Kevin S. LaBar and Nicole C. Huff

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Kevin S. LaBar and Nicole C. Huff
Brain Mechanisms for Generalization and
Specialization of Conditioned Fear Learning
Center for Cognitive Neuroscience Department of
Psychology and Neuroscience Duke
University Department of Psychiatry and
Behavioral Science Duke University Medical School
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Outline of talk

• Classical conditioning and generalization
  Definitions and behavior
• Neural mechanisms of instance-based
  generalization Conditioned fear acquisition to
  cues and contexts
• Neural mechanisms of specialization Extinction
  and contextual recovery of fear
• Overgeneralization Phobias and PTSD

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Outline of talk

• Classical conditioning and generalization
  Definitions and behavior
• Neural mechanisms of instance-based
  generalization Conditioned fear acquisition to
  cues and contexts
• Neural mechanisms of specialization Extinction
  and contextual recovery of fear
• Overgeneralization Phobias and PTSD

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Classical conditioning and generalization
Historical accounts

• Little Albert B.
• 9 mo. old
• no fear to rats, rabbits, dogs, etc.
• distress (crying UR) to hammer striking steel
  bar (US)
• 11 mo. old
• when reached for white rat (CS), presented
  w/noise (US) 7 trials
• distress (crying, crawling away CRs) to white
  rat
• learning transfered to objects w/similar
  features (rabbit, dogs, fur coats, etc.)

Watson Raynor, 1920
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Classical conditioning and specialization
Historical accounts

• Stimulus generalization and discrimination
• Dogs conditioned to salivate to a tone (CS)
  predicting a food reward (US)
• also salivated to an unreinforced light (CS-)
• Over time, salivation was selective to tone but
  generalized to tones of similar
• frequencies

Pavlov, 1927
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Classical conditioning and generalization
Historical accounts
It is doubtful whether the generalization of
the conditioned reflex should be considered to
be the same process as other forms of
generalization for it seems to depend on the
absence of psychological activity whereas the
process of relating stimuli is essentially
positive active
Humphrey, pp. 266-267, 1951
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Defining generalization

• Two forms of generalization for rule-based
  learning
• 1. Instance-based new rule is produced to
  predict properties found in observed instances of
  a known category
• 2. Condition-simplifying drop a condition to
  make rule more general
• - specialization forming a new rule by adding
  constraints to an existing rule

Holyoak Nisbett, 1988
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Applying generalization to fear conditioning

• 1. Instance-based
• a. acquisition of novel fears to cues and
  environments that predict reinforcers
• b. presence of conditioned fear response to the
  same cue in varying contexts or situations
  (Humphrey, p. 267, 1951)
• c. presence of a conditioned fear response to
  novel cues and environments that share features
  with the exemplar
• 2. Specialization
• a. learning to discriminate which cues control
  fear behavior
• b. learning to determine when and where fear
  should be expressed

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Experimental paradigm Human fear conditioning


LaBar LeDoux, 2006
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Behavioral evidence for instance-based
generalization of fear
Conditioning
Training Day 1
Tone Shock
Test Day 2
Huff Rudy, 2004
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Behavioral evidence for instance-based
generalization of fear
Autoshaping in pigeons
Guttman Kalish, 1956
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Behavioral evidence for specialization of fear
cue discrimination
Autoshaping in pigeons
CS 1000 Hz, CS- 950 Hz
CS 1000 Hz, CS- no tone
CS continuous 1000 Hz
Jenkins Harrison, 1960
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Behavioral evidence for specialization of fear
cue discrimination
Fear conditioning in humans
CS
CS
CS-
CS-
Zorawski et al., Cogn Affect Behav Neurosci, 2005
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Theoretical perspectives on generalization and
conditioning

• Two classes of theories
• Elemental individual environmental cues or
  stimulus features are separately associated with
  reinforcers in memory (Rescorla-Wagner, 1972).
  Item similarity guides generalization.
• Configural stimulus combinations are stored as
  whole unique context representations that enter
  into associations with reinforcers (Pearce, 1994
  Rudy OReilly, 1999). Pattern completion (from
  partial input) supports generalization and
  pattern separation (from competing inputs)
  supports specialization.
• There are two partially independent neural
  systems that support these forms of stimulus
  representation

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Parallel memory systems for fear conditioning
COMPLEX CLASSICAL CONDITIONING
PFC
Squire Zola, 1996
default general - elemental
flexible specialized - configural
LaBar Disterhoft, Hippocampus, 1998
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Outline of talk

• Classical conditioning and generalization
  Definitions and behavior
• Neural mechanisms of instance-based
  generalization Conditioned fear acquisition to
  cues and contexts
• Neural mechanisms of specialization Perceptual
  tuning, extinction and contextual recovery of
  fear
• Overgeneralization Phobias and PTSD

