Hostname: page-component-77c89778f8-m42fx Total loading time: 0 Render date: 2024-07-21T10:20:06.425Z Has data issue: false hasContentIssue false
  • English
  • Français

Salience and central executive networks track overgeneralization of conditioned-fear in post-traumatic stress disorder

Published online by Cambridge University Press:  05 May 2020

Hannah Berg Open the ORCID record for Hannah Berg [Opens in a new window] ,
Yizhou Ma Open the ORCID record for Yizhou Ma [Opens in a new window] ,
Amanda Rueter Open the ORCID record for Amanda Rueter [Opens in a new window] ,
Antonia Kaczkurkin Open the ORCID record for Antonia Kaczkurkin [Opens in a new window] ,
Philip C. Burton ,
Colin G. DeYoung Open the ORCID record for Colin G. DeYoung [Opens in a new window] ,
Angus W. MacDonald III Open the ORCID record for Angus W. MacDonald III [Opens in a new window] ,
Scott R. Sponheim  and
Shmuel M. Lissek Open the ORCID record for Shmuel M. Lissek [Opens in a new window]
Hannah Berg
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Yizhou Ma
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Amanda Rueter
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Antonia Kaczkurkin
Affiliation:
Department of Psychological Sciences, Vanderbilt University, Nashville, TN, USA
Philip C. Burton
Affiliation:
Office of the CLA Associate Dean for Research, University of Minnesota, Minneapolis, MN, USA
Colin G. DeYoung
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Angus W. MacDonald III
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Scott R. Sponheim
Affiliation:
Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
Shmuel M. Lissek*
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
*
Author for correspondence: Shmuel M. Lissek, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Generalization of conditioned-fear, a core feature of post-traumatic stress disorder (PTSD), has been the focus of several recent neuroimaging studies. A striking outcome of these studies is the frequency with which neural correlates of generalization fall within hubs of well-established functional networks including salience (SN), central executive (CEN), and default networks (DN). Neural substrates of generalization found to date may thus reflect traces of large-scale brain networks that form more expansive neural representations of generalization. The present study includes the first network-based analysis of generalization and PTSD-related abnormalities therein.

Methods

fMRI responses in established intrinsic connectivity networks (ICNs) representing SN, CEN, and DN were assessed during a generalized conditioned-fear task in male combat veterans (N = 58) with wide-ranging PTSD symptom severity. The task included five rings of graded size. Extreme sizes served as conditioned danger-cues (CS+: paired with shock) and safety-cues (CS−), and the three intermediate sizes served as generalization stimuli (GSs) forming a continuum-of-size between CS+ and CS–. Generalization-gradients were assessed as behavioral and ICN response slopes from CS+, through GSs, to CS–. Increasing PTSD symptomatology was predicted to relate to less-steep slopes indicative of stronger generalization.

Results

SN, CEN, and DN responses fell along generalization-gradients with levels of generalization within and between SN and CEN scaling with PTSD symptom severity.

Conclusions

Neural substrates of generalized conditioned-fear include large-scale networks that adhere to the functional organization of the brain. Current findings implicate levels of generalization in SN and CEN as promising neural markers of PTSD.

