Transient Neural Activation in Human Amygdala Involved in Aversive Conditioning of Face and Voice

Elucidating the neural mechanisms involved in aversive conditioning helps find effective treatments for psychiatric disorders such as anxiety disorder and phobia. Previous studies using fMRI and human subjects have reported that the amygdala plays a role in this phenomenon. However, the noxious stimuli that were used as unconditioned stimuli in previous studies (e.g., electric shock) might have been ecologically invalid because we seldom encounter such stimuli in daily life. Therefore, we investigated whether a face stimulus could be conditioned by using a voice that had negative emotional valence and was collected from a real-life environment. A skin conductance response showed that healthy subjects were conditioned by using these stimuli. In an fMRI study, there was greater amygdala activation in response to the faces that had been paired with the voice than to those that had not. The right amygdala showed transient activity in the early stage of acquisition. A psychophysiological interaction analysis indicated that the subcortical pathway from the medial geniculate body to the amygdala played a role in conditioning. Modulation of the subcortical pathway by voice stimuli preceded the transient activity in the amygdala. The finding that an ecologically valid stimulus elicited the conditioning and amygdala response suggests that our brain is automatically processing unpleasant stimuli in daily life.

[1]  Thomas Weiss,et al.  Time course of amygdala activation during aversive conditioning depends on attention , 2007, NeuroImage.

[2]  Karl J. Friston,et al.  Amygdala–Hippocampal Involvement in Human Aversive Trace Conditioning Revealed through Event-Related Functional Magnetic Resonance Imaging , 1999, The Journal of Neuroscience.

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

[4]  D. Hirshfeld-Becker,et al.  The developmental psychopathology of social anxiety disorder , 2002, Biological Psychiatry.

[5]  R. Dolan,et al.  Conscious and unconscious emotional learning in the human amygdala , 1998, Nature.

[6]  C. Rorden,et al.  Stereotaxic display of brain lesions. , 2000, Behavioural neurology.

[7]  Joseph E LeDoux,et al.  Topographic organization of neurons in the acoustic thalamus that project to the amygdala , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  Manabu Honda,et al.  Cross-modal integration during vowel identification in audiovisual speech: A functional magnetic resonance imaging study , 2008, Neuroscience Letters.

[9]  S. Rauch,et al.  Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli , 2001, Neuroreport.

[10]  Joseph E LeDoux,et al.  Extinction Learning in Humans Role of the Amygdala and vmPFC , 2004, Neuron.

[11]  M. Iacoboni,et al.  The mirror neuron system and the consequences of its dysfunction , 2006, Nature Reviews Neuroscience.

[12]  J. Grafman,et al.  The Human Amygdala: An Evolved System for Relevance Detection , 2003, Reviews in the neurosciences.

[13]  David L. Neumann,et al.  The use of an unpleasant sound as an unconditional stimulus in a human aversive Pavlovian conditioning procedure , 2006, Biological Psychology.

[14]  Jean-Luc Anton,et al.  Region of interest analysis using an SPM toolbox , 2010 .

[15]  Luiz Pessoa,et al.  Affective Learning Enhances Visual Detection and Responses in Primary Visual Cortex , 2008, The Journal of Neuroscience.

[16]  S. Rauch,et al.  Fear conditioning and extinction: influence of sex and menstrual cycle in healthy humans. , 2006, Behavioral neuroscience.

[17]  Michael Erb,et al.  Deficient fear conditioning in psychopathy: a functional magnetic resonance imaging study. , 2005, Archives of general psychiatry.

[18]  S. Rauch,et al.  Fear extinction in rats: Implications for human brain imaging and anxiety disorders , 2006, Biological Psychology.

[19]  Karine Sergerie,et al.  The role of the amygdala in emotional processing: A quantitative meta-analysis of functional neuroimaging studies , 2008, Neuroscience & Biobehavioral Reviews.

[20]  Fred J Helmstetter,et al.  Neural Substrates Mediating Human Delay and Trace Fear Conditioning , 2004, The Journal of Neuroscience.

[21]  S. Kotz,et al.  Beyond the right hemisphere: brain mechanisms mediating vocal emotional processing , 2006, Trends in Cognitive Sciences.

[22]  J. Mazziotta,et al.  Neural mechanisms of empathy in humans: A relay from neural systems for imitation to limbic areas , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Belmaker,et al.  Major depressive disorder. , 2008, The New England journal of medicine.

