Emotional events often attain a privileged status in memory. Cognitive neuroscientists have begun to elucidate the psychological and neural mechanisms underlying emotional retention advantages in the human brain. The amygdala is a brain structure that directly mediates aspects of emotional learning and facilitates memory operations in other regions, including the hippocampus and prefrontal cortex. Emotion–memory interactions occur at various stages of information processing, from the initial encoding and consolidation of memory traces to their long-term retrieval. Recent advances are revealing new insights into the reactivation of latent emotional associations and the recollection of personal episodes from the remote past.
Amygdala damage in humans reduces the memory-enhancing benefits of emotional arousal on consolidation processes and on attentional focusing during encoding.
Memories for stressful and emotionally arousing events benefit from moderate doses of adrenaline and cortisol released acutely at the time of encoding. These effects have been linked to amygdala function in human and non-human animal studies.
By contrast, chronic stress or high levels of acute stress hormones impair memory retrieval and hippocampal function, as exemplified by post-traumatic stress disorder.
Encoding of emotionally arousing events recruits amygdala activity and elicits greater functional interactions between the amygdala and medial temporal lobe memory regions, which result in enhanced long-term memory.
The interactions between the amygdala and medial temporal lobe memory regions extend to retrieval of remote memories, including those from the remote personal past.
Emotional memories are retrieved with an accompanying sense of recollection rather than familiarity, an effect that depends on co-activation of the amygdala and hippocampus.
The prefrontal cortex also has a role in the encoding and retrieval of emotional events and shows regional specialization for arousal and valence effects on memory.
Across various species, the acquisition of conditioned fear depends on the integrity of the amygdala and its interactions with the thalamus and cortical structures.
The extinction of fear behaviour requires a suppressive influence of the prefrontal cortex on amygdala function, and contextual cues processed by the hippocampus can reinstate extinguished fears. These cortical control mechanisms over emotional learning are thought to contribute to relapse of fears and phobias in anxiety disorders.
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Bacon, F. The New Organon (ed. Anderson, F. H.) (Bobbs-Merrill, New York, 1620/1960).
Schacter, D. L. The seven sins of memory. Insights from psychology and cognitive neuroscience. Am. Psychol. 54, 182–203 (1999).
Hamann, S. Cognitive and neural mechanisms of emotional memory. Trends Cogn. Sci. 5, 394–400 (2001).
Zald, D. H. The human amygdala and the emotional evaluation of sensory stimuli. Brain Res. Brain Res. Rev. 41, 88–123 (2003).
Phelps, E. A. Human emotion and memory: interactions of the amygdala and hippocampal complex. Curr. Opin. Neurobiol. 14, 198–202 (2004).
Kleinsmith, L. J. & Kaplan, S. Paired-associate learning as a function of arousal and interpolated interval. J. Exp. Psychol. 65, 190–193 (1963).
LaBar, K. S. & Phelps, E. A. Arousal-mediated memory consolidation: role of the medial temporal lobe in humans. Psychol. Sci. 9, 527–540 (1998). One of the only experiments to test emotional recall in patients with amygdala lesions over multiple retention intervals to specify deficits in the consolidation phase of declarative memory.
Sharot, T. & Phelps, E. A. How arousal modulates memory: disentangling the effects of attention and retention. Cogn. Affect. Behav. Neurosci. 4, 294–306 (2004).
Phelps, E. A. et al. Specifying the contributions of the human amygdala to emotional memory: a case study. Neurocase 4, 527–540 (1998).
Markowitsch, H. J. et al. The amygdala's contribution to memory — a study on two patients with Urbach–Wiethe disease. Neuroreport 5, 1349–1352 (1994).
Cahill, L., Babinsky, R., Markowitsch, H. J. & McGaugh, J. L. The amygdala and emotional memory. Nature 377, 295–296 (1995).
Adolphs, R., Cahill, L., Schul, R. & Babinsky, R. Impaired declarative memory for emotional material following bilateral amygdala damage in humans. Learn. Mem. 4, 291–300 (1997).