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Fear pathways Simplified model
LaBar LeDoux, 2006
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Partial independence of cued and contextual fear
learning
Phillips LeDoux, 1992
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Protein synthesis blockade following training
reduces expression of cued fear in novel context
30 hrs
Huff Rudy, 2004
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Properties of amygdala function that facilitate
induction-based generalization

• partial independence of CS-US associations from
  context representation
• equipotentiality of subcortical and cortical
  input pathways (Romanski et al., 1992)
• indelibility of emotional learning in absence of
  cortex (LeDoux et al., 1989)
• relatively broad species-typical receptive
  field tuning (Bordi LeDoux, 1992)

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Functional Neuroanatomy of Fear Acquisition
Furmark et al., 1997
LaBar Cabeza, Nat Rev Neurosci, 2006
LaBar et al., Neuron, 1998
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Double dissociation of explicit knowledge and
conditioned fear in humans
amygdala lesion
amygdala lesion
amnesic
LaBar Cabeza, Nat Rev Neurosci, 2006
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Outline of talk

• Classical conditioning and generalization
  Definitions and behavior
• Neural mechanisms of instance-based
  generalization Conditioned fear acquisition to
  cues and contexts
• Neural mechanisms of specialization Extinction
  and contextual recovery of fear
• Overgeneralization Phobias and PTSD

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Specialization Learning when not to fearFear
extinction depends on vmPFC amygdala
interactions
Quirk et al., Neuron, 1997
Maren Quirk, Nat Neurosci, 2004
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vmPFC damage in rats yields fear perseveration
Morgan et al. (1993)
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Role of vmPFC in human fear extinction
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(No Transcript)
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Contextual fear reinstatement in humans is
hippocampal-dependent
W.S.
LaBar Phelps, Behav Neurosci, 2005
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Specialization of conditioned fear learning
feedback to other areas
Sotres-Bayon et al., Learn Mem, 2004
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Future directions Contextual control over
virtual fears
feedback to other areas
NSF-funded DiVE facility
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Outline of talk

• Classical conditioning and generalization
  Definitions and behavior
• Neural mechanisms of instance-based
  generalization Conditioned fear acquisition to
  cues and contexts
• Neural mechanisms of specialization Extinction
  and contextual recovery of fear
• Overgeneralization Phobias and PTSD

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Consequences of overgeneralization Anxiety
disorders

• Neural circuit model of emotional perseveration
  (Charney et al., 1993)
• - overresponsive amygdala
• - lack of prefrontal and hippocampal control

Orr et al., 2000
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Consequences of overgeneralization Anxiety
disorders
PTSD gt Ctrl during acquisition
PTSD lt Ctrl during extinction
Bremner et al., 2005
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Consequences of overgeneralization Anxiety
disorders

• Relapse following (context-specific) exposure
  therapy for specific phobias
• brief d-cycloserine administration in
  conjunction with exposure therapy facilitates
  retention of extinction training and reduces
  symptoms in acrophobics up to 3 months later
  (Ressler et al., 2004)

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Summary Fear conditioning and generalization

• Initial learning mediated by amygdala-dependent
  implicit memory system whose properties support
  generalization to novel contexts and to stimuli
  that share features
• Specialization of learning with continued
  training alters tuning of perceptual cortical
  representations and recruits prefrontal and
  hippocampal processing for temporal and
  contextual control over fear expression
• Overgeneralization related to hyperactive
  amygdala responses during learning and lack of
  cortical control contribute to emotional memory
  persistence and inappropriate expression in
  anxiety disorders

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Generalization and Conditioned Fear Epilogue
Fear takes flight Washington Post
8/15/06 High anxiety as passenger gets out of
control on D.C. flight Boston Herald 8/17/06
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Acknowledgements
LaBaratory
Funding NIDA NSF
http//www.mind.duke.edu
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Behavioral evidence for specialization of fear
context discrimination
Thomas et al., 1985
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Electrophysiological studies reveal temporal
parameters of fear acquisition
Within trial
Across trials
Quirk et al., Neuron, 1997
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Temporary inactivation of rabbit amygdala affects
plasticity in other regions
CS gt CS-
Talk et al., Behav. Neurosci., 2004
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Amygdala connectivity in the primate forebrain
Young et al., 1994
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Specialization Receptive field tuning in sensory
cortex

• Cortical pathway necessary for discrimination
  learning (Teich et al., 1989)
• Gradual training-induced, amygdala-dependent
  shift in receptive field properties of auditory
  cortex neurons role of cholinergic systems

Training-induced respiratory generalization
gradient
Weinberger, 2003