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: The Neurobiology of Decision-Making

Ifat Levy Section of Comparative Medicine Department of Neurobiology Interdepartmental Program Yale School of Medicine

Harnessing eHealth and Behavioral for HIV Prevention and Treatment April 2012 Overview

• Introduction to neuroeconomics • Decision under and behavior – Adolescent behavior – Medical decisions

Overview

• Introduction to neuroeconomics • Decision under uncertainty – Brain and behavior – Adolescent behavior – Medical decisions

Neuroeconomics

NeuroscienceNeuronal MentalPsychology states “asEconomics if” models architecture

Abstraction Neuroeconomics

Behavioral Economics

Neuroscience Economics

Abstraction Neuroscience functional MRI

VISUAL STIMULUS functional MRI: Blood Oxygenation Level Dependent signals

Neural Changes in oxygen Change in activity consumption, blood flow concentration of and blood volume deoxyhemoglobin

Change in Signal from each measured point in space at signal each point in time t = 1 t = 2 t = 3 t = 4 t = 5 t = 6

dorsal

anterior posterior lateral

ventral dorsal

anterior medial posterior

ventral

Anterior The cortex Cingulate Cortex (ACC)

Medial (MPFC) Posterior Cingulate Cortex (PCC) Ventromedial Prefrontal Cortex (vMPFC)

Orbitofrontal Cortex (OFC) Sub-cortical structures fMRI signal

• Spatial resolution: ~3x3x3mm3 Low • Temporal resolution: ~1-2s Low • Number of voxels: ~150,000 High • Typical signal change: 0.2%-2% Low • Typical noise: more than the signal… High But…

• Intact • Behaving human • Whole brain • Non-invasive Neuroeconomics

Cognitive Neuroscience

Neuroscience Psychology Economics

Abstraction New challenge: how do you make sense of such huge amounts of data?? Neuroeconomics

Mechanistic constraints of the human brain

Cognitive Economics

Economic models as normative theory Overview

• Introduction to neuroeconomics • Decision under uncertainty – Brain and behavior – Adolescent behavior – Medical decisions certainty ambiguity

100% 50% unknown partial full full relief remission remission Choose one:

A B

Risky OR Ambiguous

Most people choose A, implying that B has fewer red than blue chips: red < blue A B

Risky OR Ambiguous

Most people choose A, implying that B has fewer blue than red chips: blue < red The Ellsberg paradox: a bag cannot have fewer red chips and fewer blue chips at the same time Non-certain outcomes

• Risk – probabilities of different outcomes are known

• Ambiguity – probabilities of different outcomes are not known

• Partial ambiguity – partial information

known probability high probability low low probability high reward reward

$40

unknown probability known probability unknown probability low reward high reward

$110$0 $0$110 of risk and ambiguity

Risk and ambiguity affect the subjective value of an option in very different ways Overview

• Introduction to neuroeconomics • Decision under uncertainty – Brain and behavior – Adolescent behavior – Medical decisions

Research Question neural representation of value

multiple systems single system

reward reward punishment punishment immediate delayed cognitive cognitive delayed immediate emotional . . emotional .

Research Question neural representation of value

multiple systems single system

ambiguity vs. risk ambiguity & risk

x,y,0.5,5 Experimental design Experimental design

Amount Probability

Ambiguity level OR: - Winning color - $5 Parametric design Real bags One trial played for real Gain-risk trials