Adolphs, R., Tranel, D. & Buchanan, T. W. Amygdala damage impairs emotional memory for gist but not details of complex stimuli. Nature Neurosci. 8, 512–518 (2005). Reports that patients with amygdala damage fail to focus their emotional memories on central gist information at the expense of peripheral details, which has implications for understanding neural mechanisms underlying 'weapon focus' and 'tunnel memories
Phelps, E. A., LaBar, K. S. & Spencer, D. D. Memory for emotional words following unilateral temporal lobectomy. Brain Cogn. 35, 85–109 (1997).
Talmi, D. & Moscovitch, M. Can semantic relatedness explain the enhancement of memory for emotional words? Mem. Cognit. 32, 742–751 (2004).
Shaw, P., Brierley, B. & David, A. S. A critical period for the impact of amygdala damage on the emotional enhancement of memory? Neurology 65, 326–328 (2005).
Cahill, L. & McGaugh, J. L. Amygdaloid complex lesions differentially affect retention of tasks using appetitive and aversive reinforcement. Behav. Neurosci. 104, 532–543 (1990).
McGaugh, J. L. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu. Rev. Neurosci. 27, 1–28 (2004).
McGaugh, J. L. & Roozendaal, B. Role of adrenal stress hormones in forming lasting memories in the brain. Curr. Opin. Neurobiol. 12, 205–210 (2002).
Liang, K. C., Juler, R. & McGaugh, J. L. Modulating effects of posttraining epinephrine on memory: involvement of the amygdala noradrenergic system. Brain Res. 368, 125–133 (1986).
Ferry, B. & McGaugh, J. L. Clenbuterol administration into the basolateral amygdala post-training enhances retention in an inhibitory avoidance task. Neurobiol. Learn. Mem. 72, 8–12 (1999).
Wang, S. J. et al. Blockade of isoproterenol-induced synaptic potentiation by tetra-9-aminoacridine in the rat amygdala. Neurosci. Lett. 214, 87–90 (1996).
Huang, Y. Y. & Kandel, E. R. Modulation of both the early and late phase of mossy fiber LTP by the activation of β-adrenergic receptors. Neuron 16, 611–617 (1996).
Quirarte, G. L., Roozendaal, B. & McGaugh, J. L. Glucocorticoid enhancement of memory storage involves noradrenergic activation in the basolateral amygdala. Proc. Natl Acad. Sci. USA 94, 14048–14053 (1997).
Roozendaal, B. & McGaugh, J. L. Basolateral amygdala lesions block the memory-enhancing effect of glucocorticoid administration in the dorsal hippocampus of rats. Eur. J. Neurosci. 9, 76–83 (1997).
Liu, L., Tsuji, M., Takeda, H., Takada, K. & Matsumiya, T. Adrenocortical suppression blocks the enhancement of memory storage produced by exposure to psychological stress in rats. Brain Res. 821, 134–140 (1999).
Roozendaal, B., Nguyen, B. T., Power, A. E. & McGaugh, J. L. Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation. Proc. Natl Acad. Sci. USA 96, 11642–11647 (1999).
Roozendaal, B., Quirarte, G. L. & McGaugh, J. L. Glucocorticoids interact with the basolateral amygdala β-adrenoceptor–cAMP/PKA system in influencing memory consolidation. Eur. J. Neurosci. 15, 553–560 (2002).
Roozendaal, B., McReynolds, J. R. & McGaugh, J. L. The basolateral amygdala interacts with the medial prefrontal cortex in regulating glucocorticoid effects on working memory impairment. J. Neurosci. 24, 1385–1392 (2004).
Clark, K. B., Naritoku, D. K., Smith, D. C., Browning, R. A. & Jensen, R. A. Enhanced recognition memory following vagus nerve stimulation in human subjects. Nature Neurosci. 2, 94–98 (1999).
Cahill, L., Prins, B., Weber, M. & McGaugh, J. L. β-Adrenergic activation and memory for emotional events. Nature 371, 702–704 (1994). A landmark experiment that shows a selective role of beta-blockers in disrupting declarative emotional memory in humans, which has potential applications in the treatment of PTSD.
van Stegeren, A. H., Everaerd, W., Cahill, L., McGaugh, J. L. & Gooren, L. J. G. Memory for emotional events: differential effects of centrally versus peripherally acting beta-blocking agents. Psychopharmacology 138, 305–310 (1998).
O'Carroll, R. E., Drysdale, E., Cahill, L., Shajahan, P. & Ebmeier, K. P. Stimulation of the noradrenergic system enhances and blockade reduces memory for emotional material in man. Psychol. Med. 29, 1083–1088 (1999).
Cahill, L. & Akire, M. T. Epinephrine enhancement of human memory consolidation: interaction with arousal at encoding. Neurobiol. Learn. Mem. 79, 194–198 (2003).
van Stegeren, A. H., Everaerd, W. & Gooren, L. J. G. The effect of β-adrenergic blockade after encoding on memory of an emotional event. Psychopharmacology 163, 202–212 (2002).
Maheu, F. S., Joober, R., Beaulieu, S. & Lupien, S. J. Differential effects of adrenergic and corticosteroid hormonal systems on human short- and long-term declarative memory for emotionally arousing material. Behav. Neurosci. 118, 420–428 (2004).
Strange, B. A., Hurlemann, R. & Dolan, R. J. An emotion-induced retrograde amnesia in humans is amygdala- and β-adrenergic-dependent. Proc. Natl Acad. Sci. USA 100, 13626–13631 (2003).
O'Carroll, R. E., Drysdale, E., Cahill, L., Shajahan, P. & Ebmeier, K. P. Memory for emotional material: a comparison of central versus peripheral beta blockade. J. Psychopharmacol. 13, 32–39 (1999).
Adolphs, R., Tranel, D. & Denburg, N. Impaired emotional declarative memory following unilateral amygdala damage. Learn. Mem. 7, 180–186 (2000).
Strange, B. A. & Dolan, R. J. β-Adrenergic modulation of emotional memory-evoked human amygdala and hippocampal responses. Proc. Natl Acad. Sci. USA 101, 11454–11458 (2004).
van Stegeren, A. H. et al. Noradrenaline mediates amygdala activation in men and women during encoding of emotional material. Neuroimage 24, 898–909 (2005).
Buchanan, T. W. & Lovallo, W. R. Enhanced memory for emotional material following stress-level cortisol treatment in humans. Psychoneuroendocrinology 26, 307–317 (2001).
Cahill, L., Gorski, L. & Le, K. Enhanced human memory consolidation with post-learning stress: interaction with the degree of arousal at encoding. Learn. Mem. 10, 270–274 (2003).
Jelicic, M., Geraerts, E., Merckelbach, H. & Guerrieri, R. Acute stress enhances memory for emotional words, but impairs memory for neutral words. Int. J. Neurosci. 114, 1343–1351 (2004).
Zorawski, M., Cook, C. A., Kuhn, C. M. & LaBar, K. S. Sex, stress, and fear: individual differences in conditioned learning. Cogn. Affect. Behav. Neurosci. 5, 191–201 (2005).
Kuhlmann, S., Kirschbaum, C. & Wolf, O. T. Effects of oral cortisol treatment in healthy young women on memory retrieval of negative and neutral words. Neurobiol. Learn. Mem. 83, 158–162 (2005).
Kuhlmann, S., Piel, M. & Wolf, O. T. Impaired memory retrieval after psychosocial stress in healthy young men. J. Neurosci. 25, 2977–2982 (2005).
Abercrombie, H. C., Kalin, N. H., Thurow, M. E., Rosenkranz, M. A. & Davidson, R. J. Cortisol variation in humans affects memory for emotionally laden and neutral information. Behav. Neurosci. 117, 505–516 (2003).
Rimmele, U., Domes, G., Mathiak, K. & Hautzinger, M. Cortisol has different effects on human memory for emotional and neutral material. Neuroreport 14, 2485–2488 (2003).
Buss, C., Wolf, O. T., Witt, J. & Hellhammer, D. H. Autobiographic memory impairment following acute cortisol administration. Psychoneuroendocrinology 29, 1093–1096 (2004).
Lupien, S. J., Gillin, J. C. & Hauger, R. L. Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans. Behav. Neurosci. 113, 420–430 (1999).
Wolf, O. T. et al. Cortisol differentially affects memory in young and elderly men. Behav. Neurosci. 115, 1002–1011 (2001).
Elzinga, B. M. & Roelofs, K. Cortisol-induced impairments of working memory require acute sympathetic activation. Behav. Neurosci. 119, 98–103 (2005).
Lupien, S. J. et al. Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nature Neurosci. 1, 69–73 (1998).
Belanoff, J. K., Kalehzan, M., Sund, B., Fleming Ficek, S. K. & Schatzberg, A. F. Cortisol activity and cognitive changes in psychotic major depression. Am. J. Psychiatry 158, 1612–1616 (2001).
de Quervian, D. J. et al. Glucocorticoid-induced impairment of declarative memory retrieval is associated with reduced blood flow in the medial temporal lobe. Eur. J. Neurosci. 17, 1296–1302 (2003).
Cahill, L. et al. Amygdala activity at encoding correlated with long-term, free recall of emotional information. Proc. Natl Acad. Sci. USA 93, 8016–8021 (1996).
Kilpatrick, L. & Cahill, L. Amygdala modulation of parahippocampal and frontal regions during emotionally influenced memory storage. Neuroimage 20, 2091–2099 (2003).
Hamann, S. B., Ely, T. D., Grafton, S. T. & Kilts, C. D. Amygdala activity related to enhanced memory for pleasant and aversive stimuli. Nature Neurosci. 2, 289–293 (1999). Using PET, the authors showed that the amygdala's role in emotional memory is similar across positive and negative valence.
Canli, T., Zhao, Z., Brewer, J., Gabrieli, J. D. E. & Cahill, L. Event-related activation in the human amygdala associates with later memory for individual emotional experience. J. Neurosci. 20, RC99 (2000).
Cahill, L. et al. Sex-related difference in amygdala activity during emotionally influenced memory storage. Neurobiol. Learn. Mem. 75, 1–9 (2001).
Canli, T., Desmond, J. E., Zhao, Z. & Gabrieli, J. D. Sex differences in the neural basis of emotional memories. Proc. Natl Acad. Sci. USA 99, 10789–10794 (2002). A functional neuroimaging view of how emotional memory processing differs in male and female brains.
Cahill, L., Uncapher, M., Kilpatrick, L., Alkire, M. T. & Turner, J. Sex-related hemispheric lateralization of amygdala function in emotionally influenced memory: an fMRI investigation. Learn. Mem. 11, 261–266 (2004).
Dolcos, F., LaBar, K. S. & Cabeza, R. Interaction between the amygdala and the medial temporal lobe memory system predicts better memory for emotional events. Neuron 42, 855–863 (2004). This experiment provides strong support for the memory-modulation hypothesis by identifying fMRI activation in and interactions between the amygdala and MTL memory regions that differentiate successful memory encoding as a function of emotional content.
Kensinger, E. A. & Corkin, S. Two routes to emotional memory: distinct neural processes for valence and arousal. Proc. Natl Acad. Sci. USA 101, 3310–3315 (2004).
Richardson, M. P., Strange, B. A. & Dolan, R. J. Encoding of emotional memories depends on amygdala and hippocampus and their interactions. Nature Neurosci. 7, 278–285 (2004). An experimental tour de force that combines structural and functional MRI of patients with MTL epilepsy to show co-dependencies between the amygdala and hippocampus during encoding that yield emotional memories accompanied by a sense of recollection.
Sergerie, K., Lepage, M. & Armony, J. L. A face to remember: emotional expression modulates prefrontal activity during memory formation. Neuroimage 24, 580–585 (2005).
Paller, K. A. & Wagner, A. D. Observing the transformation of experience into memory. Trends Cogn. Sci. 6, 93–102 (2002).
Dolcos, F. & Cabeza, R. Event-related potentials of emotional memory: encoding pleasant, unpleasant, and neutral pictures. Cogn. Affect. Behav. Neurosci. 2, 252–263 (2002).
Erk, S. et al. Emotional context modulates subsequent memory effect. Neuroimage 18, 439–447 (2003).
Aggleton, J. P., Burton, M. J. & Passingham, R. E. Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta). Brain Res. 190, 347–368 (1980).
