Rapid Amygdala Responses during Trace Fear Conditioning without Awareness

The role of consciousness in learning has been debated for nearly 50 years. Recent studies suggest that conscious awareness is needed to bridge the gap when learning about two events that are separated in time, as is true for trace fear conditioning. This has been repeatedly shown and seems to apply to other forms of classical conditioning as well. In contrast to these findings, we show that individuals can learn to associate a face with the later occurrence of a shock, even if they are unable to perceive the face. We used a novel application of magnetoencephalography (MEG) to non-invasively record neural activity from the amygdala, which is known to be important for fear learning. We demonstrate rapid (∼170–200 ms) amygdala responses during the stimulus free period between the face and the shock. These results suggest that unperceived faces can serve as signals for impending threat, and that rapid, automatic activation of the amygdala contributes to this process. In addition, we describe a methodology that can be applied in the future to study neural activity with MEG in other subcortical structures.

[1]  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.

[2]  Jeffrey S. Maxwell,et al.  Human Amygdala Responsivity to Masked Fearful Eye Whites , 2004, Science.

[3]  M. Flaten,et al.  Fear potentiated startle at short intervals following conditioned stimulus onset during delay but not trace conditioning. , 2009, Psychophysiology.

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

[5]  William E. Lorensen,et al.  The NA-MIC Kit: ITK, VTK, pipelines, grids and 3D slicer as an open platform for the medical image computing community , 2006, 3rd IEEE International Symposium on Biomedical Imaging: Nano to Macro, 2006..

[6]  Catherine Tallon-Baudry,et al.  The roles of gamma-band oscillatory synchrony in human visual cognition. , 2009, Frontiers in bioscience.

[7]  Fred J Helmstetter,et al.  Activity in the human amygdala corresponds to early, rather than late period autonomic responses to a signal for shock. , 2007, Learning & memory.

[8]  J. Hsieh,et al.  The effects of face spatial frequencies on cortical processing revealed by magnetoencephalography , 2005, Neuroscience Letters.

[9]  Riitta Hari,et al.  Removal of magnetoencephalographic artifacts with temporal signal‐space separation: Demonstration with single‐trial auditory‐evoked responses , 2009, Human brain mapping.

[10]  Ralph Adolphs,et al.  Fear, faces, and the human amygdala , 2008, Current Opinion in Neurobiology.

[11]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[12]  Yuan Yang,et al.  Early event-related potential components in face perception reflect the sequential neural activities. , 2011, Sheng li xue bao : [Acta physiologica Sinica].

[13]  M. Jung,et al.  Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review , 2006, Neuroscience & Biobehavioral Reviews.

[14]  Elliot A. Stein,et al.  Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning , 2007 .

[15]  A. Ohman,et al.  Recognizing masked threat: fear betrays, but disgust you can trust. , 2008, Emotion.

[16]  A. Hamm,et al.  Fear acquisition requires awareness in trace but not delay conditioning. , 2007, Psychophysiology.

[17]  E. Capaldi,et al.  The organization of behavior. , 1992, Journal of applied behavior analysis.

[18]  T. Holroyd,et al.  Emotional Automaticity Is a Matter of Timing , 2010, The Journal of Neuroscience.

[19]  Dimitri J. Bayle,et al.  Unconsciously Perceived Fear in Peripheral Vision Alerts the Limbic System: A MEG Study , 2009, PloS one.

[20]  L. Pessoa To what extent are emotional visual stimuli processed without attention and awareness? , 2005, Current Opinion in Neurobiology.

[21]  D. Paré,et al.  Coherent gamma oscillations couple the amygdala and striatum during learning , 2009, Nature Neuroscience.

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

[23]  A. R. Wagner SOP: A Model of Automatic Memory Processing in Animal Behavior , 2014 .

[24]  E. Krusemark,et al.  Do All Threats Work the Same Way? Divergent Effects of Fear and Disgust on Sensory Perception and Attention , 2011, The Journal of Neuroscience.

[25]  Timothy J Jarome,et al.  Memory consolidation in both trace and delay fear conditioning is disrupted by intra-amygdala infusion of the protein synthesis inhibitor anisomycin. , 2011, Learning & memory.

[26]  O. Bertrand,et al.  Oscillatory gamma activity in humans and its role in object representation , 1999, Trends in Cognitive Sciences.

[27]  F. Carver,et al.  Visual Awareness, Emotion, and Gamma Band Synchronization , 2008, Cerebral cortex.

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

[29]  S. Taulu,et al.  Suppression of Interference and Artifacts by the Signal Space Separation Method , 2003, Brain Topography.

