Cited by 543Memory and Neural MechanismsNeural and Behavioral Psychology StudiesAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

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Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review

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Sehlmeyer, Christina, Schöning, Sonja, Zwitserlood, Pienie, Pfleiderer, Bettina, Kircher, Tilo, Arolt, Volker, Konrad, Carsten·2009·PLoS ONE

DOI 10.1371/journal.pone.0005865PMC PMC2692002

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Abstract

Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm. A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending on specific design parameters. These include stronger hippocampal activation in trace conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli enhance activation of pain related, motor, and somatosensory areas. Differences concerning experimental factors may partly explain the variance between neuroimaging investigations on human fear conditioning and extinction and should, therefore, be taken into serious consideration in the planning and the interpretation of research projects.

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Emotion circuits in the brain
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444
Pain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex
Rainville, P., Duncan, G. H., Price, D. D., Carrier, B., & Bushnell, M. C. (1997) · Science · doi:10.1126/science.277.5328.968 · Cited by 2,629
Extinction Learning in Humans
Phelps, E. A., Delgado, M. R., Nearing, K. I., & LeDoux, J. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.042 · Cited by 1,753
Neurobiology of Pavlovian fear conditioning
Maren, S. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.897 · Cited by 1,543
Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study
LaBar, K. S., Gatenby, J. C., Gore, J. C., LeDoux, J. E., & Phelps, E. A. (1998) · Neuron · doi:10.1016/s0896-6273(00)80475-4 · Cited by 1,402
Recall of Fear Extinction in Humans Activates the Ventromedial Prefrontal Cortex and Hippocampus in Concert
Milad, M. R., Wright, C. I., Orr, S. P., Pitman, R. K., Quirk, G. J., & Rauch, S. L. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.10.011 · Cited by 1,197
The conditioning theory of fearacquisition: A critical examination
Rachman, S. (1977) · Behaviour Research and Therapy · doi:10.1016/0005-7967(77)90041-9 · Cited by 1,191 · cited 1×
“Fear conditioning has proven to be an extremely robust, rapid, and precise experimental approach for studying the neurobiological substrates of fear [2,7–15], while fear extinction most probably represents the main therapeutic ingredient of exposure-based psychotherapies.”
Background
Dissociating pain from its anticipation in the human brain
Ploghaus, A., Tracey, I., Gati, J. S., Clare, S., Menon, R. S., Matthews, P. M., & Rawlins, J. N. P. (1999) · Science · doi:10.1126/science.284.5422.1979 · Cited by 1,151
Distributed and interactive brain mechanisms during emotion face perception: Evidence from functional neuroimaging
Vuilleumier, P., & Pourtois, G. (2007) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2006.06.003 · Cited by 1,115
Prevalence and incidence studies of anxiety disorders: A systematic review of the literature
Somers, J. M., Goldner, E. M., Waraich, P., & Hsu, L. (2006) · The Canadian Journal of Psychiatry · doi:10.1177/070674370605100206 · Cited by 1,114
The neuroanatomical and neurochemical basis of conditioned fear
Fendt, M., & Fanselow, M. S. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00016-0 · Cited by 1,092
Classical fear-conditioning in the anxiety disorders: a meta-analysis
Lissek, S., Powers, A. S., McClure, E. B., Phelps, E. A., Woldehawariat, G., Grillon, C., & Pine, D. S. (2005) · Behaviour Research and Therapy · doi:10.1016/j.brat.2004.10.007 · Cited by 1,034
Brain systems mediating aversive conditioning: an event-related fMRI study
Büchel, C., Morris, J., Dolan, R. J., & Friston, K. J. (1998) · Neuron · doi:10.1016/s0896-6273(00)80476-6 · Cited by 951
Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons
Quirk, G. J., Likhtik, E., Pelletier, J. G., & Paré, D. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-25-08800.2003 · Cited by 927
Behavioral and Neural Analysis of Extinction
Myers, K. M., & Davis, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)01064-4 · Cited by 918
Activation of the left amygdala to a cognitive representation of fear
