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Neural correlates of trait anxiety in fear extinction

Published online by Cambridge University Press:  16 June 2010

C. Sehlmeyer ,
U. Dannlowski ,
S. Schöning ,
H. Kugel ,
M. Pyka ,
B. Pfleiderer ,
P. Zwitserlood ,
H. Schiffbauer ,
W. Heindel  and
V. Arolt
...Show all authors
C. Sehlmeyer
Affiliation:
Department of Psychiatry, University Hospital of Muenster, Germany
U. Dannlowski
Affiliation:
Department of Psychiatry, University Hospital of Muenster, Germany
S. Schöning
Affiliation:
Department of Psychiatry, University Hospital of Muenster, Germany Interdisciplinary Center for Clinical Research, University Hospital of Muenster, Germany
H. Kugel
Affiliation:
Department of Clinical Radiology, University Hospital of Muenster, Germany
M. Pyka
Affiliation:
Department of Psychiatry, University Hospital of Muenster, Germany
B. Pfleiderer
Affiliation:
Department of Clinical Radiology, University Hospital of Muenster, Germany
P. Zwitserlood
Affiliation:
Department of Psychology, University of Muenster, Germany
H. Schiffbauer
Affiliation:
Department of Clinical Radiology, University Hospital of Muenster, Germany Department of Radiology, University Hospital of Bonn, Germany
W. Heindel
Affiliation:
Department of Clinical Radiology, University Hospital of Muenster, Germany
V. Arolt
Affiliation:
Department of Psychiatry, University Hospital of Muenster, Germany
C. Konrad*
Affiliation:
Department of Psychiatry, University Hospital of Muenster, Germany Interdisciplinary Center for Clinical Research, University Hospital of Muenster, Germany Department of Psychiatry and Psychotherapy, Philipps University of Marburg, Germany
*
*Address for correspondence: C. Konrad, M.D., Department of Psychiatry, University of Marburg, Rudolf-Bultmann-Straße 8, D-35039Marburg, Germany. (Email: [email protected])
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Abstract

Background

Fear conditioning involves the amygdala as the main neural structure for learning fear responses whereas fear extinction mainly activates the inhibitory prefrontal cortex (PFC). In this study we investigated whether individual differences in trait anxiety affect amygdala and dorsal anterior cingulate cortex (dACC) activation during fear conditioning and extinction.

Method

Thirty-two healthy subjects were investigated by functional magnetic resonance imaging (fMRI) at 3 T while performing a cued fear-conditioning task. All participants completed the trait version of the State-Trait Anxiety Inventory (STAI-T). Activations of the amygdala and the dACC were examined with respect to the effects of trait anxiety.

Results

Analysis of the fMRI data demonstrated enhanced activation in fear-related brain areas, such as the insula and the ACC, during both fear conditioning and extinction. Activation of the amygdala appeared only during the late acquisition phase whereas deactivation was observed during extinction. Regression analyses revealed that highly trait-anxious subjects exhibited sustained amygdala activation and reduced dACC involvement during the extinction of conditioned responses.

Conclusions

This study reveals that high levels of trait anxiety are associated with both increased amygdala activation and reduced dACC recruitment during the extinction of conditioned fear. This hyper-responsitivity of the amygdala and the deficient cognitive control during the extinction of conditioned fear in anxious subjects reflect an increased resistance to extinct fear responses and may thereby enhance the vulnerability to developing anxiety disorders.

Keywords

ACCamygdalaconditioningextinctionfeartrait anxiety
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 4 , April 2011 , pp. 789 - 798
Copyright
Copyright © Cambridge University Press 2010

