Reward Versus Nonreward Sensitivity of the Medial Versus Lateral Orbitofrontal Cortex Relates to the Severity of Depressive Symptoms
Open accessAbstract
BACKGROUND: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. METHODS: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. RESULTS: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). CONCLUSIONS: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.
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At age 19, blunted reward-related central OFC activation correlated with more anhedonic symptoms, whereas potentiated non-reward lateral OFC activation correlated with sadness.
“Moreover, at age 19, blunted reward-related central OFC activation correlated with more anhedonic symptoms, whereas potentiated non-reward lateral OFC activation correlated with sadness.”
From Prefrontal cortex and depression (2022) · cites this paper as [114]
The age-19 association analyses report that lateral OFC activation correlated with symptoms including feeling overwhelmed by sadness, while medial OFC activation had a nominally significant negative association with anhedonia. The discussion likewise links reduced medial OFC reward sensitivity to anhedonia and increased lateral OFC nonreward sensitivity to negative feelings. The claim calls the reward-related region “central” rather than medial OFC and omits the nominal significance qualifier for the anhedonia association. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn the IMAGEN study, during reward anticipation, individuals with higher depression severity had reduced sensitivity to differing reward values in central OFC (areas 11 and 13) but higher lateral OFC (area 12) activation to non-rewards at both age 14 and 19.
“In the IMAGEN study (N = 1877 at age 14, N = 1140 at age 19), during reward anticipation, individuals with higher depression severity had reduced sensitivity to differing reward values in the central regions of OFC (areas 11 and 13) but higher lateral OFC (area 12) activation to non-rewards (no-win outcome) at both age 14 and 19 (Fig. 5) [114]”
From Prefrontal cortex and depression (2022) · cites this paper as [114]
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Experimental — accuracy not yet measuredDepressive symptoms at ages 16 and 19 could be predicted by potentiated lateral OFC activation to nonrewards, but not central OFC activation to rewards, at age 14.
“Critically, depressive symptoms at ages 16 and 19 could be predicted by potentiated lateral OFC activation to nonrewards, but not central OFC activation to rewards, at age 14.”
From Prefrontal cortex and depression (2022) · cites this paper as [114]
The Longitudinal Approach section reports that lateral OFC activation to no win versus large win at age 14 was associated with depressive symptom scores at ages 16 and 19. It also reports that medial OFC activation at age 14 did not predict scores at either age. The claim says “central OFC,” whereas the paper identifies this reward-responsive region as medial OFC; it does not establish that the two labels refer to the same region. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIndividuals with elevated depression severity have reduced sensitivity to differing reward values in the central orbitofrontal cortex during reward anticipation compared to controls.
“Central orbitofrontal cortex (see green) and lateral orbitofrontal cortex (see red) region in which individuals with elevated depression severity (see squares) had reduced sensitivity to differing reward values and potentiated activation to non-rewards (no-win outcome) during reward anticipation compared to the control group (see circles) [114].”
From Prefrontal cortex and depression (2022) · cites this paper as [114]
The age-14 and age-19 subgroup Results report reduced sensitivity to reward magnitude during anticipation in adolescents with high depressive-symptom severity compared with controls. The paper identifies the affected region as the medial orbitofrontal cortex, not the central orbitofrontal cortex named in the claim. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIndividuals with elevated depression severity have potentiated activation to non-rewards (no-win outcome) in the lateral orbitofrontal cortex during reward anticipation compared to controls.
“potentiated activation to non-rewards (no-win outcome) during reward anticipation compared to the control group (see circles) [114].”
From Prefrontal cortex and depression (2022) · cites this paper as [114]
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Cites
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Cited by
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Prefrontal cortex and depression
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- Authors
- Xie, C., Jia, T., Rolls, E. T., Robbins, T. W., Sahakian, B. J., Zhang, J., Liu, Z., Cheng, W., Luo, Q., Zac Lo, C.-Y., Wang, H., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Büchel, C., Quinlan, E. B., Desrivières, S., Flor, H., Grigis, A., Garavan, H., Gowland, P., Heinz, A., Hohmann, S., Ittermann, B., Martinot, J.-L., Paillère Martinot, M.-L., Nees, F., Orfanos, D. P., Paus, T., Poustka, L., Fröhner, J. H., Smolka, M. N., Walter, H., Whelan, R., Schumann, G., Feng, J., Artiges, E., Aydin, S., Banaschewski, T., Barbot, A., Barker, G., Becker, A., Bezivin-Frere, P., Biondo, F., Bokde, A., Büchel, C., Chu, C., Conrod, P., Daedelow, L., Dalley, J., Desrivieres, S., Dooley, E., Filippi, I., Fillmer, A., Flor, H., Fröhner, J., Frouin, V., Garavan, H., Gowland, P., Grimmer, Y., Heinz, A., Hohmann, S., Ihlenfeld, A., Ing, A., Isensee, C., Ittermann, B., Jia, T., Lemaitre, H., Lethbridge, E., Martinot, J.-L., Millenet, S., Miller, S., Miranda, R., Nees, F., Paillere, M.-L., Papadopoulos, D., Paus, T., Pausova, Z., Pentilla, J., Poline, J.-B., Poustka, L., Burke, E., Rapp, M., Robbins, T., Robert, G., Rogers, J., Ruggeri, B., Schumann, G., Smolka, M., Stringaris, A., van Noort, B., Walter, H., Whelan, R., Simon, R., Williams, S., & Zhang, Y.