Phelps, E. A., O'Connor, K. J., Gatenby, J. C., Gore, J. C., Grillon, C., & Davis, M. (2001) · Nature Neuroscience · doi:10.1038/86110 · Cited by 895
Autoshaping and Conditioning Theory
Perkins, C. C., Locurto, C. W., Terrace, H. S., & Gibbon, J. (1982) · The American Journal of Psychology · doi:10.2307/1422674 · Cited by 864
Distributed processing of pain and vibration by the human brain
Coghill, R., Talbot, J., Evans, A., Meyer, E., Gjedde, A., Bushnell, M., & Duncan, G. (1994) · The Journal of Neuroscience · doi:10.1523/jneurosci.14-07-04095.1994 · Cited by 808
The subjective experience of pain: where expectations become reality
Koyama, T., McHaffie, J. G., Laurienti, P. J., & Coghill, R. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408576102 · Cited by 747
Prefrontal mechanisms in extinction of conditioned fear
Quirk, G. J., Garcia, R., & González-Lima, F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.010 · Cited by 682
Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review
Kim, J. J., & Jung, M. W. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.06.005 · Cited by 636
Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: A single-trial fMRI study
Bornhövd, K., Quante, M., Glauche, V., Bromm, B., Weiller, C., & Büchel, C. (2002) · Brain · doi:10.1093/brain/awf137 · Cited by 584
Fear Conditioning Enhances Different Temporal Components of Tone-Evoked Spike Trains in Auditory Cortex and Lateral Amygdala
Quirk, G. J., Armony, J. L., & LeDoux, J. E. (1997) · Neuron · doi:10.1016/s0896-6273(00)80375-x · Cited by 563
Does anticipation of pain affect cortical nociceptive systems?
Porro, C. A., Baraldi, P., Pagnoni, G., Serafini, M., Facchin, P., Maieron, M., & Nichelli, P. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03206.2002 · Cited by 469
Direct Activation of the Ventral Striatum in Anticipation of Aversive Stimuli
Jensen, J., McIntosh, A. R., Crawley, A. P., Mikulis, D. J., Remington, G., & Kapur, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00724-4 · Cited by 455
Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex
Sotres-Bayon, F., Cain, C. K., & LeDoux, J. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.012 · Cited by 433
From Fear to Safety and Back: Reversal of Fear in the Human Brain
Schiller, D., Levy, I., Niv, Y., LeDoux, J. E., & Phelps, E. A. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2265-08.2008 · Cited by 429
The relevance of recent developments in classical conditioning to understanding the etiology and maintenance of anxiety disorders
Mineka, S., & Oehlberg, K. A. (2008) · Acta Psychologica · doi:10.1016/j.actpsy.2007.11.007 · Cited by 428
Amygdala–Hippocampal Involvement in Human Aversive Trace Conditioning Revealed through Event-Related Functional Magnetic Resonance Imaging
Büchel, C., Dolan, R. J., Armony, J. L., & Friston, K. J. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-24-10869.1999 · Cited by 409
Functional neuroanatomy of aversion and its anticipation
Nitschke, J. B., Sarinopoulos, I., Mackiewicz, K. L., Schaefer, H. S., & Davidson, R. J. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.06.068 · Cited by 398
Extending animal models of fear conditioning to humans
Delgado, M. R., Olsson, A., & Phelps, E. A. (2006) · Biological Psychology · doi:10.1016/j.biopsycho.2006.01.006 · Cited by 366
Classical fear conditioning in functional neuroimaging
Büchel, C. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00078-7 · Cited by 360
Neurophysiology and Functional Neuroanatomy of Pain Perception
Schnitzler, A., & Ploner, M. (2000) · Journal of Clinical Neurophysiology · doi:10.1097/00004691-200011000-00005 · Cited by 356
Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value
Gottfried, J. A., & Dolan, R. J. (2004) · Nature Neuroscience · doi:10.1038/nn1314 · Cited by 353
Aversive Learning Enhances Perceptual and Cortical Discrimination of Indiscriminable Odor Cues
Li, W., Howard, J. D., Parrish, T. B., & Gottfried, J. A. (2008) · Science · doi:10.1126/science.1152837 · Cited by 351
The neuropsychology of fear learning and fear regulation
Hamm, A. O., & Weike, A. I. (2005) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2005.01.006 · Cited by 308
Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala
Sotres-Bayón, F., Bush, D. E. A., & LeDoux, J. E. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301316 · Cited by 298
A functional anatomical study of associative learning in humans.
