1. Please Pay attention now (it could change your brain): mechanisms of mindfulness. Judson Brewer MD PhD Director of Research Center for Mindfulness judson.brewer@umassmed.edu

2. “Money makes people funny” -Scott Kriens 1440 Foundation

3. Disclosures There is no money in mindfulness trainingThere is no money in mindfulness training There is no money for researchThere is no money for research –Write your congressperson! –Formed goBlue labs (Claritas Mindsciences) Yale spin-off startup companyYale spin-off startup company –Working with social entrepreneurs to translate research into clinical practice

5. For our consideration Why Facebook (and love) is like crack cocaineWhy Facebook (and love) is like crack cocaine Why McDonald’s has served over 250 BillionWhy McDonald’s has served over 250 Billion How Lolo Jones could have won the Olympic gold medalHow Lolo Jones could have won the Olympic gold medal How we can become a Buddha in nine minutes (and quit smoking too!)How we can become a Buddha in nine minutes (and quit smoking too!)

6. Talking about ourselves is rewarding! Tamir PNAS (2012) Nucleus Accumbens Meshi Front Hum (2013)

7. Facebook Addiction Disorder (FAD) Lee et al (2012) POSI = Preference for Online Social Interaction

8. Bartels, Andreas; Zeki, Semir NeuroReport (2000). Neural Correlates of Romantic Love

9. Aron A et al. J Neurophysiol (2005) ©2005 by American Physiological Society

10. “Love hurts, love scars, love wounds And mars, any heart Not tough or strong enough To take a lot of pain, take a lot of pain Love is like a cloud Holds a lot of rain Love hurts......ooh, ooh love hurts” -Nazareth

11. “In their quest for happiness, people mistake excitement of the mind for real happiness.’” -Ven. Sayadaw U. Pandita, In This Very Life

12. Sensory Information Changes how we see the world

13. Sensory Information Changes how we see the world

14. Sensory Information

15. Cue/Trigger Pleasan t Unpleasant CRAVING Behavior Memory (“me”) (sight, smell, thought, emotion, body sensation) Birth (of self-identity) Brewer, Elwafi and Davis Psych of Addictive Behavior (2012)

16. Automated Neutral Cue (get in your car) Neutral Cue (get in your car) Negative Cue (get yelled at by your boss) Negative Cue (get yelled at by your boss) Positive Cue (have a good meal or sex) Positive Cue (have a good meal or sex) Negative Affect (stressed out) Positive Affect (happy or relaxed) AVOIDANCE OF CUES SUBSTITUTE BEHAVIORS CRAVING I n c r e a s e d a l i e n c e S P o s i t i v e R e i n f o r c e m e n t I n c r e a s e d a l i e n c e S t v e R e i n f o r c e m e n N e a i g 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

17. “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)

18. “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

20. Self-control: competing systems Affective (self-referential?)/hot processingAffective (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 processingDeliberative/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

21. HOT COLD How to improve the balance between cold and hot processing?

23. Why study mindfulness? (a Darwinian perspective) t 1/2 =? Ab machine CBT Penicillin PsychoanalysisMindfulness

24. Overview of Mindfulness Two 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

25. Sensory Information

26. Mindfulness-based treatments Effective 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)

27. The paradox of Mindfulness: less is more Pay attention, and everything else will take care of itself (really). Brewer Davis and Goldstein Mindfulness (2013)

28. Greater smoking abstinence with MT vs. Freedom from Smoking *p =.063 *p =.063 **p =.012 * ** Brewer et al Drug and Alcohol Dependence (2011)

29. Working hypothesis Hypothesis: MT works by decoupling craving and behavior (e.g. smoking)Hypothesis: MT works by decoupling craving and behavior (e.g. smoking) Prediction: should see dissociation between craving and smoking BEFORE they both subsidePrediction: 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

30. Craving and cigarette use become dissociated during treatment Baseline (Week 0) End of Treatment (Week 4) 6-Week Follow-Up 3-Month Follow-Up 4-Month Follow-Up Craving (QSU) X Cigarette Use r = 0.582 p < 0.001 N = 32 r = 0.126 p = 0.491 N=32 r = 0.474 p = 0.020 N = 25 r = 0.788 p < 0.00001 N=28 r = 0.768 p < 0.00001 N=29 p =.04 p =.04 Predictor of SmokingrR2R2 βpEffect size Overall Model Baseline Craving Baseline Cigarette Use End of Treatment Craving Informal practice (days/wk) Craving*Informal (days/wk) 0.735 0.540 0.266 -0.053 0.208 -1.522 0.515 0.001 0.591 0.53 0.652 <0.0001 0.026 1.17 Mindfulness practice moderates dissociation Elwafi et al Drug and Alcohol Dependence (2013)

