Lower grey matter, increased white matter: What pregnancy does to the maternal brain

The woman's brain shows widespread neuronal alterations before, during, and after pregnancy.

The mother's breasts may begin producing milk weeks or months before the baby arrives. During pregnancy, the abdominal muscles actively separate to accommodate the developing belly. During the second stage of labour, the pelvic bones spread to allow the baby's shoulders to pass through, resulting in permanently larger hips, stretch marks, and loose skin. Everyone is aware of these developments. What about the brain?

A recent study using repeated brain scans of pregnant women shed light on this unexplored area, resulting in the first-ever map of the human brain throughout pregnancy. Surprisingly, pregnancy causes profound changes in a woman's brain. Pregnancy lowers grey matter, the wrinkly outer part of the brain and increases white matter deep inside. The study, published in the most recent issue of Nature Neuroscience, was undertaken by a team of researchers from the Universities of California, Santa Barbara, and Irvine.

“We wanted to look at the trajectory of brain changes specifically within the gestational window," said Laura Pritschet. Previous studies had taken snapshots of the brain before and after pregnancy. In contrast, the nine months of pregnancy was a black box.

Cognitive neuroscientist Liz Chrastil, one of the research team members, was the subject of the study whose brain was mapped. She went in for in-vitro fertilisation and volunteered for the study.

The researchers used precision imaging to analyse the changes in the brain during pregnancy in a healthy 38-year-old woman. They began brain imaging three weeks before she conceived and continued to take brain scans and blood samples once every few weeks for two years after the kid was delivered. The brain scans captured the dynamic brain reorganisation during the gestation. "Leveraging precision imaging, we mapped neuroanatomical changes in an individual," say the authors. They added that the brain "undergoes adaptive, hormonally-driven neuroanatomical changes" during pregnancy.

Nearly one in every five women has prenatal depression, yet there is no early diagnosis procedure. Pregnancy can exacerbate or aggravate neurological problems such as epilepsy, headaches, and intracranial pressure. "Precision imaging studies could offer clues about an individual's risk for or resilience to depression and other neurological disorders, before symptom onset, helping clinicians better determine when and how to intervene," says the authors.

Cognitive neuroscientist Liz Chrastil, one of the research team members, was the subject of the study whose brain was mapped. She went in for in-vitro fertilisation and volunteered for the study.

In addition to decreasing grey matter volume and increasing white matter, the researchers discovered that the cortical layer decreased. In contrast, ventricle volume and cerebrospinal fluid rose. Nonetheless, the transition to motherhood left certain parts of the brain unaffected. "We observed widespread reductions in cortical grey matter volume (GMV) and cortical thickness (CT) occurring in step with advancing gestational week and the dramatic rise in sex hormone production," says the authors.

Pregnancy induces profound changes in the mother's body to support the growing fetus. "Over an approximately 40-week gestational window, the maternal body undergoes profound physiological adaptations to support the development of the fetus, including increases in plasma volume, metabolic rate, oxygen consumption, and immune regulation," observe the authors.

Serum hormone concentrations rose considerably throughout pregnancy and fell sharply after childbirth. Hormone synthesis increased by 100- to 1,000-fold, including estrogen and progesterone. Hormones such as estrogen and progesterone act as neuromodulators, driving brain reconfiguration. For example, the microscopic structure of human white matter brain tissue has been linked to information processing speed and cognitive abilities. The study indicated that during pregnancy, white matter microscopic integrity increased in tandem with the rise in levels of 17β-estradiol and progesterone hormones. "Broad physiological changes occur in tandem with the rise in steroid hormones, including changes in body mass composition, water retention, immune function and sleep patterns", says the authors.

The researchers mapped the neuroanatomical changes throughout pregnancy in only one individual, which limits their capacity to generalise. As we age, our brains grow and alter. Thus, the observed differences might be due to normal brain development, not pregnancy. Nonetheless, the researchers compared the alterations detected during pregnancy to data from nonpregnant individuals, proving that pregnancy-related neuroanatomical adjustments vastly outnumber normal development and change.

Earlier studies have indicated that the women's brain undergoes a major overhaul in adolescence. This study suggests that matrescence, that is, becoming a mother, is yet another stage in the development of the female brain.

Grey matter, which is present in the brain and spinal cord, regulates memory, movement, and emotions. White matter, a kind of brain tissue that links different areas of the brain, allows impulses to be sent and received. This has implications for many aspects of cognition and behaviour, including learning, problem-solving, and balance.

The researchers used high-resolution imaging to identify changes in the brain as pregnancy progressed. The researchers discovered a considerable decrease in grey matter in brain areas responsible for sensory processing, attention, and the default mode network, which stays active while the brain rests or engages in self-referential thought. The reduction in grey matter was as high as 4 % in some brain regions. However, a decrease in grey matter volume is not necessarily alarming; perhaps the brain is undergoing cortical refinement, shedding excess parts.

Similarly, the brain areas that promote communication between white matter's emotional and visual processing hubs expanded. "These cellular changes are pronounced in brain circuits that promote maternal behaviour," say the authors.

The extent of brain changes throughout pregnancy is astonishing and consistent during the gestational weeks. For example, researchers discovered that white matter grew throughout the first and second trimesters before reverting to baseline levels in the postpartum period. However, grey matter volume decreased linearly throughout gestation and appeared to somewhat rebound afterwards. The lateral ventricles, two enormous chambers containing cerebrospinal fluid, grew during the second and third trimesters before contracting fast after birth. Nevertheless, “There was no significant change in other subregions or total volume of the hippocampal body, or in the parahippocampal gyrus,” say the authors. A more in-depth look at cellular and system-level processes will help us understand how pregnancy alters particular circuits to support maternal behaviour.

Some alterations, such as decreased grey matter volume and cortical thinning, remain for two to six years after the child’s birth, and some may be lifelong. Others, such as white matter integrity, seem to be temporary. “We observed large increases in white matter microstructural integrity throughout the first and second trimesters of pregnancy, but these measures fully returned to baseline values by the first postpartum scan,” says the authors.

Pregnancy is a highly dynamic period of brain remodelling, yet until this study, "neuroscientists lacked a detailed map of how the human brain changes throughout the gestational period", says the authors. Understanding how the changes in the grey and white matter unfold in the maternal brain is "key to understanding the behavioural adaptions that emerge during and after pregnancy, such as honing the brain's visual and auditory responses to infant cues and eliciting maternal behaviour", says the authors. Further, they added, “This dataset serves as a comprehensive map of the human brain across gestation, providing an open-access resource for the brain imaging community to further explore and understand the maternal brain.”

The research team included Laura Pritchett, Caitlin M. Taylor, Tyler Santander, Hannah Grotzinger, Evan Layher and Emily G. Jacobs from Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA, USA, Daniela Cossio and Elizabeth R. Chrastil from Department of Neurobiology and Behaviour, University of California, Irvine, CA, USA, Joshua Faskowitz and Daniel A. Handwerker from Section on Functional Imaging Methods, Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

The paper was published in Nature Neuroscience's September 16, 2024 issue. (https://doi.org/10.1038/s41593-024-01741-0)