Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (481 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus OF the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon; mesencephalon; and limbic system as well as cortical afferents of visual, auditory, and somatic origin.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Cortex, Prefrontal; Frontal Sulcus; Sulcus, Frontal; Superior Frontal Gyrus; Frontal Gyrus, Superior; Gyrus, Superior Frontal; Marginal Gyrus; Gyrus, Marginal.
Where it fits in the MeSH classification
- Broader topics
- Frontal Lobe
- Narrower topics
- Broca Area; Dorsolateral Prefrontal Cortex
Related concepts
- Mediodorsal Nucleus
- The Thalamus
- Diencephalon
- Mesencephalon
- Limbic System
Research landscape
PubMed indexes 39,676 records tagged with the MeSH heading “Prefrontal Cortex” (counts retrieved 2026-10-29). 12,672 of them (31.9%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 16,953 records.
Reviews account for 3,085 records (7.8%) and meta-analyses for 400. Randomized controlled trials number 1,999 (5.0%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 1,334 |
| 2000-2009 | 8,717 |
| 2010-2019 | 16,953 |
| 2020 onward | 12,672 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 3,085 | 7.8% |
| Meta-analyses | 400 | 1.0% |
| Randomized controlled trials | 1,999 | 5.0% |
Method: PubMed query "Prefrontal Cortex"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in neuroscience
Neuroscience draws on tools with different strengths: cellular and animal work can manipulate circuits directly, while human imaging and electrophysiology observe the living brain at lower resolution. Small imaging studies are prone to false positives, and findings in animals do not always carry over to people. Clinical neurology and psychiatry rely on trials and cohort studies whose outcomes are often symptom scales. Check the species, the sample size, how the outcome was measured and whether results were replicated.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| The prefrontal cortex controls memory organization in the hippocampus | 2026 | Research article Design not recorded in structured metadata | 8 | cc by PMID 42049880 · DOI · PMC13156042 |
| A prefrontal cortex-lateral hypothalamus circuit controls stress-driven increased food intake | 2026 | Research article Design not recorded in structured metadata | 5 | cc by PMID 41912543 · DOI · PMC13199376 |
| Single-nucleus atlas of cell-type specific genetic regulation in the human brain | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 42778721 · DOI · PMC13649572 |
The prefrontal cortex controls memory organization in the hippocampus [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Prior memories can be integrated with novel experiences during learning to facilitate memory organization.
- Closing excerpt
- Together, our results provide new insights into the mechanisms controlling crucial processes of memory organization in the mammalian brain.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (124 words)
Prior memories can be integrated with novel experiences during learning to facilitate memory organization. This process must be tightly regulated to prevent inappropriate integration of unrelated memories. However, the biological mechanisms underlying such control are currently unknown. Using multiple imaging, chemogenetic and optogenetic techniques in mice, we demonstrate that the ventromedial prefrontal cortex is recruited over time to control memory integration in the hippocampus according to contextual similarities between experiences. This control is achieved through direct projections to the medial entorhinal cortex that modulate entorhinal activity, ensemble overlap in the dorsal hippocampus, memory linking, activity of neurogliaform cells in the dorsal CA1 and memory allocation. Together, our results provide new insights into the mechanisms controlling crucial processes of memory organization in the mammalian brain.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42049880 · DOI · PMC13156042
A prefrontal cortex-lateral hypothalamus circuit controls stress-driven increased food intake [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Stress can drive overconsumption of high-fat foods.
- Closing excerpt
- Overall, we identify the mPFC-LHA as a multi-branched network, indispensable for stress-eating.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Stress can drive overconsumption of high-fat foods. The medial prefrontal cortex (mPFC) is implicated in such stress-eating, but the underlying circuit mechanisms remain unclear. Here, we show that mPFC projections to the lateral hypothalamus (LHA) are required for stress-induced fat intake in male mice. We find that mPFC-LHA stimulation in sated states increases fat intake. Social stress acutely engages mPFC-LHA neurons, and inhibiting this pathway selectively prevents stress-driven excess fat intake. Circuit mapping shows that mPFC neurons innervate GABAergic and glutamatergic LHA (LHAVGLUT2) neurons, but that social stress preferentially engages mPFC-LHAVGLUT2 neurons and causes plasticity at mPFC-LHAVGLUT2 synapses. Specifically, stress weakens mPFC synapses onto LHAVGLUT2 neurons that curtail food intake, while strengthening mPFC synapses onto midbrain-projecting LHAVGLUT2 neurons linked to stress-eating. We show that LHAVGLUT2 neurons are required downstream mPFC targets for transforming stress into heightened fat intake. Overall, we identify the mPFC-LHA as a multi-branched network, indispensable for stress-eating.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41912543 · DOI · PMC13199376
Single-nucleus atlas of cell-type specific genetic regulation in the human brain [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression.