Amaral, D. G. & Price, J. L. Amygdalo–cortical projections in the monkey (Macaca fascicularis). J. Comp. Neurol. 230, 465–496 (1984).
Dolcos, F., LaBar, K. S. & Cabeza, R. Dissociable effects of arousal and valence on prefrontal activity indexing emotional evaluation and subsequent memory: an event-related potential study. Neuroimage 23, 64–74 (2004).
Nader, K., Schafe, G. E. & Le Doux, J. E. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406, 722–726 (2000).
Taylor, S. F. et al. The effect of emotional content on visual recognition memory: a PET activation study. Neuroimage 8, 188–197 (1998).
Tabert, M. H. et al. Differential amygdala activation during emotional decision and recognition memory tasks using unpleasant words: an fMRI study. Neuropsychologia 39, 556–573 (2001).
Dolan, R. J., Lane, R., Chua, P. & Fletcher, P. Dissociable temporal lobe activations during emotional episodic memory retrieval. Neuroimage 11, 203–209 (2000).
Maratos, E. J., Dolan, R. J., Morris, J. S., Henson, R. N. A. & Rugg, M. D. Neural activity associated with episodic memory for emotional context. Neuropsychologia 39, 910–920 (2001).
Maratos, E. J. & Rugg, M. D. Electrophysiological correlates of the retrieval of emotional and non-emotional context. J. Cogn. Neurosci. 13, 877–891 (2001).
Smith, A. P. R., Dolan, R. J. & Rugg, M. D. Event-related potential correlates of the retrieval of emotional and nonemotional context. J. Cogn. Neurosci. 16, 760–775 (2004).
Smith, A. P., Henson, R. N., Dolan, R. J. & Rugg, M. D. fMRI correlates of the episodic retrieval of emotional contexts. Neuroimage 22, 868–878 (2004).
Medford, N. et al. Emotional memory: separating content and context. Psychiatry Res. 138, 247–258 (2005).
Yonelinas, A. P., Otten, L. J., Shaw, K. N. & Rugg, M. D. Separating the brain regions involved in recollection and familiarity in recognition memory. J. Neurosci. 25, 3002–3008 (2005).
Ochsner, K. N. Are affective events richly recollected or simply familiar? The experience and process of recognizing feelings past. J. Exp. Psychol. 129, 242–261 (2000).
Talarico, J. M., LaBar, K. S. & Rubin, D. C. Emotional intensity predicts autobiographical memory experience. Mem. Cogn. 32, 1118–1132 (2004).
Dolcos, F., LaBar, K. S. & Cabeza, R. Remembering one year later: role of the amygdala and the medial temporal lobe memory system in retrieving emotional memories. Proc. Natl Acad. Sci. USA 102, 2626–2631 (2005). Shows that functional interactions between the amygdala and MTL memory regions extend beyond encoding and consolidation to promote recollection-based successful retrieval of 1-year-old emotional memories.
Sharot, T., Delgado, M. R. & Phelps, E. A. How emotion enhances the feeling of remembering. Nature Neurosci. 7, 1376–1380 (2004).
Markowitsch, H. J. Which brain regions are critically involved in the retrieval of old episodic memory? Brain Res. Rev. 21, 117–127 (1995).
Kroll, N. E., Markowitsch, H. J., Knight, R. T. & von Cramon, D. Y. Retrieval of old memories: the temporofrontal hypothesis. Brain 120, 1377–1399 (1997).
Levine, B. et al. Episodic memory and the self in a case of isolated retrograde amnesia. Brain 121, 1951–1973 (1998).
Fink, G. R. et al. Cerebral representation of one's own past: neural networks involved in autobiographical memory. J. Neurosci. 16, 4275–4282 (1996).
Markowitsch, H. J. et al. Right amygdalar and temporofrontal activation during autobiographic, but not during fictitious memory retrieval. Behav. Neurol. 12, 117–127 (2000).
Maguire, E. A., Vargha-Khadem, F. & Mishkin, M. The effects of bilateral hippocampal damage on fMRI regional activations and interactions during memory retrieval. Brain 124, 1156–1170 (2001).
