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Pregnancy Leads to Long Lasting Changes in Human Brain Structure

Abstract

Sex hormones are known to be regulators of neurons and the profound hormone changes that occur during pregnancy are thought to cause alterations in brain structure and function. This study investigated cortical gray matter volume in primiparous women compared to their baseline, to nulliparous women and their male counterparts. They saw gray matter reductions only in primiparous women. The affected areas overlapped with the theory of mind network and the gray matter reductions predicted the quality of mother-infant attachment. These regions also exhibited high activity when women were shown pictures of their babies. The volume changes endured 2 years postpartum, except for partial volume recovery in the hippocampus. This research suggests that the female brain undergoes maturation and specialization induced by sex hormones during pregnancy and that these changes are integral for attachment with the child.

Introduction

The female body undergoes tremendous physical changes throughout pregnancy to ensure the proper development of the fetus, which includes the maintenance of incredibly high levels of sex hormones over a prolonged period. There is up to a 15 fold increase in progesterone and up to a 30 fold increase in estrogen and these levels have lasting effects on the mother, in addition to the baby (Casey et al., 1993). Sex hormones act as regulators of neurons and thus produce profound changes in brain structure and function (Toffoletto et. al 2014). For instance, previous studies demonstrate that hormonal changes during puberty enact long-lasting changes in the brain, such as decreasing gray matter volume (Peper et al., 2011).

Very few studies have examined the brain during pregnancy and report enlargement of the pituitary gland, increased ventricle size, and decreased brain volume in postpartum women compared to their baseline (Hililerer et al., 2014). Other changes observed at the cellular level include alterations in gene expression, changes in cell density, and differences in dendritic morphology (Toffoletto et. al 2014). Researchers hypothesize that these changes serve to regulate maternal behaviors and are crucial for proper neonatal development (Casey et al., 1993).

This study investigated the cortical gray matter volume over time to discern whether pregnancy was associated with neural changes. They compared the brains of primiparous mothers to nulliparous women and first-time fathers to determine if gray matter reductions are attributed to the hormonal changes of pregnancy. They also investigated the link between the changes and measures of maternal attachment.

Methods

A total of 25 primiparous women, 20 nulliparous women, 19 first-time fathers, and 17 childless men were recruited via the Instituto Valenciano de Infertilidad. Participants received MRI brain scans at baseline and during a post-assessment after time had passed in which they either had a child or did not. They were evaluated using the Maternal Postnatal Attachment Scale and cognitive tests including worklist and backward digit tasks. A two-sample t-test was performed to compare the gray matter volume changes between the groups. Additional analyses were conducted to determine if other pregnancy-related variables influenced the results. Surface-based analyses were performed to identify changes in surface area and cortical thickness.

A linear support vector machine classification was applied to the post-pre difference maps to examine if the reductions in gray matter could be used to predict if a woman had undergone a pregnancy. Next, the researchers determined the intersection between the map of the reductions in gray matter volume and the theory of mind network. Additionally, they investigated whether changes in gray matter volume were associated with the results of the Maternal Postnatal Attachment Scale and fMRI activity patterns during a test in which mothers were shown pictures of their baby.

Results

There were no differences between the baseline scans, which suggests the absence of preexisting differences between the groups. Reductions in gray matter volume were observed in primiparous women compared to their baseline and to nulliparous women. The changes were absent in first-time fathers and childless men. 95.6% of women could be classified as either primiparous or nulliparous based on the examination of their average gray matter volume change. Gray matter thickness and cortical surface area, two measures that influence gray matter volume, were also both reduced in the primiparous mothers. There were no significant changes in the results when researchers included other variables such as type of conception and delivery, breastfeeding status, number and gender of the fetus and depression diagnosis.

The cortical areas that had reduced gray matter volume in primiparous women were localized to specific regions that were consistent across individuals. The greatest reductions were observed in the anterior and posterior midline, bilateral lateral prefrontal cortex, and bilateral temporal cortex. These areas play a role in social cognition and have significant overlap with the functional networks involved in theory of mind tasks.