p = 0.75 p (chose (chose risky) p

Amount [$] $5

subject 1 Gain-risk trials

p = 0.75 p (chose (chose risky) p

Amount [$] $5

subject 1 Gain-risk trials

p = 0.75 p (chose (chose risky) p

Amount [$] $5

subject 1 Gain-risk trials

p = 0.75 p (chose (chose risky) p

Amount [$] $5

subject 1 Gain-risk trials

p = 0.75 p (chose (chose risky) p

Amount [$] $5

subject 1 Gain-risk trials

p = 0.75 p = 0.50 p (chose (chose risky) p

Amount [$] $5

subject 1 Gain-risk trials

p = 0.75 p = 0.50

p (chose (chose risky) p p = 0.38

Amount [$] $5

subject 1 Gain-risk trials

p = 0.75 p = 0.50

p (chose (chose risky) p p = 0.38 p = 0.25

Amount [$] $5

subject 1 Gain-risk trials

p = 0.75 p = 0.50

p (chose (chose risky) p p = 0.38 p = 0.25 p = 0.13

Amount [$] $5

subject 1 Gain ambiguity trials

A = 0.25 p (chose (chose ambiguous) p

Amount [$] $5

subject 1 Gain ambiguity trials

A = 0.25 p (chose (chose ambiguous) p

Amount [$] $5

subject 1 Gain ambiguity trials

A = 0.25 A = 0.50 p (chose (chose ambiguous) p

Amount [$] $5

subject 1 Gain ambiguity trials

A = 0.25 A = 0.50 A = 0.75 p (chose (chose ambiguous) p

Amount [$] $5

subject 1 Behavioral model MaxMin, Gilboa and Schmeidler 1989

subjective value

ambiguity level − β A α ( p ) · V risk 2 amount probability ambiguity aversion

stochastic choice model p (chose lottery) α

= 0.55, S1: gains Amount [$] β = 0.89

α

= 0.58, S2: gains Amount [$] β = - 0.03

0.75 A = 0.50 A = 0.25 A = 0.13 = p 0.25 = p 0.38 = p 0.50 = p 0.75 = p S1: gains S1: losses

α = 0.55, β = 0.89 α = 0.58, β = -0.04

p = 0.75

p = 0.50 p = 0.38 p = 0.25 p = 0.13 A = 0.25 A = 0.50 p (chose p (chose lottery) A = 0.75

Amount [$] Amount [$] Losses Ambiguity aversion Risk aversionRisk Risk aversion Gains Gains

Ambiguity aversion Risk aversion Losses Gains

A ( p − β )⋅V α 2

under risk subjectivevalue under ambiguity … … time Subjective value under ambiguity

ACC / MPFC

R L

caudate posterior amygdala cingulate

19 subjects, random effect analysis P<0.002 P<0.0001 Subjective value under risk

ACC / MPFC

R L

caudate posterior amygdala cingulate

19 subjects, random effect analysis P<0.01 P<0.001 Unique areas for SV under ambiguity?

PCC amygdala

No… %signal change %signal change

risk ambiguity risk ambiguity Research Question neural representation of value

multiple systems single system

ambiguity vs. risk ambiguity & risk

x,y,0.5,5 Uncertainty Summary 1

• High variability in risk and ambiguity attitudes across individuals • Areas in MPFC and represent subjective value under both risk and ambiguity

Can attitudes towards risk and ambiguity explain phenomena like risk-taking in adolescents and overeating in obese individuals?

Overview

• Introduction to neuroeconomics • Decision under uncertainty – Brain and behavior – Adolescent behavior – Medical decisions

Adolescents take

• 200% increase in morbidity and mortality rates in adolescence compared to childhood (Dahl, 2004)

• Adolescents are physically healthier and stronger than both children and adults (Dey et al., 2004)

• Increase mostly attributed to risky behaviors: car accidents, alcohol and substance abuse, violence, eating disorders, unsafe sex (Reyna and Farley, 2006)

• Not due to flawed reasoning capabilities, poor decision- making skills or failure to understand the consequences of their actions (Reyna and Farley, 2006)

Subjects

Age \ Female Male Total Gender 12-17 17 16 33 21-25 18 16 34 30-50 17 15 32 65-90 18 17 35 Total: 70 64 134

In collaboration with

Adolescents vs. adults Uncertainty Summary 2

• Adolescents are more risk averse, but less ambiguity averse than adults • Young organisms need to learn about their world

Do people treat risk and ambiguity similarly in different domains?

In collaboration with Terri Fried Overview

• Introduction to neuroeconomics • Decision under uncertainty – Brain and behavior – Adolescent behavior – Medical decisions

“You were involved in a car accident and as a result suffered traumatic brain injury. You were immediately rushed to the nearest hospital and were informed by the doctor that without immediate treatment you will not survive.”

Gains and losses in medical decisions

Gains: cognitive improvement

No effect Slight improvement Moderate improvement Major improvement Recovery

Worst outcome Best outcome

Major improvement = Mild cognitive disability: mild memory impairment resulting in forgetting some appointments, forgetting people’s names, needing a list to do food shopping No effect

Slight improvement or

recovery Major improvement

Slight improvement or

No effect Gains and losses in medical decisions

Losses: headache as an adverse effect

Critical headache Severe headache Moderate headache Mild headache Recovery

Worst outcome Best outcome

Moderate headache: improves but does not resolve with acetaminophen (Tylenol); requires you to lie down occasionally to relieve ; occurs a couple of times a week. moderate headache

Mild headache or

recovery Severe headache

Mild headache or

recovery Decision under risk 1 Positive outcomes 1 Negative outcomes 0.9 0.9

0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 Proportionof choices lottery 0.1 0.1 0 0 0.13 0.25 0.38 0.5 0.75 0.13 0.25 0.38 0.5 0.75 Outcome probability Outcome probability Money Medical N = 29 Decision under ambiguity 1 Money 1 Medical

0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3

Proportionof choices lottery 0.2 0.2 0.1 0.1 0 0 gain loss improvement adverse effect

Ambiguity level: 0 0.25 0.50 0.75 N = 29 Uncertainty Summary 3

• Ambiguity aversion was observed both under gains and under losses when making medical decisions