Molchan, S. E., Sunderland, T., McIntosh, A. R., Herscovitch, P., & Schreurs, B. G. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.17.8122 · Cited by 290
Functional anatomy of human eyeblink conditioning determined with regional cerebral glucose metabolism and positron-emission tomography.
Logan, C., & Grafton, S. T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7500 · Cited by 287
Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning
Knight, D. C., Smith, C. N., Cheng, D. T., Stein, E. A., & Helmstetter, F. J. (2004) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/cabn.4.3.317 · Cited by 249
The insula is not specifically involved in disgust processing: an fMRI study
Schienle, A., Stark, R. M., Walter, B., Blecker, C. R., Ott, U., Kirsch, P., Sammer, G., & Vaitl, D. (2002) · Neuroreport · doi:10.1097/00001756-200211150-00006 · Cited by 242
Neural Substrates Mediating Human Delay and Trace Fear Conditioning
Knight, D. C., Cheng, D. T., Smith, C. N., Stein, E. A., & Helmstetter, F. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0433-03.2004 · Cited by 239
Dissociable roles for the hippocampus and the amygdala in human cued versus context fear conditioning
Marschner, A., Kalisch, R., Vervliet, B., Vansteenwegen, D., & Büchel, C. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1651-08.2008 · Cited by 235
The role of the human amygdala in the production of conditioned fear responses
Knight, D. C., Nguyen, H. T., & Bandettini, P. A. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.03.020 · Cited by 223
Cannabinoid CB1 Receptor Mediates Fear Extinction via Habituation-Like Processes
Kamprath, K., Marsicano, G., Tang, J., Monory, K., Bisogno, T., Marzo, V. D., Lutz, B., & Wotjak, C. T. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0153-06.2006 · Cited by 217
Neural substrates underlying human delay and trace eyeblink conditioning
Cheng, D. T., Disterhoft, J. F., Power, J., Ellis, D., & Desmond, J. E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800374105 · Cited by 215
Predicting events of varying probability: uncertainty investigated by fMRI
Volz, K. G., Schubotz, R. I., & von Cramon, D. Y. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00122-8 · Cited by 214 · cited 1×
“Phelps and co-workers (2001) assume that the insula cortex conveys a cortical representation of fear to the amygdala [52], and that uncertainty about the advent of the aversive stimulus during intermittent pairing is reflected by insula and dorsal prefrontal cortex activation [31,32,76].”
Background
Functional Mapping of Human Learning: A Positron Emission Tomography Activation Study of Eyeblink Conditioning
Blaxton, T. A., Zeffiro, T. A., Gabrieli, J. D. E., Bookheimer, S. Y., Carrillo, M. C., Theodore, W. H., & Disterhoft, J. F. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-12-04032.1996 · Cited by 211
Predictability modulates the affective and sensory-discriminative neural processing of pain
Carlsson, K., Andersson, J., Petrovic, P., Petersson, K. M., Öhman, A., & Ingvar, M. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.05.027 · Cited by 208
Trace Conditioning and the Hippocampus: The Importance of Contiguity
Bangasser, D. A., Waxler, D. E., Santollo, J., & Shors, T. J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1742-06.2006 · Cited by 185
The role of the amygdala in the extinction of conditioned fear.
Barad, M., Gean, P., & Lutz, B. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.05.029 · Cited by 168
Memory traces of trace memories: neurogenesis, synaptogenesis and awareness
Shors, T. J. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.03.007 · Cited by 167
Neural responses to salient visual stimuli
Morris, J. S., Friston, K. J., & Dolan, R. J. (1997) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1997.0109 · Cited by 164
Cingulate cortex: Its role in Pavlovian conditioning.
Buchanan, S. L., & Powell, D. A. (1982) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0077925 · Cited by 164
Human fear conditioning is related to dopaminergic and serotonergic biological markers.
