ArticleScience advances2023
An energy costly architecture of neuromodulators for human brain evolution and cognition.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
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- From metabolic intermediary to neurotransmitter: purinergic signaling in neurophysiology and vulnerability of brain circuits.Bioscience reports · 2026Review
- Network-specific metabolic cost of functional connectivity in the human brain.bioRxiv : the preprint server for biology · 2026Article
- Metabolism-weighted brain connectome reveals synaptic integration and vulnerability to neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular and cellular correlates of human cortical lateralization.Communications biology · 2026Article
- Linking human brain functional connectivity to underlying neurotransmission.bioRxiv : the preprint server for biology · 2026Article
- Decoupling of neurophysiological activity from structure mirrors global microarchitectural and neuromodulatory trends.Communications biology · 2026Article
- Brain energetic landscapes shape state dysregulation in major depressive disorder: a morphological network controllability perspective.Translational psychiatry · 2026Article
- Brain-inspired energy efficient technologies for next-generation artificial intelligence.Biological cybernetics · 2026Review
- The Fronto-Temporal Cortex Has Increased Subcortical Connectivity In Utero and Plasticity in Adulthood.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Bridging glucose metabolism and intrinsic functional organization of the human cortex.Communications biology · 2026Article
- Brain glucodynamic variability is an essential feature of the metabolism-cognition relationship.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Inter-individual variability of neurotransmitter receptor and transporter density in the human brain.Brain structure & function · 2026Article
- Controllability of morphometric network colocalize with underlying neurobiology in major depression.Psychological medicine · 2026Article
- Energetic implications of fMRI-based nodal complex network metrics: a complex picture unfolds across diverse brain states.bioRxiv : the preprint server for biology · 2026Article
- From chemistry to cognition: the adaptive origins of consciousness under constraint.Frontiers in neuroscience · 2026Article
- Five energy metabolism pathways show distinct regional distributions and lifespan trajectories in the human brain.PLoS biology · 2026Article
- JAK/STAT signaling pathway inhibitors in neurodegenerative diseases: current status and future perspectives.Frontiers in aging neuroscience · 2026Review
- Chronic gut inflammation differentially modulates mitochondrial and antioxidant transcriptional programs in limbic brain structures.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In comparison to other species, the human brain exhibits one of the highest energy demands relative to body metabolism. It remains unclear whether this heightened energy demand uniformly supports an enlarged brain or if specific signaling mechanisms necessitate greater energy. We hypothesized that the regional distribution of energy demands will reveal signaling strategies that have contributed to human cognitive development. We measured the energy distribution within the brain functional connectome using multimodal brain imaging and found that signaling pathways in evolutionarily expanded regions have up to 67% higher energetic costs than those in sensory-motor regions. Additionally, histology, transcriptomic data, and molecular imaging independently reveal an up-regulation of signaling at G-protein-coupled receptors in energy-demanding regions. Our findings indicate that neuromodulator activity is predominantly involved in cognitive functions, such as reading or memory processing. This study suggests that an up-regulation of neuromodulator activity, alongside increased brain size, is a crucial aspect of human brain evolution.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.