Anhedonia and general distress show dissociable ventromedial prefrontal cortex connectivity in major depressive disorder
Open accessAbstract
Anhedonia, the reduced ability to experience pleasure in response to otherwise rewarding stimuli, is a core symptom of major depressive disorder (MDD). Although the posterior ventromedial prefrontal cortex (pVMPFC) and its functional connections have been consistently implicated in MDD, their roles in anhedonia remain poorly understood. Furthermore, it is unknown whether anhedonia is primarily associated with intrinsic 'resting-state' pVMPFC functional connectivity or an inability to modulate connectivity in a context-specific manner. To address these gaps, a pVMPFC region of interest was first identified using activation likelihood estimation meta-analysis. pVMPFC connectivity was then examined in relation to anhedonia and general distress symptoms of depression, using both resting-state and task-based functional magnetic resonance imaging involving pleasant music, in current MDD and healthy control groups. In MDD, pVMPFC connectivity was negatively correlated with anhedonia but not general distress during music listening in key reward- and emotion-processing regions, including nucleus accumbens, ventral tegmental area/substantia nigra, orbitofrontal cortex and insula, as well as fronto-temporal regions involved in tracking complex sound sequences, including middle temporal gyrus and inferior frontal gyrus. No such dissociations were observed in the healthy controls, and resting-state pVMPFC connectivity did not dissociate anhedonia from general distress in either group. Our findings demonstrate that anhedonia in MDD is associated with context-specific deficits in pVMPFC connectivity with the mesolimbic reward system when encountering pleasurable stimuli, rather than a static deficit in intrinsic resting-state connectivity. Critically, identification of functional circuits associated with anhedonia better characterizes MDD heterogeneity and may help track of one of its core symptoms.
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A study using music listening vs scrambled stimuli as a reward paradigm found a negative correlation between anhedonia and functional connectivity of the posterior vmPFC (seed region) with the NAc, VTA/substantia nigra, left OFC, and right insula.
“A study using music listening vs scrambled stimuli as reward paradigm found a negative correlation between anhedonia and functional connectivity of the posterior vmPFC (seed region) and the NAc, VTA/substantia nigra, OFC (left), and insula (right) (Young et al., 2016).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Young et al., 2016
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Functional brain abnormalities in major depressive disorder using the Hilbert-Huang transform
Yu, H., Li, F., Wu, T., Li, R., Yao, L., Wang, C., & Wu, X. (2018) · Brain Imaging and Behavior · doi:10.1007/s11682-017-9816-6 · Cited by 17 · see citing works
Zheng, W., Gu, L.-M., Zhou, Y.-L., Wang, C.-Y., Lan, X.-F., Zhang, B., Shi, H.-S., Wang, D.-F., & Ning, Y.-P. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.780975 · Cited by 12 · see citing works
- Authors
- Young, C. B., Chen, T., Nusslock, R., Keller, J., Schatzberg, A. F., & Menon, V
- Affiliations
- Northwestern University (US)
- Stanford Medicine (US)
- Corresponding author
- Young, C B
- Menon, V
- Venue
- Translational Psychiatry
- Published
- 2016-05-17
- Volume
- 6
- Issue
- 5
- Pages
- e810-e810
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC5070048
- OpenAlex
- W2403484840
- Cited by
- 108
- References
- 91
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 9 · 2023: 13 · 2022: 14 · 2021: 15 · 2020: 6 · 2019: 13 · 2018: 10 · 2017: 3
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0824162)
- J.B. and M.K. Pritzker Family Foundation
- National Alliance for Research on Schizophrenia and Depression
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- anhedonia, major depressive disorder, ventromedial prefrontal cortex, resting-state functional connectivity, task-based functional connectivity, mesolimbic reward system, nucleus accumbens, ventral tegmental area, substantia nigra, orbitofrontal cortex, insula, music listening, reward processing, depression heterogeneity
- MeSH terms
- Adult, Brain, Cerebral Cortex, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Nucleus Accumbens, Reward, Stress, Psychological, Substantia Nigra, Temporal Lobe, Case-Control Studies, Prefrontal Cortex, Ventral Tegmental Area, Anhedonia, Functional Neuroimaging
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