Garpenstrand, H., Annas, P., Ekblom, J., Oreland, L., & Fredrikson, M. G. (2001) · Behavioral Neuroscience · doi:10.1037//0735-7044.115.2.358 · Cited by 163
Functional MRI of human amygdala activity during Pavlovian fear conditioning: Stimulus processing versus response expression.
Cheng, D. T., Knight, D. C., Smith, C. N., Stein, E. A., & Helmstetter, F. J. (2003) · Behavioral Neuroscience · doi:10.1037//0735-7044.117.1.3 · Cited by 163
Fear acquisition requires awareness in trace but not delay conditioning
Weike, A. I., Schupp, H. T., & Hamm, A. O. (2007) · Psychophysiology · doi:10.1111/j.1469-8986.2006.00469.x · Cited by 163
Distinct amygdala–autonomic arousal profiles in response to fear signals in healthy males and females
Williams, L. M., Barton, M., Kemp, A. H., Liddell, B. J., Peduto, A. S., Gordon, E., & Bryant, R. A. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.06.035 · Cited by 161
The amygdala and individual differences in human fear conditioning
Furmark, T., Fischer, H., Wik, G., Larsson, M., & Fredrikson, M. (1997) · Neuroreport · doi:10.1097/00001756-199712220-00021 · Cited by 160
Dissociable amygdala and orbitofrontal responses during reversal fear conditioning
Morris, J. S., & Dolan, R. J. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.01.012 · Cited by 157
Contingency awareness in human aversive conditioning involves the middle frontal gyrus
Carter, R. M., O’Doherty, J. P., Seymour, B., Koch, C., & Dolan, R. J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.09.011 · Cited by 149
Experience–dependent modulation of tonotopic neural responses in human auditory cortex
Morris, J. S., Friston, K. J., & Dolan, R. J. (1998) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1998.0343 · Cited by 140
Lateralization and Behavioral Correlation of Changes in Regional Cerebral Blood Flow With Classical Conditioning of the Human Eyeblink Response
Schreurs, B. G., McIntosh, A. R., Bahro, M., Herscovitch, P., Sunderland, T., & Molchan, S. E. (1997) · Journal of Neurophysiology · doi:10.1152/jn.1997.77.4.2153 · Cited by 140
Single Neurons in CA1 Hippocampus Encode Trace Interval Duration during Trace Heart Rate (Fear) Conditioning in Rabbit
McEchron, M. D., Tseng, W., & Disterhoft, J. F. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01535.2003 · Cited by 137
Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning.
Dunsmoor, J. E., Bandettini, P. A., & Knight, D. C. (2007) · Behavioral Neuroscience · doi:10.1037/0735-7044.121.4.635 · Cited by 137
Orbitofrontal thickness, retention of fear extinction, and extraversion
Rauch, S. L., Milad, M. R., Orr, S. P., Quinn, B. T., Fischl, B. R., & Pitman, R. K. (2005) · Neuroreport · doi:10.1097/01.wnr.0000186599.66243.50 · Cited by 136
Attentional modulation of the amygdala varies with personality
Most, S. B., Chun, M. M., Johnson, M. R., & Kiehl, K. A. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.12.031 · Cited by 135
Theta activity in neurons and networks of the amygdala related to long‐term fear memory
Pape, H., Narayanan, R. T., Smid, J., Stork, O., & Seidenbecher, T. (2005) · Hippocampus · doi:10.1002/hipo.20120 · Cited by 133
Human amygdala activity during the expression of fear responses.