- Closing excerpt
- This high-resolution atlas provides insight into the cell type-specific regulatory architecture of the human brain, and offers novel mechanistic targets for understanding the genetic basis of neuropsychiatric and neurodegenerative diseases.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (207 words)
Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. Here we present a comprehensive, single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.6 million nuclei from 1,384 donors of diverse ancestries. Through multi-resolution analyses spanning eight major cell classes and 27 subclasses, we identify genetic regulation for 14,258 genes, with 981 showing cell type-specific regulatory effects at the class level and 857 at the subclass level. Colocalization of genetic variants associated with gene regulation and disease traits uncovers novel cell type-specific genes implicated in Alzheimer's disease, schizophrenia and other disorders that were not detectable in bulk tissue analyses. Analysis of dynamic genetic regulation at the single-nucleus level identifies 2,073 genes with regulatory effects that vary across developmental trajectories, inferred from a broad age range of donors. We also uncover 1,655 genes with trans-regulatory effects, revealing distal regulation of gene expression. This high-resolution atlas provides insight into the cell type-specific regulatory architecture of the human brain, and offers novel mechanistic targets for understanding the genetic basis of neuropsychiatric and neurodegenerative diseases.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42778721 · DOI · PMC13649572
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions [4]
- Research article The role of prefrontal cortex in cognitive control and executive function [5]
- Research article The Interaction of Person-Affect-Cognition-Execution (I-PACE) model for addictive behaviors: Update, generalization to addictive behaviors beyond internet-use disorders, and specification of the process character of addictive behaviors [6]
- Research article Rumination and the default mode network: Meta-analysis of brain imaging studies and implications for depression [7]
- Research article The role of PFC networks in cognitive control and executive function [8]
- Research article The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology [9]
References
- de Sousa AF, Zeidler ZE, Almeida-Filho DG, Shen Y, Luchetti A, Simanian S, et al.. The prefrontal cortex controls memory organization in the hippocampus. . 2026. PMID 42049880 · DOI · PMC13156042
- Supiot LF, Kooij KL, Du W, Benschop AAC, Nicolson ASJ, Haak R, et al.. A prefrontal cortex-lateral hypothalamus circuit controls stress-driven increased food intake. . 2026. PMID 41912543 · DOI · PMC13199376
- Zeng B, Yang H, N M P, Venkatesh S, Mathur D, Auluck P, et al.. Single-nucleus atlas of cell-type specific genetic regulation in the human brain. . 2026. PMID 42778721 · DOI · PMC13649572
- Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, et al.. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci. 2019. PMID 30718901 · DOI · PMC6522363
- Friedman NP, Robbins TW. The role of prefrontal cortex in cognitive control and executive function. Neuropsychopharmacology. 2022. PMID 34408280 · DOI · PMC8617292
- Brand M, Wegmann E, Stark R, Müller A, Wölfling K, Robbins TW, et al.. The Interaction of Person-Affect-Cognition-Execution (I-PACE) model for addictive behaviors: Update, generalization to addictive behaviors beyond internet-use disorders, and specification of the process character of addictive behaviors. Neurosci Biobehav Rev. 2019. PMID 31247240 · DOI
- Zhou HX, Chen X, Shen YQ, Li L, Chen NX, Zhu ZC, et al.. Rumination and the default mode network: Meta-analysis of brain imaging studies and implications for depression. Neuroimage. 2020. PMID 31655111 · DOI
- Menon V, D'Esposito M. The role of PFC networks in cognitive control and executive function. Neuropsychopharmacology. 2022. PMID 34408276 · DOI · PMC8616903
- Belleau EL, Treadway MT, Pizzagalli DA. The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology. Biol Psychiatry. 2019. PMID 30470559 · DOI · PMC6380948
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.