Summary • Economic models can be used to make sense of neural data • High variability across subjects in attitudes towards risk and ambiguity • Adolescents are more risk averse and less ambiguity averse than adults • Ambiguity aversion in medical decision- making for both positive and negative outcomes

Acknowledgements

Lab Collaborators Sarah Abdallah Paul Glimcher, NYU Jennifer Fanning Aldo Rustichini, Minnesota U Ellen Furlong Agnieszka Tymula, NYU Patrick Kenney Amy Roy, Fordham Genny Ladiges Terri Fried, Yale Kirk Manson Scott Huettel, Duke Helen Pushkarskaya Linda Mayes, Yale Lior Rosenberg Belmaker Michael Crowley, Yale Lital Ruderman Ashley Gearhardt, Yale Sana Samnani Eric Jackson, Yale Jeannie Tran Daniela Schiller, Mount Sinai Zhihao Zhang

Funding NIA, Pepper Center

Sense of incompetence (Heath and Tversky, 1991)

People prefer to bet on events in their field of expertise, even when they judge the probabilities as equal Comparative ignorance (Fox and Tversky, 1995)

How much will you pay for playing the lottery?

Within subject Between subject > =

More recent study: Ambiguity aversion is reduced but not abolished (Chow and Sarin 2001) Informed opponent (Kuhberger and Perner, 1991)

Subjects chose the ambiguous option more when the person who filled the bag was a partner than when it was an opponent Experimental design Risk

Ambiguity

Real bags!

Experimental design

• Subjects were endowed with $125 • Gain and loss trials • Choice between a lottery and a certain amount (±$5) • 3 ambiguity levels: 0.25, 0.5, 0.75 • 5 risk levels: 0.75, 0.5, 0.38, 0.25, 0.13 • 5 outcome levels: ±$5, ±$8, ±$20, ±$50, ±$125 • 320 trials • 1 trial randomly selected and played for real money Behavioral model MaxMin, Gilboa and Schmeidler 1989

subjective value

ambiguity level − β A α ( p ) · V risk 2 preference amount probability ambiguity aversion

stochastic choice model S2: gains S2: losses

α = 0.58, β = -0.03 α = 0.86, β = 0.72

p = 0.75

p = 0.50 p = 0.38 p = 0.25 p = 0.13 A = 0.25 A = 0.50 p (chose p (chose lottery) A = 0.75

Amount [$] Amount [$] Subjective value in ambiguity defined regions

MPFC striatum

%signal change %signal change

risk ambiguity risk ambiguity Subjective value in risk defined regions

MPFC striatum

%signal change %signal change

risk ambiguity risk ambiguity Adolescents take risks

• 200% increase in morbidity and mortality rates in adolescence compared to childhood (Dahl, 2004)

• Adolescents are physically healthier and stronger than both children and adults (Dey et al., 2004)

• Increase mostly attributed to risky behaviors: car accidents, alcohol and substance abuse, violence, eating disorders, unsafe sex (Reyna and Farley, 2006)

• Not due to flawed reasoning capabilities, poor decision- making skills or failure to understand the consequences of their actions (Reyna and Farley, 2006)

And in the brain…

• Gray matter maturation processes in PFC and striatum continue into adolescence (Giedd et al., 1996, 1999, 2004) • Frontal increase in white matter occurs late and extends into adulthood (Fuster, 2002) • Structural atrophy and decline in receptors in striatum and PFC in aging (Backman et al., 2000; Volkow et al., 1998) • Altered striatal activation during gain anticipation in adolescents compared to adults (Ernst et al., 2005; Galvan et al., 2006; Bjork et al., 2004) • Reduction in activation in striatal areas during loss anticipation in older adults (Samanez-Larkin et al., 2007).

Adolescents vs. adults Controls Controls Controls “Cognitive” blocks No effect = The treatment failed. You end up in a vegetative state. Slight improvement = Severe cognitive disability: severe memory impairment resulting in inability to recognize your loved ones. Moderate improvement = Moderate cognitive disability: moderate memory impairment resulting in inability to work and participate in leisure activities such as playing cards or doing crossword puzzles. Major improvement = Mild cognitive disability: mild memory impairment resulting in forgetting some appointments, forgetting people’s names, needing a list to do food shopping. Recovery = return to your initial cognitive ability prior to the accident. “Headache” blocks Recovery = successful treatment with no side effects. Mild headache: responds to acetaminophen (Tylenol); does not interfere with daily activities; occurs a couple of times a week. Moderate headache: improves but does not resolve with acetaminophen (Tylenol); requires you to lie down occasionally to relieve pain; occurs a couple of times a week. Severe headache: not responsive to acetaminophen (Tylenol); requires stronger pain medication, which does not fully relieve pain; requires you to lie down frequently to relieve pain; occurs daily. Critical Headache: Severe headache (as above) accompanied by other symptoms, such as nausea and vomiting.