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References

Anderson, KC, Insel, TR (2006). The promise of extinction research for the prevention and treatment of anxiety disorders. Biological Psychiatry 60, 319–321.CrossRefGoogle ScholarPubMed
Barrett, J, Armony, JL (2009). Influence of trait anxiety on brain activity during the acquisition and extinction of aversive conditioning. Psychological Medicine 39, 255–265.Google Scholar
Bienvenu, OJ, Brown, C, Samuels, JF, Liang, KY, Costa, PT, Eaton, WW, Nestadt, G (2001). Normal personality traits and comorbidity among phobic, panic and major depressive disorders. Psychiatry Research 102, 73–85.CrossRefGoogle ScholarPubMed
Bishop, SJ (2007). Neurocognitive mechanisms of anxiety: an integrative account. Trends in Cognitive Sciences 11, 307–316.CrossRefGoogle ScholarPubMed
Bishop, SJ (2009). Trait anxiety and impoverished prefrontal control of attention. Nature Neuroscience 12, 92–98.CrossRefGoogle ScholarPubMed
Bishop, SJ, Duncan, J, Lawrence, AD (2004). State anxiety modulation of the amygdala response to unattended threat-related stimuli. Journal of Neuroscience 24, 10364–10368.CrossRefGoogle ScholarPubMed
Blechert, J, Michael, T, Vriends, N, Margraf, J, Wilhelm, FH (2007). Fear conditioning in posttraumatic stress disorder: evidence for delayed extinction of autonomic, experiential, and behavioural responses. Behaviour Research and Therapy 45, 2019–2033.CrossRefGoogle ScholarPubMed
Bradley, MM, Lang, PJ (1994). Measuring emotion: the Self-Assessment Manikin and the Semantic Differential. Journal of Behavior Therapy and Experimental Psychiatry 25, 49–59.Google Scholar
Bremner, JD, Vermetten, E, Schmahl, C, Vaccarino, V, Vythilingam, M, Afzal, N, Grillon, C, Charney, DS (2005). Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder. Psychological Medicine 35, 791–806.Google Scholar
Buchel, C, Dolan, RJ (2000). Classical fear conditioning in functional neuroimaging. Current Opinion in Neurobiology 10, 219–223.Google Scholar
Bush, G, Luu, P, Posner, MI (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences 4, 215–222.CrossRefGoogle ScholarPubMed
Carlson, JM, Greenberg, T, Rubin, D, Mujica-Parodi, LR (2010). Feeling anxious: anticipatory amygdalo-insular response predicts the feeling of anxious anticipation. Social Cognitive and Affective Neuroscience. Published online: 5 March 2010. doi:10.1093/scan/nsq017.Google ScholarPubMed
Chambers, JA, Power, KG, Durham, RC (2004). The relationship between trait vulnerability and anxiety and depressive diagnoses at long-term follow-up of generalized anxiety disorder. Journal of Anxiety Disorders 18, 587–607.Google Scholar
Chan, CK, Lovibond, PF (1996). Expectancy bias in trait anxiety. Journal of Abnormal Psychology 105, 637–647.CrossRefGoogle ScholarPubMed
Dannlowski, U, Ohrmann, P, Konrad, C, Domschke, K, Bauer, J, Kugel, H, Hohoff, C, Schoning, S, Kersting, A, Baune, BT, Mortensen, LS, Arolt, V, Zwitserlood, P, Deckert, J, Heindel, W, Suslow, T (2009). Reduced amygdala-prefrontal coupling in major depression: association with MAOA genotype and illness severity. International Journal of Neuropsychopharmacology 12, 11–22.CrossRefGoogle ScholarPubMed
Dickie, EW, Armony, JL (2008). Amygdala responses to unattended fearful faces: interaction between sex and trait anxiety. Psychiatry Research 162, 51–57.CrossRefGoogle ScholarPubMed
Etkin, A, Klemenhagen, KC, Dudman, JT, Rogan, MT, Hen, R, Kandel, ER, Hirsch, J (2004). Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Neuron 44, 1043–1055.Google Scholar
Etkin, A, Wager, TD (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164, 1476–1488.CrossRefGoogle ScholarPubMed
Fischer, H, Andersson, JL, Furmark, T, Fredrikson, M (2000). Fear conditioning and brain activity: a positron emission tomography study in humans. Behavioral Neuroscience 114, 671–680.Google Scholar
Forman, SD, Cohen, JD, Fitzgerald, M, Eddy, WF, Mintun, MA, Noll, DC (1995). Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magnetic Resonance in Medicine 33, 636–647.CrossRefGoogle ScholarPubMed
Gottfried, JA, Dolan, RJ (2004). Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value. Nature Neuroscience 7, 1144–1152.CrossRefGoogle ScholarPubMed
