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Neural systems underlying approach and avoidance in anxiety disorders
Open accessAbstract
Approach-avoidance conflict is an important psychological concept that has been used extensively to better understand cognition and emotion. This review focuses on neural systems involved in approach, avoidance, and conflict decision making, and how these systems overlap with implicated neural substrates of anxiety disorders. In particular, the role of amygdala, insula, ventral striatal, and prefrontal regions are discussed with respect to approach and avoidance behaviors. Three specific hypotheses underlying the dysfunction in anxiety disorders are proposed, including: (i) over-representation of avoidance valuation related to limbic overactivation; (ii) under- or over-representation of approach valuation related to attenuated or exaggerated striatal activation respectively; and (iii) insufficient integration and arbitration of approach and avoidance valuations related to attenuated orbitofrontal cortex activation. These dysfunctions can be examined experimentally using versions of existing decision-making paradigms, but may also require new translational and innovative approaches to probe approach-avoidance conflict and related neural systems in anxiety disorders.
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“The PFC likely regulates play in a multifactorial manner, contributing to expression of the behavior through its roles in suppressing aggression, monitoring approach/avoid conflict, and modulating the stress response via its projections to the MeA and other stress-modulatory nodes (Aupperle & Paulus, 2010; McEwen & Morrison, 2013; Takahashi et al., 2014).”
From Developmental origins of sex differences in the neural circuitry of play (2020) · cites this paper as Aupperle & Paulus, 2010
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“For example, anxiety disorders and mood disorders share hyperactive amygdala responses to negatively valenced stimuli [2,3]”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [2]
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InfluentialWalker, E. A., Aupperle, R., Paulus, M., & Ironside, M. (2022) · Current Psychology · doi:10.1007/s12144-022-03448-6 · Cited by 5
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“…(vmPFC) — regions that show altered functioning and connectivity in anxiety disorders (e.g., Klumpp et al., 2012; McClure et al., 2007; Monk et al., 2008; Prater et al., 2013; Stein et al., 2007; Thomas et al., 2001) — play key roles in avoidance behavior (Aupperle and Martin, 2010; Martin, 2022).”
Social Effort Discounting Reveals Domain-General and Social-Specific Motivation Components
Savage, C., Prettyman, G. E., Jenkins, A. C., Kable, J. W., Didier, P. R., Leme, L. F. V. D. M., & Wolf, D. H. (2024) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2024.07.020 · Cited by 2
The Organization of Anxiety Symptoms Along the Threat Imminence Continuum
Somerville, Y., & Abend, R. (2024) · Current topics in behavioral neurosciences · doi:10.1007/7854_2024_548 · Cited by 4
Hunt, C., Caudle, M. M., Paulus, M. P., Stein, M. B., Taylor, C. T., & Bomyea, J. A. (2025) · Journal of Mood and Anxiety Disorders · doi:10.1016/j.xjmad.2025.100110 · Cited by 2
“Hypoactivity in these regions is thought to contribute to deficient motivation to pursue social rewards and inability to translate positive social reward signals into actual approach decisions [6,10].”
Carli, S., Schirripa, A., Mirino, P., Capirchio, A., & Caligiore, D. (2025) · Biological Cybernetics · doi:10.1007/s00422-025-01005-5 · Cited by 2
Mehta, M., Hakimi, N., Pena, O., Torres, T. M., Goldman, C. M., Lavalley, C. A., Stewart, J. L., Berg, H. E., Ironside, M., Paulus, M. P., et al. (2025) · Computational Psychiatry · doi:10.5334/cpsy.131 · Cited by 2
Petrosini, L., Cutuli, D., Bartolo, P. D., & Laricchiuta, D. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800648-1.00007-3 · Cited by 2
Brain structural and functional abnormalities in Fahr’s disease : a report of two cases
Messina, R., Rocca, M. A., Colombo, B., Falini, A., Comı, G., & Filippi, M. (2013) · Journal of Neurology · doi:10.1007/s00415-013-6973-4 · Cited by 2
“In line with MRI studies of patients with neuropsychiatric syndromes [5, 6, 8], patients with Fahr’s disease showed OFG atrophy, which plays a central role in topdown regulation of emotional response [2], and RS FC abnormalities of the salience network, that is involved in salience processing [12].”
