A brain in the making, long before birth

In 5 seconds Neuroscientist Tomáš Paus investigates the effect of smoking during pregnancy on the size of the baby’s visual cortex and uncovers a mechanism never before observed in humans.
The study shows that the surface area of the primary visual cortex was smaller in individuals whose mothers smoked during pregnancy.

We tend to think of a fetus’s brain as a construction site guided by a blueprint imprinted in the genes. But even before birth, other things are happening. The fetus moves, responds to muffled sounds, receives stimuli and, crucially, its own nervous system is already generating activity.

A study supervised by Tomáš Paus, a professor of psychiatry and neuroscience at Université de Montréal and a researcher at Sainte-Justine hospital, sheds new light on this prenatal activity. One important finding is that signals spontaneously generated by the retina may help shape the primary visual cortex, the brain region that processes visual information.

Smoking during pregnancy was the factor that revealed this process.

A window on the brain

The story begins in Quebec’s Saguenay–Lac-Saint-Jean region more than two decades ago, when Paus and his UdeM colleague Dr. Zdenka Pausova launched a large cohort study to investigate how adversities experienced in the womb affect brain development and cardiometabolic health.

More than 1,000 adolescents aged 12 to 18 were recruited and assessed over the years, with some followed into adulthood. One of the factors studied was smoking during pregnancy, a relatively common prenatal exposure. Cigarette smoke has multiple effects. It can reduce oxygen and nutrient supply to the fetus, contributing to lower birth weight. It also contains an array of chemicals, including nicotine, which binds to brain receptors that normally respond to acetylcholine, a key neurotransmitter.

In the current study, the team focused specifically on the primary visual cortex, or area V1. Among the 11 brain regions examined, V1 showed the most pronounced difference between individuals who were exposed to cigarette smoke prenatally and those who were not.

The team then investigated the same question in a completely different population: roughly 20,000 adults from a British biobank. Once again, area V1 stood out. In both of the unrelated cohorts, the surface area of the primary visual cortex was smaller in individuals whose mothers smoked during pregnancy.

The eyes talk to the brain

The retina, at the back of the eye, contains cells specialized for receiving light. But even before a baby can actually see, these cells spontaneously produce waves of activity, Paus explained.

“These waves travel through the visual system and reach the cortex,” he said. “Animal studies had already shown that if this activity is blocked, the development of the visual cortex is disrupted. So the brain doesn’t necessarily wait for external images to arrive before it starts developing. Before that, it already receives a kind of ‘stimulation’ produced from within.”

This is where nicotine enters the picture.

The waves of spontaneous activity in the retina rely on acetylcholine, a neurotransmitter whose signaling is disrupted by nicotine. Paus and his team hypothesized that nicotine exposure could alter these waves and hence influence the development of the primary visual cortex. They tested this hypothesis using causal variants to investigate whether the nicotine exposure was truly the cause, not just statistically correlated. The results confirmed the hypothesis.

Does a smaller cortex mean poorer vision?

That’s a tougher question.

“Think of the primary visual cortex as a TV screen,” Paus said. “The larger its surface area, the more pixels—that is to say, neurons—it can potentially contain, allowing for more detailed representation of visual information.”

But Paus cautioned that this may not be a perfect analogy: a direct link between V1 surface area and visual resolution has been observed in animals, but not as directly in humans.

However, in the British biobank data, the team did find that a larger primary visual cortex was associated with abilities that suggest better shape-perception.

The brain begins learning in utero

In addition to showing yet again that smoking during pregnancy is harmful to the fetus, this study confirms that experience and environment shape the brain long before birth.

“A young child who hears speech, observes their surroundings and experiments with new movements literally transforms their brain through those experiences,” said Paus. “The spontaneous waves produced by the retina constitute a form of ‘internal experience’ for the fetus. They give the visual system activity that supports its own development, even before the baby starts looking at the world.”

To understand how the human brain develops, then, we must look not only at genes and what happens after birth, but also at the very first experiences, which occur before the fetus has access to the outside world.

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