[30]  Margot J. Taylor,et al.  Unattended emotional faces elicit early lateralized amygdala–frontal and fusiform activations , 2010, NeuroImage.

[31]  Manfred Herrmann,et al.  Time course of implicit processing and explicit processing of emotional faces and emotional words , 2011, Biological Psychology.

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

[33]  Hans-Jochen Heinze,et al.  Magnetoencephalography (MEG) determined temporal modulation of visual and auditory sensory processing in the context of classical conditioning to faces , 2006, NeuroImage.

[34]  O. Bertrand,et al.  Oscillatory gamma activity in humans: a possible role for object representation. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[35]  E. Pang,et al.  Recognising upright and inverted faces: MEG source localisation , 2011, Brain Research.

[36]  Yue-jia Luo,et al.  The time course of implicit processing of erotic pictures: An event-related potential study , 2011, Brain Research.

[37]  Ana Susac,et al.  17th International Conference on Biomagnetism Advances in Biomagnetism – Biomag2010 , 2010 .

[38]  O. Bertrand,et al.  Attention modulates gamma-band oscillations differently in the human lateral occipital cortex and fusiform gyrus. , 2005, Cerebral cortex.

[39]  C. Koch,et al.  Working memory and fear conditioning , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[40]  L. Vaina,et al.  Mapping the signal‐to‐noise‐ratios of cortical sources in magnetoencephalography and electroencephalography , 2009, Human brain mapping.

[41]  Rainer Goebel,et al.  Subcortical Connections to Human Amygdala and Changes following Destruction of the Visual Cortex , 2012, Current Biology.

[42]  Margot J. Taylor,et al.  Attention inhibition of early cortical activation to fearful faces , 2010, Brain Research.

[43]  K. Hugdahl,et al.  Electrodermal conditioning to potentially phobic stimuli in male and female subjects , 1976, Biological Psychology.

[44]  Andreas Keil,et al.  Cortical activation during Pavlovian fear conditioning depends on heart rate response patterns: an MEG study. , 2005, Brain research. Cognitive brain research.

[45]  Yasuki Noguchi,et al.  Neural mechanisms of visual backward masking revealed by high temporal resolution imaging of human brain , 2005, NeuroImage.

[46]  Marco Tamietto,et al.  Standing up for the body. Recent progress in uncovering the networks involved in the perception of bodies and bodily expressions , 2010, Neuroscience & Biobehavioral Reviews.

[47]  Rony Paz,et al.  Gamma Oscillations Coordinate Amygdalo-Rhinal Interactions during Learning , 2007, The Journal of Neuroscience.

[48]  R M Leahy,et al.  A sensor-weighted overlapping-sphere head model and exhaustive head model comparison for MEG. , 1999, Physics in medicine and biology.

[49]  Sandra N. Moses,et al.  Dynamic neural activity recorded from human amygdala during fear conditioning using magnetoencephalography , 2007, Brain Research Bulletin.

[50]  M. Seligman On the generality of the laws of learning , 1970 .

[51]  R D Pascual-Marqui,et al.  Standardized low-resolution brain electromagnetic tomography (sLORETA): technical details. , 2002, Methods and findings in experimental and clinical pharmacology.

[52]  Reza Habib,et al.  A left amygdala mediated network for rapid orienting to masked fearful faces , 2009, Neuropsychologia.

[53]  M. Seligman Phobias and preparedness , 1971 .

[54]  Arne Öhman,et al.  Skin conductance conditioning to potentially phobic stimuli as a function of interstimulus interval and delay versus trace paradigm. , 1980, Psychophysiology.

[55]  M. McEchron,et al.  Single neurons in the medial prefrontal cortex of the rat exhibit tonic and phasic coding during trace fear conditioning. , 2005, Behavioral neuroscience.

[56]  Walter Heindel,et al.  Amygdala activation during masked presentation of emotional faces predicts conscious detection of threat-related faces , 2006, Brain and Cognition.

[57]  M. Tamietto,et al.  Neural bases of the non-conscious perception of emotional signals , 2010, Nature Reviews Neuroscience.

[58]  Louis D. Matzel,et al.  The Role of the Hippocampus in Trace Conditioning: Temporal Discontinuity or Task Difficulty? , 2001, Neurobiology of Learning and Memory.

[59]  Evian Gordon,et al.  A Direct Brainstem–amygdala–cortical Dalarmt System for Subliminal Signals of Fear , 2004 .

[60]  R. Ilmoniemi,et al.  Interpreting magnetic fields of the brain: minimum norm estimates , 2006, Medical and Biological Engineering and Computing.

[61]  Yohan Attal,et al.  MEG Study of Amygdala Responses during the Perception of Emotional Faces and Gaze , 2010 .

