Neuroprotective Effects of Motherhood on Brain Function in Late Life: A Resting-State fMRI Study

Abstract

The maternal brain undergoes structural and functional plasticity during pregnancy and the postpartum period. Little is known about functional plasticity outside caregiving-specific contexts and whether changes persist across the lifespan. Structural neuroimaging studies suggest that parenthood may confer a protective effect against the aging process; however, it is unknown whether parenthood is associated with functional brain differences in late life. We examined the relationship between resting-state functional connectivity and number of children parented in 220 healthy older females (73.82 ± 3.53 years) and 252 healthy older males (73.95 ± 3.50 years). We compared the patterns of resting-state functional connectivity with 3 different models of age-related functional change to assess whether these effects may be functionally neuroprotective for the aging human parental brain. No relationship between functional connectivity and number of children was obtained for males. For females, we found widespread decreasing functional connectivity with increasing number of children parented, with increased segregation between networks, decreased connectivity between hemispheres, and decreased connectivity between anterior and posterior regions. The patterns of functional connectivity related to the number of children an older woman has parented were in the opposite direction to those usually associated with age-related cognitive decline, suggesting that motherhood may be beneficial for brain function in late life.

Trial registration: ClinicalTrials.gov NCT01038583.

Keywords: aging; neuroprotection; parenthood; resting-state functional connectivity.

© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1

Cartoon schematics for 3 patterns of age-related functional brain changes in the late-life parental brain. Red denotes increased resting-state functional connectivity, and blue denotes decreased resting-state functional connectivity. In order to assess hemispheric asymmetry and frontal compensation, regions are ordered according to anatomy (hemispheres and lobe assignment), whereas assessing network integration/segregation requires a functional organization (networks). (a) Hemispheric asymmetry: Cartoon schematic of the HAROLD effect (Cabeza 2002). Aging is associated with reduced functional lateralization. Therefore, results consistent with aging in the HAROLD pattern would show “increased” functional connectivity between hemispheres (left–right/right–left), shown in red. Decreased functional connectivity between hemispheres would be consistent with a reduced HAROLD effect (increased hemispheric asymmetry), indicative of resilient aging, shown in blue. (b) Posterior-to-anterior shift: Cartoon schematic of the PASA pattern (posterior–anterior shift in aging; Davis et al. 2008). Aging is associated with increased connectivity between anterior (prefrontal) regions and other areas (shown in red), consistent with a shift from posterior to anterior processing. Decreased functional connectivity between nodes of the frontal lobe and other regions would be consistent with a reduced PASA effect (less frontal compensation), indicative of resilient aging (shown in blue). (c) Network integration/segregation: Cartoon schematic of integration and segregation. Within-network connections lie on the diagonal (e.g., visual–visual), and between-network connections lie on the off-diagonal (e.g., visual–default mode). Aging is associated with increased integration and decreased segregation of functional networks. Results consistent with age-related changes would show increased functional connectivity between networks (integration), shown in red. Decreased functional connectivity between networks (segregation) would therefore indicate resilient aging, shown in blue.

Figure 2

Mean functional connectivity for healthy older males (n = 252) and females (n = 220) who parented between 1 and 6 children. Each row and column of the 82 × 82 matrix represents a node (41 nodes in the left hemisphere and 41 in the right), organized by anatomical division (i.e., frontal, parietal, subcortical, temporal, occipital). Each cell represents the functional connectivity between 2 nodes, after adjusting for age, education, hemoglobin, and cortical thickness. Blue cells indicate negative edge weights and red cells indicate positive edge weights. The matrix has diagonal symmetry, such that the upper and lower triangles are mirrored. These matrices show the global functional connectivity for mothers and fathers and do not reflect results of any significance tests.

Figure 3

(a) Resting-state functional connectivity for mothers: Adjacency matrix of pairwise correlations for the 47 edges associated with motherhood. The 82 ROIs are arranged by hemisphere then by anatomical division (frontal, parietal, subcortical, temporal, occipital) such that each row and column of the 82 × 82 matrix represents one node (41 nodes in the left hemisphere and 41 in the right). Each cell represents a significant edge between 2 nodes. The matrix has diagonal symmetry, such that the upper and lower triangles are mirrored, and each contains 47 edges. Blue cells signify negative edge weights and red cells signify positive edge weights. All edges related to motherhood are negatively weighted, showing decreasing functional connectivity between node pairs as number of children increases. (b) Schematic of results in relation to HAROLD (Cabeza 2002): The blue quadrants highlight between-hemisphere connections (33 left–right and right–left edges), which is 1.4 times as many edges between hemispheres as would be expected by chance. The lighter colored quadrants highlight within-hemisphere connections; left–left (8 edges; one-third [0.34] as many edges as would be expected by chance) and right–right (6 edges; one-quarter [0.25] of what would be expected by chance). Older mothers show decreased functional connectivity between hemispheres with increasing number of children. Seventy percent (33/47) of the observed edges are between-hemisphere connections. Decreasing functional connectivity between the left and right hemispheres indicates “increased” hemispheric asymmetry with increased number of children mothered. This pattern is consistent with a “reduced HAROLD effect,” indicative of resilient aging in mothers. (c) Schematic of results in relation to PASA (Davis et al. 2008): The blue bars highlight connections with the left and right prefrontal cortex, colored to compare the observed edges with the number that would be expected by chance. For example, there are 3.2 times as many edges between left anterior (frontal) regions and right posterior regions than would be expected by chance. Sixty-four percent (30/47) of the observed edges show decreased functional connectivity between regions of the prefrontal cortex and other regions, indicating “less” frontal compensation with increasing number of children mothered. This pattern is consistent with a “reduced PASA effect,” indicative of resilient aging.

Figure 4

Functional connectivity within and between brain networks (i.e., frontoparietal, dorsal attention, ventral attention, default mode, somatomotor, limbic, subcortical, and visual; as classified by Yeo et al. (2011). (a) MNI space network graph of the edges associated with motherhood (left: axial; top: coronal; bottom: sagittal). The nodes are weighted by degree, such that nodes with a higher number of connections are larger. Edges are weighted by the strength of Spearman’s Rho, such that edges with stronger connectivity are darker and thicker. (b) Segregation and integration: Functional connectivity within and between networks. Within-network connections lie on the diagonal (e.g., visual–visual), and between-network connections lie on the off-diagonal (e.g., visual–default mode). The numbers denote how many more edges are observed between networks, compared with what we would expect by chance, after adjusting for the capacity of the network, for example, we observed 7.1 times more edges between the frontoparietal network and the visual network than we would expect by chance. All edges related to motherhood are negatively weighted; therefore, decreasing connectivity between networks (off-diagonal) indicates increased network segregation with increasing number of children mothered.