Expectations and individual differences in cognitive and affective control

1. Expectations and individual differences in cognitive and affective control Columbia Kevin Ochsner Ed Smith Martin Lindquist Emily Stern Joy Hirsch University of Michigan Christian Waugh Barb Fredrickson Steve Taylor Israel Liberzon Ken Casey Doug Noll Tom Nichols Jon-Kar Zubieta MBBH Brain Group Jim Rilling Jonathan Cohen Bob Rose Ed Smith Steve Kosslyn Richie Davidson Margaret Kemmeny Collaborators

2. One who has control over the mind is tranquil in heat and cold, in pleasure and pain, and in honor and dishonor. • Bhagavad Gita

3. If you are distressed by anything external, the pain is not due to the thing itself, but to your estimate of it; and this you have the power to revoke at any moment • Marcus Aurelius

4. Abraham, sacrificing his son Iago, manipulating Othello

5. Structure • What is control? • Define terms: goals, expectations, and control • Control theory and principles of self-regulation • Brain mechanisms of expectancy • Expectations in the control of attention • Expectations in the control of pain • Expectations in the control of emotion

6. What is control? • Control: The use of goals to regulate a process • Goal: A representation of an ideal state to be achieved • May change depending on current state • Two ways goals shape regulation: by comparison with feedback and/or expectations • Feedback: A representation of a state or process to be regulated • Expectation: A prediction about a future state of the world or self • Control: The comparison of feedback and/or predictions with ideal states, and the use of comparison information to alter an ongoing process

7. Developments in control theory • Ancient macedonia: Float regulators, passive control systems • Enlightenment/Industrial era: Bernoulli, Maxwell, Routh • 1960’s: classical control theory • Feedback systems to maintain equilibrium • Adopted by neurobiologists and cognitive scientists • Critical ideas: equilibrium, set points, comparators Ideal/goal: Built into the machine From Cabanac, 2001

8. Developments in control theory • Ancient macedonia: Float regulators, passive control systems • Enlightenment/Industrial era: Bernoulli, Maxwell, Routh • 1960’s: classical control theory • Feedback systems to maintain equilibrium • Adopted by neurobiologists and cognitive scientists • Critical ideas: equilibrium, set point, comparators Input From Cabanac, 2001

9. Control in brain self-regulation • Physiological homeostasis: (food intake, blood pressure, temperature) • Feedback is everywhere: Basic neural circuits are composed of feedback mechanisms • Set point: A primitive representation of an ideal or goal state of the system. How much should I weigh? • Debate about whether these processes are ‘controlled’ through feedback or not Neural representation of goal Neural error-detection mechanism From Cabanac, 2001 Interoception

10. Control of Emotions and emotional behavior • Goals (ideals) are an essential component • Internal regulatory goal: control behavior & experience for its own sake • External regulatory goal: Control outcomes • Situational context leads to goal formation Neural representation of goal Neural error-detection mechanism Interoception or exteroception

11. Developments in control theory • Ancient macedonia: Float regulators, passive control systems • Enlightenment/Industrial era: Bernoulli, Maxwell, Routh • 1960’s: classical control theory • Feedback systems to maintain equilibrium • Adopted by neurobiologists and cognitive scientists • Critical ideas: equilibrium, set point, comparators • Modern control theory • Adaptive control: control settings adjust to optimize performance (Analogue to strategy) • Neural networks • Borrows concepts from neurobiology • Focus on reactive control; Expectations largely absent

12. Structure • What is control? • Define terms: goals, expectations, and control • Control theory and principles of self-regulation • Brain mechanisms of expectancy • Expectations in the control of attention • Expectations in the control of pain • Expectations in the control of emotion

13. Control of attention • Cognitive science/neuroscience • Use tasks that tap basic information processing • Highly controlled tasks • Identify mechanisms for voluntarily focusing attention and selecting responses • Assumed to generalize: ‘free will’ or ‘cognitive flexibility’

14. Control of attention • Instructions: If the center letter you are about to see is an H, raise one index finger. If the center letter is an S, raise two fingers.

