Stress Hormones, Cortical Control and
Decision Making
Israel Liberzon M.D.
Theophile Raphael Professor of Neuroscience,
Professor of Psychiatry and Psychology, U of Michigan
Mental Health Service, Ann Arbor VAMC
Acknowlegments
Psychiatry, U of M:
Stephan Taylor, James Abelson, Luan Phan, Robert Welsh
Shaun Ho, Sarah Garfinkel
Psychology U of M:
Richard Gonzales
Psychology, Columbia:
Kevin Ochsner, Tor Wager, Ed Smith
This work is supported by
NIMH R24 MH075999
Disclosure and Conflict of
Interest: None
Developing Translational Center
University of Michigan
& Columbia University
Cognition
Hypotheses:
1. Cognitive, emotional, and somatic
(CES) processes interact in
reciprocally interconnected feedback
loops
2. Ineffective CES interaction can lead
to dysfunctional behavior and
psychopathology
Strategy:
Using somatic (cortisol) manipulations,
we evaluated impacts in the domains
of memory and decision making
using neuroanatomical (fMRI),
Appraisal, Memory and Decision Making
behavioral, and neuroendocrine
outcome measures
Decision Making and Stress
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The curvature of the decision weighting function (γ) is associated with
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DLPFC (Tobler, 2008)
Ventral Striatum (Hsu, 2009)
dACC (Paulus, 2006)
The loss aversion is associated with
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VMPFC & ventral striatum (Tom, 2007)
Stress is known to affect decision making (e.g. Starcke, Wolf, Markowitsch & Brand,
2008) and in turn decision making under risk can be stress inducing leading to
cortisol release.
Animal data suggest that high corticosterone (cortisol analogue) affects food choices
(rats Teegarden and Bale 2008), aggressive food seeking and the ability to problem
solve in the future (seabird chicks Kitaysky, Kitaiskaia, Piatt & Wingfield 2003)
To date, no study has investigated the neurocircuitry underlying modulation of
decision making induced by cortisol.
Limbic-Hypothalamic-Pituitary-Adrenal Axis
A system with a rhythm!
A system that responds to
challenges!
Glucocorticoids- cortisol
•Mobilization of glucose from stores
•Mobilization of a.a. from protein stores
•Increase cardio-vascular tone
•Inhibit all other functions that are not
essential for immediate survival
Adrenocorticotropin
Hormone (ACTH)
cortisol
The Limbic-Hypothalamic-Pituitary-Adrenal
Axis
Hippocampus
PVN
CRH
AVP
CRH
AVP
Pituitary
ACTH
Adrenal
LHPA “STRESS” AXIS
Glucocorticoids
(cortisol)
Loss Aversion fMRI Study by Tom et al. (2007)
“Neural” loss aversion should have “Mixed Gamble” vs. the mean of “Gains
Only” and “Losses only” Gambles
Non-Linearity of Decision Weighting Function & the
Difference between Prospect Theory and EU Theory Hsu, et al 2009
Prospect Theory (Curved Line)
Expected Utility Theory (Diagonal Line)
Prospect Theory – EU Theory
Decision Making Task
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40 subjects, 20 M, 20F (age: 18~37 years old, mean = 22.7 yr)
Treatment groups:
Hydrocortisone (100mg) (10 M, 10 F)
Placebo Group (10 M, 10 F)
2 Sessions for each subjects started at 1 or 2pm
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1st session: Decision Making Task at Baseline
fMRI at 3:20 or 4:20 pm (~100 min after oral intake)
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2nd session: Decision Making Task (Treatment effect)
P
1-p
3.8~9.8 seconds
X
Y
X’
Y’
P’
1-p’
Self-paced, < 6000 ms, median = 2.48 sec
•Three types of trials:
Gains Only, Losses Only, Mixed (42 trials/type)
•Each trial has two gambles (left and right)
each gamble has two possible outcomes (X, Y)
each possible outcome has a probability (p, 1-p)
Gains Only
Mixed
Losses only
Loss aversion (λ)
Non-Mixed vs Mixed
Reward Discriminability (α)
Gains Only
Value Function (v(x) = xα, if x > 0; v = - λxα, if x < 0)
Probability Discriminability (γ )
All DM trials
Decision Weighting Function
(w(p) = δpγ / (δpγ + (1-p)γ))
Drug
(Cort/Plcb)
1st session Baseline
~18 mins long
2nd session Treatment On
~ 120 mins after drug
Behavioral Results
Value Function (v(x) = xα, if x > 0; v = - λxα, if x < 0)
Value Function (v(x) = xα, if x > 0; v = - λxα, if x < 0)
Cortisol
Placebo
Baseline
In scanner
Behavioral Results ~contd
Decision Weighting Function (w(p) =
δpγ / (δpγ + (1-p)γ))
Cortisol
Placebo
Baseline
In scanner
Cortisol and Decision Making
Striatum
(Caudate and
Putamen)
Cortisol
Amygdala/SLEA
Insula
Reduced probability
processing
Reward processing
sensitization
Thank You