Keywords

Central executive networkconditioned-feardefault networkgeneralizationpost-traumatic stress disordersalience network
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 15 , November 2021 , pp. 2610 - 2619
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abram, S. V., Wisner, K. M., Grazioplene, R. G., Krueger, R. F., MacDonald, A. W. III, & DeYoung, C. G. (2015). Functional coherence of insula networks is associated with externalizing behavior. Journal of Abnormal Psychology, 124(4), 1079–1091. doi: 10.1037/abn0000078.CrossRefGoogle ScholarPubMed
Akiki, T. J., Averill, C. L., & Abdallah, C. G. (2017). A network-based neurobiological model of PTSD: Evidence from structural and functional neuroimaging studies. Current Psychiatry Reports, 19(11), 81. doi: 10.1007/s11920-017-0840-4.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: Author.Google Scholar
Andrews-Hanna, J. R., Reidler, J. S., Sepulcre, J., Poulin, R., & Buckner, R. L. (2010). Functional-anatomic fractionation of the brain's default network. Neuron, 65(4), 550–562. doi: 10.1016/j.neuron.2010.02.005.CrossRefGoogle ScholarPubMed
Andrews-Hanna, J. R., Smallwood, J., & Spreng, R. N. (2014). The default network and self-generated thought: Component processes, dynamic control, and clinical relevance. Annals of the New York Academy of Sciences, 1316(1), 29–52. doi: 10.1111/nyas.12360.CrossRefGoogle ScholarPubMed
Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., Gusman, F. D., Charney, D. S., & Keane, T. M. (1995). The development of a Clinician-Administered PTSD Scale. Journal of Traumatic Stress, 8(1), 75–90. doi: 10.1007/BF02105408.CrossRefGoogle ScholarPubMed
Boggio, P. S., Rocha, M., Oliveira, M. O., Fecteau, S., Cohen, R. B., Campanhã, C., … Fregni, F. (2010). Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder. The Journal of Clinical Psychiatry, 71(8), 992–999. doi: 10.4088/JCP.08m04638blu.CrossRefGoogle ScholarPubMed
Brown, V. M., LaBar, K. S., Haswell, C. C., Gold, A. L., Workgroup, M.-A. M., Beall, S. K., … Morey, R. A. (2014). Altered resting-state functional connectivity of basolateral and centromedial amygdala complexes in posttraumatic stress disorder. Neuropsychopharmacology, 39(2), 361–369. doi: 10.1038/npp.2013.197.CrossRefGoogle ScholarPubMed
Cain, C. K., & LeDoux, J. E. (2008). Brain mechanisms of Pavlovian and instrumental aversive conditioning. In Blanchard, R. J., Blanchard, D. C., Griebel, G., & Nutt, D. (Eds.), Handbook of Anxiety and Fear (Vol. 17, pp. 103–124). Handbook of Behavioral Neuroscience.. doi:10.1016/S1569-7339(07)00007-0CrossRefGoogle Scholar
Chand, G. B., & Dhamala, M. (2015). Interactions among the brain default-mode, salience, and central-executive networks during perceptual decision-making of moving dots. Brain Connectivity, 6(3), 249–254. doi: 10.1089/brain.2015.0379.CrossRefGoogle Scholar
Chen, J. E., Glover, G. H., Greicius, M. D., & Chang, C. (2017). Dissociated patterns of anti-correlations with dorsal and ventral default-mode networks at rest. Human Brain Mapping, 38(5), 2454–2465. doi: 10.1002/hbm.23532.CrossRefGoogle ScholarPubMed
Cole, M. W., Repovš, G., & Anticevic, A. (2014). The frontoparietal control system: A central role in mental health. The Neuroscientist, 20(6), 652–664.CrossRefGoogle ScholarPubMed
Craske, M. G., Hermans, D., & Vervliet, B. (2018). State-of-the-art and future directions for extinction as a translational model for fear and anxiety. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 373(1742), 20170025. doi: 10.1098/rstb.2017.0025.CrossRefGoogle ScholarPubMed
