Amygdala–prefrontal connectivity during appraisal of symptom-related stimuli in obsessive–compulsive disorder
Open accessAbstract
Background: Cognitive models of obsessive–compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala–prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala–prefrontal connections. However, abnormalities in amygdala–prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly. Methods: Amygdala–prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples. Results: During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala–ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest. Conclusions: Our finding of abnormal amygdala–prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala–prefrontal coupling in affective models of OCD.
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Neuroimaging studies have reported increased amygdala activity, reduced dorsal prefrontal activity, and reduced prefrontal-amygdala functional connectivity during provocation and cognitive reappraisal of OCD-provoking stimuli.
“Consistent with these clinical observations, neuroimaging studies have reported increased amygdala activity, reduced dorsal prefrontal activity and reduced prefrontal-amygdala functional connectivity during the provocation and cognitive reappraisal of stimuli that provoke OCD symptoms and increase physiological arousal [36, 39].”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [39]
ERP appears to be mediated at least partly by modulation of amygdala-vmPFC connectivity, while cognitive reappraisal dampens fronto-limbic activity through top-down dorsal prefrontal regions.
“ERP seems to be mediated, at least in part, by modulation of amygdala-vmPFC connectivity, while cognitive reappraisal appears to dampen fronto-limbic activity via the engagement of top-down dorsal prefrontal regions [35–36, 39, 51].”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [39]
Difficulties recruiting dorsal prefrontal regions during cognitive reappraisal of OCD-provoking stimuli may contribute to persistent fear-related symptoms.
“difficulties recruiting dorsal prefrontal regions for efficient emotion regulation has been reported during cognitive reappraisal of OCD-provoking stimuli in OCD [39, 60] and may contribute to the persistence of fear-related obsessive-compulsive symptoms.”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [39]
The cognitive reappraisal component of CBT engages dorsal prefrontal regions.
“The cognitive reappraisal component of CBT (Table 3) trains patients to change their thoughts and emotional responses to OCD symptoms and is known to engage dorsal prefrontal regions [35–36, 39, 51].”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [39]
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- Authors
- Paul, S., Beucke, J. C., Kaufmann, C., Mersov, A., Heinzel, S., Kathmann, N., & Simon, D.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- University of Toronto (CA)
- Corresponding author
- Paul, Sandra
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2018-04-06
- Volume
- 49
- Issue
- 2
- Pages
- 278-286
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2796432381
- Cited by
- 33
- References
- 40
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 6 · 2018: 1
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- edoc Publication server (Humboldt University of Berlin) (submittedVersion)
- edoc Publication server (Humboldt University of Berlin)
- Funders
- Deutsche Forschungsgemeinschaft (SI 1131/2-3, 01GW0724, SI 1131/2-1)
- Bundesministerium für Bildung und Forschung (01GW0724, BMBF-01GW0724)
- National Institutes of Health (1s10rr023043-01)
- National Center for Research Resources (S10-RR-023043, S10RR023401)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- obsessive-compulsive disorder, amygdala-prefrontal connectivity, orbitofrontal cortex, ventromedial prefrontal cortex, symptom provocation, affective circuits, fear extinction, emotion regulation, resting-state functional connectivity
- MeSH terms
- Emotional Regulation, Adult, Amygdala, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Obsessive-Compulsive Disorder, Pattern Recognition, Visual, Case-Control Studies, Prefrontal Cortex, Connectome
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