Cheng, D. T., Knight, D. C., Smith, C. N., & Helmstetter, F. J. (2006) · Behavioral Neuroscience · doi:10.1037/0735-7044.120.5.1187 · Cited by 131
Correlation between Human Personality and Neural Activity in Cerebral Cortex
Sugiura, M., Kawashima, R., Nakagawa, M., Okada, K., Sato, T., Goto, R., Sato, K., Ono, S., Schormann, T., Zilles, K., et al. (2000) · NeuroImage · doi:10.1006/nimg.2000.0564 · Cited by 129
Brain Response to Visceral Aversive Conditioning: A Functional Magnetic Resonance Imaging Study
Yágüez, L., Coen, S. J., Gregory, L. J., Amaro, E., Altman, C., Brammer, M. J., Bullmore, E. T., Williams, S., & Aziz, Q. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.02.068 · Cited by 129
Dissociation of neural responses and skin conductance reactions during fear conditioning with and without awareness of stimulus contingencies
Tabbert, K., Stark, R. M., Kirsch, P., & Vaitl, D. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.03.038 · Cited by 123
The influence of personality on neural mechanisms of observational fear and reward learning
Hooker, C. I., Verosky, S. C., Miyakawa, A., Knight, R. T., & D’Esposito, M. (2008) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2008.05.005 · Cited by 122
Hemodynamic brain correlates of disgust and fear ratings
Stark, R., Zimmermann, M., Kagerer, S., Schienle, A., Walter, B., Weygandt, M., & Vaitl, D. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.05.005 · Cited by 119
Neural correlates of unconditioned response diminution during Pavlovian conditioning
Dunsmoor, J. E., Bandettini, P. A., & Knight, D. C. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.11.042 · Cited by 116
Personality influences limbic-cortical interactions during sad mood induction
Keightley, M. (2003) · NeuroImage · doi:10.1016/j.neuroimage.2003.08.022 · Cited by 114
Two Types of Intrinsic Oscillations in Neurons of the Lateral and Basolateral Nuclei of the Amygdala
Pape, H., Paré, D., & Driesang, R. B. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.1.205 · Cited by 113
The use of an unpleasant sound as an unconditional stimulus in a human aversive Pavlovian conditioning procedure
Neumann, D. L., & Waters, A. M. (2006) · Biological Psychology · doi:10.1016/j.biopsycho.2006.03.004 · Cited by 110
Neural, electrodermal and behavioral response patterns in contingency aware and unaware subjects during a picture–picture conditioning paradigm
Klucken, T., Kagerer, S., Schweckendiek, J., Tabbert, K., Vaitl, D., & Stark, R. M. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.09.049 · Cited by 107
Affective and attentive neural networks in humans
Fredrikson, M., Wik, G., Fischer, H., & Andersson, J. (1995) · Neuroreport · doi:10.1097/00001756-199512000-00023 · Cited by 103
The lateral amygdala processes the value of conditioned and unconditioned aversive stimuli
Blair, H. T., Sotres-Bayón, F., Moita, M. A. P., & LeDoux, J. E. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.02.043 · Cited by 100
Brain mechanisms in human classical conditioning
Hugdahl, K., Berardi, A., Thompson, W. L., Kosslyn, S. M., Macy, R., Baker, D. P., Alpert, N. M., & LeDoux, J. E. (1995) · Neuroreport · doi:10.1097/00001756-199509000-00005 · Cited by 91
Personality factors correlate with regional cerebral perfusion
Tuura, R., Kumari, V., Williams, S., Zelaya, F. O., Connor, S. E. J., Alsop, D. C., & Gray, J. A. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.12.048 · Cited by 90
The Promise of Extinction Research for the Prevention and Treatment of Anxiety Disorders
Anderson, K. C., & Insel, T. R. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.022 · Cited by 89
The impact of tryptophan depletion and 5-HTTLPR genotype on passive avoidance and response reversal instrumental learning tasks
Finger, E. C., Marsh, A. A., Buzas, B., Kamel, N., Rhodes, R., Vythilingham, M., Pine, D. S., Goldman, D., & Blair, J. R. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301182 · Cited by 86
Functional MRI of human Pavlovian fear conditioning
Knight, D. C., Smith, C. N., Stein, E. A., & Helmstetter, F. J. (1999) · Neuroreport · doi:10.1097/00001756-199911260-00037 · Cited by 84
Improved BOLD detection in the medial temporal region using parallel imaging and voxel volume reduction
Bellgowan, P. S. F., Bandettini, P. A., van Gelderen, P., Martin, A., & Bodurka, J. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.08.042 · Cited by 84
The role of awareness in delay and trace fear conditioning in humans
KNIGHT, D. C., NGUYEN, H. T., & BANDETTINI, P. A. (2006) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/cabn.6.2.157 · Cited by 83 · cited 1×
“It seems clear that awareness of the CS-US contingency bridges the CS-US gap in trace conditioning [95,96].”
