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

TitleFunctional consequences of neurite orientation dispersion and density in humans across the adult lifespan.
Publication TypeJournal Article
Year of Publication2015
AuthorsNazeri A, Chakravarty MM, Rotenberg DJ, Rajji TK, Rathi Y, Michailovich OV, Voineskos AN
JournalJ Neurosci
Date Published2015 Jan 28
KeywordsAdult, Aged, Aged, 80 and over, Aging, Anisotropy, Brain, Brain Mapping, Cell Count, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Neurites, Neurons, Oxygen, Rest, Statistics, Nonparametric, Young Adult

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.

Alternate JournalJ. Neurosci.
PubMed ID25632148
PubMed Central IDPMC4308611
Grant ListR01 MH097979 / MH / NIMH NIH HHS / United States
R01MH099167 / MH / NIMH NIH HHS / United States
R01MH102324 / MH / NIMH NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada