Functional Consequences of Neurite Orientation Dispersion and Density in Humans across the Adult Lifespan
Open accessAbstract
As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21–84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo.
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Neurite morphology is a substrate of neural function.
“Our study tests the hypothesis that the variability of neurite orientations is a biomarker of multiple sclerosis pathology, and is motivated by recent findings demonstrating that neurite morphology is a substrate of neural function23, 24 and is affected by multiple sclerosis.25”
From Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology? (2017) · cites this paper as [23]
In GM, decreased ODI in the neocortex with increasing age has been reported.
“In GM, decreased ODI in the neocortex with increasing age has been reported (Nazeri et al., 2015)”
From NODDI in clinical research (2020) · cites this paper as Nazeri et al., 2015
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- Authors
- Nazeri, A., Chakravarty, M. M., Rotenberg, D. J., Rajji, T. K., Rathi, Y., Michailovich, O. V., & Voineskos, A. N.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- University of Waterloo (CA)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-01-28
- Volume
- 35
- Issue
- 4
- Pages
- 1753-1762
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4308611
- OpenAlex
- W2036969062
- Cited by
- 162
- References
- 6
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 18 · 2023: 20 · 2022: 16 · 2021: 16 · 2020: 18 · 2019: 15 · 2018: 11 · 2017: 7 · 2016: 8 · 2015: 3
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Centre for Addiction and Mental Health
- W. Garfield Weston Foundation
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Mental Health (R01MH099167, R01MH102324, R01MH097979)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- NODDI, gray matter microstructure, aging, neocortex, hippocampus, cerebellum, resting-state functional connectivity, default mode network, executive function, frontal pole, compensatory neural mechanisms
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Brain, Brain Mapping, Cell Count, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Neurons, Oxygen, Rest, Neurites, Anisotropy, Statistics, Nonparametric, Young Adult, Diffusion Tensor Imaging
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