31. Reduction of craving scores with MT * p = 0.03 Elwafi et al Drug and Alcohol Dependence (2013)

32. Neutral Cue (get in your car) Neutral Cue (get in your car) Negative Cue (get yelled at by your boss) Negative Cue (get yelled at by your boss) Positive Cue (have a good meal or sex) Positive Cue (have a good meal or sex) Negative Affect (stressed out) Positive Affect (happy or relaxed) AVOIDANCE OF CUES SUBSTITUTE BEHAVIORS CRAVING I n c r e a s e d a l i e n c e S P o s i t i v e R e i n f o r c e m e n t I n c r e a s e d a l i e n c e S t v e R e i n f o r c e m e n N e a i g 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

33. “The destruction of craving conquers all suffering.” -Dhammapada (354)

34. Craving to Quit (iPhone App) 21 day training for smoking cessation21 day training for smoking cessation Daily modulesDaily modules –animations In vivo exercisesIn vivo exercises Experience SamplingExperience Sampling –Test efficacy

35. Applied mindfulness: RAIN RECOGNIZERECOGNIZE –“Oh that’s a craving” ACCEPT/ALLOWACCEPT/ALLOW –See if you are resisting the experience INVESTIGATEINVESTIGATE –“what’s happening in my body right now?” NOTENOTE –Label or mentally note the body sensations from moment to moment

36. Mechanisms of Mindfulness? Improved attentional focus (Jha 2007; Lutz 2009)Improved attentional focus (Jha 2007; Lutz 2009) Improved cognitive flexibility (Moore 2009)Improved cognitive flexibility (Moore 2009) Reduced affective reactivity (Frewen 2008; Farb 2010; Goldin 2010)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)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?What’s going on in the brain?

39. DAYDREAMING STRESS ADDICTION The Underperformance Continuum

40. Default Mode Network (DMN) Andrews-Hanna Neuron (2010)

41. Overlap between DMN and Self-referential processing Whitfield-Gabrieli Neuroimage (2011)

42. Resting state anti-coupling between monitoring (dACC) and default mode network Castellanos et al Biological Psychiatry (2008) default mode network self/conflic t monitoring

43. Mindfulness meditation practices Concentration Loving- kindness Choiceless 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

44. 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.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!)(Don’t feed the self!)

45. Experienced meditator study (n=12) Meditation hours Mindfulness7748.3+4250.5 Loving Kindness1060.1+958.9 Other1756.8+2476.6 Total10565.2+5148.9

46. 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)

47. Decreased DMN activity during meditation in experienced meditators z = 21 (all meditations, Experienced > Novice) x = -6 Brewer et al PNAS (2011)

48. z = 21 x = -6 Meditators Controls

49. 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)

52. “For people who Have agitated thoughts And intense passion, And who are focused on what’s pleasant, Craving grows more and more. Indeed, they strengthen their bonds” -Dhammapada (349)

53. “Romantic love is one of the most addictive substances on earth.” -Helen Fisher

54. Neural substrate of loving kindness meditation Reduced BOLD signal in meditators (n=20) v. novices (n=26) Garrison et al (2014) Brain and Behavior

55. Hold the door for someone

56. “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

57. Does practice make perfect? Relatively specific deactivation of DMN during meditationRelatively 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?Do state changes during meditation correlate with changes in default brain activation patterns after (a lot of) practice? Functional connectivityFunctional connectivity –Seed-based using DMN (Andrews-Hanna 2010) –Helps to control for control state (i.e. what if experienced meditators are meditating during baseline)

58. meditator > control x = 0 Connectivity z-score MeditatorsControls Altered DMN connectivity in experienced meditators (PCC seed region) Brewer et al PNAS (2011)

59. Connectivity z-score MeditatorsControls Brewer et al PNAS (2011) z = 24 z = 15 meditator > control Baseline z = 24 meditator > control z = 15 Meditation (PCC seed region)

60. State to trait? Meditators have a different Default Mode!

61. 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

62. “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

63. 1 min baseline Real-time meditation feedback 3 min meditate “active” feedback “dummy” feedback Garrison et al NeuroImage (2013)

64. Real-time Neurofeeback (PCC ROI, n = 22/group) Run 1 Run 4 ExpertNovice Decreased self-related activation Increased self-related activation Correspondence Correspondence : 7.4 ± 0.16 7.7 ± 0.29

65. 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…

66. …and then I sort of immediately settled in and I was really getting into it… Meditate by watching graph (graph of PCC, active feedback)

67. …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)

68. … 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)

69. …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)

70. …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)

71. 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)

72. What about me and the PCC? Andrews-Hanna et al (2014) Ann NYAS

73. Can we take a deeper dive into the PCC? Active during a number of cognitive statesActive during a number of cognitive states –Activation seen across multiple populations Deactivated during mindful statesDeactivated during mindful states What exactly does PCC activity correlate with?What exactly does PCC activity correlate with?

