Expectations and individual differences in cognitive and affective control Collaborators Columbia Kevin Ochsner Ed Smith Martin Lindquist Emily Stern Joy

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Expectations and individual differences in cognitive and affective control

CollaboratorsColumbiaKevin Ochsner Ed SmithMartin LindquistEmily SternJoy Hirsch

University of MichiganChristian WaughBarb Fredrickson Steve TaylorIsrael LiberzonKen CaseyDoug NollTom NicholsJon-Kar Zubieta

MBBH Brain GroupJim RillingJonathan Cohen Bob RoseEd SmithSteve KosslynRichie DavidsonMargaret Kemmeny

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

– Bhagavad Gita

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

Abraham, sacrificing his son

Iago, manipulating Othello

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

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

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

From Cabanac, 2001

Ideal/goal:Built into the machine



– Feedback systems to maintain equilibrium– Adopted by neurobiologists and cognitive scientists– Critical ideas: equilibrium, set point, comparators

From Cabanac, 2001

Input

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

From Cabanac, 2001

Neural representation of goal

Neural error-detection mechanism

Interoception

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



– 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

Structure



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’


• 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.


HHH


SSS


SHS

Comparing Response Interference Tasks

B

X

M

S-R Compatibility Flanker Go-No/go

blocked compatible or incompatible

responses

blocked congruent or incongruent

flankers

blocked 80% “go” versus 50% “go”

responses;Event related

analysis

Wager, T. D., Sylvester, C. C., Lacey, S., Nee, D. E., Franklin, M. S., and Jonides, J. (2005), Neuroimage

Triple inhibition: Results

Go / no-go

Flanker

SRC

y = 20 mm x = 6 mm z = 45 mm

(FDR corrected) Wager et al., 2005

Common response selection regions

Activated in each task Performance-related

Control of attention• How did you perform the task?

– Instruction: “Respond to the center item”– Goal: make a correct response– Generate expectation: Important information in center, irrelevant

information peripheral. – Maintain expectation: 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’

A computational model of controlExample task: name the color in which this word is

printed: RED

Activation of task demand (context) by cue:Expectancy-based control

Activation of task demand (context) by error monitoring:Feedback-based control

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

tasks

Common response selection regions

Performance-related

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?

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

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

Cued attention: Evidence for expectancy-based control

Cue period:• Activation of dorsal frontal, cingulate, parietal cortices

Hopfinger et al., Nat. Neurosci. 2000

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?

6 s

Response:UP

Response:UP

No response

2200ms

N

W UP

W

W UP

Informative trials(P or W)

Non-informative trials

(N/P or N/W)

6 s

6 s

XControl trials

+

Cued-attention interference

• 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

Stern et al., in preparation

Informative vs. Non-informative cues during Anticipation

‘Attention network’

L IFJ/PMC

Ant. insula

Stern et al., in preparation


• 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

Structure



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

Pain processing systems

From VLPFC, OFC

(medial)

Pain Expectancy

Escape

Endure/Ignore

Fight

Decision circuit

Immobilize/Recover

Control circuit

Off

On

Right: Fields, 2004, Nat. Rev. Neurosci

Placebo

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

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

Are placebo effects real?

• 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

Active mechanisms?

Placebo effects in reported pain

Behavior

Appraisal

Sensation

Emotion

Painful stimulus

Belief /expectancy

Gate control

Experience

Demandcharacteristic

n = 50

Placebo causes 22%decrease in pain

0.001.002.003.004.005.006.007.00

1

Pain Rating

PlaceboControlPlacebo

The demand characteristic hypothesis

Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus


fMRI predictions:No changes in pain regions during pain

Opioids and placebo effects

Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus

• 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)

Opioids

Opioids

Opioids?

?

The gate control hypothesis

Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus

Gate control

fMRI predictions:Placebo reduces activity throughout sensory and affective pain processing regions

Opioids

Active mechanisms of placebo

Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus

Gate control

Experience


Opioids

(medial)


Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus

Gate control

Experience


fMRI predictions:Placebo reduces activity in affective pain networks

Opioid binding effects in frontal and limbic regions


Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus

Gate control

Experience


From VLPFC, OFC

(medial)

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

fMRI trial design

Time during Trials

+

20 s

Heat Rate pain

rating

4 s

Rest

+

40 - 50 s

Ready!

