SBM results demonstrating the four independent white matter components that were identified. White matter components 2 and 4 were significantly related to age [r₍₄₁₎ = −0.49, p < 0.001 and r₍₄₁₎ = −0.32, p < 0.05, respectively]. Only white matter component 2 was significantly related to Connections Simple processing speed [r₍₄₁₎ = 0.44, p < 0.005].

Combined and unique gray matter components 2, 4, and 7 associations with Connections Simple processing speed. Note that gray matter component 2 is driven in part by two young subjects with elevated gray matter (positive values), which is represented by the relatively lower correlation estimates with Connections Simple presented in Table 3.

Structural covariance between cerebellar gray matter and brainstem white matter. (A) Gray matter component 4 is displayed with white matter component 2 to demonstrate the space correspondence between the components (left hemisphere: top row; right hemisphere: bottom row). Note that the white matter component abuts regions of the gray matter component, including in regions throughout the cerebellum, parietal cortex, and parietal–occipital–temporal cortex (red arrows). (B) Individual variation in the volume estimates for gray matter component 4 and white matter component 2 are significantly correlated [r₍₄₁₎ = .68, p < 0.001]. People with elevated cerebellar gray matter had elevated white matter within regions that project to the cerebellum. The circles are shaded to indicate that both components predict performance on the Connections Simple processing speed measure.

Results demonstrating the seven independent gray matter components that were identified using SBM. Components 1, 2, 4, and 5 in particular, have spatial patterns that are frequently observed in analyses of functional imaging data (Raichle et al., 2001; Greicius et al., 2003; Beckmann et al., 2005; Damoiseaux et al., 2006; Calhoun et al., 2008). Components 1, 3, 4, 6, and 7 exhibited age-related changes. Components 2, 3, 4, and 7 exhibited significant associations with processing speed, as defined by the Connections Simple task involving perceptual and motor speed. Only component 6 was related to higher order processing speed function (working memory and inhibition) as measured by Connections Complex after controlling for Connections Simple performance. Left/right refers to left and right hemisphere.

Images from the youngest and oldest adults required the most volume displacement during normalization, but visual inspection demonstrates that there were no DARTEL normalization errors due to this displacement. (A) Jacobian determinant images, that reflect the degree of volumetric displacement during normalization, were obtained from the DARTEL gray matter flow fields. There was significant age-related variation in the extent to which regions surrounding the ventricles and CSF in general required displacement during normalization (1% FDR). The results are overlaid on the study-specific DARTEL template. (B) An estimate [eigenvariate from the age-related effect shown in (A)] of how much each subject's lateral ventricles had to be displaced to fit to the template is plotted across age demonstrating that many younger, middle-aged, and older subjects required little ventricle displacement. Note that total gray matter volume was not related to the amount of ventricular displacement (GM, gray matter). (C) Visual inspection of the normalized gray matter images in three young female subjects and three of the oldest female subjects [labeled numerically in (B)] requiring the most volume displacement demonstrates that all were appropriately normalized to a common space. Note the close correspondence in the position of the head of the caudate across the six subjects (red arrows). Note also that there were areas where white matter regions were segmented as gray matter in the older adults (yellow arrows) and identified using SBM (Figure 2).

The impact of cerebral small vessel disease on processing speed. (A) A probability map of WMH. WMH were observed with the highest probability in periventricular regions, as well as the optic radiations. The orange arrows indicate the location of WMH where white matter was segmented as gray matter and identified as part of component 7 (Figure 2 – orange arrow). (B) Nonparametric lesion-mapping results demonstrating locations of WMH most consistently associated with slow processing speed. (C) The presence of a WMH anywhere within the regions presented in (B) was determined for each subject in order to examine the impact of WMH in these regions on processing speed (1% FDR = Z score threshold of 2.33). The scatter plots compare Connections Simple performance for people with and without WMH in the right corona radiata (blue arrow), left posterior periventricular white matter (pink arrow), and right anterior periventricular white matter (orange arrow) regions. The circles are shaded to indicate the degree to which each subject's lateral ventricles had to be displaced during normalization (Figure 1A). Note that the people with WMH had images requiring the most displacement during normalization [WMH classification comparison with ventricle displacement: F_(2,41) = 8.95, p < .001]. Left/right refers to left and right hemisphere.