Association of Resting Metabolism in the Fear Neural Network With Extinction Recall Activations and Clinical Measures in Trauma-Exposed Individuals
Open accessAbstract
OBJECTIVE: Exposure-based therapy, an effective treatment for posttraumatic stress disorder (PTSD), relies on extinction learning principles. In PTSD patients, dysfunctional patterns in the neural circuitry underlying fear extinction have been observed using resting-state or functional activation measures. It remains undetermined whether resting activity predicts activations during extinction recall or PTSD symptom severity. Moreover, it remains unclear whether trauma exposure per se affects resting activity in this circuitry. The authors employed a multimodal approach to examine the relationships among resting metabolism, clinical symptoms, and activations during extinction recall. METHOD: Three cohorts were recruited: PTSD patients (N=24), trauma-exposed individuals with no PTSD (TENP) (N=20), and trauma-unexposed healthy comparison subjects (N=21). Participants underwent a resting positron emission tomography scan 4 days before a functional MRI fear conditioning and extinction paradigm. RESULTS: Amygdala resting metabolism negatively correlated with clinical functioning (as measured by the Global Assessment of Functioning Scale) in the TENP group, and hippocampal resting metabolism negatively correlated with clinical functioning in the PTSD group. In the PTSD group, dorsal anterior cingulate cortex (dACC) resting metabolism positively correlated with PTSD symptom severity, and it predicted increased dACC activations but decreased hippocampal and ventromedial prefrontal cortex activations during extinction recall. The TENP group had lower amygdala resting metabolism compared with the PTSD and healthy comparison groups, and it exhibited lower hippocampus resting metabolism relative to the healthy comparison group. CONCLUSIONS: Resting metabolism in the fear circuitry correlated with functioning, PTSD symptoms, and extinction recall activations, further supporting the relevance of this network to the pathophysiology of PTSD. The study findings also highlight the fact that chronic dysfunction in the amygdala and hippocampus is demonstrable in PTSD and other trauma-exposed individuals, even without exposure to an evocative stimulus.
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These findings are consistent with some of the findings of Milad et al. related to impaired extinction recall.
“These findings are consistent with some of the findings of Milad et al. [164–166] related to impaired extinction recall, discussed in the next section.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [164]
The dACC appears to be associated with more PTSD symptoms at rest.
“The dACC also appears to be associated with more PTSD symptoms at rest. Marin et al. [164] found that dACC resting activity positively correlated with PTSD symptom severity and predicted increased dACC activations during extinction recall.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [164]
Marin et al. found that dACC resting activity positively correlated with PTSD symptom severity and predicted increased dACC activations during extinction recall.
“Marin et al. [164] found that dACC resting activity positively correlated with PTSD symptom severity and predicted increased dACC activations during extinction recall.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [164]
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- Authors
- Marin, M.-F., Song, H., VanElzakker, M. B., Staples-Bradley, L. K., Linnman, C., Pace-Schott, E. F., Lasko, N. B., Shin, L. M., & Milad, M. R.
- Affiliations
- Tufts University (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2016-09-01
- Volume
- 173
- Issue
- 9
- Pages
- 930-938
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC13035175
- OpenAlex
- W2283929383
- Cited by
- 74
- References
- 13
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 8 · 2018: 9 · 2017: 9 · 2016: 2
- FWCI
- 12.49
- Type
- journal article
- Language
- en
- Open access
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh081975-05)
- National Institute of Mental Health (R01-MH081975)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- post-traumatic stress disorder, fear extinction, resting metabolism, amygdala, hippocampus, dorsal anterior cingulate cortex, ventromedial prefrontal cortex, fear circuitry, trauma exposure, PTSD symptom severity, extinction recall, fear conditioning, functional connectivity
- MeSH terms
- Adult, Amygdala, Arousal, Basal Metabolism, Blood Glucose, Brain Mapping, Conditioning, Classical, Extinction, Psychological, Fear, Female, Galvanic Skin Response, Gyrus Cinguli, Hippocampus, Humans, Implosive Therapy, Magnetic Resonance Imaging, Male, Nerve Net, Mental Recall, Statistics as Topic, Stress Disorders, Post-Traumatic, Cohort Studies, Prefrontal Cortex, Positron-Emission Tomography, Young Adult
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