[62]  Yue-jia Luo,et al.  Human brain responsivity to different intensities of masked fearful eye whites: An ERP study , 2009, Brain Research.

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

[64]  Richard M. Leahy,et al.  Brainstorm: A User-Friendly Application for MEG/EEG Analysis , 2011, Comput. Intell. Neurosci..

[65]  M. Sarlo,et al.  The time course of implicit processing of facial features: An event-related potential study , 2011, Neuropsychologia.

[66]  S. Rauch,et al.  A functional MRI study of human amygdala responses to facial expressions of fear versus anger. , 2001, Emotion.

[67]  N. Balderston,et al.  Conditioning with masked stimuli affects the timecourse of skin conductance responses. , 2010, Behavioral neuroscience.

[68]  Nicholas L. Balderston,et al.  The human amygdala plays a stimulus specific role in the detection of novelty , 2011, NeuroImage.

[69]  L. Pessoa,et al.  Emotion processing and the amygdala: from a 'low road' to 'many roads' of evaluating biological significance , 2010, Nature Reviews Neuroscience.

[70]  S. Mineka,et al.  Fears, phobias, and preparedness: toward an evolved module of fear and fear learning. , 2001, Psychological review.

[71]  Joseph E LeDoux,et al.  Neural Circuitry Underlying the Regulation of Conditioned Fear and Its Relation to Extinction , 2008, Neuron.

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

[73]  T. Kochiyama,et al.  Rapid Amygdala Gamma Oscillations in Response to Eye Gaze , 2011, PloS one.

[74]  K. Mogg,et al.  Coarse threat images reveal theta oscillations in the amygdala: A magnetoencephalography study , 2009, Cognitive, affective & behavioral neuroscience.

[75]  J. D. Nichols,et al.  Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. , 1997, Science.

[76]  Anders M. Dale,et al.  Sequence-independent segmentation of magnetic resonance images , 2004, NeuroImage.

[77]  Keiko Usui,et al.  Temporal Profile of Amygdala Gamma Oscillations in Response to Faces , 2012, Journal of Cognitive Neuroscience.

[78]  Walter Heindel,et al.  5-HTTLPR Biases Amygdala Activity in Response to Masked Facial Expressions in Major Depression , 2008, Neuropsychopharmacology.

[79]  E. Phelps,et al.  Social learning of fear , 2007, Nature Neuroscience.

[80]  Ralph R. Miller,et al.  Information processing in animals : memory mechanisms , 1983 .

[81]  M. McEchron,et al.  Single neurons in the dentate gyrus and CA1 of the hippocampus exhibit inverse patterns of encoding during trace fear conditioning. , 2005, Behavioral neuroscience.

[82]  Sylvain Baillet,et al.  MEG-Clinic: A Comprehensive Software Solution for Routine MEG Analysis , 2010 .

[83]  F. Helmstetter,et al.  Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex. , 2010, Learning & memory.

[84]  B. de Gelder,et al.  Sentinels in the Visual System , 2011, Front. Behav. Neurosci..

[85]  Sylvain Baillet,et al.  How to Detect Amygdala Activity with Magnetoencephalography using Source Imaging , 2013, Journal of visualized experiments : JoVE.

[86]  F. Helmstetter,et al.  Classical conditioning of autonomic fear responses is independent of contingency awareness. , 2010, Journal of experimental psychology. Animal behavior processes.

[87]  Catherine Tallon-Baudry,et al.  Induced gamma-band oscillations correlate with awareness in hemianopic patient GY , 2006, Neuropsychologia.

[88]  A. Ohman,et al.  The premise of equipotentiality in human classical conditioning: conditioned electrodermal responses to potentially phobic stimuli. , 1976, Journal of experimental psychology. General.

[89]  H. T. Nguyen,et al.  The role of awareness in delay and trace fear conditioning in humans , 2006, Cognitive, affective & behavioral neuroscience.

[90]  Peter A. Bandettini,et al.  Neural substrates of explicit and implicit fear memory , 2009, NeuroImage.

[91]  T. Kochiyama,et al.  Rapid amygdala gamma oscillations in response to fearful facial expressions , 2011, Neuropsychologia.

[92]  P. Ekman Pictures of Facial Affect , 1976 .

[93]  Andreas Keil,et al.  Fear but not awareness predicts enhanced sensory processing in fear conditioning. , 2006, Psychophysiology.

[94]  National Alliance for Medical Image Computing , 2007 .

[95]  S. Tobimatsu,et al.  Neural responses in the occipital cortex to unrecognizable faces , 2011, Clinical Neurophysiology.