Rest-activity rhythms and white matter microstructure across the lifespan

Abstract

Study objectives: The purpose of this study was to examine how rest-activity (RA) rhythm stability may be associated with white matter microstructure across the lifespan in healthy adults free of significant cardiovascular risk.

Methods: We analyzed multi-shell diffusion tensor images from 103 healthy young and older adults using tract-based spatial statistics (TBSS) to examine relationships between white matter microstructure and RA rhythm stability. RA measures were computed using both cosinor and non-parametric methods derived from 7 days of actigraphy data. Fractional anisotropy (FA) and mean diffusivity (MD) were examined in this analysis. Because prior studies have suggested that the corpus callosum (CC) is sensitive to sleep physiology and RA rhythms, we also conducted a focused region of interest analysis on the CC.

Results: Greater rest-activity rhythm stability was associated with greater FA across both young and older adults, primarily in the CC and anterior corona radiata. This effect was not moderated by age group. While RA measures were associated with sleep metrics, RA rhythm measures uniquely accounted for the variance in white matter integrity.

Conclusions: This study strengthens existing evidence for a relationship between brain white matter structure and RA rhythm stability in the absence of health risk factors. While there are differences in RA stability between age groups, the relationship with brain white matter was present across both young and older adults. RA rhythms may be a useful biomarker of brain health across both periods of adult development.

Keywords: actigraphy; aging; circadian rhythms; neuroimaging; sleep and the brain.

Figure 1.

Calculation of rest-activity rhythm amplitude for two example older adult participants with high and low rhythm amplitudes. Subject 1. Examination of activity level data for the high amplitude participant shows well-defined rest intervals (in blue). These rest and active intervals repeat in a similar way from day to day, indicating greater day-to-day stability in rest-activity rhythm, which results in a greater rhythm amplitude value. Subject 2. In contrast, the low amplitude participant shows less defined rest intervals with greater variation across in both rest interval duration and frequency, resulting in a lower rhythm amplitude value.

Figure 2.

Results of TBSS analyses examining age group differences in (A) FA and (B) MD between healthy young and older adults superimposed on the MNI standard. The average white-matter skeleton is presented in green. Red and blue colored areas indicate regions of the skeleton in which significant age group differences in diffusion metrics were observed at p < 0.05 (TFCE; corrected for multiple comparisons). Areas where younger adults showed greater values for diffusion metrics are shown in warm colors, whereas areas where younger adults showed lower values are shown in cool colors. Surrounding voxels were augmented for visual purposes.

Figure 3.

Results of TBSS analyses examining correlations between rhythm amplitude and FA superimposed on the MNI standard. The average white-matter skeleton is presented in green. Warm colors indicate areas of the white matter skeleton for which there was a positive correlation between rhythm amplitude and FA across all subjects at p < 0.05 (TFCE; corrected for multiple comparisons). Surrounding voxels were augmented for visual purposes.

Figure 4.

Scatter plots showing relationships between (A) rhythm amplitude and corpus callosum (CC) FA, (B) rhythm amplitude and CC volume, and (C) CC volume and CC FA.