Piefke, M., Weiss, P. H., Zilles, K., Markowitsch, H. J. & Fink, G. R. Differential remoteness and emotional tone modulate the neural correlates of autobiographical memory. Brain 126, 650–668 (2003).
Gilboa, A., Winocur, G., Grady, C. L., Hevenor, S. J. & Moscovitch, M. Remembering our past: functional neuroanatomy of recollection of recent and very remote personal events. Cereb. Cortex 14, 1214–1225 (2004).
Greenberg, D. L. et al. Co-activation of the amygdala, hippocampus, and inferior frontal gyrus during autobiographical memory retrieval. Neuropsychologia 43, 659–674 (2005).
Ohman, A. & Soares, J. J. F. On the automatic nature of phobic fear: conditioned electrodermal responses to masked fear-relevant stimuli. J. Abnorm. Psychol. 102, 121–132 (1993).
Olsson, A., Ebert, J. P., Banaji, M. R. & Phelps, E. A. The role of social groups in the persistence of learned fear. Science 309, 785–787 (2005).
Kapp, B. S., Frysinger, R. C., Gallagher, M. & Haselton, J. R. Amygdala central nucleus lesions: effect on heart rate conditioning in the rabbit. Physiol. Behav. 23, 1109–1117 (1979).
Phillips, R. G. & LeDoux, J. E. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav. Neurosci. 106, 274–285 (1992).
Romanski, L. M., Clugnet, M. C., Bordi, F. & LeDoux, J. E. Somatosensory and auditory convergence in the lateral nucleus of the amygdala. Behav. Neurosci. 104, 444–450 (1993).
Quirk, G. J., Repa, J. C. & LeDoux, J. E. Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat. Neuron 15, 1029–1039 (1995).
Armony, J. L., Quirk, G. J. & LeDoux, J. E. Differential effects of amygdala lesions on early and late plastic components of auditory cortex spike trains during fear conditioning. J. Neurosci. 18, 2592–2601 (1998).
Maren, S., Yap, S. A. & Goosens, K. A. The amygdala is essential for the development of neuronal plasticity in the medial geniculate nucleus during auditory fear conditioning in rats. J. Neurosci. 21, RC135 (2001).
Rogan, M. T., Staubli, U. V. & LeDoux, J. E. Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390, 604–607 (1997).
McKernan, M. G. & Shinnick-Gallagher, P. Fear conditioning induces a lasting potentiation of synaptic currents in vitro. Nature 390, 607–611 (1997).
Tsvetkov, E., Carlezon, W. A., Benes, F. M., Kandel, E. R. & Bolshakov, V. Y. Fear conditioning occludes LTP-induced presynaptic enhancement of synaptic transmission in the cortical pathway to the lateral amygdala. Neuron 34, 289–300 (2002).
Lamprecht, R. & LeDoux, J. E. Structural plasticity and memory. Nature Rev. Neurosci. 5, 45–54 (2004).
Maren, S. & Quirk, G. J. Neuronal signalling of fear memory. Nature Rev. Neurosci. 5, 844–852 (2004).
Sotres-Boyen, F., Bush, D. E. A. & LeDoux, J. E. Emotional perseveration: an update on prefrontal–amygdala interactions in fear extinction. Learn. Mem. 11, 525–535 (2004).
Bechara, A. et al. Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. Science 269, 1115–1118 (1995). An excellent example of the value of neuropsychological approaches showing how patients with selective lesions to adjacent MTL structures perform differently on declarative and non-declarative aspects of the same emotional learning task.
LaBar, K. S., LeDoux, J. E., Spencer, D. D. & Phelps, E. A. Impaired fear conditioning following unilateral temporal lobectomy in humans. J. Neurosci. 15, 6846–6855 (1995).
Peper, M., Karcher, S., Wohlfarth, R., Reinshagen, G. & LeDoux, J. E. Aversive learning in patients with unilateral lesions of the amygdala and hippocampus. Biol. Psychol. 58, 1–23 (2001).
Angrilli, A. et al. Startle reflex and emotion modulation impairment after a right amygdala lesion. Brain 119, 1991–2000 (1996).
