What constitutes the prefrontal cortex?
Abstract
During evolution, the prefrontal region grew in size relative to the rest of the cortex. It reached its largest extent in the human brain, where it constitutes 30% of the total cortical area. This growth was accompanied by phylogenetic differentiation of the cortical areas. It has been argued that the human brain holds prefrontal regions that are both qualitatively and functionally unique. Present-day neuroscientists studying the prefrontal cortex increasingly use mice. An important goal is to reveal how the prefrontal cortex enables complex behavior. However, the prefrontal cortex still lacks a conclusive definition. The structure and function of this brain area across species remain unresolved. This state of affairs is often overlooked, warranting renewed focus on what the prefrontal cortex is and does.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The human brain possesses prefrontal regions that are both qualitatively and functionally exclusive.
“In fact, it has been argued that the human brain possesses prefrontal regions that are both qualitatively and functionally exclusive [15].”
From Development of prefrontal cortex (2022) · cites this paper as [15]
Cites
An Integrative Theory of Prefrontal Cortex Function
Miller, E. K., & Cohen, J. D. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.167 · Cited by 12,803 · see citing works
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572 · see citing works
The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture
Fan, L., Li, H., Zhuo, J., Zhang, Y., Wang, J., Chen, L., Yang, Z., Chu, C., Xie, S., Laird, A. R., et al. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw157 · Cited by 2,956 · see citing works
A mesoscale connectome of the mouse brain
Oh, S. W., Harris, J. A., Ng, L., Winslow, B., Cain, N., Mihalas, S., Wang, Q., Lau, C., Kuan, L., Henry, A. M., et al. (2014) · Nature · doi:10.1038/nature13186 · Cited by 2,612 · see citing works
(1909) · Cited by 2,575 · see citing works
The Prefrontal Cortex—An Update
Fuster, J. M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00285-9 · Cited by 1,760 · see citing works
Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates
Dalley, J. W., Cardinal, R. N., & Robbins, T. W. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.09.006 · Cited by 1,329 · see citing works
The cognitive revolution: a historical perspective
Miller, G. A. (2003) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(03)00029-9 · Cited by 1,285 · see citing works
Do rats have a prefrontal cortex?
Uylings, H. B. M., Groenewegen, H. J., & Kolb, B. (2003) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.09.028 · Cited by 1,013 · see citing works
Architectonic subdivision of the human orbital and medial prefrontal cortex
Öngür, D., Ferry, A. T., & Price, J. L. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10609 · Cited by 944 · see citing works
Buzsáki, G. (2005) · Hippocampus · doi:10.1002/hipo.20113 · Cited by 872 · see citing works
Ferrier, D. (1876) · G P Putnam's Sons eBooks · doi:10.1037/12860-000 · Cited by 872 · see citing works
Leonard, C. M. (1969) · Brain Research · doi:10.1016/0006-8993(69)90003-1 · Cited by 850 · see citing works
Do Rats Have Prefrontal Cortex? The Rose-Woolsey-Akert Program Reconsidered
Preuss, T. M. (1995) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.1995.7.1.1 · Cited by 666 · see citing works
Skinner, B. F. (1963) · Science · doi:10.1126/science.140.3570.951 · Cited by 488 · see citing works
Forward frontal fields: phylogeny and fundamental function
Wise, S. P. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.08.008 · Cited by 478 · see citing works
Architectonic map of neocortex of the normal mouse
Caviness, V. S. (1975) · The Journal of Comparative Neurology · doi:10.1002/cne.901640207 · Cited by 448 · see citing works
The role of prefrontal cortex in working memory: a mini review
Lara, A. H., & Wallis, J. D. (2015) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00173 · Cited by 402 · see citing works
The Neurobiology of the Prefrontal Cortex: Anatomy, Evolution, and the Origin of Insight
Passingham, R. E., & Wise, S. P. (2012) · doi:10.1093/acprof:osobl/9780199552917.001.0001 · Cited by 379 · see citing works
The orbitofrontal cortex and its connections with the mediodorsal nucleus in rabbit, sheep and cat.
