New Study Finds Sex Differences in Fetal Brain Development

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Brain development, especially before birth, is crucial to one’s mental health later in life. We know from previous research that disturbed development in the womb is linked to disorders such as autism and schizophrenia. For this reason, researchers are developing new ways to track brain development in the womb by measuring the complexity of fetal brain signals.

According to results of our study published last week (February 23) in Nature Mental Health, even as birth nears, the complexity of brain activity decreases with fetal maturation and continues to decline after birth. More surprising still, male and female fetuses show different changes in complexity, with boys declining faster than girls.

These findings are based on magnetic brain activity recorded from fetuses and newborns in response to sequences of auditory tones. Our findings carry important implications for future efforts to predict one’s risk of psychiatric disorders based on the complexity of brain activity recorded before birth: "The earlier we identify the risk for the development of neuropsychiatric and metabolic disorders, the more effectively we can support brain development to prevent serious disease progression," said co-senior author Professor Alireza Gharabaghi, director of the Institute for Neuromodulation and Neurotechnology at the University of Tuebingen, in a press release.

As a postdoctoral researcher at the University of Tuebingen and lead author of this study, I'm fascinated by how our sex findings might relate to the greater vulnerability of the male brain during gestation. Neurodevelopmental disorders with a genetic basis, like autism and ADHD, are diagnosed more frequently in boys than girls, suggesting that sex impacts the development of the brain from its earliest developmental stages. While it’s still unclear whether the complexity of brain activity before birth relates to psychiatric outcomes, earlier work by others has predicted the onset of autism years later from the complexity of brain activity recorded in young infants. We know from this earlier work, such as studies by Prof. Charles Nelson’s lab at Harvard, that complexity matters for predicting health outcomes, and this motivates our research into fetal brain complexity.

Recording brain activity in human newborns, and especially in fetuses, is a challenging feat that our team accomplished using a technology called magnetoencephalography or MEG, which measures magnetic brain signals. Specifically, my colleagues at the Tuebingen fMEG Center recorded magnetic brain responses to auditory irregularities as part of an earlier study designed to investigate learning in third trimester fetuses and newborns.

This earlier study, led by Julia Moser, who is also a coauthor of the present study, found evidence that magnetic brain signals show a deflection in fetuses, starting from 35 weeks gestation, and newborns when a pattern in a sequence of auditory beeps is broken, almost as if the fetus is saying “huh?”. This surprise response suggests that both newborns and late-term fetuses can learn patterns. "Sensory stimulation provides us with a unique opportunity to observe how young brains process information from the outside," said co-senior author Professor Hubert Preissl, director of the fMEG Center, in a press release. "And in a completely safe way."

A pregnant woman demonstrates how red light can be projected through the womb during a fetal MEG recording at the University of Tuebingen, Germany.

Source: Photo by Joel Frohlich, with written consent of the volunteer subject

Although we expected to see brain activity growing more complex with fetal development, our results showed exactly the opposite. I was surprised. Intuitively, I thought that as the brain matures, its activity should grow more complex just as its anatomy and function grows more complex. In hindsight though, our findings make a lot of sense, especially considering the fact that we recorded brain responses to sounds, rather than spontaneous activity. As the brain matures and develops, it moves away from “disorder” toward ordered patterns of connections within brain circuits. These patterns essentially tell the brain how to respond to stimuli such as the auditory beeps in the experiments led by Moser. Thus, a more developed brain has fewer ways of responding to the same stimulus, and therefore lower complexity.

If our team’s findings come as a surprise, it may be in part because studies of brain activity in human fetuses are rare. Only two machines in the world, including the device at the fMEG Center in Tuebingen, are solely dedicated to recording MEG from human fetuses. We can learn a lot about the fetal brain, probably more than what many people assume is possible. MEG technology is becoming more sophisticated, and there will soon be many more groups studying fetal brain activity with the next generation of MEG devices.

As a precursor to our current work, we published a study in April of last year describing the advantages of using sensory stimulation–such as auditory beeps or light flashes–to understand the developing minds of fetuses and newborns, including the potential for early consciousness. Most forms of brain stimulation used in adults might be risky or harmful if applied to the developing brains of infants or fetuses, and so sensory stimulation gives us a unique opportunity to see how these young brains respond to new input from the outside world.

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This post has adapted text from a press release.

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Source: Created with the aid of Midjourney generative AI