedback

Garrison et al NeuroImage (2013)

Real-time Neurofeeback (PCC ROI, n = 22/group)

Run 1

Run 4

ExpertNovice

Decreased self-related

activationIncreased

self-related activation

Correspondence: 7.4 ± 0.16 7.7 ± 0.29

Meditate by watching graph (graph of PCC, active feedback)

So at the beginning, I caught myself, that I was sort of trying to guess when the words were going to end and when the meditation was going to begin. So I was kind of trying to be like “okay ready, set, go!” and then there was an additional word that popped up and I was like “oh shit” and so that’s the red spike you see there…

…and then I sort of immediately settled in and I was really getting into it…

Meditate by watching graph (graph of PCC, active feedback)

…and then I thought “oh my gosh this is amazing it’s describing exactly what I am saying” and then you see that red spike...

Meditate by watching graph (graph of PCC, active feedback)

… and I was like “okay, wait don’t get distracted” and then I got back into it and then it got blue again…

Meditate by watching graph (graph of PCC, active feedback)

…and I was like “oh my gosh this is unbelievable, it’s doing exactly what my mind is doing” and so [chuckles] then it got red again…

Meditate by watching graph (graph of PCC, active feedback)

…So I just find it really funny because it’s…that’s…to the next question, that’s a perfect map of what my mind was going through.

Meditate by watching graph (graph of PCC, active feedback)

The curious case of the PCC– “Resting state” (Raichle 2001)

– Mind-wandering/Disruption of attention (Greicius 2003, Weissman 2006, Mason 2007, Li 2007, Eichele 2008, Wen 2013)

– Autobiographical memory, Past and future “self” (Schacter 2007, Andrews-Hanna 2010, others)

– Judgment about trait adjectives (Kelley 2002, Whitfield-Gabrieli 2011, others)

– Self-attribution in social situations (Cabanis 2013)

– Liking a choice you made (Jarcho 2011, Kitayama 2012)

– Prevention goals (Strauman 2013)

– Induced immoral behavior (van Veen 2009)

– Care and justice issues (Caceda 2011)

– Guilt (Morey 2012)

– Emotional processing (Peyron 2000, Maddock 2002, Zhao 2007, Gentili 2009, Bluhm 2012)

– Craving (Garavan 2007, Brody 2002 & 2007, Jarraya 2010)

What about me and the PCC?

Andrews-Hanna et al (2014) Ann NYAS

Can we take a deeper dive into the PCC?

• Active during a number of cognitive states–Activation seen across multiple

populations • Deactivated during mindful states• What exactly does PCC activity correlate

with?

• Use first-person self-report to better understand cognitive processes related to third-person physiological (e.g., brain imaging) data

• Grounded Theory Method (GTM)– Qualitative analysis of self-report data– Derive theory from empirical data

Neurophenomenology(Lutz and Thompson 2003)

Not “efforting”

Contentment

Open awareness

Not “efforting”

Acceptance

Calm

Tranquility

Relaxation

Focus on the body

Focus on the nostrils

Focus on the graph

Focus on sensations

Focus on visual input

Thinking about work

Remembering

Thinking about a place

Thinking about an object

Interpreting the task

Interpreting the graph

Interpreting experience

Discomfort

Emotion

Surprise

Restlessness

Confusion

Searching

Not “efforting”

Pleasure

Equanimity

Focus

Clarity

Physical sensations

Mental objects

Auditory objects

Visual objects

Deliberating

Remembering

Self-related thinking

Displeasure

“Efforting”

Muddled

Observing sensory experience

Concentration

Engaging with …

Discontentment

“Efforting”

Distraction

Interpreting

Open CodeCentral Code

Theoretical Code

Garrison et al (2013) Frontiers in Hum Neuroscience

DistractedAwareness

Controlling

Distractionn = 64

Interpretingn = 56

“Efforting”n = 19

Discontentmentn = 14

Muddled Deliberating MemoriesSelf-related

thinking

Activation

Auditoryobjects

Physicalsensations

Visualobjects

Mental objects

Displeasure

Garrison et al (2013) Frontiers in Hum Neuroscience

“I worried that I wasn’t using the graph as an object of meditation, so I tried, like, to look at it harder or somehow pay attention more to it”

PCC Activation

UndistractedAwareness

EffortlessDoing

Concentrationn = 99

Observing Sensory Experience

n = 76

Not “efforting”n = 48

Contentmentn = 28

Focus ClarityPhysical

sensationsFocus on

breath

Deactivation

Mentalobjects

Visualobjects

Auditoryobjects

Equanimity Pleasure

Garrison et al (2013) Frontiers in Hum Neuroscience

“I noticed …that the more I relaxed and stopped trying to do anything, the bluer it went”

“Toward the middle I had some thoughts which I don’t see on the graph maybe because I let them kind of flow by”

PCC Deactivation

How do studies of the PCC converge?