Haas, BW, Omura, K, Constable, RT, Canli, T (2007). Emotional conflict and neuroticism: personality-dependent activation in the amygdala and subgenual anterior cingulate. Behavioral Neuroscience 121, 249–256.CrossRefGoogle ScholarPubMed
Hooker, CI, Verosky, SC, Miyakawa, A, Knight, RT, D'Esposito, M (2008). The influence of personality on neural mechanisms of observational fear and reward learning. Neuropsychologia 46, 2709–2724.Google Scholar
Johnson, KA, Cunnington, R, Iansek, R, Bradshaw, JL, Georgiou, N, Chiu, E (2001). Movement-related potentials in Huntington's disease: movement preparation and execution. Experimental Brain Research 138, 492–499.CrossRefGoogle ScholarPubMed
Kienast, T, Hariri, AR, Schlagenhauf, F, Wrase, J, Sterzer, P, Buchholz, HG, Smolka, MN, Grunder, G, Cumming, P, Kumakura, Y, Bartenstein, P, Dolan, RJ, Heinz, A (2008). Dopamine in amygdala gates limbic processing of aversive stimuli in humans. Nature Neuroscience 11, 1381–1382.CrossRefGoogle ScholarPubMed
LaBar, KS, Gatenby, JC, Gore, JC, LeDoux, JE, Phelps, EA (1998). Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study. Neuron 20, 937–945.CrossRefGoogle ScholarPubMed
Lang, S, Kroll, A, Lipinski, SJ, Wessa, M, Ridder, S, Christmann, C, Schad, LR, Flor, H (2009). Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex. European Journal of Neuroscience 29, 823–832.Google Scholar
LaRowe, SD, Patrick, CJ, Curtin, JJ, Kline, JP (2006). Personality correlates of startle habituation. Biological Psychology 72, 257–264.CrossRefGoogle ScholarPubMed
Laux, L, Glanzmann, P, Schaffner, P, Spielberger, CD (1981). State-Trait-Angstinventar (Testmappe mit Handanweisung, Fragebogen STAI-G Form X 1 und Fragebogen STAI-G Form X 2). Beltz: Weinheim.Google Scholar
Lissek, S, Powers, AS (2003). Sensation seeking and startle modulation by physically threatening images. Biological Psychology 63, 179–197.Google Scholar
Lissek, S, Powers, AS, McClure, EB, Phelps, EA, Woldehawariat, G, Grillon, C, Pine, DS (2005). Classical fear conditioning in the anxiety disorders: a meta-analysis. Behaviour Research and Therapy 43, 1391–1424.Google Scholar
Lopez-Sola, M, Pujol, J, Hernandez-Ribas, R, Harrison, BJ, Ortiz, H, Soriano-Mas, C, Deus, J, Menchon, JM, Vallejo, J, Cardoner, N (2010). Dynamic assessment of the right lateral frontal cortex response to painful stimulation. NeuroImage 50, 1177–1187.Google Scholar
MacCallum, RC, Zhang, S, Preacher, KJ, Rucker, DD (2002). On the practice of dichotomization of quantitative variables. Psychological Methods 7, 19–40.Google Scholar
Maren, S (2001). Neurobiology of Pavlovian fear conditioning. Annual Review of Neuroscience 24, 897–931.CrossRefGoogle ScholarPubMed
Mathews, A, MacLeod, C (2005). Cognitive vulnerability to emotional disorders. Annual Review of Clinical Psychology 1, 167–195.Google Scholar
Michael, T, Blechert, J, Vriends, N, Margraf, J, Wilhelm, FH (2007). Fear conditioning in panic disorder: enhanced resistance to extinction. Journal of Abnormal Psychology 116, 612–617.CrossRefGoogle ScholarPubMed
Morgan, MA, Romanski, LM, LeDoux, JE (1993). Extinction of emotional learning: contribution of medial prefrontal cortex. Neuroscience Letters 163, 109–113.Google Scholar
Morris, JS, Dolan, RJ (2004). Dissociable amygdala and orbitofrontal responses during reversal fear conditioning. NeuroImage 22, 372–380.CrossRefGoogle ScholarPubMed
Most, SB, Chun, MM, Johnson, MR, Kiehl, KA (2006). Attentional modulation of the amygdala varies with personality. NeuroImage 31, 934–944.Google Scholar
Mujica-Parodi, LR, Korgaonkar, M, Ravindranath, B, Greenberg, T, Tomasi, D, Wagshul, M, Ardekani, B, Guilfoyle, D, Khan, S, Zhong, Y, Chon, K, Malaspina, D (2009). Limbic dysregulation is associated with lowered heart rate variability and increased trait anxiety in healthy adults. Human Brain Mapping 30, 47–58.Google Scholar
Myers, KM, Davis, M (2002). Behavioral and neural analysis of extinction. Neuron 36, 567–584.Google Scholar
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113.CrossRefGoogle ScholarPubMed
Omura, K, Todd Constable, R, Canli, T (2005). Amygdala gray matter concentration is associated with extraversion and neuroticism. NeuroReport 16, 1905–1908.CrossRefGoogle ScholarPubMed