Dice, L. R. (1945). Measures of the amount of ecologic association between species. Ecology, 26(3), 297–302. doi: 10.2307/1932409.CrossRefGoogle Scholar
Dunsmoor, J. E., Prince, S. E., Murty, V. P., Kragel, P. A., & LaBar, K. S. (2011). Neurobehavioral mechanisms of human fear generalization. NeuroImage, 55(4), 1878–1888. doi: 10.1016/j.neuroimage.2011.01.041.CrossRefGoogle ScholarPubMed
Eysenck, M. W., Derakshan, N., Santos, R., & Calvo, M. G. (2007). Anxiety and cognitive performance: Attentional control theory. Emotion (Washington, D.C.), 7(2), 336–353. doi: 10.1037/1528-3542.7.2.336.CrossRefGoogle ScholarPubMed
Greenberg, T., Carlson, J. M., Cha, J., Hajcak, G., & Mujica-Parodi, L. R. (2013a). Neural reactivity tracks fear generalization gradients. Biological Psychology, 92(1), 2–8. doi: 10.1016/j.biopsycho.2011.12.007.CrossRefGoogle Scholar
Greenberg, T., Carlson, J. M., Cha, J., Hajcak, G., & Mujica-Parodi, L. R. (2013b). Ventromedial prefrontal cortex reactivity is altered in generalized anxiety disorder during fear generalization. Depression and Anxiety, 30(3), 242–250. doi: 10.1002/da.22016.CrossRefGoogle Scholar
Haber, S. N. (2016). Corticostriatal circuitry. Dialogues in Clinical Neuroscience, 18(1), 7–21.Google ScholarPubMed
Hayes, J. P., Hayes, S. M., & Mikedis, A. M. (2012). Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biology of Mood & Anxiety Disorders, 2, 9. doi: 10.1186/2045-5380-2-9.CrossRefGoogle ScholarPubMed
Heine, L., Soddu, A., Gómez, F., Vanhaudenhuyse, A., Tshibanda, L., Thonnard, M., … Demertzi, A. (2012). Resting state networks and consciousness: Alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness States. Frontiers in Psychology, 3, 295. doi: 10.3389/fpsyg.2012.00295.CrossRefGoogle ScholarPubMed
Henderson, H. A., Pine, D. S., & Fox, N. A. (2015). Behavioral inhibition and developmental risk: A dual-processing perspective. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 40(1), 207–224. doi: 10.1038/npp.2014.189.CrossRefGoogle ScholarPubMed
Hochberg, Y. (1988). A sharper Bonferroni procedure for multiple tests of significance. Biometrika, 75(4), 800–802. doi: 10.1093/biomet/75.4.800.CrossRefGoogle Scholar
Kaczkurkin, A. N., Burton, P. C., Chazin, S. M., Manbeck, A. B., Espensen-Sturges, T., Cooper, S. E., … Lissek, S. (2017). Neural substrates of overgeneralized conditioned fear in PTSD. American Journal of Psychiatry, 174(2), 125–134. doi: 10.1176/appi.ajp.2016.15121549.CrossRefGoogle ScholarPubMed
Kim, S. H., & Hamann, S. (2007). Neural correlates of positive and negative emotion regulation. Journal of Cognitive Neuroscience, 19(5), 776–798. doi: 10.1162/jocn.2007.19.5.776.CrossRefGoogle ScholarPubMed
Kimchi, E. Y., & Laubach, M. (2009). Dynamic encoding of action selection by the medial striatum. Journal of Neuroscience, 29(10), 3148–3159. doi: 10.1523/JNEUROSCI.5206-08.2009.CrossRefGoogle ScholarPubMed
Laird, A. R., Fox, P. M., Eickhoff, S. B., Turner, J. A., Ray, K. L., McKay, D. R., … Fox, P. T. (2011). Behavioral interpretations of intrinsic connectivity networks. Journal of Cognitive Neuroscience, 23(12), 4022–4037. doi: 10.1162/jocn_a_00077.CrossRefGoogle ScholarPubMed
Lange, I., Goossens, L., Michielse, S., Bakker, J., Lissek, S., Papalini, S., … Schruers, K. (2017). Behavioral pattern separation and its link to the neural mechanisms of fear generalization. Social Cognitive and Affective Neuroscience, 12(11), 1720–1729. doi: 10.1093/scan/nsx104.CrossRefGoogle ScholarPubMed