15. Control of attention HHH

16. Control of attention SSS

17. Control of attention SHS

18. Comparing Response Interference Tasks S-R Compatibility Flanker Go-No/go B X M blocked 80% “go” versus 50% “go” responses; Event related analysis blocked compatible or incompatible responses blocked congruent or incongruent flankers Wager, T. D., Sylvester, C. C., Lacey, S., Nee, D. E., Franklin, M. S., and Jonides, J. (2005), Neuroimage

19. y = 20 mm z = 45 mm x = 6 mm Go / no-go Flanker SRC Triple inhibition: Results (FDR corrected) Wager et al., 2005

20. Common response selection regions Activated in each task Performance-related

21. Control of attention • How did you perform the task? • Instruction: “Respond to the center item” • Goal: make a correct response • Generateexpectation: Important information in center, irrelevant information peripheral. • Maintainexpectation: activity in brain must be maintained to interact with later stimulus processing • Bias perceptual mechanisms: Subgoal: enhance perception of center, block periphery • Expectancy generation = establishing a task set • This expectation of relevance, and the subsequent shaping of perception, is ‘attention’

22. A computational model of control Example task: name the color in which this word is printed: RED Activation of task demand (context) by error monitoring: Feedback-based control Activation of task demand (context) by cue: Expectancy-based control

23. Meta-analysis of executive working memory: common regions in control tasks

24. Common response selection regions • More frontal and insular activity: • Poorer performance • Why? • Less neural efficiency for poor performers, requiring more activation? • More difficult task for that participant, more control necessary? • Activations reflect reactive control needed more in poor performers? Performance-related

25. Feedback- or expectancy-based control? • Activation could reflect: • Expectancy generation • Expectancy maintenance • Error signal • Application of feedback-based control • Adjustments to the controller (strategy/learning shifts) • Meta-cognitive evaluation of performance

26. Cued attention: Evidence for expectancy-based control • Cue period: • Enhances visual cortex responses to attended locations • Responses significant even before stimulus appears • -- Evidence for expectation-based control Hopfinger et al., Nat. Neurosci. 2000

27. Cued attention: Evidence for expectancy-based control • Cue period: • Activation of dorsal frontal, cingulate, parietal cortices Hopfinger et al., Nat. Neurosci. 2000

28. Feedback- or expectancy-based control? • Activation likely to reflect: • Expectancy generation • Expectancy maintenance • But is frontal activity due to a general alerting response, or to specific task preparation?

29. X W N W UP W UP + Cued-attention interference Informative trials (P or W) Response: UP 6 s • ER fMRI, N=15 • P’s respond to position or meaning (W) of words (up, down, left, right) • Cues are informative (P/W) or not (N) • 50% catch trials to separate task-set preparation from response selection Non-informative trials (N/P or N/W) Response: UP 6 s 2200ms Control trials No response 6 s Stern et al., in preparation

30. Informative vs. Non-informative cues during Anticipation L IFJ/ PMC Ant. insula ‘Attention network’ Stern et al., in preparation

31. Control of attention • Anterior prefrontal, insular, cingulate, and parietal cortices • Commonly activated in many tasks that require ‘controlled’ response selection and attention • All regions can be activated by expectations, even anterior insula / frontal operculum; but most frequently superior frontal regions. • Failure to exercise expectancy-based control (poor performers) may result in reactive, feedback-based activation

32. Structure • What is control? • Define terms: goals, expectations, and control • Control theory and principles of self-regulation • Brain mechanisms of expectancy • Expectations in the control of attention • Expectations in the control of pain • Expectations in the control of emotion

33. Control of pain • Does ‘cognitive control’ over attention generalize to other domains, like pain and emotion? • Does affective information activate the ‘attention network,’ and is this information linked to affective regulation? • Strategy: Manipulate expectancies about pain, examine neural correlates of expectancies and their impact on pain processing

34. Pain processing systems ACC (medial) S1 DLPFC S2 VLPFC OFC AINS From VLPFC, OFC Thalamus PAG OFC BSTEM Spinal input

35. Decision circuit Control circuit Placebo Fight Off Endure/ Ignore Pain Expectancy Escape On Immobilize/ Recover Right: Fields, 2004, Nat. Rev. Neurosci

