Does a Baby Have a Nervous System at 12 Weeks]

From autism to schizophrenia, many encephalon disorders take long been idea to ascend from issues with the connections among nervus cells in the encephalon.¹ Billions of threadlike fibers crisscross the encephalon, forming labyrinthine networks that relay messages between unlike brain regions.^two Scientists telephone call this signaling spaghetti the "connectome,"¹ and it makes up a blueprint of the trillions of neural connections in the encephalon.

Some researchers hypothesize that these connections encode essential aspects of personality, beliefs, cognition, and memory. As neuroscientist Sebastian Seung subtitled his 2012 book Connectome, our neural wiring makes us who we are.³

In the by decade, advances in a neuroimaging technique called functional magnetic resonance imaging (fMRI) have offered researchers an unprecedented look at how those connections form earlier and shortly subsequently birth. With these advances, they have also begun to unlock some of the signatures of aberrant brain development.

fMRI is not perfect. The images generated by the engineering often must exist manipulated to right for baloney and to scale brain scans to a consequent, comparable template. Motion causes problems with data analysis and interpretation—and babies and fetuses are notoriously wriggly unless asleep or sedated. Finally, technical issues potentially result in artifacts that may non be recognized as errors.⁴

Even so, fMRI has also provided a new level of access to the developing brain. In addition, understanding the origins of neurodevelopment—and where brain function goes awry—may provide new insights on the impact of ecology exposures.⁵ The findings could one day provide avenues for novel neuroprotective strategies.

The process that volition ultimately give rise to the connectome begins almost 25 days subsequently conception, when the neural tube begins to form. By the terminate of the embryonic period (gestational week x), the basics of the neural system are established. All the structures continue to develop throughout the fetal period and early babyhood. By 6 years of historic period, the brain has reached 90% of its adult volume. Past historic period 25, it typically is fully developed. Image: © TheVisualMD/Science Source.

The Black Box of Brain Development

Human being encephalon development starts soon afterward conception and continues into early adulthood. The fetal encephalon begins to develop during the third week of gestation. Neural progenitor cells begin to divide and differentiate into neurons and glia, the two cell types that grade the footing of the nervous organisation.⁶

Past the ninth calendar week, the brain appears as a modest, smooth structure. Over the class of pregnancy, the structure of the encephalon volition change equally information technology grows and begins to grade the characteristic folds that designate distinct brain regions. Changes in brain anatomy reverberate dramatic changes at the cellular level. Neurons in the dissimilar brain regions begin producing the chemical signaling molecules that will enable communication betwixt nerve cells. The fiber pathways that will become the brain'southward data state highway are forming. The cells that will make up the neocortex—the part of the brain that coordinates sight, sound, spatial reasoning, conscious thought, and language—begin to communicate.⁶

Although the foundation of a functioning brain is assembled prenatally, encephalon part itself continues to develop after nascence, driven largely past sensory input. The number of neural connections explode in the first years of life—a miracle sometimes referred to as a synaptic "big bang."⁷ After age 2 years, the number of neural connections decreases. In a process known as synaptic pruning, the brain organizes its connectome to perform more efficiently, removing inefficient connections to maximize performance.

A large body of animate being and epidemiological research suggests that prenatal exposures to harmful environmental stimuli, such equally maternal stress or toxic agents, may alter the developmental trajectory of the fetal brain.⁸ Withal, until recently, prenatal neurodevelopment was a black box.

"Nosotros don't know a lot about what happens in fetal life, considering nosotros haven't had the tools to measure encephalon development in fetal life," says Robert Wright, an environmental epidemiologist and pediatrician at the Icahn Schoolhouse of Medicine at Mount Sinai in New York. "It may fifty-fifty differ from [postnatal] evolution, as the sensory inputs are largely biochemical and passed from mother to child, dissimilar the direct feel of sound, light, temperature, and movement that a child experiences."