Background
Hemodynamic responses of the amygdala, the orbitofrontal cortex and the visual cortex during a fear conditioning paradigm
Tabbert, K., Stark, R. M., Kirsch, P., & Vaitl, D. (2005) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2005.01.007 · Cited by 76
Improved functional mapping of the human amygdala using a standard functional magnetic resonance imaging sequence with simple modifications
Morawetz, C., Holz, P., Lange, C., Baudewig, J., Weniger, G., Irle, E., & Dechent, P. (2007) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2007.04.014 · Cited by 74
Dependence of amygdala activation on echo time: Results from olfactory fMRI experiments
Stöcker, T., Kellermann, T., Schneider, F. W., Habel, U., Amunts, K., Pieperhoff, P., Zilles, K., & Shah, N. J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.09.050 · Cited by 73
Genes and Mechanisms in the Amygdala Involved in the Formation of Fear Memory
Pape, H., & Stork, O. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07074.x · Cited by 73
Fear conditioning and brain activity: A positron emission tomography study in humans.
Fischer, H., Andersson, J., Furmark, T., & Fredrikson, M. G. (2000) · Behavioral Neuroscience · doi:10.1037//0735-7044.114.4.671 · Cited by 69
Activity in the human amygdala corresponds to early, rather than late period autonomic responses to a signal for shockPreprint
Cheng, D. T., Richards, J., & Helmstetter, F. J. (2007) · Learning & Memory · doi:10.1101/lm.632007 · Cited by 68
Prediction of “fear” acquisition in healthy control participants in a de novo fear-conditioning paradigm
Otto, M. W., Leyro, T. M., Christian, K., Deveney, C. M., Reese, H., Pollack, M. H., & Orr, S. P. (2007) · Behavior Modification · doi:10.1177/0145445506295054 · Cited by 66
Neurocircuitry of disgust and anxiety in obsessive-compulsive disorder: a positron emission tomography study
Stein, D. J., Arya, M., Pietrini, P., Rapoport, J. L., & Swedo, S. E. (2006) · Metabolic Brain Disease · doi:10.1007/s11011-006-9021-6 · Cited by 64
Stimulus type and design influence hemodynamic responses towards visual disgust and fear elicitors
Schäfer, A., Schienle, A., & Vaitl, D. (2005) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2005.01.011 · Cited by 64
Methods for developmental studies of fear conditioning circuitry
Pine, D. S., Fyer, A., Grun, J., Phelps, E. A., Szeszko, P. R., Koda, V., Li, W., Ardekani, B., Maguire, E. A., Burgess, N., et al. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01159-3 · Cited by 62
Fear-related activity in subgenual anterior cingulate differs between men and women
Butler, T., Pan, H., Epstein, J., Protopopescu, X., Tüscher, O., Goldstein, M., Cloître, M., Yang, Y., Phelps, E. A., Gorman, J. M., et al. (2005) · Neuroreport · doi:10.1097/00001756-200508010-00020 · Cited by 61
Time course of amygdala activation during aversive conditioning depends on attention
Straube, T., Weiß, T., Mentzel, H.-J., & Miltner, W. H. R. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.08.021 · Cited by 60
Partial reinforcement effects in classical aversive conditioning in rabbits and human beings.
Leonard, D. W. (1975) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0076419 · Cited by 58
Fear conditioning and brain activity: A positron emission tomography study in humans.