36. What is the placebo effect? • Placebo effect: Improvement of signs or symptoms caused by administration of a treatment with no intrinsic beneficial effects. • In pain, analgesia caused by a sham treatment (e.g., an injection of saline, an inert ointment) • Placebo treatment is a manipulation of expectancy and appraisal of meaning. • A tool for studying meaning generation, mechanisms of belief, and brain-body interactions

37. The placebo panacea • Over 4,000 ancient remedies, largely placebo Shapiro; in Harrington, Anne (ed.), The placebo effect • Modern placebo effects in major clinical disorders: heart disease, arthritis, pain, depression, Parkinson’s disease

38. Are placebo effects real? Active mechanisms? • Many things have been called ‘placebo effects’ (Klein, Shapiro, Kirsch, Hrobartsson) • Natural history • Spontaneous symptom fluctuation • Regression to the mean • Sampling bias • Hawthorne effects • Demand characteristics in reporting

39. Demand characteristic Emotion Experience Belief / expectancy Appraisal Gate control Painful stimulus Sensation Placebo effects in reported pain n = 50 Behavior Placebo Placebo causes 22% decrease in pain

40. The demand characteristic hypothesis fMRI predictions: No changes in pain regions during pain Behavior Demand characteristic Emotion Belief / expectancy Appraisal Painful stimulus Sensation

41. ? Opioids Opioids ? Opioids and placebo effects • Placebo effects are reversible by the opioid antagonist naloxone (Fields, Levine, Gracely, Benedetti) • Taken as evidence that placebo effects are not only demand characteristics • Evidence for psychological control of pain at the spinal level? (Melzack and Wall, 1965) Behavior Emotion Belief / expectancy Appraisal Opioids Painful stimulus Sensation

42. The gate control hypothesis Behavior Emotion Belief / expectancy Appraisal Opioids Gate control fMRI predictions: Placebo reduces activity throughout sensory and affective pain processing regions Painful stimulus Sensation

43. Active mechanisms of placebo ACC (medial) S1 Behavior Demand characteristic S2 Emotion Experience Belief / expectancy AINS Thalamus Appraisal Opioids Gate control PAG BSTEM Painful stimulus Sensation Spinal input

44. Active mechanisms of placebo Behavior Demand characteristic fMRI predictions: Placebo reduces activity in affective pain networks Opioid binding effects in frontal and limbic regions Emotion Experience Belief / expectancy Appraisal Gate control Painful stimulus Sensation

45. Active mechanisms of placebo ACC (medial) S1 Behavior Demand characteristic DLPFC S2 Emotion Experience VLPFC Belief / expectancy OFC AINS From VLPFC, OFC Thalamus Appraisal Gate control PAG OFC BSTEM Painful stimulus Sensation Spinal input

46. fMRI studies • Study 1: Shock on R forearm (n = 24) • Study 2: Heat on L forearm (n = 23, selected placebo responders) • Treatment with an inert ointment (Vasoline) • Placebo treatment: participants told that treatment was lidocaine • Control treatment: participants told that treatment was a ‘control cream’ to control for having ointment applied to skin • Testing on placebo and control-treated skin • fMRI design: Separate anticipation from experience of pain

47. Anticipatory activity Pain-induced activity Cue Anticipation Heat Rest Rate pain Rest Ready! + + + + 1 s 1-16 s 20 s 1-12 s 4 s 40 - 50 s x = 9.77 SD = 6.04 x = 6.82 SD = 4.18 rating Time during Trials fMRI trial design

48. Study 1 A B Shock Early Heat, correlation rACC C D Late Heat, main effects (C > P) CL-INS PHCP CL-INS Late Heat, main effects (C > P) E F Shock CL-INS CL-TH CL-TH Study 2 Placebo effects during pain • Placebo-induced decreases in: • Insula • ‘interoception’ (Craig) • correlates with subjective pain • Anterior cingulate • ‘pain affect’ (Rainville, hypnosis) • Dorsomedial thalamus • ‘limbic’ thalamus • involved in emotional responses • Parahippocampal cortex • Pain anxiety (Ploghaus) Shock CL-INS

49. C B Study 2 Study 1 OFC DLPFC Anticipation of pain: Placebo > Control A Study 1 DLPFC D E Study 2 Midbrain r = .51 r = .60

50. Opioid release correlated with reported placebo in [11C] Carfentinil PETDirect effects of opioids in appraisal