ROSE, J. E., & Woolsey, C. N. (1948) · PubMed · Cited by 374 · see citing works
Petrides, M., Tomaiuolo, F., Yeterian, E. H., & Pandya, D. Ν. (2011) · Cortex · doi:10.1016/j.cortex.2011.07.002 · Cited by 353 · see citing works
Rodent models of prefrontal cortical function
Brown, V. J., & Bowman, E. M. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02164-1 · Cited by 320 · see citing works
The Scalable Brain Atlas: Instant Web-Based Access to Public Brain Atlases and Related Content
Bakker, R., Tiesinga, P. H. E., & Kötter, R. (2015) · Neuroinformatics · doi:10.1007/s12021-014-9258-x · Cited by 298 · see citing works
Comparative cytoarchitectonic atlas of the C57BL/6 and 129/Sv mouse brains
Hof, P. R. (2000) · Elsevier eBooks · Cited by 289 · see citing works
Understanding Behaviorism: Behavior, Culture, and Evolution
Baum, W. M. (2003) · Cited by 275 · see citing works
Anatomy of the Prefrontal Cortex
Fuster, J. M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-407815-4.00002-7 · Cited by 272 · see citing works
Comparing the prefrontal cortex of rats and primates: Insights from electrophysiology
Seamans, J. K., Lapish, C. C., & Durstewitz, D. (2008) · Neurotoxicity Research · doi:10.1007/bf03033814 · Cited by 244 · see citing works
Werd, H. J. J. M. V. D., Rajkowska, G., Evers, P., & Uylings, H. B. M. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0247-z · Cited by 191 · see citing works
The Concept of Homology and the Evolution of the Nervous System (Part 1 of 2)
Campbell, C. B. G., & Hodos, W. (2008) · Brain Behavior and Evolution · doi:10.1159/000125482 · Cited by 171 · see citing works
The Emergence of Modern Neuroscience: Some Implications for Neurology and Psychiatry
Cowan, W. M., Harter, D. H., & Kandel, E. R. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.343 · Cited by 164 · see citing works
Baum, W. M. (2016) · Wiley eBooks · doi:10.1002/9781119143673 · Cited by 162 · see citing works
Ferrier, D. E. K., & Yeo, G. F. (1884) · Philosophical Transactions of the Royal Society of London · doi:10.1098/rstl.1884.0020 · Cited by 135 · see citing works
Preuss, T. M. (2000) · Brain Behavior and Evolution · doi:10.1159/000006664 · Cited by 132 · see citing works
Functional localization within the prefrontal cortex: missing the forest for the trees?
Wilson, C. R. E., Gaffan, D., Browning, P. G. F., & Baxter, M. G. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.08.001 · Cited by 126 · see citing works
Goal-direction and top-down control
Buschman, T. J., & Miller, E. K. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0471 · Cited by 122 · see citing works
Cromwell, H. C., & Panksepp, J. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.02.008 · Cited by 109 · see citing works
Mind, Body, World: Foundations of Cognitive Science
Dawson, M. R. W. (2013) · Athabasca University Press eBooks · doi:10.15215/aupress/9781927356173.01 · Cited by 97 · see citing works
Nei, M. (2002) · Journal of Heredity · doi:10.1093/jhered/93.3.157 · Cited by 72 · see citing works
Guldin, W. O., Pritzel, M., & Markowitsch, H. J. (2008) · Brain Behavior and Evolution · doi:10.1159/000121636 · Cited by 68 · see citing works
Comparison of (stereotactic) parcellations in mouse prefrontal cortex
Van De Werd, H. J. J. M., & Uylings, H. B. M. (2014) · Brain Structure and Function · doi:10.1007/s00429-013-0630-7 · Cited by 56 · see citing works
Problems of Teaching the Behaviorist Perspective in the Cognitive Revolution
Abramson, C. I. (2013) · Behavioral Sciences · doi:10.3390/bs3010055 · Cited by 50 · see citing works
The prefrontal cortex: Projection area of the thalamic mediodorsal nucleus?
