When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm
The relevance of contextual factors in shaping neural mechanisms underlying visceral pain-related fear learning remains elusive. However, benign interoceptive sensations, which shape patients’ clinical reality, may context-dependently become conditioned predictors of impending visceral pain. In a no...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811921005061 |
| _version_ | 1818456175517106176 |
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| author | Adriane Icenhour Liubov Petrakova Nelly Hazzan Nina Theysohn Christian J. Merz Sigrid Elsenbruch |
| author_facet | Adriane Icenhour Liubov Petrakova Nelly Hazzan Nina Theysohn Christian J. Merz Sigrid Elsenbruch |
| author_sort | Adriane Icenhour |
| collection | DOAJ |
| description | The relevance of contextual factors in shaping neural mechanisms underlying visceral pain-related fear learning remains elusive. However, benign interoceptive sensations, which shape patients’ clinical reality, may context-dependently become conditioned predictors of impending visceral pain. In a novel context-dependent interoceptive conditioning paradigm, we elucidated the putative role of the central fear network in the acquisition and extinction of pain-related fear induced by interoceptive cues and pain-predictive contexts.In this fMRI study involving rectal distensions as a clinically-relevant model of visceroception, N = 27 healthy men and women underwent differential conditioning. During acquisition training, visceral sensations of low intensity as conditioned stimuli (CS) predicted visceral pain as unconditioned stimulus (US) in one context (Con+), or safety from pain in another context (Con–). During extinction training, interoceptive CS remained unpaired in both contexts, which were operationalized as images of different rooms presented in the MRI scanner.Successful contextual conditioning was supported by increased negative valence of Con+ compared to Con– after acquisition training, which resolved after extinction training. Although interoceptive CS were perceived as comparatively pleasant, they induced significantly greater neural activation of the amygdala, ventromedial PFC, and hippocampus when presented in Con+, while contexts alone did not elicit differential responses. During extinction training, a shift from CS to context differentiation was observed, with enhanced responses in the amygdala, ventromedial, and ventrolateral PFC to Con+ relative to Con–, whereas no CS-induced differential activation emerged.Context-dependent interoceptive conditioning can turn benign interoceptive cues into predictors of visceral pain that recruit key regions of the fear network. This first evidence expands knowledge about learning and memory mechanisms underlying interoceptive hypervigilance and maladaptive avoidance behavior, with implications for disorders of the gut-brain axis. |
| first_indexed | 2024-12-14T22:22:30Z |
| format | Article |
| id | doaj.art-ce42d0e224084844a5dd0eb390c3b260 |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-12-14T22:22:30Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-ce42d0e224084844a5dd0eb390c3b2602022-12-21T22:45:28ZengElsevierNeuroImage1095-95722021-09-01238118229When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigmAdriane Icenhour0Liubov Petrakova1Nelly Hazzan2Nina Theysohn3Christian J. Merz4Sigrid Elsenbruch5Department of Neurology, University Hospital Essen, Hufelandstr. 55, Essen 45147, Germany; Corresponding author.Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Universitaetsstr. 150, Bochum 44801 GermanyDepartment of Neurology, University Hospital Essen, Hufelandstr. 55, Essen 45147, GermanyInstitute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, GermanyInstitute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr University Bochum, Universitaetsstr. 150, Bochum 44801, GermanyDepartment of Neurology, University Hospital Essen, Hufelandstr. 55, Essen 45147, Germany; Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Universitaetsstr. 150, Bochum 44801 GermanyThe relevance of contextual factors in shaping neural mechanisms underlying visceral pain-related fear learning remains elusive. However, benign interoceptive sensations, which shape patients’ clinical reality, may context-dependently become conditioned predictors of impending visceral pain. In a novel context-dependent interoceptive conditioning paradigm, we elucidated the putative role of the central fear network in the acquisition and extinction of pain-related fear induced by interoceptive cues and pain-predictive contexts.In this fMRI study involving rectal distensions as a clinically-relevant model of visceroception, N = 27 healthy men and women underwent differential conditioning. During acquisition training, visceral sensations of low intensity as conditioned stimuli (CS) predicted visceral pain as unconditioned stimulus (US) in one context (Con+), or safety from pain in another context (Con–). During extinction training, interoceptive CS remained unpaired in both contexts, which were operationalized as images of different rooms presented in the MRI scanner.Successful contextual conditioning was supported by increased negative valence of Con+ compared to Con– after acquisition training, which resolved after extinction training. Although interoceptive CS were perceived as comparatively pleasant, they induced significantly greater neural activation of the amygdala, ventromedial PFC, and hippocampus when presented in Con+, while contexts alone did not elicit differential responses. During extinction training, a shift from CS to context differentiation was observed, with enhanced responses in the amygdala, ventromedial, and ventrolateral PFC to Con+ relative to Con–, whereas no CS-induced differential activation emerged.Context-dependent interoceptive conditioning can turn benign interoceptive cues into predictors of visceral pain that recruit key regions of the fear network. This first evidence expands knowledge about learning and memory mechanisms underlying interoceptive hypervigilance and maladaptive avoidance behavior, with implications for disorders of the gut-brain axis.http://www.sciencedirect.com/science/article/pii/S1053811921005061Interoceptive associative learningExtinctionPain-related fearVisceral painfMRIContextual conditioning |
| spellingShingle | Adriane Icenhour Liubov Petrakova Nelly Hazzan Nina Theysohn Christian J. Merz Sigrid Elsenbruch When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm NeuroImage Interoceptive associative learning Extinction Pain-related fear Visceral pain fMRI Contextual conditioning |
| title | When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm |
| title_full | When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm |
| title_fullStr | When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm |
| title_full_unstemmed | When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm |
| title_short | When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm |
| title_sort | when gut feelings teach the brain to fear pain context dependent activation of the central fear network in a novel interoceptive conditioning paradigm |
| topic | Interoceptive associative learning Extinction Pain-related fear Visceral pain fMRI Contextual conditioning |
| url | http://www.sciencedirect.com/science/article/pii/S1053811921005061 |
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