Neural Signatures of Conditioning, Extinction Learning, and Extinction Recall in Posttraumatic Stress Disorder: a Meta-analysis of Functional Magnetic Resonance Imaging Studies

Overview

Journal Psychol Med

Publisher Cambridge University Press

Specialty Psychology

Date 2019 Jul 2

PMID 31258096

Citations 39

Authors

Benjamin Suarez-Jimenez

Anton Albajes-Eizagirre

Amit Lazarov

Xi Zhu

Ben J Harrison

Joaquim Radua

Yuval Neria

Miquel A Fullana

Affiliations

Soon will be listed here.

Abstract

Background: Establishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers.

Methods: Here, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-based d-mapping, to contrast neural correlates of experimental phases, namely conditioning, extinction learning, and extinction recall.

Results: Patients with PTSD, as compared to TEHCs, exhibited increased activation in the anterior hippocampus (extending to the amygdala) and medial prefrontal cortex during conditioning; in the anterior hippocampus-amygdala regions during extinction learning; and in the anterior hippocampus-amygdala and medial prefrontal areas during extinction recall. Yet, patients with PTSD have shown an overall decreased activation in the thalamus during all phases in this meta-analysis.

Conclusion: Findings from this metanalysis suggest that PTSD is characterized by increased activation in areas related to salience and threat, and lower activation in the thalamus, a key relay hub between subcortical areas. If replicated, these fear network alterations may serve as objective diagnostic markers for PTSD, and potential targets for novel treatment development, including pharmacological and brain stimulation interventions. Future longitudinal studies are needed to examine whether these observed network alteration in PTSD are the cause or the consequence of PTSD.

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References

Corcoran K, Quirk G . Recalling safety: cooperative functions of the ventromedial prefrontal cortex and the hippocampus in extinction. CNS Spectr. 2007; 12(3):200-6. DOI: 10.1017/s1092852900020915. View

Shvil E, Rusch H, Sullivan G, Neria Y . Neural, psychophysiological, and behavioral markers of fear processing in PTSD: a review of the literature. Curr Psychiatry Rep. 2013; 15(5):358. PMC: 3674105. DOI: 10.1007/s11920-013-0358-3. View

Gottfried J, Dolan R . Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value. Nat Neurosci. 2004; 7(10):1144-52. DOI: 10.1038/nn1314. View

Steiger F, Nees F, Wicking M, Lang S, Flor H . Behavioral and central correlates of contextual fear learning and contextual modulation of cued fear in posttraumatic stress disorder. Int J Psychophysiol. 2015; 98(3 Pt 2):584-93. DOI: 10.1016/j.ijpsycho.2015.06.009. View

Douglas Bremner J, Vermetten E, Schmahl C, Vaccarino V, Vythilingam M, Afzal N . 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. Psychol Med. 2005; 35(6):791-806. PMC: 3233760. DOI: 10.1017/s0033291704003290. View

Liberzon I, Abelson J . Context Processing and the Neurobiology of Post-Traumatic Stress Disorder. Neuron. 2016; 92(1):14-30. PMC: 5113735. DOI: 10.1016/j.neuron.2016.09.039. View

Lonsdorf T, Menz M, Andreatta M, Fullana M, Golkar A, Haaker J . Don't fear 'fear conditioning': Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear. Neurosci Biobehav Rev. 2017; 77:247-285. DOI: 10.1016/j.neubiorev.2017.02.026. View

Mechias M, Etkin A, Kalisch R . A meta-analysis of instructed fear studies: implications for conscious appraisal of threat. Neuroimage. 2009; 49(2):1760-8. DOI: 10.1016/j.neuroimage.2009.09.040. View

Harrison B, Fullana M, Via E, Soriano-Mas C, Vervliet B, Martinez-Zalacain I . Human ventromedial prefrontal cortex and the positive affective processing of safety signals. Neuroimage. 2017; 152:12-18. DOI: 10.1016/j.neuroimage.2017.02.080. View

10.

Wager T, Lindquist M, Kaplan L . Meta-analysis of functional neuroimaging data: current and future directions. Soc Cogn Affect Neurosci. 2008; 2(2):150-8. PMC: 2555451. DOI: 10.1093/scan/nsm015. View

11.

Fullana M, Harrison B, Soriano-Mas C, Vervliet B, Cardoner N, Avila-Parcet A . Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies. Mol Psychiatry. 2015; 21(4):500-8. DOI: 10.1038/mp.2015.88. View

12.

Laird A, Eickhoff S, Kurth F, Fox P, Uecker A, Turner J . ALE Meta-Analysis Workflows Via the Brainmap Database: Progress Towards A Probabilistic Functional Brain Atlas. Front Neuroinform. 2009; 3:23. PMC: 2715269. DOI: 10.3389/neuro.11.023.2009. View

13.

Suarez-Jimenez B, Bisby J, Horner A, King J, Pine D, Burgess N . Linked networks for learning and expressing location-specific threat. Proc Natl Acad Sci U S A. 2018; 115(5):E1032-E1040. PMC: 5798349. DOI: 10.1073/pnas.1714691115. View

14.

Liberzon I, Sripada C . The functional neuroanatomy of PTSD: a critical review. Prog Brain Res. 2007; 167:151-69. DOI: 10.1016/S0079-6123(07)67011-3. View

15.

Sehlmeyer C, Schoning S, Zwitserlood P, Pfleiderer B, Kircher T, Arolt V . Human fear conditioning and extinction in neuroimaging: a systematic review. PLoS One. 2009; 4(6):e5865. PMC: 2692002. DOI: 10.1371/journal.pone.0005865. View

16.

Muller V, Cieslik E, Laird A, Fox P, Radua J, Mataix-Cols D . Ten simple rules for neuroimaging meta-analysis. Neurosci Biobehav Rev. 2017; 84:151-161. PMC: 5918306. DOI: 10.1016/j.neubiorev.2017.11.012. View

17.

Schiller D, Levy I, Niv Y, LeDoux J, Phelps E . From fear to safety and back: reversal of fear in the human brain. J Neurosci. 2008; 28(45):11517-25. PMC: 3844784. DOI: 10.1523/JNEUROSCI.2265-08.2008. View

18.

Phillips R, LeDoux J . Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci. 1992; 106(2):274-85. DOI: 10.1037//0735-7044.106.2.274. View

19.

Phan K, Fitzgerald D, Nathan P, Moore G, Uhde T, Tancer M . Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study. Biol Psychiatry. 2005; 57(3):210-9. DOI: 10.1016/j.biopsych.2004.10.030. View

20.

Kalin N, Shelton S, Davidson R . The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. J Neurosci. 2004; 24(24):5506-15. PMC: 6729317. DOI: 10.1523/JNEUROSCI.0292-04.2004. View