The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach
Abstract
Any investigation of the total number of neurons in a given brain region must first address the following questions. What is the best method for estimating the total number of neurons? What are the validity and the expected precision of the obtained data? What precision must the estimates attain with respect to the scientific question? In the present study, these questions were addressed using a computer simulation. Virtual brain regions with various spatial distributions of virtual neurons were modeled. The total numbers of virtual neurons in the modeled brain regions were repeatedly estimated by simulation of modern design-based stereology, either by using the 'fractionator' method or by the established method based on the product of estimated neuron density and estimated volume of the reference space. We show that estimates of total numbers of neurons obtained using the fractionator are from a statistical and economical standpoint more efficient than corresponding estimates obtained using the density/volume procedure. Furthermore, the use of two simple prediction methods (one for homogeneous and the other for clustered neuron distributions) permits satisfactory predictions about the variation of presumably any estimates of total numbers of neurons obtained using the fractionator. Finally, we show that assessing the reliability of estimates of mean total neuronal numbers using the ratio between the mean of the squared coefficients of error of the estimates and the squared coefficient of variation of the estimated total neuronal numbers, a frequently employed method in stereological studies, is neither useful nor informative. The present results may constitute a new set of recommendations for the rigorous usage of design-based stereology. In particular, we strongly recommend counting considerably more neurons than is currently done in the literature when estimating total neuronal numbers using design-based stereology.
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“On average, the coefficient of error (56) of optical disector analyses was 0.085 ± 0.018 (mean ± SD).”
From Evolution of increased glia–neuron ratios in the human frontal cortex (2006) · cites this paper as [56]
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von Bartheld, C. S., Bahney, J., & Herculano‐Houzel, S. (2016) · Journal of Comparative Neurology · doi:10.1002/cne.24040 · Cited by 1,063
Design-based stereology in neuroscience.
Schmitz, C., & Hof, P. R. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.08.050 · Cited by 681
Self-citationKellendonk, C., Simpson, E. H., Polan, H. J., Malleret, G., Vronskaya, S., Winiger, V., Moore, H., & Kandel, E. R. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.023 · Cited by 520
Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms
Andorfer, C., Acker, C. M., Kress, Y., Hof, P. R., Duff, K., & Davies, P. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4637-04.2005 · Cited by 511
“The coefficient of error was calculated according to Schmitz and Hof (2000).”
MethodSelf-citationHof, P. R., Haroutunian, V., Friedrich, V. L., Byne, W., Buitron, C., Perl, D. P., & Davis, K. L. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00237-3 · Cited by 433
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Metadata
- Authors
- Schmitz, C., & Hof, P. R.
- Affiliations
- RWTH Aachen University (DE)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Schmitz, Christoph
- Venue
- Journal of Chemical Neuroanatomy
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 20
- Issue
- 1
- Pages
- 93-114
- ISSN
- 0891-0618 (ISSN-L)
- OpenAlex
- W2168092251
- Cited by
- 272
- References
- 53
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 22 · 2021: 6 · 2020: 8 · 2019: 4 · 2018: 12 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 11 · 2013: 11 · 2012: 16
- FWCI
- 23.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Chemical Neuroanatomy (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG-02219, AG 05138, P50AG005138, P01AG002219)
- National Institute of Mental Health (MH-58911, P50MH058911)
- Topics
- Physical Sciences › Mathematics › Applied Mathematics › Point processes and geometric inequalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Physical Sciences › Mathematics › Statistics and Probability › Census and Population Estimation
- Keywords
- neuron counting, design-based stereology, neuronal density, coefficient of variation, estimation precision
- MeSH terms
- Algorithms, Brain, Cell Count, Computer Simulation, Image Interpretation, Computer-Assisted, Models, Neurological, Terminology as Topic, Random Allocation
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