The developing encephalon relies on ecology and endogenous stimuli such as these to help it make up one's mind which connections should be pruned and which should not. "When a neuron fires afterwards a proper signal, its synaptic connections are solidified," Wright explains. "If a neuron's synaptic connection is rarely fired, it regresses and is removed."

Toxic exposures can interfere with the brain's power to distinguish important connections from unimportant ones, altering the development of the connectome. For instance, atomic number 82 can cause neurons to burn down spontaneously in the absence of a proper indicate, Wright says. "By inducing neuronal activity inappropriately, [lead] can alter the normal trajectory of synaptic formation and synaptic pruning that underlies the formation of the connectome," he explains. Ultimately, this type of interference can lead to the evolution of maladaptive brain signaling networks.

The connectome is shaped by internal and external stimuli throughout the course of life. In the fetus and young kid, sure chemical exposures and situational factors (such as maternal stress and low socioeconomic status) are hazard factors for neurodevelopmental problems. Nonetheless, positive influences, such every bit parental date, may assistance to build resilience and mitigate any negative impacts. Prototype: © Daniel Atkin/Alamy Stock Photo.

Developing the Tools to Study the Brain in Utero

Nigh of what scientists know near fetal brain development comes from looking at creature brains or analyzing man postmortem samples.⁵ This research has provided insights on the development of brain structure simply offers few clues about how functional systems become organized.

The primeval investigations of human being fetal encephalon function date dorsum to the 1950s. When researchers placed electrodes on a meaning woman's abdomen and on the walls of her cervix during labor, they could discover electrical impulses that signaled fetal brain action.⁵ Researchers began to notice that certain patterns of electrical activity were associated with neurological abnormalities.^nine

In the 1990s, scientists began experimenting with fMRI to map the connections in different regions in the brain.⁵ fMRI detects changes in encephalon activity associated with changes in claret flow. During fMRI, the patient typically performs a task—looking at pictures of faces or finger tapping, for instance—while the machine scans his or her brain. Researchers look for areas of the encephalon that light up during the chore.

By that point, neuroscientists knew at that place was much more than happening functionally than could be probed with a stimulus or task, but information technology was unclear how to best examine these functions. So, in 1995, then–graduate student Bharat Biswal made a fortuitous observation: The brain produces signals all the fourth dimension, even when information technology is not engaged in a task.¹⁰ Manipulating fMRI to measure these resting-state signals allowed scientists for the showtime fourth dimension to investigate encephalon activity without the subject area needing to so much as tap a finger.

Resting-state fMRI offered a more nuanced expect at the highways and interstates connecting dissimilar brain regions. These connections form the basis of how different regions of the encephalon communicate with each other. Whereas investigators previously were express to studying function within a item encephalon region, they could now begin to ask big-motion-picture show, network-level questions nearly brain function.^vii

In the search for answers about how and when brain networks grade, researchers turned to preterm infants.^xi Nearly 10% of all babies worldwide are born preterm, meaning before the end of the 37th week of pregnancy.¹² Compared with term babies, these children are more likely to develop autism spectrum disorders, attending deficit/hyperactivity disorder, emotional disorders, and neurological abnormalities.^thirteen Preterm infants likewise are more likely to have cerebral difficulties and problem in school later on on.¹³ A growing body of research suggests that these cognitive impairments may be caused by disruptions in the way the brain is wired earlier or shortly after nascence.⁵

Christopher Smyser, a pediatric neurologist at Washington University in St. Louis, Missouri, used fMRI images of preterm infant brains to study prenatal evolution of the connectome. In 2010, he showed that babies born equally early on as 26 weeks possessed immature forms of many of the functional encephalon networks seen in adults.¹⁴

These first studies by Smyser and others showed that the encephalon's communication channels were present before term birth, albeit in an young country. Preterm babies offered researchers the opportunity to study the development of neural patterns that commonly takes place inside the womb. However, researchers found it difficult to know if the patterns they were seeing in these infants reflected the normal development of brain advice networks. What did functional connectivity await like in a healthy term pregnancy?