Ostrowsky, K, Magnin, M, Ryvlin, P, Isnard, J, Guenot, M, Mauguiere, F (2002). Representation of pain and somatic sensation in the human insula: a study of responses to direct electrical cortical stimulation. Cerebral Cortex 12, 376–385.Google Scholar
Pavlov, IP (1927). Conditioned Reflexes. Oxford University Press: Oxford.Google Scholar
Phelps, EA, Delgado, MR, Nearing, KI, LeDoux, JE (2004). Extinction learning in humans: role of the amygdala and vmPFC. Neuron 43, 897–905.CrossRefGoogle ScholarPubMed
Phelps, EA, O'Connor, KJ, Gatenby, JC, Gore, JC, Grillon, C, Davis, M (2001). Activation of the left amygdala to a cognitive representation of fear. Nature Neuroscience 4, 437–441.Google Scholar
Pineles, SL, Vogt, DS, Orr, MR (2009). Personality and fear responses during conditioning: beyond extraversion. Personality and Individual Differences 46, 48–53.Google Scholar
Ploghaus, A, Tracey, I, Gati, JS, Clare, S, Menon, RS, Matthews, PM, Rawlins, JN (1999). Dissociating pain from its anticipation in the human brain. Science 284, 1979–1981.CrossRefGoogle ScholarPubMed
Pujol, J, Lopez, A, Deus, J, Cardoner, N, Vallejo, J, Capdevila, A, Paus, T (2002). Anatomical variability of the anterior cingulate gyrus and basic dimensions of human personality. NeuroImage 15, 847–855.CrossRefGoogle ScholarPubMed
Quirk, GJ, Garcia, R, Gonzalez-Lima, F (2006). Prefrontal mechanisms in extinction of conditioned fear. Biological Psychiatry 60, 337–343.Google Scholar
Quirk, GJ, Likhtik, E, Pelletier, JG, Pare, D (2003). Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. Journal of Neuroscience 23, 8800–8807.Google Scholar
Rauch, SL, Milad, MR, Orr, SP, Quinn, BT, Fischl, B, Pitman, RK (2005). Orbitofrontal thickness, retention of fear extinction, and extraversion. NeuroReport 16, 1909–1912.Google Scholar
Rauch, SL, Shin, LM, Phelps, EA (2006). Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research: past, present, and future. Biological Psychiatry 60, 376–382.CrossRefGoogle ScholarPubMed
Remy, P, Zilbovicius, M, Leroy-Willig, A, Syrota, A, Samson, Y (1994). Movement- and task-related activations of motor cortical areas: a positron emission tomographic study. Annals of Neurology 36, 19–26.Google Scholar
Sarinopoulos, I, Grupe, DW, Mackiewicz, KL, Herrington, JD, Lor, M, Steege, EE, Nitschke, JB (2010). Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala. Cerebral Cortex 20, 929–940.Google Scholar
Schiller, D, Levy, I, Niv, Y, LeDoux, JE, Phelps, EA (2008). From fear to safety and back: reversal of fear in the human brain. Journal of Neuroscience 28, 11517–11525.Google Scholar
Schmidt, NB, Mitchell, MA, Richey, JA (2008). Anxiety sensitivity as an incremental predictor of later anxiety symptoms and syndromes. Comprehensive Psychiatry 49, 407–412.Google Scholar
Sehlmeyer, C, Schoning, S, Zwitserlood, P, Pfleiderer, B, Kircher, T, Arolt, V, Konrad, C (2009). Human fear conditioning and extinction in neuroimaging: a systematic review. PLoS One 4, e5865.Google Scholar
Sotres-Bayon, F, Cain, CK, LeDoux, JE (2006). Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex. Biological Psychiatry 60, 329–336.Google Scholar
Spielberger, CD (1972). Anxiety: Current Trends in Theory and Research, vol. 1. Academic Press: New York, NY.Google Scholar
Spielberger, CD (1979). Understanding Stress and Anxiety. Harper & Row: London.Google Scholar
Spielberger, CD (1983). Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press: Palo Alto, CA.Google Scholar
Straube, T, Weiss, T, Mentzel, HJ, Miltner, WH (2007). Time course of amygdala activation during aversive conditioning depends on attention. NeuroImage 34, 462–469.Google Scholar
Tottenham, N, Borscheid, A, Ellertsen, K, Marcus, DJ, Nelson, CA (2002). Categorization of facial expressions in children and adults: establishing a larger stimulus set. Journal of Cognitive Neuroscience 14 (Suppl.), S74.Google Scholar
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273–289.Google Scholar
Wang, MH, Zhu, YH, Li, JC, Weng, XC (2007). Functional magnetic resonance imaging of whole brain related to motor preparation and execution [in Chinese]. Zhonghua Yi Xue Za Zhi 87, 971–974.Google Scholar
Wittchen, H-U, Wunderlich, U, Gruschwitz, S, Zaudig, M (1997). SCID-I. Structured Clinical Interview for DSM-IV [in German]. Hogrefe: Göttingen.Google Scholar
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