1 s

Cue

+

1-16 s

Anticipation

x = 9.77SD = 6.04

x = 6.82SD = 4.18

+

1-12 s

Rest

Anticipatory activity Pain-induced activity

Placebo effects during pain

CL-INS

Shock

Early Heat, correlation Shock

Late Heat, main effects (C > P)

A B

C

rACC

CL-INS

CL-INS

CL-TH

CL-TH

CL-INS

D

E FShockLate Heat, main effects

(C > P)

PHCP

Study 1 Study 2

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)

Anticipation of pain: Placebo > ControlB Study 1

OFCStudy 1A

Midbrain

DLPFC

C Study 2

DLPFC

r = .51

r = .60

Study 2D E

Opioid release correlated with reported placebo in [11C] Carfentinil PET

Direct effects of opioids in appraisal

Expectancy-induced control

• DLPFC activation, as in cognitive control

• OFC activation: Generation of expectancies– Expectancies of pain relief– Altered significance of incoming nociceptive stimuli– Opioid activity directly altered by placebo in OFC

• PAG activation– Opioid activity elicited in expectation of placebo (?)– ‘Affective decision’ circuit– Opioid activity correlated with placebo in PAG

Structure



General mechanisms of expectancy?

• Appraisal as a general mechanism– In pain, leads to altered significance of stimulation– In emotions, leads to altered thoughts, feelings and action

tendencies – In Parkinson’s disease, leads to increased self-efficacy

Ochsner et al.Regulation of emotion Mayberg et al.

Placebo in depression

Opioid increasesF Firestone 1996A Adler 1997N Wagner 2001P Petrovic 2002

Emotion regulationL Levesque 2003C Ochsner 2002O Ochsner 2004H Phan 2004B Bishop 2004

PlaceboW Wager 2004, antic.G Wager 2004, painI Lieberman 2004V Petrovic 2002T Petrovic 2005M Mayberg 2002

Dorsal Frontal Orbitofrontal

Lateral Frontal

Medial Frontal

Increased activity in self-regulation tasks

L R

L R

Expectations and Emotion

• How does expectation of an emotional picture influence neural responses?

• Do patterns of expectancy distinguish emotionally resilient individuals from nonresilient ones?

• Resilience: Ability to deal effectively with life adversity• Sample: 15 resilient and 15 nonresilient individuals

picked from extremes of sample on ego resilience scale (e.g., Block 1989).

Task Design

Aversive – Expected: VMPFC

0, 59, -21

-40

-30-20

-100

1020

3040

5060

70AversiveReliefExpected

* Aversive – Relief is significant at p <.005

Aversive – Expected: Temporal pole

28, 3, -39

-50

-40

-30

-20

-10

0

10

20

30

40Aversive

Relief

Expected

* Relief – Expected is significant at p <.05

Aversive – Expected/Relief: Amygdala

24, -6, -22

-20

-10

0

10

20

30

40

50

AversiveReliefExpected

Threat – Safety: LOFCNonresil > Resil

41, 38, -18

-60

-50

-40

-30

-20

-10

0

10

20

30

Resilient Nonresilient

ThreatSafety

OFC: Negative expectancy, less for resilient individuals• Nonresilient individuals respond to aversive cue

Threat – Safety: LOFCNonresil > Resil

OFC: Negative expectancy, less for resilient individuals• Nonresilient individuals respond to aversive cue

Aversive – Expected*: LOFCResil > Nonresil

44, 31, -12

-80

-60

-40

-20

0

20

40

60

80


Aversive

Relief

Expected

* Aversive – Relief is significant at p <.05

OFC: Resilient individuals do not respond until aversive picture

Aversive – Relief: RVLPFCResil > Nonresil

50, 25, 0

-80

-60

-40

-20

0

20

40

60

80


AversiveReliefExpect

RVLPFC: Resilient individuals show decrease in response to neutral pictures when expecting aversive. Nonresilient show increases.

Correlations – Safety-VMPFCDuring expectation

VMPFC during Safety cue

Resilience .53**

Hope- Agency .50**

Extraversion .40*

BAS – Reward resp. .51**

Positive emotions – 2 weeks .45*

Negative emotions – 2 weeks

-.50**

Correlations of LOFC during Threat to Pictures

Relief Neutral Picture

Aversive Picture

Emotion and expectancy

• Expectation of aversive stimuli elicits OFC activity. More expectancy in nonresilient individuals.

• Co-localized with expectancy effects in pain

• Lower aversive OFC expectancy effects correlated with greater deactivation of VMPFC to ‘relief’ pictures, and with broad measures of optimism

• Resilience: shift away from aversive expectations

Final conclusions• Expectancy, or predictions about future states (including emotional

experiences) is an important factor in shaping experience.

• Expectations provide ways of controlling behavior without experiencing adverse consequences first.

• Emerging circuit in ventrolateral PFC/anterior insula and orbitofrontal cortex links expectancies across cognitive and emotional domains

• Much more to learn! Underlying functions of these regions; impact on emotional health and cognitive ability; ways of modifying expectations and their effects in the brain.

Thank you!

Threat cues in the brain

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are needed to see this picture.