74. Use first-person self-report to better understand cognitive processes related to third-person physiological (e.g., brain imaging) dataUse first-person self-report to better understand cognitive processes related to third-person physiological (e.g., brain imaging) data Grounded Theory Method (GTM)Grounded Theory Method (GTM) –Qualitative analysis of self-report data –Derive theory from empirical data Neurophenomenology (Lutz and Thompson 2003)

75. 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 Code Central Code Theoretical Code Garrison et al (2013) Frontiers in Hum Neuroscience

76. Distracted Awareness Controlling Distraction n = 64 Interpreting n = 56 “Efforting” n = 19 Discontentment n = 14 MuddledDeliberatingMemories Self-related thinking Activation Auditory objects Physical sensations Visual objects Mental objects Displeasure Garrison et al (2013) Frontiers in Hum Neuroscience

77. “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

78. Undistracted Awareness Effortless Doing Concentration n = 99 Observing Sensory Experience n = 76 Not “efforting” n = 48 Contentment n = 28 FocusClarity Physical sensations Focus on breath Deactivation Mental objects Visual objects Auditory objects EquanimityPleasure Garrison et al (2013) Frontiers in Hum Neuroscience

79. “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

80. How do studies of the PCC converge? What about the self is processed in the PCC? (Brewer, Garrison and Whitfield- Gabrieli, 2013)What about the self is processed in the PCC? (Brewer, Garrison and Whitfield- Gabrieli, 2013) –“getting caught up” in experience? –Mental contraction?

81. 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

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

83. There was a sense of flow, being with the breath…flow deepened in the middle. “ “ -Experienced Meditator

84. Are you kidding? I have to practice 10,000 hours to change my default mode?

85. "Practice does not make perfect. Only perfect practice makes perfect.” -Vince Lombardi

86. What ingredients are needed for mindfulness practice? Pay attention

87. R UN 1 R UN 2 R UN 3 R UN 4 “felt a lot more relaxed, like it was less of a struggle to prevent my mind from wandering” N OVICE M EDITATOR

88. Pay attention Relax What ingredients are needed for mindfulness practice?

89. E XPERIENCED M EDITATOR “focus on the breath and in particular the feeling of interest, wonder, and joy that arises in conjunction with subtle, mindful breathing”

90. Pay attention Relax What ingredients are needed for mindfulness practice? Be interested

91. N OVICE M EDITATOR R UN 1 R UN 2 R UN 3 R UN 4 Thinking about the breath ”focused more on the physical sensation instead of thinking in and out”

92. Pay attention Relax What ingredients are needed for mindfulness practice? Be interested Drop the self

93. Run 1 Run 6 On run 6, I had a familiar memory image appear, one of a pond, willow tree and fields of my parents farm. I noticed the strong red deflection in response to this, although I don't appear in the image. I went back to the image to see if there was a sense of watcher-subject and noticed that image has a sense of being seen through a child's eyes. The somewhat desolate feeling landscape corresponds to that child's subjectivity. So there is a subject there, even though I never noticed it before, the scanner feedback made me look for it. If you look at run 6 you can see me exploring the image in a long run of red in the middle. Then I remembered I wasn't doing the task so I let it go for a while. Then I started imaginging myself in the future, telling Jud about what I had discovered about childhoold memories, which you can see clearly in the second run of red at the end of run 6. Repeating name Exploring image Future thinking On task E XPERIENCED M EDITATOR

94. Next steps to move into clinical utility: EEG source-estimated neurofeedback from the PCC

95. HOT COLD Mindfulness may increase cold while decreasing hot processing ACC dlPFC PCC

96. “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

97. Thanks! www.umassmed.edu/cfm FUNDING: 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 Subjects Keri 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 Druker Hani Elwafi Kathleen Garrison Jeremy Gray (Yale) Sean (Dae) Houlihan Catherine Kerr (Brown) Hedy Kober (Yale) Cheryl Lacadie (Yale) Sarah Mallik G. Alan Marlatt (UW) Linda Mayes (Yale) Candace Minnix-Cotton Stephanie Noble Alex Ossadtchi (SSI) Prasanta Pal Xenios Papademetris (Yale) Lori Pbert Mark 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 Thornhill Nicholas Van Dam (NYU) Katie Witkiewitz (UNM) Jochen Weber (Columbia) Sue Whitfield-Gabrieli (MIT) Patrick Worhunsky (Yale)

99. z = 21 x = -6 Meditators Controls