- Affiliations
- University of Warwick (GB)
- University of Cambridge (GB)
- Massachusetts General Hospital (US)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Fudan University (CN)
- ORCID
- Xie, Chao
- Rolls, Edmund T.
- Robbins, Trevor W.
- Sahakian, Barbara J.
- Zhang, Jie
- Cheng, Wei
- Luo, Qiang
- Quinlan, Erin Burke
- Grigis, Antoine
- Smolka, Michael N.
- Feng, Jianfeng
- Becker, Andreas
- Biondo, Francesca
- Chu, Congying
- Conrod, Patricia
- Daedelow, Laura
- Dalley, Jeffrey
- Filippi, Irina
- Fillmer, Ariane
- Frouin, Vincent
- Grimmer, Yvonne
- Ing, Alex
- Millenet, Sabina
- Miller, Sarah
- Poline, Jean-Baptiste
- Rapp, Michael
- Ruggeri, Barbara
- Stringaris, Argyris
- Zhang, Yuning
- Venue
- Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 6
- Issue
- 3
- Pages
- 259-269
- ISSN
- 2451-9022 (ISSN-L)
- OpenAlex
- W3086739795
- Cited by
- 64
- References
- 7
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 19 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 2
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biological Psychiatry Cognitive Neuroscience and Neuroimaging (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, other-oa)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by-nc-nd)
- Warwick Research Archive Portal (University of Warwick) (submittedVersion)
- HAL (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- publish.UP (University of Potsdam) (submittedVersion, cc-by-nc-nd)
- publish.UP (University of Potsdam) (submittedVersion)
- Universität Potsdam
- Funders
- Science Foundation Ireland (16/ERCD/3797)
- Agence Nationale de la Recherche (AF12-NEUR0008-01\u2013WM2NA, ANR-12-SAMA-0004)
- Horizon 2020 (695313)
- National Key Research and Development Program of China (2019YFA0709502, 2018YFC1312900)
- Higher Education Discipline Innovation Project (B18015)
- King’s College London
- Seventh Framework Programme
- Institut National de la Santé et de la Recherche Médicale
- Svenska Forskningsrådet Formas
- Sixth Framework Programme (LSHM-CT- 2007-037286)
- EU Joint Programme – Neurodegenerative Disease Research (MR/N027558/1)
- Medical Research Council (MR/N000390/1)
- National Institute for Health and Care Research
- National Institutes of Health (RO1 MH085772-01A1, U54 EB020403)
- European Commission
- South London and Maudsley NHS Foundation Trust
- Université Paris-Sud
- National Natural Science Foundation of China (81801773, 81873909, 91630314)
- Fondation pour la Recherche Médicale
- Fudan University
- Fondation de France
- Deutsche Forschungsgemeinschaft (SM 80/7-2, SFB 940/2)
- Xi'an Eurasia University
- Science and Technology Commission of Shanghai Municipality (2018SHZDZX01)
- Innovative Medicines Initiative (115300-2)
- Chongqing University of Science and Technology
- Bundesministerium für Bildung und Forschung (01EV0711, 01EE1406B, AERIAL 01EE1406A, 01GS08152)
- King's College London
- European Research Council
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- orbitofrontal cortex, medial orbitofrontal cortex, lateral orbitofrontal cortex, reward sensitivity, depressive symptoms, depression, monetary incentive delay task, adolescent brain development, IMAGEN cohort
- MeSH terms
- Adolescent, Adult, Depression, Frontal Lobe, Humans, Magnetic Resonance Imaging, Reward, Prefrontal Cortex, Young Adult
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