Functional MRI of human amygdala activity during Pavlovian fear conditioning: Stimulus processing versus response expression

Although laboratory animal studies have shown that the amygdala plays multiple roles in conditional fear, less is known about the human amygdala. Human subjects were trained in a Pavlovian fear conditioning paradigm during functional magnetic resonance imaging (fMRI). Brain activity maps correlated with reference waveforms representing the temporal pattern of visual conditional stimuli (CSs) and subject-derived autonomic responses were compared. Subjects receiving paired CS–shock presentations showed greater amygdala activity than subjects receiving unpaired CS–shock presentations when their brain activity was correlated with a waveform generated from their behavioral responses. Stimulusbased waveforms revealed learning differences in the visual cortex, but not in the amygdala. These data support the view that the amygdala is important for the expression of learned behavioral responses during Pavlovian fear conditioning.

[1]  D. Paré,et al.  Differential fear conditioning induces reciprocal changes in the sensory responses of lateral amygdala neurons to the CS(+) and CS(-). , 2000, Learning & memory.

[2]  R. Adolphs,et al.  Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans , 1995, Science.

[3]  J. Aggleton The functional effects of amygdala lesions in humans: A comparison with findings from monkeys. , 1992 .

[4]  E. DeYoe,et al.  Mapping striate and extrastriate visual areas in human cerebral cortex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[5]  H. Lachnit,et al.  Are anticipatory first and second interval skin conductance responses indicators of predicted aversiveness? , 1993, Integrative physiological and behavioral science : the official journal of the Pavlovian Society.

[6]  W. F. Prokasy,et al.  Electrodermal Activity in Psychological Research , 1973 .

[7]  C. Rennie,et al.  Dynamics of SCR, EEG, and ERP activity in an oddball paradigm with short interstimulus intervals. , 1999, Psychophysiology.

[8]  Joseph E LeDoux Emotion: clues from the brain. , 1995, Annual review of psychology.

[9]  S. Rauch,et al.  Masked Presentations of Emotional Facial Expressions Modulate Amygdala Activity without Explicit Knowledge , 1998, The Journal of Neuroscience.

[10]  J. Rajapakse,et al.  Human Brain Mapping 6:283–300(1998) � Modeling Hemodynamic Response for Analysis of Functional MRI Time-Series , 2022 .

[11]  Leslie G. Ungerleider,et al.  An area specialized for spatial working memory in human frontal cortex. , 1998, Science.

[12]  Norman M. Weinberger,et al.  Classical conditioning induces CS-specific receptive field plasticity in the auditory cortex of the guinea pig , 1990, Brain Research.

[13]  J J Kim,et al.  Acquisition of fear conditioning in rats requires the synthesis of mRNA in the amygdala. , 1999, Behavioral neuroscience.

[14]  R. Turner,et al.  Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Fred J. Helmstetter,et al.  Contribution of the amygdala to learning and performance of conditional fear , 1992, Physiology & Behavior.

[16]  Joseph E LeDoux,et al.  Fear Conditioning Enhances Different Temporal Components of Tone-Evoked Spike Trains in Auditory Cortex and Lateral Amygdala , 1997, Neuron.

[17]  Mark S. Cohen,et al.  Localization of brain function using magnetic resonance imaging , 1994, Trends in Neurosciences.

[18]  E C Wong,et al.  Processing strategies for time‐course data sets in functional mri of the human brain , 1993, Magnetic resonance in medicine.

[19]  J L McGaugh,et al.  Amygdala activity at encoding correlated with long-term, free recall of emotional information. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Mark S. Cohen,et al.  Parametric Analysis of fMRI Data Using Linear Systems Methods , 1997, NeuroImage.

[21]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[22]  Joseph E LeDoux,et al.  Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  Joseph E LeDoux Emotion Circuits in the Brain , 2000 .

[24]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[25]  R. C. Oldfield THE ASSESSMENT AND ANALYSIS OF HANDEDNESS , 1971 .

[26]  Norman M. Weinberger,et al.  Physiological Memory in Primary Auditory Cortex: Characteristics and Mechanisms , 1998, Neurobiology of Learning and Memory.

[27]  L. Walrath,et al.  Orienting responses and conditioning of electrodermal responses. , 1977, Psychophysiology.

[28]  P. Bellgowan,et al.  Neural systems for the expression of hypoalgesia during nonassociative fear. , 1996, Behavioral neuroscience.

[29]  Hanna Damasio,et al.  Intact electrodermal skin conductance responses after bilateral amygdala damage , 1989, Neuropsychologia.

[30]  Gary H. Glover,et al.  fMRI identifies a network of structures correlated with retention of positive and negative emotional memory , 1999, Psychobiology.

[31]  H. Critchley,et al.  Neural Activity Relating to Generation and Representation of Galvanic Skin Conductance Responses: A Functional Magnetic Resonance Imaging Study , 2000, The Journal of Neuroscience.

[32]  E A Stein,et al.  Functional MRI of human Pavlovian fear conditioning: patterns of activation as a function of learning. , 1999, Neuroreport.

[33]  V. Bowden,et al.  The Journal of Neuropsychiatry and Clinical Neurosciences , 1992 .

[34]  Joseph E LeDoux,et al.  Human Amygdala Activation during Conditioned Fear Acquisition and Extinction: a Mixed-Trial fMRI Study , 1998, Neuron.

[35]  Michael Davis,et al.  Neurobiology of fear responses: the role of the amygdala. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[36]  Stephen Maren,et al.  Long-term potentiation in the amygdala: a mechanism for emotional learning and memory , 1999, Trends in Neurosciences.

[37]  P. Bellgowan,et al.  Effects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats. , 1994, Behavioral neuroscience.

[38]  P. Holland,et al.  Amygdala circuitry in attentional and representational processes , 1999, Trends in Cognitive Sciences.

[39]  E. Bullmore,et al.  Society for Neuroscience Abstracts , 1997 .

[40]  H Fischer,et al.  Affective and attentive neural networks in humans: a PET study of Pavlovian conditioning , 1995, Neuroreport.

[41]  Karl J. Friston,et al.  Brain Systems Mediating Aversive Conditioning: an Event-Related fMRI Study , 1998, Neuron.

[42]  A. Damasio,et al.  The Covert Learning of Affective Valence Does Not Require Structures in Hippocampal System or Amygdala , 1997, Journal of Cognitive Neuroscience.

[43]  John P. Aggleton,et al.  The amygdala: Neurobiological aspects of emotion, memory, and mental dysfunction. , 1992 .

[44]  S M Kosslyn,et al.  Brain mechanisms in human classical conditioning: a PET blood flow study , 1995, Neuroreport.

[45]  Joseph E LeDoux,et al.  Impaired fear conditioning following unilateral temporal lobectomy in humans , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[47]  M. Davis,et al.  Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  A. Anderson,et al.  Emotional memory: What does the amygdala do? , 1997, Current Biology.