Fischer, H., Andersson, J., Furmark, T., et al. (2000) · Behavioral Neuroscience · doi:10.1037/0735-7044.114.4.671 · Cited by 57
Novel vistas of calcium-mediated signalling in the thalamus
Pape, H., Munsch, T., & Budde, T. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1234-5 · Cited by 55
Limbic thalamic, cingulate cortical and hippocampal neuronal correlates of discriminative approach learning in rabbits
Freeman, J. H., Cuppernell, C., Flannery, K., & Gabriel, M. (1996) · Behavioural Brain Research · doi:10.1016/0166-4328(96)00027-7 · Cited by 49
Association between cerebral glutamate and human behaviour: The sensation seeking personality trait
Gallinat, J., Kunz, D., Lang, U. E., Neu, P., Kassim, N., Kienast, T., Seifert, F. C., Schubert, F., & Bajbouj, M. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.10.004 · Cited by 49
Characterization of a psychophysiological model of classical fear conditioning in healthy volunteers: influence of gender, instruction, personality and placebo
Guimarães, F. S., Hellewell, J. S. E., Hensman, R., Wang, M., & Deakin, J. F. W. (1991) · Psychopharmacology · doi:10.1007/bf02244184 · Cited by 48
Learning affective values for faces is expressed in amygdala and fusiform gyrus
Petrović, P., Kalisch, R., Pessiglione, M., Singer, T., & Dolan, R. J. (2008) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsn002 · Cited by 45
Backward conditioning in Pavlovian type studies
Hall, J. F. (1984) · Pavlovian Journal of Biological Science · doi:10.1007/bf03004514 · Cited by 43
Cognitive Coping Style Modulates Neural Responses to Emotional Faces in Healthy Humans: A 3-T fMRI Study
Rauch, A. V., Ohrmann, P., Bauer, J., Kugel, H., Engelien, A., Arolt, V., Heindel, W. L., & Suslow, T. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhl158 · Cited by 42
Self-citation
Cerebellar activation during classical conditioning of the human flexion reflex
Timmann, D., Kolb, F. P., Baier, P. C., Rijntjes, M., Müller, S. P., Diener, H., & Weiller, C. (1996) · Neuroreport · doi:10.1097/00001756-199608120-00041 · Cited by 37
GABAergic Neurons: Gate Masters of the Amygdala, Mastered by Dopamine
Pape, H. (2005) · Neuron · doi:10.1016/j.neuron.2005.12.002 · Cited by 37
Right-sided human prefrontal brain activation during acquisition of conditioned fear.
Fischer, H., Anderson, J. L. R., Furmark, T., Wik, G., & Fredrikson, M. G. (2002) · Emotion · doi:10.1037/1528-3542.2.3.233 · Cited by 37
Brain systems mediating aversive conditioning: An event related fMRI study
Büchel, C., Morris, J., Dolan, R. J., & Friston, K. J. (1998) · NeuroImage · doi:10.1016/s1053-8119(18)31750-6 · Cited by 34
Interactions of prefrontal cortex during eyeblink conditioning as a function of age
Schreurs, B. G., Bahro, M., Molchan, S. E., Sunderland, T., & McIntosh, A. R. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00224-4 · Cited by 27
Cerebellar activation during leg withdrawal reflex conditioning: an fMRI study
Dimitrova, A., Kolb, F. P., Elles, H.-G., Maschke, M., Gerwig, M., Gizewski, E. R., & Timmann, D. (2004) · Clinical Neurophysiology · doi:10.1016/j.clinph.2003.11.030 · Cited by 22
Neural basis of fear conditioning induced by video clip: Positron emission tomography study
DORONBEKOV, T. K., Tokunaga, H., Ikejiri, Y., Kazui, H., HATTA, N., MASAKI, Y., Ogino, A., MIYOSHI, N., Oku, N., Nishikawa, T., et al. (2005) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2005.01351.x · Cited by 21
Genes and neurons: molecular insights to fear and anxiety
Stoppel, C. M., Albrecht, A., Pape, H., & Stork, O. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00229.x · Cited by 21
Trace fear conditioning: a role for context?
Marchand, A. R., Luck, D., & Scala, G. D. (2004) · PubMed · Cited by 19
Acquisition and extinction of human eyelid conditioned response as a function of schedule of reinforcement and unconditioned stimulus intensity under two masked conditioning procedures.
