Functional Consequences of Neurite Orientation Dispersion and Density in Humans across the Adult Lifespan

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.

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

“…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…”

“…Neurites allow the exchange of information among neurons, and there is evidence to believe that changes of their architecture can impact directly on neural function 23. Alteration of dendrite morphology could account per se for impairment beyond mere neuronal death 24.…”

Gray Matter Neuritic Microstructure Deficits in Schizophrenia and Bipolar Disorder

“…NODDI-gray matter-based spatial statistics (NODDI-GBSS) to perform voxel-wise statistical analysis on GM microstructure has been described elsewhere in more details (19,26). Briefly, GM fraction maps were estimated in the native diffusion space by subtracting CSF fraction (f CSF maps from NODDI) and WM fraction (estimated by twotissue class segmentation of FA images using Atropos (35)) from 1 in each voxel (19).…”

“…This technique characterizes: the spatial configuration of the neurites with the orientation dispersion index (ODI); and tissue microstructural composition with the neuritic density index (NDI), the volume fraction of neurites in brain tissue (15). We have recently shown in healthy individuals that these measures are: sensitive to GM changes secondary to aging; associated with cognitive performance; and a better predictor of chronological age than cortical thickness or WM microstructure (19).…”

“…Using NODDI to characterize GM microstructure, our primary objective was to assess potential differences among individuals with schizophrenia, those with BD-I or those who are healthy (19,26). As the majority of the neuropathological findings described in people with schizophrenia and BD-I are located in frontal and temporal lobes (27), we hypothesized that we would find neuritic abnormalities in the same areas among individuals with schizophrenia and BD-I, but with smaller effects in those with BD-I.…”