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J Neurosci. 2015 Jan 28;35(4):1753-62. doi: 10.1523/JNEUROSCI.3979-14.2015.

Functional consequences of neurite orientation dispersion and density in humans across the adult lifespan.

Author information

1
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.
2
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8, Cerebral Imaging Centre, Douglas Institute, Verdun, Quebec, Canada H4H 1R3, Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec, Canada H3A 2B4.
3
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.
4
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8, Geriatric Mental Health Service, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M6J 1H4.
5
Laboratory of Mathematics in Imaging, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, and.
6
Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
7
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8, Geriatric Mental Health Service, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M6J 1H4, Aristotle.Voineskos@camh.ca.

Abstract

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.

KEYWORDS:

GBSS; cognitive aging; diffusion-weighted MRI; gray matter; neurite orientation dispersion; structure–function relationship

PMID:
25632148
PMCID:
PMC4308611
DOI:
10.1523/JNEUROSCI.3979-14.2015
[Indexed for MEDLINE]
Free PMC Article

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