Schurr, B. C., & Runquist, W. N. (1973) · Journal of Experimental Psychology · doi:10.1037/h0035234 · Cited by 12
Processing of a simple aversive conditioned stimulus in a divided visual field paradigm: an fMRI study
Anders, S., Lotze, M., Wildgruber, D., Erb, M., Grodd, W., & Birbaumer, N. (2004) · Experimental Brain Research · doi:10.1007/s00221-004-2145-1 · Cited by 11
Extinction after partial reinforcement: Predicted vs. judged persistence
Svartdal, F. (2003) · Scandinavian Journal of Psychology · doi:10.1111/1467-9450.00321 · Cited by 10
Intertrial Interval Range Shift in Classical Eyelid Conditioning
Prokasy, W. F., & Whaley, F. L. (1963) · Psychological Reports · doi:10.2466/pr0.1963.12.1.55 · Cited by 9
Cellular processes in the amygdala: gates to emotional memory?
Pape, H., Driesang, R. B., Heinbockel, T., Laxmi, T. R., Meis, S., Seidenbecher, T., Szinyei, C., Frey, U., & Stork, O. (2001) · Zoology · doi:10.1078/0944-2006-00029 · Cited by 7
Correlation between human personality and neural activity in cerebral cortex
Sugiura, M., Kawashima, R., Nakagawa, M., Okada, K., Satoh, T., Gotoh, R., Satoh, K., Ono, S., Schormann, T., Zilles, K., et al. (2000) · NeuroImage · doi:10.1016/s1053-8119(00)91717-8 · Cited by 6

Flagged first, then by citations

Research works printed but not linked: 2

[2]Pavlov IP 1927 Conditioned reflexes Oxford, England Oxford University Press
[85]Jenkins HM Barnes R Barrera FJ 1981 Why autoshaping depends on trial spacing. Locurto CM Terrace HS Gibbon J Autoshaping and conditioning theory New York Academy Press 255 284

Sorted by citations

The integration of negative affect, pain and cognitive control in the cingulate cortex
Shackman, A. J., Salomons, T. V., Slagter, H. A., Fox, A. S., Winter, J. J., & Davidson, R. J. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn2994 · Cited by 2,082
The contextual brain: implications for fear conditioning, extinction and psychopathology
Maren, S., Phan, K. L., & Liberzon, I. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3492 · Cited by 1,547
Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear
Pape, H.-C., & Pare, D. (2010) · Physiological Reviews · doi:10.1152/physrev.00037.2009 · Cited by 994
Don’t fear “fear conditioning”: Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear
Lonsdorf, T. B., Menz, M. M., Andreatta, M., Fullana, M. A., Golkar, A., Haaker, J., Heitland, I., Hermann, A., Kuhn, M., Kruse, O., et al. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.02.026 · Cited by 837
Chronic Stress, Cortisol Dysfunction, and Pain: A Psychoneuroendocrine Rationale for Stress Management in Pain Rehabilitation
Hannibal, K. E., & Bishop, M. D. (2014) · Physical Therapy · doi:10.2522/ptj.20130597 · Cited by 729

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Authors: Sehlmeyer, C., Schöning, S., Zwitserlood, P., Pfleiderer, B., Kircher, T., Arolt, V., & Konrad, C.
Affiliations: University of Münster (DE)
Philipps University of Marburg (DE)
Corresponding author: Konrad, Carsten
ORCID: Zwitserlood, Pienie
Pfleiderer, Bettina
Kircher, Tilo
Arolt, Volker
Konrad, Carsten
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2009-06-10
Volume: 4
Issue: 6
Pages: e5865
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0005865
PMC: PMC2692002
OpenAlex: W2064135174
Cited by: 543
References: 123
Citations by year: 2026: 10 · 2025: 21 · 2024: 18 · 2023: 23 · 2022: 18 · 2021: 31 · 2020: 28 · 2019: 30 · 2018: 33 · 2017: 34 · 2016: 46 · 2015: 45 · 2014: 45 · 2013: 63 · 2012: 37
FWCI: 2.46
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Bundesministerium für Bildung und Forschung
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords: fear conditioning, fear extinction, associative learning, anxiety disorders, amygdala, insula, anterior cingulate cortex, hippocampus, trace conditioning, methodological heterogeneity, brain activation patterns
MeSH terms: Adult, Amygdala, Avoidance Learning, Brain, Brain Mapping, Conditioning, Psychological, Electrophysiology, Extinction, Psychological, Fear, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged

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Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review

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