Relief: VLPFC Expect: VLPFC

Resilience -.60** -.20

Optimism -.62** -.48*

Extraversion -.42* -.12

Positive feelings -.51** -.33

BAS – Reward responsiveness

-.55** -.32

Trait positivity -.51** -.27

Threat – Safety: VMPFCNonresil > Resil

-3, 47, -27

-80

-60

-40

-20

0

20

40

60


ThreatSafety

Conclusions

• Nonresilient activate more MPFC/LOFC in response to the threat cue

• Nonresilient activate more RVLPFC to relief pictures than Resilient

• This activation in the LOFC to the threat cue predicts RVLPFC response to the relief neutral pictures

• If LOFC -> negative expectations and RVLPFC -> negative labelling, then for NR, their negative expectations drive their negative labelling of a neutral picture.

• Resilient people are better able to discriminate negative from neutral events -> may lead to quicker recovery

Relief – Expected: SMGOverall

38, -31, 39

-40

-30

-20

-10

0

10

20

30

All P's

Aversive

Relief

Expected

Expected – Relief: ACC/MPFC

6, 47, -9

-80

-60

-40

-20

0

20

40

AversiveReliefExpected

Increases in activity with placeboStudy 1 - AnticipationStudy 2 - AnticipationStudy 2 - Pain

Placebo effects in S2• Use meta-analysis as a broad ROI• Identify S2 in individual participants by individual pain response

Evidence against early blockade of nociception as a major factor

Opioid drug effects in S2

• Increases in S2 with verum opioid analgesics (e.g., Casey)

• Increased inhibitory input– Metabolic activity in interneurons -> Tonic increase– Could make S2 more responsive to frontal input

Opioid drug effects in prefrontal cortex

Casey et al., 2000

Wagner et al., 2001Adler et al., 1997


Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus

Gate control

Experience


Demand characteristic• Activation of appraisal networks before and during pain• Changes in pain-processing regions

Opioids

x

Pain experience• Reductions in ‘affective’ pain regions• Opioid release directly in appraisal networks

Gate control (early blockade)• Reductions in ‘affective’ pain regions• Increased activation in S2

x

Wagner 2001 - Remi produces dose-dependent decrease in PAG

Wagner, 2001Remifentanil-induceddecreases

Opioid drug effects in S2

• Increases in S2 with verum opioid analgesics (e.g., Casey)

• Increased inhibitory input– Metabolic activity in interneurons -> Tonic increase– Could make S2 more responsive to frontal input

Y = 1 Y = 1

Experiment 1 Experiment 2

dorsal amygdala dorsal amygdala

Amygdala: Control > Placebo

Peak Heat: Placebo activates right frontal, sensorimotor, and parietal cortex

Heat-responsiveRegions of interest (ROIs)

Inferior parietalPremotor

Dorsolateral PFC

A process model of expectancy-based regulation

Warning cue

Belief

Placebo treatment

Expectancy

pre-appraisal

Noxious stimulus

Pain

appraisal

Context level

Input level

Lateral PFC

ACC, OFC, VLPFC ACC, OFC, VLPFC

Insula, thalamus, S2

Anxiety

Vase et al., Price et al.

Attention

Petrovic et al., Brooks et al., others

Peak Heat: Placebo activates right frontal, sensorimotor, and parietal cortex

P > C, .005 / 60 voxels

Superior parietal lobule/precuneus

Sensorimotor cortex

Dorsolateral andDorsomedial prefrontal cortex

Premotor cortex

* Replicated in Rilling, Wager et al., in prep.

Clustering in component space• Make meaningful groups of regions• Inferential testing of null hypothesis: no grouping

Black: + correlation Blue: - correlation (p < .05 corrected)

The importance of S2

Pain in insula - colors are regions

Wager & Feldman Barrett, 2004

• Identified 4 insular regions based on anatomy (Mesulam)

• Studied four task domains:• Pain• Negative emotions• Attention shifting• Working memory

• Computed P(Task | Activity) in each region

Task prediction in the insula

Pain

Recall of emotion

Diagnostic value - colors are tasks

Can we predict task given brain activity?

Green = pain, red = emotional recall, blue = attention, yellow = WM

S2 activity is highly diagnostic of pain

Bilateral S2 activity occurs ONLY in pain studies

If I observe S2 activity, I’m probably in pain.

Implications for psychological vs. emotional pain

S2 in individual participantsDecreases (C > P) in anticipation

Increases (P > C) in early and late heat

Behavioral placebo effects correlated with…


Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus

Gate control

Experience


Opioids

From VLPFC, OFC

(medial)


Belief /expectancy

Appraisal

Sensation

Emotion

Behavior

Painful stimulus

Gate control

Experience


Opioids

From VLPFC, OFC

(medial)

From VLPFC, OFC

(medial)

Placebo effects in reported pain

Behavior

Appraisal

Sensation

Emotion

Painful stimulus

Belief /expectancy

Gate control

Experience


n = 50

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

Manipulation Test

Pai

n R

atin

g

PlaceboControl

Placebo causes 22%decrease in pain

Documents

Expectations and individual differences in cognitive and affective control Collaborators Columbia Kevin Ochsner Ed Smith Martin Lindquist Emily Stern Joy