Funayama, E. S., Grillon, C., Davis, M. & Phelps, E. A. A double dissociation in the affective modulation of startle in humans: effects of unilateral temporal lobectomy. J. Cogn. Neurosci. 13, 721–729 (2001).
Buchanan, T. W., Tranel, D. & Adolphs, R. Anteromedial temporal lobe damage blocks startle modulation by fear and disgust. Behav. Neurosci. 118, 429–437 (2004).
LaBar, K. S. & Phelps, E. A. Reinstatement of conditioned fear in humans is context-dependent and impaired in amnesia. Behav. Neurosci. 119, 677–686 (2005).
LaBar, K. S. & Disterhoft, J. F. Conditioning, awareness, and the hippocampus. Hippocampus 8, 620–626 (1998).
Bouton, M. E. Context, time, and memory retrieval in the interference paradigms of Pavlovian learning. Psychol. Bull. 114, 80–99 (1993).
Corcoran, K. A. & Maren, S. Factors regulating the effects of hippocampal inactivation on renewal of conditional fear after extinction. Learn. Mem. 11, 598–603 (2004).
Vansteenwegen, D. et al. Return of fear in a human differential conditioning paradigm caused by a return to the original acquisition context. Behav. Res. Ther. 43, 323–336 (2005).
Milad, M. R., Orr, S. P., Pitman, R. K. & Rauch, S. L. Context modulation of memory for fear extinction in humans. Psychophysiology 42, 456–464 (2005).
Mineka, S., Mystkowski, J. L., Hladek, D. & Rodriquez, B. I. The effects of changing contexts on return of fear following exposure treatment for spider fear. J. Consult. Clin. Psychol. 67, 599–604 (1999).
Fredrikson, M., Wik, G., Fischer, H. & Andersson, J. Affective and attentive neural networks in humans: a PET study of Pavlovian conditioning. Neuroreport 7, 97–101 (1995).
Hugdahl, D. et al. Brain mechanisms in human classical conditioning: a PET blood flow study. Neuroreport 6, 1723–1728 (1995).
Buchel, C., Morris, J. S., Dolan, R. J. & Friston, K. J. Brain systems mediating aversive conditioning: an event-related fMRI study. Neuron 20, 947–957 (1998).
LaBar, K. S., Gatenby, J. C., Gore, J. C., LeDoux, J. E. & Phelps, E. A. Human amygdala activation during conditioned fear acquisition and extinction: a mixed trial fMRI study. Neuron 20, 937–945 (1998). This study uses event-related fMRI to reveal time-delimited amygdala activation during the acquisition and extinction of fear conditioning.
Morris, J. S., Friston, K. J. & Dolan, R. J. Experience-dependent modulation of tonotopic neural responses in human auditory cortex. Proc. R. Soc. Lond. B Biol. Soc. 265, 649–657 (1998).
Buchel, C., Dolan, R. J., Armony, J. L. & Friston, K. J. Amygdala–hippocampal involvement in human aversive trace conditioning revealed through event-related functional magnetic resonance imaging. J. Neurosci. 19, 10869–10876 (1999).
Cheng, D. T., Knight, D. C., Smith, C. N., Stein, E. A. & Helmstetter, F. J. Functional MRI of human amygdala activity during Pavlovian fear conditioning: stimulus processing versus response expression. Behav. Neurosci. 117, 3–10 (2003).
Knight, D. C., Cheng, D. T., Smith, C. N., Stein, E. A. & Helmstetter, F. J. Neural substrates mediating human delay and trace fear conditioning. J. Neurosci. 24, 218–228 (2004).
Morris, J. S., Friston, K. J. & Dolan, R. J. Neural responses to salient visual stimuli. Proc. Biol. Sci. 264, 769–775 (1997).
Morris, J. S., Buchel, C. & Dolan, R. J. Parallel neural responses in amygdala subregions and sensory cortex during implicit fear conditioning. Neuroimage 13, 1044–1052 (2001).
Critchley, H. D., Mathias, C. J. & Dolan, R. J. Fear conditioning in humans: the influence of awareness and autonomic arousal on functional neuroanatomy. Neuron 33, 653–663 (2002).