The psychotherapeutic implications of functional neuroimaging studies of anxiety disorders
Cheung, P. (2013) · Australasian Psychiatry · doi:10.1177/1039856213496854 · Cited by 2
The modulatory effects of depression on pain perception: A review of animal model studies
Wang, N., Wei, X., Wang, J., & Luo, F. (2018) · Chinese Science Bulletin (Chinese Version) · doi:10.1360/n972017-01255 · Cited by 1
Mental Health Concerns in Athletes
Rowan, M. R., Sarafin, S. R., Willoughby, K., & O’Brien, K. H. M. (2023) · Contemporary pediatric and adolescent sports medicine · doi:10.1007/978-3-031-25126-9_2 · Cited by 3
Placing Approach-Avoidance Conflict Within the Framework of Multi-objective Reinforcement Learning
Enkhtaivan, E., Nishimura, J., & Cochran, A. L. (2023) · Bulletin of Mathematical Biology · doi:10.1007/s11538-023-01216-6 · Cited by 2
“TheincreasinginterestinAACisdrivenbyitsdirectconnectionwithvariousmental healthconditions(AupperleandPaulus2010;Weaveretal.2020;SripadaandWeigard 2021;McDermottetal.2022;Smithetal.021a).”
Khine, M. S. (2024) · Springer eBooks · doi:10.1007/978-981-97-9247-4_2 · Cited by 1
Feeling good, approaching the positive
Kobrock, K., Solzbacher, J., Gotzner, N., & Peter König, B. (2024) · Frontiers in Psychology · doi:10.3389/fpsyg.2024.1491612 · Cited by 1
An integrated approach to understanding negative math experiences
Grabowska, A. A., Daker, R. J., Ho, K., & Lyons, I. M. (2025) · Psychological Research · doi:10.1007/s00426-025-02096-2 · Cited by 2
“Probing the depth of this connection in the math domain at the level of neural structures that drive approach/avoidance behaviors (Lyons & Beilock, 2012; Aupperle et al., 2010, 2015; Ito & Lee, 2016), may be a fruitful area for future research.”
Ding, P., Zhao, L., Gong, A., Nan, W., & Fu, Y. (2025) · Sensors · doi:10.3390/s25113522 · Cited by 1
“The suppression observed in these regions during NFT suggests that the PNDA-MMNet model captures key neurophysiological changes relevant to PTSD symptomatology [37], offering a computational perspective on NFT’s potential mechanism of action.”
Parameswaran, S., & Balasubramanian, V. (2026) · Learning and Motivation · doi:10.1016/j.lmot.2026.102251 · Cited by 1
Anxiety symptoms interact with approach motivations in adolescent risk-taking
Baker, A. E., Padgaonkar, N. T., Enriquez, I., Peris, T. S., & Galván, A. (2026) · Development and Psychopathology · doi:10.1017/s0954579426101266 · Cited by 1
Adamis, A. M., Gardner, J. S., & Olatunji, B. O. (2026) · Cognitive Therapy and Research · doi:10.1007/s10608-026-10746-x · Cited by 1
“Indeed, anxiety is typically associated with excessive motivation to avoid threats rather than approach rewards (Robin L. & Martin, 2010).”
InfluentialChristian, C., Vanzhula, I. A., Ciotti, V., & Levinson, C. A. (2023) · Assessment · doi:10.1177/10731911231174469 · Cited by 1
“In addition, although fear approach is challenging in the moment, rewarding aspects of fear approach may influence approach-avoidance decision-making (Aupperle et al., 2015; Aupperle & Paulus, 2010).”
InfluentialOxytocin’s role in the interaction between emotion and cognitive control
Ganzel, A. R., Shalev, H., Hochman, S., Zultan, R., Cohen, N., & Naparstek, S. (2025) · Biological Psychology · doi:10.1016/j.biopsycho.2025.109004 · Cited by 2
Insights into Overlapping Brain Networks for Anxiety and Alcohol Use Disorders
Zabik, N. L., & Blackford, J. U. (2025) · Current topics in behavioral neurosciences · doi:10.1007/7854_2025_592 · Cited by 1
A Network Approach to PTSD: Comparing Interview and Self-Report Networks
Rosencrans, P. L. (2019) · ResearchWorks at the University of Washington (University of Washington) · Cited by 1
Rolle, C. E., Amemori, K., Johnson, N. D., Yan, M., Caudle, T., Meštrović, A. H., Gross, J. J., & Etkin, A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.27.501746 · Cited by 2
“As avoidance has been shown to be elevated in those with anxiety [17, 18, 20, 21], these findings are in line with our findings that frontal, cingulate and parietal regions negatively associate, and temporal power positively, with avoidance behavior specific to conflict.”