• What about the self is processed in the PCC? (Brewer, Garrison and Whitfield-Gabrieli, 2013)

– “getting caught up” in experience?–Mental contraction?

Life is an art, and like perfect art it should be self forgetting; there ought not to be any

trace of effort or painful feeling…As soon as there are signs of elaboration, a man is

doomed, he is no more a free being.

—Suzuki, 1964

Flowa mental state when a person is fully immersed in the present in a feeling of energized focus.

There was a sense of flow, being with the breath…flow deepened in the middle.

“ “

-Experienced Meditator

Are you kidding?

I have to practice 10,000 hours to change my default mode?

"Practice does not make perfect. Only perfect practice makes

perfect.”

-Vince Lombardi

What ingredients are needed for mindfulness practice?

Pay attention

RUN 1 RUN 2 RUN 3 RUN 4

“felt a lot more relaxed, like it was less of a

struggle to prevent my mind from wandering”

NOVICE MEDITATOR

Pay attention

Relax

What ingredients are needed for mindfulness practice?

EXPERIENCED MEDITATOR“focus on the breath and in particular the feeling of

interest, wonder, and joy that arises in conjunction with subtle, mindful breathing”

Pay attention

Relax

What ingredients are needed for mindfulness practice?

Be interested

NOVICE MEDITATOR

RUN 1 RUN 2 RUN 3 RUN 4

Thinking about the

breath

”focused more on the physical

sensation instead of thinking in and

out”

Pay attention

Relax

What ingredients are needed for mindfulness practice?

Be interested

Drop the self

Run 1 Run 6

Repeating name Exploring image Future thinking

On task

EXPERIENCED MEDITATOR

Next steps to move into clinical utility:

EEG source-estimated neurofeedback from the

PCC

HOT COLD

Mindfulness may increase cold while decreasing hot processing

ACC

dlPFCPCC

“To study Buddhism is to study the self. To study the self is to forget the self.

To forget the self is to be enlightened by all things. To be enlightened by all things is to be free from

attachment to the body and mind of one's self and of others.”

—Dogen

Thanks!

www.umassmed.edu/cfmFUNDING: NCCAM (R01 AT007922-01), NIDA (R03 DA029163-01A1, K12 DA00167, P50 DA09241), Mind and Life Institute (Varela award), Yale Center for Clinical Investigation (UL1 RR024139),Yale Stress Center (UL1 DE019586-02), VAMC MIRECC

SubjectsKeri Bergquist (Yale)Sarah Bowen (UW)

Willoughby Britton (Brown)Kathy Carroll (Yale)Neha Chawla (UW)

Todd Constable (Yale)Michael Crowley (Yale)

Jake Davis (CUNY)Gaëlle Desbordes (MGH)Cameron Deleone (Yale)

Susan DrukerHani Elwafi

Kathleen GarrisonJeremy Gray (Yale)Sean (Dae) Houlihan

Catherine Kerr (Brown)

Hedy Kober (Yale)Cheryl Lacadie (Yale)

Sarah MallikG. Alan Marlatt (UW)Linda Mayes (Yale)

Candace Minnix-CottonStephanie Noble

Alex Ossadtchi (SSI)Prasanta Pal

Xenios Papademetris (Yale)

Lori PbertMark Pflieger (SSI)

Marc Potenza (Yale)Maolin Qiu (Yale)

Rahil Rojiani

Bruce Rounsaville (Yale)Juan Santoyo (Brown)Cliff Saron (UC Davis)

Dustin Scheinost (Yale)Rajita Sinha (Yale)

Yi-Yuan Tang (Texas Tech)Evan Thompson (Toronto)

Tommy ThornhillNicholas Van Dam (NYU)Katie Witkiewitz (UNM)

Jochen Weber (Columbia)Sue Whitfield-Gabrieli

(MIT)Patrick Worhunsky (Yale)

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