The degree of gray matter volume reduction significantly predicted the quality of mother-infant attachment. Greater reductions in volume were associated with improved quality of attachment and decreased hostility of mothers towards their children. Additionally, upon being shown images of their babies, the strongest neural activity occurred in the regions of the brain that had reduced gray matter volume. There were also no significant changes in cognitive test results due to pregnancy. Finally, the gray matter volume reductions were highly preserved in the 11 mothers who had not undergone a second pregnancy two years later. Besides slight volume recovery in the left hippocampus, there were no further changes in gray matter volume.

Discussion

The reductions in gray matter in the brains of primiparous women compared to their baseline suggests that these changes are associated with pregnancy. Additionally, women who had not undergone a pregnancy did not display these neural changes and reductions in gray matter were also absent in first-time fathers and the control men. This pattern suggests that the changes in brain structure are attributed to hormonal changes in the pregnant body, not psychosocial changes during the onset of parenthood.

The gray matter reductions were not randomly distributed throughout the brain; instead, they were localized to specific regions, particularly the theory of mind network. The theory of mind network is an integral part of the maternal brain because it helps the mother to accurately identify her infant’s mental state. This ability is essential for secure bonding and attachment with the infant, which provides a basis for the appropriate development of the child's own social cognitive functioning.

Along these lines, it was demonstrated reductions in gray matter volume predict greater mother-infant attachment quality and the absence of hostility towards the child. The areas of reduced gray matter were correlated with the areas of the strongest response to the pictures of a mother’s own child. These results suggest that the structural changes in the theory of mind network lead to alterations in the functioning of the theory of mind network. The reductions in gray matter volume were preserved in primiparous women at the 2 year follow up, and the only noted change was partial volume recovery in the hippocampus. This may explain the memory deficits that are associated with pregnancy but are recovered soon afterward.

Conclusion

This research demonstrated that there are pronounced changes in the brain of women who undergo pregnancy and they are likely caused by high hormone levels. Previous studies have shown that during puberty, increased estradiol levels lead to cortical thinning as a result of synaptic pruning of the functional networks in the maturing brain. This evidence supports the hypothesis that the female brain undergoes maturation and specialization during pregnancy in preparation for the postpartum period. The enhancement of the mother’s emotional recognition as a result will prove essential in determining the needs of her child. Future research could investigate the molecular mechanisms of the reduced gray matter volume in first-time mothers and examine neural changes after multiple pregnancies. In sum, this research provides further evidence for the dynamic nature of the cortex and demonstrates that plasticity across pregnancy has the advantage of facilitating maternal attachment.

References

Casey, M.L., MacDonald, P.C., Sargent, I.L. & Starkey, P.M. Placental endocrinology. in The Human Placenta (ed. Redman, C.W.G.) 237–272 (Blackwell Scientific, Oxford, 1993)

Hillerer, K.M., Jacobs, V.R., Fischer, T. & Aigner, L. The maternal brain: an organ with peripartal plasticity. Neural Plast. 2014, 574159 (2014).

Hoekzema, E., Barba-Müller, E., Pozzobon, C., Picado, M., Lucco, F., García-García, D., … Vilarroya, O. (2016). Pregnancy leads to long-lasting changes in human brain structure. Nature Neuroscience, 20(2), 287–296. doi: 10.1038/nn.4458

Peper, J.S., Hulshoff Pol, H.E., Crone, E.A. & van Honk, J. Sex steroids and brain structure in pubertal boys and girls: a mini-review of neuroimaging studies. Neuroscience 191, 28–37 (2011).

Toffoletto, S., Lanzenberger, R., Gingnell, M., Sundström-Poromaa, I. & Comasco, E. Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: a systematic review. Psychoneuroendocrinology 50, 28–52 (2014).