InfluentialYamamori, Y., Robinson, O., & Roiser, J. (2023) · bioRxiv · doi:10.1101/2023.04.04.535526 · Cited by 10
“…approach-avoidance conflict are thought to drive the development and maintenance of anxiety-related (Hayes 1976, Stein and Paulus 2009, Aupperle and Paulus 2010, Mkrtchian, Aylward et al. 2017, Struijs, Lamers et al. 2018) and other psychiatric disorders (Aldao, Nolen-Hoeksema et al. 2010,…”
InfluentialYamamori, Y., Robinson, O. J., & Roiser, J. P. (2023) · eLife · doi:10.7554/elife.87720.2 · Cited by 1
RECORD: A high-throughput system for complex naturalistic decision-making in rodentsPreprint
Friedman, A., Alcalá, R. J. I., Beck, D. W., Salcido, A. A., Davila, L. D., Giri, A., Heaton, C. N., Rodriguez, K., Rakocevic, L. I., Hossain, S., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3482882/v1 · Cited by 1
Transdiagnostic psychiatric symptom dimensions predict behavioural cautiousnessPreprint
Sporrer, J. K., Melinščak, F., & Bach, D. R. (2024) · PsyArXiv (OSF Preprints) · doi:10.31234/osf.io/3u47k · Cited by 1
Computational Primitives for Cost-Benefit Decision-MakingPreprint
Rakocevic, L. I., Davila, L. D., Heaton, C. N., Beck, D. W., Alcalá, R. J. I., Hossain, S., Reyes, N. F., Macias, A. Y., Salcido, A. A., Tyulmankov, D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.09.627657 · Cited by 1
Li, C. J., Pineda, D., Reimer, A. E., Hu, S. M., Angstman, M. R., Chang, J., & Widge, A. S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.01.679640 · Cited by 1
“While identifying these distinct strategies, and the underlying mechanisms, is a crucial step, the clinical relevance of these findings may be limited by paradigms that do not fully capture this strategic complexity (Aupperle & Paulus, 2010; Kirlic et al., 2017, Ball & Gunaydin, 2022).”
Cortical and Subcortical correlates of emotional control across adolescent development
Porter, J. N. (2013) · University of Minnesota Digital Conservancy (University of Minnesota)
Angst og depression: Emotionsregulering i psykoterapi
O’Toole, M. S., & Hougaard, E. (2016) · Tidsskrift for Forskning i Sygdom og Samfund · doi:10.7146/tfss.v13i24.20223
“Dette har personer med angst og depression imidlertid vanskeligt ved (Aupperle & Paulus, 2010; Higgins, 2001; Mennin & Fresco, 2014).”
Hamel, L. (2014) · TSpace (University of Toronto)
Report Human Hippocampus Arbitrates Approach-Avoidance Conflict
Bach, D. R., Guitart‐Masip, M., Packard, P. A., & Dolan, R. J. (2014)
A Factor Analysis of PTSD with Latino Samples with Substance Use Disorders
DiGangi, J. A., Ohanian, D. M., & Jason, L. A. (2016) · Journal of Addiction & Prevention · doi:10.13188/2330-2178.1000031
“Specifically, the amygdala, insula, ventral striatal, and prefrontal regions appear to be neural substrates that underpin the approach-avoidance cycle [38].”
Gattie, M., Lieven, E., & Kluk, K. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.24.396283
Metadata
- Authors
- Robin L., A., & Martin, P. P.
- Affiliations
- Department of Psychiatry, University of California, San Diego (UCSD), California, USA
- Psychiatry Service, Veterans Affairs San Diego Health Care System, San Diego, California, USA
- Venue
- Dialogues in Clinical Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2010-12-31
- Volume
- 12
- Issue
- 4
- Pages
- 517-531
- ISSN
- 1294-8322 (ISSN-L)
- 1958-5969
- PMC
- PMC3181993
- OpenAlex
- W1574357942
- Cited by
- 227
- References
- 251
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 18 · 2023: 22 · 2022: 25 · 2021: 18 · 2020: 21 · 2019: 8 · 2018: 7 · 2017: 11 · 2016: 15 · 2015: 12 · 2014: 14 · 2013: 8 · 2012: 7
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Dialogues in Clinical Neuroscience (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- approach-avoidance conflict, anxiety disorders, decision-making, amygdala, insula, ventral striatum, orbitofrontal cortex
- MeSH terms
- Anxiety Disorders, Avoidance Learning, Brain, Decision Making, Emotions, Humans, Models, Biological, Social Behavior
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