Transcript From Intoxication to addiction

The Intoxication of Power: From Neurosciences to
Hubris in Healthcare and Public Life.
Royal Society of Medicine October 2012
From Intoxication to Addiction:
Neurobiological Substrates for
Hubris?
Paul Fletcher
[email protected]
Bernard Wolfe Health
Neuroscience Fund
Speculations on the neurobiology
of hubris syndrome
• Impaired risk appraisal
• Inability to foresee undesirable outcomes
• Dangerous decision-making (with ensuing
harm).
Highly unlikely to be localisable to a single
region or neurotransmitter system
From Intoxication to Addiction:
Neurobiological Substrates for
Hubris?
What do we mean by addiction?
• Drug addiction – a chronic relapsing state
characterised by:
– Compulsion to seek/take drugs
– Loss of control
– Emergence of a negative emotional state
• Latterly, research focus has shifted from the
acute effects (the high and the come-down) to
addiction as an evolving condition characterised
by neuroadaptation
Koob and Volkow, Neuropsychopharmacology, 2010
Binge/Intoxication
Preoccupation/
anticipation
(Craving)
Withdrawal/
Negative affect
Impulsive (arousal/excitement)  Drug  Pleasure
Goal-directed
behaviours
Habitual
behaviours
Compulsive (anxiety/stress)  Drug  Relief
(+)ve
Koob and Volkow, Neuropsychopharmacology, 2010
(-)ve
From Intoxication to Addiction:
Neurobiological Substrates for
Hubris?
Interim summary
• We have two syndromes that entail
• impaired risk appraisal
• inability to foresee undesirable outcomes
• dangerous decision-making (with consequent harm)
• And for one (addiction) we have a sophisticated,
though incomplete, understanding of the
endophenotype and neurobiological basis.
• Does the addiction model help us to understand
Hubris Syndrome?
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Summary…
Addiction
Hubris
Low self-esteem
Poor Decisions
Impaired risk
appraisal
Guilt
Anxiety
Depression
Incorrigbility
Habitual behaviours
-Stimulus-driven
-Narrowed repertoire
-Devoid of goals
further thoughts – dopamine
function in an uncertain world.
A few simple principles…
• Successful interaction with our
environment entails accurate predictions
• Prediction-based actions are rapid and
efficient
• We must therefore be sensitive to
(sometimes) subtle environmental
regularities
Prediction error – a key signal in
learning
ΔV = α β (λ – ΣV)
Fiorillo et al
Brain marker for PE-dependent learning
Fletcher et al
Nature Neurosci, 2001
Corlett et al
Neuron, 2004
Turner et al
Cereb Cortex, 2004
Murray et al, Molecular Psych, 2007; Corlett et al, Arch Gen Psych 2006; Brain 2007
Update signal
Prior
knowledge
Prediction
Error
Current
input
What happens when uncertainty is
great?
Update signal
Prior
knowledge
Prediction
Error
Current
input
Stress
Arousal Personality
Intoxication
Update signal
Prior
knowledge
Prediction
Error
Current
input
From Intoxication to Addiction:
Neurobiological Substrates for
Hubris?