Prolonged myelination in human neocortical evolution
Open accessAbstract
Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees ( N = 20) and humans ( N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.
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The shift in the social context of human child rearing, occurring together with a protracted postnatal development of cortical connectivity, likely created new opportunities for imitative learning and cumulative, intergenerational development of cultural traditions to become central features of the human adaptive complex.
“This shift in the social context of human child rearing, occurring together with a protracted postnatal development of cortical connectivity (54,55), likely created new opportunities for imitative learning and cumulative, intergenerational development of cultural traditions to become central features of the human adaptive complex (56,57).”
From Metabolic costs and evolutionary implications of human brain development (2014) · cites this paper as [54]
Myelination is one of the most prolonged neurodevelopmental processes, continuing until the third decade of life.
“Myelination is one of the most prolonged neurodevelopmental processes, continuing until the third decade of life (Benes et al., 1994; Fleschig, 1901; Miller et al., 2012; Yakovlev, 1967).”
From Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination (2016) · cites this paper as Miller et al., 2012
In the neocortex, mature myelination patterns are attained only in adulthood, reflecting protracted maturation in humans compared with non-human primates.
“In the neocortex, mature myelination patterns are attained only in adulthood, reflecting a protracted maturation of this brain region in humans compared with that in non-human primates215.”
From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [215]
In chimpanzees, but not in humans, myelination becomes complete at about the time of sexual maturity.
“In chimpanzees, but not in humans, myelination becomes complete at about the time of sexual maturity (25).”
From Emerging Adulthood, a Pre-adult Life-History Stage (2020) · cites this paper as [25]
Myelination is developmentally protracted in humans compared to chimpanzees, in which myelination is largely completed in mid-adolescence.
“Myelination is developmentally protracted in humans compared to chimpanzees in which myelination is largely completed in mid-adolescence (Miller et al., 2012).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Miller et al., 2012
The generation of glial cells generally follows neurogenesis, peaks around birth, and is a protracted postnatal process in humans.
“The generation of glial cells generally follows neurogenesis, peaking around birth, and is also a protracted postnatal process in humans (Jakovcevski et al., 2009; Miller et al., 2012; O’Rourke et al., 1992; Roessmann and Gambetti, 1986; Yeung et al., 2014).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Miller et al., 2012
Human brain development is protracted compared with other species, so despite having a more mature brain at birth than rats, humans remain vulnerable to insult.
“development of the human brain is protracted compared to other species (Clancy et al., 2001; Miller et al, 2012; Semple et al., 2013), so despite having a more “mature” brain at birth compared to rats, vulnerability to insult remains.”
From The effects of early life stress on reward processing (2018) · cites this paper as Miller et al, 2012
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Self-citationMesocorticolimbic Dopamine Pathways Across Adolescence: Diversity in Development
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- Authors
- Miller, D. J., Duka, T., Stimpson, C. D., Schapiro, S. J., Baze, W. B., McArthur, M. J., Fobbs, A. J., Sousa, A. M. M., Šestan, N., Wildman, D. E., Lipovich, L., Kuzawa, C. W., Hof, P. R., & Sherwood, C. C.
- Affiliations
- George Washington University (US)
- The University of Texas MD Anderson Cancer Center (US)
- National Museum of Health and Medicine, SIlver Spring, MD 20910;
- Universidade do Porto (PT)
- Yale University (US)
- Wayne State University (US)
- Northwestern University (US)
- New York Consortium in Evolutionary Primatology (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-09-24
- Volume
- 109
- Issue
- 41
- Pages
- 16480-16485
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3478650
- OpenAlex
- W2079246150
- Cited by
- 699
- References
- 60
- Citations by year
- 2026: 45 · 2025: 51 · 2024: 55 · 2023: 63 · 2022: 62 · 2021: 45 · 2020: 86 · 2019: 59 · 2018: 53 · 2017: 41 · 2016: 46 · 2015: 39 · 2014: 29 · 2013: 24 · 2012: 1
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (BCS-0824531, 0515484, 0549117, 220020293, 0801634)
- James S. McDonnell Foundation (220020293, 220020165, 22002078)
- Johns Hopkins University
- National Institutes of Health (RR‐00165)
- National Institute of Mental Health (U01MH081896)
- National Institute of Neurological Disorders and Stroke (NS42867, R01NS042867)
- National Center for Research Resources (RR-00 165, P51RR000165)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- myelination, neocortex, human evolution, chimpanzees, postnatal development, myelin proteins, cortical maturation, adolescence, cognitive development, schizophrenia, psychiatric vulnerability, comparative neuroanatomy
- MeSH terms
- Adolescent, Adult, Animals, Child, Pan troglodytes, Biological Evolution, Humans, Infant, Infant, Newborn, Motor Cortex, Myelin Proteins, Myelin Sheath, Somatosensory Cortex, Time Factors, Visual Cortex, Blotting, Western, Prefrontal Cortex, Myelin-Associated Glycoprotein, Neocortex, Young Adult
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.
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