Li, L. M., Violante, I. R., Leech, R., Hampshire, A., Opitz, A., McArthur, D., … Sharp, D. J. (2019). Cognitive enhancement with Salience Network electrical stimulation is influenced by network structural connectivity. NeuroImage, 185, 425–433. doi: 10.1016/j.neuroimage.2018.10.069.CrossRefGoogle ScholarPubMed
Lissek, S., Bradford, D. E., Alvarez, R. P., Burton, P., Espensen-Sturges, T., Reynolds, R. C., & Grillon, C. (2014a). Neural substrates of classically conditioned fear-generalization in humans: A parametric fMRI study. Social Cognitive and Affective Neuroscience, 9(8), 1134–1142. doi: 10.1093/scan/nst096.CrossRefGoogle Scholar
Lissek, S., & Grillon, C. (2012). Learning models of PTSD. In Beck, J. G. & Sloan, D. M. (Eds.), The oxford handbook of traumatic stress disorders. New York: Oxford University Press 10.1093/oxfordhb/9780195399066.013.0013.Google Scholar
Lissek, S., Kaczkurkin, A. N., Rabin, S., Geraci, M., Pine, D. S., & Grillon, C. (2014b). Generalized anxiety disorder is associated with overgeneralization of classically conditioned fear. Biological Psychiatry, 75(11), 909–915. doi: 10.1016/j.biopsych.2013.07.025.CrossRefGoogle Scholar
Lissek, S., Rabin, S., Heller, R. E., Luckenbaugh, D., Geraci, M., Pine, D. S., & Grillon, C. (2010). Overgeneralization of conditioned fear as a pathogenic marker of panic disorder. American Journal of Psychiatry, 167(1), 47–55. doi: 10.1176/appi.ajp.2009.09030410.CrossRefGoogle ScholarPubMed
Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15(10), 483–506. doi: 10.1016/j.tics.2011.08.003.CrossRefGoogle ScholarPubMed
Morawetz, C., Bode, S., Derntl, B., & Heekeren, H. R. (2017). The effect of strategies, goals and stimulus material on the neural mechanisms of emotion regulation: A meta-analysis of fMRI studies. Neuroscience & Biobehavioral Reviews, 72, 111–128. doi: 10.1016/j.neubiorev.2016.11.014.CrossRefGoogle ScholarPubMed
Morey, R. A., Dunsmoor, J. E., Haswell, C. C., Brown, V. M., Vora, A., Weiner, J., … LaBar, K. S. (2015). Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder. Translational Psychiatry, 5, e700. doi: 10.1038/tp.2015.196.CrossRefGoogle ScholarPubMed
Nicholson, A., Rabellino, D., Densmore, M., Frewen, P., Paret, C., Kluetsch, R., … Lanius, R. (2018). Intrinsic connectivity network dynamics in PTSD during amygdala downregulation. Human Brain Mapping, 39. doi: 10.1002/hbm.24244.CrossRefGoogle ScholarPubMed
Onat, S., & Büchel, C. (2015). The neuronal basis of fear generalization in humans. Nature Neuroscience, 18(12), 1811–1818. doi: 10.1038/nn.4166.CrossRefGoogle ScholarPubMed
Pavlov, I. (1927). Conditioned reflexes. New York: Oxford University Press.Google Scholar
Peters, S. K., Dunlop, K., & Downar, J. (2016). Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment. Frontiers in Systems Neuroscience, 10, 104. doi: 10.3389/fnsys.2016.00104.CrossRefGoogle ScholarPubMed
Poppe, A. B., Wisner, K., Atluri, G., Lim, K. O., Kumar, V., & MacDonald, A. W III. (2013). Toward a neurometric foundation for probabilistic independent component analysis of fMRI data. Cognitive, Affective, & Behavioral Neuroscience, 13(3), 641–659. doi: 10.3758/s13415-013-0180-8.CrossRefGoogle Scholar
