A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex.
Bibliographic record
Abstract
Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the cortex follows a unimodal-to-transmodal gradient. Situated at the apex of this processing hierarchy-where it plays a central role in the integrative processes underpinning complex, human-defining cognition-the transmodal cortex has disproportionately expanded across human development and evolution. Notably, the adult human transmodal cortex is especially rich in 5-HT2AR expression and recent evidence suggests that, during early brain development, 5-HT2AR signalling on neural progenitor cells stimulates their proliferation-a critical process for evolutionarily-relevant cortical expansion. Drawing on multimodal neuroimaging and cross-species investigations, we argue that, by contributing to the expansion of the human cortex and being prevalent at the apex of its hierarchy in the adult brain, 5-HT2AR signalling plays a major role in both human cortical expansion and functioning. Owing to its unique excitatory and downstream cellular effects, neuronal 5-HT2AR agonism promotes neuroplasticity, learning and cognitive and psychological flexibility in a context-(hyper)sensitive manner with therapeutic potential. Overall, we delineate a dual role of 5-HT2ARs in enabling both the expansion and modulation of the human transmodal cortex.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".