Morris, J. S., Ohman, A. & Dolan, R. J. Conscious and unconscious emotional learning in the human amygdala. Nature 393, 467–470 (1998).
Morris, J. S., Ohman, A. & Dolan, R. J. A subcortical pathway to the right amygdala mediating 'unseen' fear. Proc. Natl Acad. Sci. USA 96, 1680–1685 (1999).
Furmark, T., Fischer, H., Wik, G., Larsson, M. & Fredrikson, M. The amygdala and individual differences in human fear conditioning. Neuroreport 8, 3957–3960 (1997).
Phelps, E. A., Delgado, M. R., Nearing, K. I. & LeDoux, J. E. Extinction learning in humans: role of the amygdala and vmPFC. Neuron 43, 897–905 (2004).
Kessler, R. C., Sonnega, A., Bromet, E., Hughes, M. & Nelson, C. B. Posttraumatic stress disorder in the National Comorbidity Survey. Arch. Gen. Psychiatry 52, 1048–1060 (1995).
Baker, D. G. et al. Higher levels of basal CSF cortisol in combat veterans with posttraumatic stress disorder. Am. J. Psychiatry 162, 992–994 (2005).
Bremner, J. D. et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am. J. Psychiatry 152, 973–981 (1995).
Rausch, S. L. et al. A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Arch. Gen. Psychiatry 53, 380–387 (1996).
Shin, L. M. et al. Visual imagery and perception in posttraumatic stress disorder. Arch. Gen. Psychiatry 54, 233–241 (1997).
Orr, S. P., Lasko, N. B., Shalev, A. Y. & Pitman, R. K. Physiologic response to loud tones in Vietnam veterans with posttraumatic stress disorder. J. Abnorm. Psychol. 104, 75–82 (1995).
Grillon, C. & Morgan, C. A. Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder. J. Abnorm. Psychol. 108, 134–142 (1999).
Orr, S. P. et al. De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. J. Abnorm. Psychol. 109, 290–298 (2000).
Pitman, R. K. et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol. Psychiatry 51, 189–192 (2002).
Research was supported by grants from US National Institutes of Health and a US National Science Foundation CAREER award.
A dimension of emotion that varies from calm to excitement.
A dimension of emotion that varies from unpleasant (negative) to pleasant (positive), with neutral often considered an intermediate value.
- Declarative memory
(Or explicit memory). Conscious memories for events and facts that depend on the integrity of the MTL.
- Non-declarative memory
(Or implicit memory). Various non-conscious memories that are independent of MTL function and are expressed as a facilitation in behavioural performance due to previous exposure.
Episodic retrieval that is accompanied by recovery of specific contextual details about a past event.
- Urbach–Wiethe syndrome
(Or lipoid proteinosis). A rare, hereditary, congenital disorder characterized by systemic deposits of hyaline material that are prominent in the skin, oral mucosa and pharynx. About 50% of all cases have additional intracranial deposits in the MTL, which occasionally target the amygdala selectively.
- Working memory
A form of memory in which stimulus representations are actively maintained and/or manipulated in conscious awareness over a short period of time.
- Dm effect
An index of brain activity at encoding that distinguishes subsequently remembered from subsequently forgotten items and is assumed to reflect successful encoding processes.
Episodic retrieval that is accompanied by a feeling that an event happened in the past, although no contextual details are available.
- Biological preparedness theory
A theory proposed by Martin Seligman that considers phobias as arising from a selective set of biological associations that the organism is evolutionarily tuned ('prepared') to learn, which leads to rapid fear acquisition and persistence of fear.
- Visual masking
A psychophysical technique that can be used to reduce perceptual awareness of visual stimuli by presenting them briefly (for typically <33 msec) on a computer screen or tachistoscope and immediately displaying another stimulus of equal or greater complexity ('backward' masking). Participants report seeing only the second stimulus, although the visual system processes aspects of the masked stimulus.
After extinction training, conditioned fear can be renewed by presenting the conditioned stimulus in a novel context.
After extinction training, conditioned fear can be reinstated by presenting the conditioned stimulus in a context in which a noxious or stressful stimulus was recently encountered.
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