Rabellino, D., Tursich, M., Frewen, P. A., Daniels, J. K., Densmore, M., Théberge, J., & Lanius, R. A. (2015). Intrinsic connectivity networks in post-traumatic stress disorder during sub- and supraliminal processing of threat-related stimuli. Acta Psychiatrica Scandinavica, 132(5), 365–378. doi: 10.1111/acps.12418.CrossRefGoogle ScholarPubMed
Raichle, M. E. (2015). The brain's default mode network. Annual Review of Neuroscience, 38, 433–447. doi: 10.1146/annurev-neuro-071013-014030.CrossRefGoogle ScholarPubMed
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., … Greicius, M. D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. Journal of Neuroscience, 27(9), 2349–2356. doi: 10.1523/JNEUROSCI.5587-06.2007.CrossRefGoogle ScholarPubMed
Smith, S. M., Fox, P. T., Miller, K. L., Glahn, D. C., Fox, P. M., Mackay, C. E., … Beckmann, C. F. (2009). Correspondence of the brain's functional architecture during activation and rest. Proceedings of the National Academy of Sciences of the United States of America, 106(31), 13040–13045. doi: 10.1073/pnas.0905267106.CrossRefGoogle Scholar
Son, S., Miyata, J., Mori, Y., Isobe, M., Urayama, S., Aso, T., … Takahashi, H. (2017). Lateralization of intrinsic frontoparietal network connectivity and symptoms in schizophrenia. Psychiatry Research: Neuroimaging, 260, 23–28. doi: 10.1016/j.pscychresns.2016.12.007.CrossRefGoogle Scholar
Sripada, R. K., King, A. P., Welsh, R. C., Garfinkel, S. N., Wang, X., Sripada, C. S., & Liberzon, I. (2012). Neural dysregulation in posttraumatic stress disorder: Evidence for disrupted equilibrium between salience and default mode brain networks. Psychosomatic Medicine, 74(9), 904–911. doi: 10.1097/PSY.0b013e318273bf33.CrossRefGoogle ScholarPubMed
Tomasi, D., Chang, L., Caparelli, E. C., & Ernst, T. (2007). Different activation patterns for working memory load and visual attention load. Brain Research, 1132(1), 158–165. doi: 10.1016/j.brainres.2006.11.030.CrossRefGoogle ScholarPubMed
Tuominen, L., Boeke, E., DeCross, S., Wolthusen, R. P. F., Nasr, S., Milad, M., … Holt, D. (2019). The relationship of perceptual discrimination to neural mechanisms of fear generalization. NeuroImage, 188, 445–455. doi: 10.1016/j.neuroimage.2018.12.034.CrossRefGoogle ScholarPubMed
Uddin, L. Q. (2015). Salience processing and insular cortical function and dysfunction. Nature Reviews Neuroscience, 16(1), 55–61. doi: 10.1038/nrn3857.CrossRefGoogle ScholarPubMed
Vincent, J. L., Snyder, A. Z., Fox, M. D., Shannon, B. J., Andrews, J. R., Raichle, M. E., & Buckner, R. L. (2006). Coherent spontaneous activity identifies a hippocampal-parietal memory network. Journal of Neurophysiology, 96(6), 3517–3531. doi: 10.1152/jn.00048.2006.CrossRefGoogle ScholarPubMed
Wang, D., Buckner, R. L., & Liu, H. (2014). Functional specialization in the human brain estimated by intrinsic hemispheric interaction. Journal of Neuroscience, 34(37), 12341–12352. doi: 10.1523/JNEUROSCI.0787-14.2014.CrossRefGoogle ScholarPubMed
Weathers, F. W., Keane, T. M., & Davidson, J. R. T. (2001). Clinician-administered PTSD scale: A review of the first ten years of research. Depression and Anxiety, 13(3), 132–156. doi: 10.1002/da.1029.CrossRefGoogle ScholarPubMed
Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., … Buckner, R. L. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106(3), 1125–1165. doi: 10.1152/jn.00338.2011.Google ScholarPubMed
Supplementary material: File

Berg et al. supplementary material

Berg et al. supplementary material

Download Berg et al. supplementary material(File)
File 305.5 KB