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Beyond t test and ANOVA: applications of mixed-effects models for more rigorous statistical analysis in neuroscience research
Open accessAbstract
In basic neuroscience research, data are often clustered or collected with repeated measures, hence correlated. The most widely used methods such as t test and ANOVA do not take data dependence into account and thus are often misused. This Primer introduces linear and generalized mixed-effects models that consider data dependence and provides clear instruction on how to recognize when they are needed and how to apply them. The appropriate use of mixed-effects models will help researchers improve their experimental design and will lead to data analyses with greater validity and higher reproducibility of the experimental findings.
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For all experiments involving animals, linear mixed-effects models (LMEMs) were used to account for the nonindependence of cells nested within animals while testing for treatment or genotype effects.
“For all experiments involving animals, linear mixed-effects models (LMEMs) were used to account for the nonindependence of cells nested within animals while testing for treatment or genotype effects (88).”
From Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1 (2026) · cites this paper as [88]
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“The use of a Bayesian 475 approach and Bayes factors has been sometimes advocated as an alternative to p-values since 476 the Bayes factor represents a direct measure of the evidence of one model versus the other 477 (Benjamin and Berger, 2019; Held and Ott, 2018; Kass and Raftery, 1995).”
MethodInfluentialMixed-effects modeling with crossed random effects for subjects and items
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“For example, resampling methods have been proposed as robust alternatives to LME 688 (Halekoh and Højsgaard, 2014; Zeger et al., 1988).”
MethodA call for transparent reporting to optimize the predictive value of preclinical research
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What exactly is ‘N’ in cell culture and animal experiments?
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Metadata
- Authors
- Yu, Z., Guindani, M., Grieco, S. F., Chen, L., Holmes, T. C., & Xu, X.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Yu, Zhaoxia
- Xu, Xiangmin
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 110
- Issue
- 1
- Pages
- 21-35
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC8763600
- OpenAlex
- W3213971514
- Cited by
- 563
- References
- 17
- Citations by year
- 2026: 114 · 2025: 149 · 2024: 125 · 2023: 116 · 2022: 56
- FWCI
- 13.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation (SES 1659921)
- National Institutes of Health (R01EY028212, R01MH105427, R01NS104897, R35GM127102)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Spatial and Panel Data Analysis
- Life Sciences › Agricultural and Biological Sciences › Agronomy and Crop Science › Agriculture, Soil, Plant Science
- Keywords
- mixed models, linear mixed models, generalized mixed models, correlated data, repeated measures, clustered data, experimental design, statistical validity, reproducibility, neuroscience data analysis
- MeSH terms
- Analysis of Variance, Neurosciences, Research Design, Reproducibility of Results, Models, Statistical, Linear Models
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