from intoxication to addiction: neurobiological substrates for hubris? paul fletcher [email protected]...
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From Intoxication to Addiction: Neurobiological Substrates for
Hubris?Paul Fletcher
Bernard Wolfe Health Neuroscience Fund
The Intoxication of Power: From Neurosciences to Hubris in Healthcare and Public Life.Royal Society of Medicine October 2012
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
Koob and Volkow, Neuropsychopharmacology, 2010
Withdrawal/Negative affect
Preoccupation/anticipation(Craving)
Binge/Intoxication
Impulsive (arousal/excitement) Drug Pleasure
Compulsive (anxiety/stress) Drug Relief
(+)ve (-)ve
Goal-directedbehaviours
Habitualbehaviours
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…
HubrisAddiction
Poor Decisions
Impaired risk appraisal
Incorrigbility
Low self-esteem
GuiltAnxiety
Depression
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
Turner et al Cereb Cortex, 2004
Corlett et al Neuron, 2004
Murray et al, Molecular Psych, 2007; Corlett et al, Arch Gen Psych 2006; Brain 2007
Priorknowledge
Currentinput
PredictionError
Update signal
What happens when uncertainty is great?
Priorknowledge
Currentinput
PredictionError
Update signal
Priorknowledge
PredictionError
Update signal
StressPersonality
Intoxication
Arousal
Currentinput
From Intoxication to Addiction: Neurobiological Substrates for
Hubris?