Age and sex effects on corpus callosum morphology across the lifespan

Abstract

The corpus callosum (CC) is the largest interhemispheric white matter tract in the human brain, and is characterized by pronounced differences in morphology among individuals. There are limited data, however, regarding typical development, sex differences, and the neuropsychological correlates of individual differences within CC subregions. Magnetic resonance (MR) imaging exams were collected in a large cohort (N = 305) of healthy individuals (ages 8-68). We used a highly reliable program to automatically identify the midsagittal plane and obtain CC subregion measures according to approaches described by Witelson [1989]: Brain 112:799-835 and Hampel et al. [1998]: Arch Neurol 55:193-198 and a measure of whole CC shape (i.e., circularity). CC measurement parameters, including area, perimeter, length, circularity, and CC subregion area values were generally characterized by inverted U-shaped curves across the observed age range. Peak values for CC subregions were observed between ages 32 and 45, and descriptive linear correlations were consistent with sharper area changes in development. We also observed differing age-associated changes across the lifespan between males and females in the CC subregion corresponding to the genu (Witelson's subregion 2), as well as CC circularity. Mediation analysis using path modeling indicated that genu area mediated the relationship between age and processing speed for females, and the relationship between age and visual learning and executive functioning for males. Taken together, our findings implicate sex differences in CC morphology across the lifespan that are localized to the genu, which appear to mediate neuropsychological functions.

Keywords: corpus callosum; lifespan; neuropsychological functioning; sex differences.

Figure 1

Witelson Subregion Segmentation. Notes. Segmentation using the Witelson [1989] approach was performed automatically by placing five perpendicular lines across the maximum length of the CC at 1/5, 1/3, and 1/2 the distance from the outer limits of the genu and splenium. Subregion 1 (W1, red) corresponds to the rostrum, W2 (orange) corresponds to the genu, W3 (yellow) corresponds to the rostral body, W4 (green) corresponds to the anterior midbody, W5 (blue) corresponds to the posterior midbody, W6 (purple) corresponds to the isthmus, and W7 (lavender) corresponds to the splenium. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Hampel Subregion Segmentation. Notes. The segmentation scheme proposed by Hampel et al. [1998] was automatically performed by forming a rectangle bordering anterior, posterior, dorsal, and ventral aspects of the CC and projecting 10 rays spaced 36° apart around the center point (+) of the ventral line segment. Four rays within the rectangle constraining the CC divided it into five subregions including C1 (red, genu inclusive of the rostrum), C2 (orange, anterior midbody), C3 (yellow, posterior midbody), C4 (green, isthmus), and C5 (blue, splenium). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Witelson Region 2 (W2) Values by Age and Sex. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 4

Circularity Values by Age and Sex. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 5

Path diagram reflecting significant maximum likelihood estimates (standard errors) for male subjects. Significance level of maximum likelihood estimates: *≤0.05, **≤0.01, ***≤0.001. Black lines reflect significant maximum likelihood estimates (P ≤ 0.05), gray lines reflect nonsignificant findings (P > 0.05).

Figure 6

Path diagram reflecting significant maximum likelihood estimates (standard errors) for female subjects. Significance level of maximum likelihood estimates: *≤0.05, **≤0.01, ***≤0.001. Black lines reflect significant maximum likelihood estimates (P ≤ 0.05), gray lines reflect nonsignificant findings (P > 0.05).