[24]  K. Scherer,et al.  The voices of wrath: brain responses to angry prosody in meaningless speech , 2005, Nature Neuroscience.

[25]  Gregor Hasler,et al.  Cerebral Blood Flow in Immediate and Sustained Anxiety , 2007, The Journal of Neuroscience.

[26]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[27]  Steven C.R. Williams,et al.  Time courses of left and right amygdalar responses to fearful facial expressions , 2001, NeuroImage.

[28]  D. Paré,et al.  Stimulation of Medial Prefrontal Cortex Decreases the Responsiveness of Central Amygdala Output Neurons , 2003, The Journal of Neuroscience.

[29]  Karl J. Friston,et al.  Brain systems mediating aversive conditioning: An event related fMRI study , 1998, NeuroImage.

[30]  Nikolaus Weiskopf,et al.  Context-Dependent Human Extinction Memory Is Mediated by a Ventromedial Prefrontal and Hippocampal Network , 2006, The Journal of Neuroscience.

[31]  R. J Dolan,et al.  Dissociable Amygdala and Orbitofrontal Responses during Reversal Fear Conditioning , 2022 .

[32]  Joseph E LeDoux,et al.  Emotional perseveration: an update on prefrontal-amygdala interactions in fear extinction. , 2004, Learning & memory.

[33]  G. Rizzolatti,et al.  The mirror system and its role in social cognition , 2008, Current Opinion in Neurobiology.

[34]  Gang Chen,et al.  Contextual Fear Conditioning in Humans: Cortical-Hippocampal and Amygdala Contributions , 2008, The Journal of Neuroscience.

[35]  Raymond J. Dolan,et al.  Contingency awareness in human aversive conditioning involves the middle frontal gyrus , 2006, NeuroImage.

[36]  Peter A. Bandettini,et al.  Neural correlates of unconditioned response diminution during Pavlovian conditioning , 2008, NeuroImage.

[37]  R. J. Dolan,et al.  Parallel Neural Responses in Amygdala Subregions and Sensory Cortex during Implicit Fear Conditioning , 2001, NeuroImage.

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

[39]  H. Ackermann,et al.  Cerebral processing of linguistic and emotional prosody: fMRI studies. , 2006, Progress in brain research.

[40]  J. Gläscher,et al.  Formal Learning Theory Dissociates Brain Regions with Different Temporal Integration , 2005, Neuron.

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

[42]  R. Dolan,et al.  Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value , 2004, Nature Neuroscience.

[43]  S. Kapur,et al.  Direct Activation of the Ventral Striatum in Anticipation of Aversive Stimuli , 2003, Neuron.

[44]  Fred J Helmstetter,et al.  Functional MRI of human amygdala activity during Pavlovian fear conditioning: stimulus processing versus response expression. , 2003, Behavioral neuroscience.

[45]  J. Delgado-García,et al.  Electrical stimulation of the rostral medial prefrontal cortex in rabbits inhibits the expression of conditioned eyelid responses but not their acquisition , 2007, Proceedings of the National Academy of Sciences.

[46]  R. Dolan,et al.  A subcortical pathway to the right amygdala mediating "unseen" fear. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[47]  R. K. Simpson Nature Neuroscience , 2022 .

[48]  Peter A. Bandettini,et al.  The role of the human amygdala in the production of conditioned fear responses , 2005, NeuroImage.

[49]  Richard J. Davidson,et al.  Functional neuroanatomy of aversion and its anticipation , 2006, NeuroImage.

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

[51]  R. Dolan,et al.  Distinct spatial frequency sensitivities for processing faces and emotional expressions , 2003, Nature Neuroscience.

[52]  Gereon R. Fink,et al.  Developmental changes in neural activation and psychophysiological interaction patterns of brain regions associated with interference control and time perception , 2008, NeuroImage.

[53]  G. Calvert Crossmodal processing in the human brain: insights from functional neuroimaging studies. , 2001, Cerebral cortex.

[54]  Karl J. Friston,et al.  Cholinergic Modulation of Experience-Dependent Plasticity in Human Auditory Cortex , 2002, Neuron.

[55]  N. Sadato,et al.  Forming a negative impression of another person correlates with activation in medial prefrontal cortex and amygdala. , 2011, Social cognitive and affective neuroscience.

[56]  Leslie G. Ungerleider,et al.  Repetition suppression of faces is modulated by emotion. , 2004, Proceedings of the National Academy of Sciences of the United States of America.