The objective of this work was to test the hypotheses that a) more frequent cognitive activity in late life is associated with higher brain diffusion anisotropy and lower trace of the diffusion tensor, and b) brain diffusion characteristics partially mediate the association of late life cognitive activity with cognition. As part of a longitudinal cohort study, 379 older people without dementia rated their frequency of participation in cognitive activities, completed a battery of cognitive function tests, and underwent diffusion tensor imaging. We used tract-based spatial statistics to test the association between late life cognitive activity and brain diffusion characteristics. Clusters with statistically significant findings defined regions of interest in which we tested the hypothesis that diffusion characteristics partially mediate the association of late life cognitive activity with cognition. More frequent cognitive activity in late life was associated with higher level of global cognition after adjustment for age, sex, education, and indicators of early life cognitive enrichment (p=0.001). More frequent cognitive activity was also related to higher fractional anisotropy in the left superior and inferior longitudinal fasciculi, left fornix, and corpus callosum, and lower trace in the thalamus (p<0.05, FWE-corrected). After controlling for fractional anisotropy or trace from these regions, the regression coefficient for the association of late life cognitive activity with cognition was reduced by as much as 26 %. These findings suggest that the association of late life cognitive activity with cognition may be partially mediated by brain diffusion characteristics.

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Resting-state functional magnetic resonance imaging has been increasingly used for examining connectivity across brain regions. The spatial scale by which hemodynamic imaging can resolve functional connections at rest remains unknown. To examine this issue, deoxyhemoglobin-weighted intrinsic optical imaging data were acquired from the visual cortex of lightly anesthetized ferrets. The neural activity of orientation domains, which span a distance of 0.7-0.8 mm, has been shown to be correlated during evoked activity and at rest. We performed separate analyses to assess the degree to which the spatial and temporal characteristics of spontaneous hemodynamic signals depend on the known functional organization of orientation columns. As a control, artificial orientation column maps were generated. Spatially, resting hemodynamic patterns showed a higher spatial resemblance to iso-orientation maps than artificially generated maps. Temporally, a correlation analysis was used to establish whether iso-orientation domains are more correlated than orthogonal orientation domains. After accounting for a significant decrease in correlation as a function of distance, a small but significant temporal correlation between iso-orientation domains was found, which decreased with increasing difference in orientation preference. This dependence was abolished when using artificially synthetized orientation maps. Finally, the temporal correlation coefficient as a function of orientation difference at rest showed a correspondence with that calculated during visual stimulation suggesting that the strength of resting connectivity is related to the strength of the visual stimulation response. Our results suggest that temporal coherence of hemodynamic signals measured by optical imaging of intrinsic signals exists at a submillimeter columnar scale in resting state.

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