Markowitsch, H. J., & Pritzel, M. (1979) · Physiological Psychology · doi:10.3758/bf03326611 · Cited by 49 · see citing works
Evolution, behavior and the prefrontal cortex.
Jm, W. (1972) · PubMed · Cited by 25 · see citing works
Finding prefrontal cortex in the rat
Leonard, C. M. (2016) · Brain Research · doi:10.1016/j.brainres.2016.02.002 · Cited by 23 · see citing works
Generalizations in Neuropsychology
Warren, J. M., & Kolb, B. E. (1978) · Springer eBooks · doi:10.1007/978-1-4615-7723-2_2 · Cited by 20 · see citing works
Kolb, B. E. (2015) · Elsevier eBooks · doi:10.1016/b978-0-08-097086-8.55045-4 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Three-dimensional intact-tissue sequencing of single-cell transcriptional states
Wang, X., Allen, W. E., Wright, M. A., Sylwestrak, E. L., Samusik, N., Vesuna, S., Evans, K., Liu, C., Ramakrishnan, C., Liu, J., et al. (2018) · Science · doi:10.1126/science.aat5691 · Cited by 1,620 · see citing works
Understanding the Higher-Order Approach to Consciousness
Brown, R., Lau, H., & LeDoux, J. E. (2019) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2019.06.009 · Cited by 573 · see citing works
Development of prefrontal cortex
Kolk, S. M., & Rakic, P. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01137-9 · Cited by 378 · see citing works
Herold, F., Törpel, A., Schega, L., & Müller, N. G. (2019) · European Review of Aging and Physical Activity · doi:10.1186/s11556-019-0217-2 · Cited by 349 · see citing works
The role of the medial prefrontal cortex in cognition, ageing and dementia
Jobson, D. D., Hase, Y., Clarkson, A. N., & Kalaria, R. N. (2021) · Brain Communications · doi:10.1093/braincomms/fcab125 · Cited by 338 · see citing works
Circuit organization of the rodent medial prefrontal cortex
Anastasiades, P. G., & Carter, A. G. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.03.006 · Cited by 314 · see citing works
Emotion Dysregulation and Emerging Psychopathology: A Transdiagnostic, Transdisciplinary Perspective
Beauchaine, T. P., & Cicchetti, D. (2019) · Development and Psychopathology · doi:10.1017/s0954579419000671 · Cited by 301 · see citing works
Single-neuron projectome of mouse prefrontal cortex
Gao, L., Liu, S., Gou, L., Hu, Y., Liu, Y., Deng, L., Ma, D., Wang, H., Yang, Q., Chen, Z., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01041-5 · Cited by 264 · see citing works
Prefrontal Cortex Development in Health and Disease: Lessons from Rodents and Humans
Chini, M., & Hanganu-Opatz, I. L. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.017 · Cited by 253 · see citing works
Bidirectional prefrontal-hippocampal dynamics organize information transfer during sleep in humans
Helfrich, R. F., Lendner, J. D., Mander, B. A., Guillen, H., Paff, M., Mnatsakanyan, L., Vadera, S., Walker, M. P., Lin, J. J., & Knight, R. T. (2019) · Nature Communications · doi:10.1038/s41467-019-11444-x · Cited by 222 · see citing works
Value-guided remapping of sensory cortex by lateral orbitofrontal cortex
Banerjee, A., Parente, G., Teutsch, J., Lewis, C., Voigt, F. F., & Helmchen, F. (2020) · Nature · doi:10.1038/s41586-020-2704-z · Cited by 199 · see citing works
Bertero, A., Liska, A., Pagani, M., Parolisi, R., Masferrer, M. E., Gritti, M., Pedrazzoli, M., Galbusera, A., Sarica, A., Cerasa, A., et al. (2018) · Brain · doi:10.1093/brain/awy111 · Cited by 120 · see citing works
Ruggiero, R. N., Rossignoli, M. T., Marques, D. B., de Sousa, B. M., Romcy-Pereira, R. N., Lopes-Aguiar, C., & Leite, J. P. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.732360 · Cited by 111 · see citing works
Behavior- and Modality-General Representation of Confidence in Orbitofrontal Cortex
Masset, P., Ott, T., Lak, A., Hirokawa, J., & Kepecs, A. (2020) · Cell · doi:10.1016/j.cell.2020.05.022 · Cited by 109 · see citing works
Liu, Y., Li, M., Fan, M., Song, Y., Yu, H., Zhi, X., Xiao, K., Lai, S., Zhang, J., Jin, X., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.11.025 · Cited by 106 · see citing works
Gabriele, M., Lopez Tobon, A., D'Agostino, G., & Testa, G. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.12.013 · Cited by 103 · see citing works
Raccah, O., Block, N., & Fox, K. C. R. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.1141-20.2020 · Cited by 96 · see citing works
Functional geometry of the cortex encodes dimensions of consciousness
Huang, Z., Mashour, G. A., & Hudetz, A. G. (2023) · Nature Communications · doi:10.1038/s41467-022-35764-7 · Cited by 101 · see citing works
Linking cortical circuit models to human cognition with laminar fMRI
Yang, J., Huber, L., Yu, Y., & Bandettini, P. A. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.005 · Cited by 52 · see citing works
Vishne, G., Gerber, E. M., Knight, R. T., & Deouell, L. Y. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112752 · Cited by 46 · see citing works
Sleep/wake changes in perturbational complexity in rats and mice
Cavelli, M. L., Mao, R., Findlay, G., Driessen, K., Bugnon, T., Tononi, G., & Cirelli, C. (2023) · iScience · doi:10.1016/j.isci.2023.106186 · Cited by 46 · see citing works
Effects of different AI-driven Chatbot feedback on learning outcomes and brain activity
Yin, J., Xu, H., Pan, Y., & Hu, Y. (2025) · npj Science of Learning · doi:10.1038/s41539-025-00311-8 · Cited by 41 · see citing works
Li, G., Hu, J., Zhang, S., Fan, W., Wen, L., Wang, G., & Zhang, D. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.603279 · Cited by 32 · see citing works
Haynes, W. I. A., Clair, A.-H., Fernandez-Vidal, S., Gholipour, B., Morgiève, M., & Mallet, L. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.01.005 · Cited by 29 · see citing works
Ren, L. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110910 · Cited by 23 · see citing works
Fornaro, S., & Vallesi, A. (2024) · Current Psychology · doi:10.1007/s12144-023-04312-x · Cited by 21 · see citing works
Regulation of Prefrontal Patterning, Connectivity and Synaptogenesis by Retinoic Acid
Shibata, M., Pattabiraman, K., Lorente-Galdos, B., Andrijevic, D., Xing, X., Sousa, A. M. M., Santpere, G., & Sestan, N. (2019) · doi:10.1101/2019.12.31.891036 · Cited by 7 · see citing works
- Authors
- Carlén, M.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Carlén, Marie
- ORCID
- Carlén, Marie
- Venue
- Science
- Published
- 2017-10-27
- Volume
- 358
- Issue
- 6362
- Pages
- 478-482
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2765507708
- Cited by
- 561
- References
- 46
- Citations by year
- 2026: 58 · 2025: 69 · 2024: 90 · 2023: 76 · 2022: 76 · 2021: 77 · 2020: 56 · 2019: 38 · 2018: 20 · 2016: 1
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Research Council (award342774, 337069)
- Karolinska Institutet (award342780)
- Knut och Alice Wallenbergs Stiftelse (award342775, KAW 2012.0208)
- Ragnar Söderberg Fellow in Medicine (award342778, M176/12)
- CIMED (award352460)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- prefrontal cortex, human brain evolution, complex behavior, comparative neuroanatomy
- MeSH terms
- Animals, Biological Evolution, Humans, Organ Size, Prefrontal Cortex, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