Imaging the Fetal Brain

Task-based fMRI had ever been a poor option for studying children also young to follow instructions. In utero, information technology was fifty-fifty less feasible. "You could never know what a fetus was upward to, whether it was performing a job or at rest," says Veronika Schöpf, a professor of neuroimaging at the University of Graz in Austria.

In 2010, Schöpf began using resting-state fMRI to study the brains of fetuses. She ultimately scanned the brains of more than 100 fetuses in their mothers' wombs.¹⁵ It was a catchy task—too much motion on the part of the fetus could mistiness the picture show. In the end, Schöpf had collected functional images of 16 healthy fetuses spanning the 20th to 36th weeks of gestation. Her study was the beginning to show that resting-state networks were nowadays—and could be detected—in a fetus.

At the fourth dimension of this study, the chronology for the emergence of the encephalon'south functional networks was still unknown. However, in a 2014 follow-up written report of 32 healthy fetuses, Schöpf et al. showed how the connectome developed over the second half of pregnancy as short- and long-range connections between different encephalon regions begin to form.^xvi They found that development of those network connections peaks between about 27 and 30 weeks.

In 2012, Veronika Schöpf et al. captured functional images of fetal brains at gestational weeks twenty–36 (the numbers in the figure above indicate gestational week). The team was the start to evidence that resting-state networks tin be detected in utero. This imaging was a major advance over the use of chore-based fMRI because, as Schöpf put information technology, "You could never know what a fetus was up to, whether information technology was performing a task or at rest." Image: Schöpf et al. (2012).⁵

Around the same time, Moriah Thomason, a pediatric neuroscientist at New York Academy School of Medicine, published the first study to demonstrate age-related changes in fetal brain networks. In a accomplice of significant Detroit women, she found differences in functional connectivity amidst 25 salubrious fetuses in the 2d versus the third trimester.¹⁷ She too plant evidence of synchronized activity between mirror regions in the 2 hemispheres of the brain. The study showed that this blueprint of coordinated activeness became stronger with each passing week of pregnancy.

Schöpf's and Thomason's early on studies offered the first evidence about the timing of functional development in the fetal brain. They also demonstrated that resting-state fMRI may be a helpful tool in identifying and better agreement critical windows of fetal neurodevelopment. With this background laid, investigators at present aim to elucidate the origins of neurological disease.

Disentangling the Pre- and Postnatal Environments

In studies of preterm infants conducted later on nascency, researchers find information technology hard to know whether developmental abnormalities ascend from the preterm birth itself (eastward.g., as a upshot of oxygen deprivation) and the stress of subsequent medical interventions, or if those abnormalities are the result of illness processes that started in the womb. Without that piece of the puzzle, it is impossible to establish whether preterm birth is a symptom or a cause of developmental problems.

The same can be said for most studies of early-life environmental exposures. "If yous cannot disentangle the prenatal from the postnatal environment, you cannot become at the genesis of affliction," says Thomason.

Pb exposure is one instance. Fetal exposure to lead has been associated with cognitive impairments in childhood.⁸ However, if atomic number 82 was present in the mother's environment during pregnancy, it's likely to be present in the child's surround, too (provided the mother and kid live together in the abode where she resided while pregnant). Therefore, whether an agin cerebral outcome is a issue of something that happened either in fetal life or when the kid was i or ii years old is difficult to make up one's mind. "Establishing when the effect started might be a clue to understanding if the critical window is fetal life or later in life," says Wright.

In the case of preterm births, researchers would ideally analyze the brains of preterm infants before birth, but it is often difficult to place which babies volition be born early. Even so, Thomason has managed to do just that by studying a subset of her accomplice of pregnant Detroit women who went on to evangelize prematurely. In 2017, Thomason presented the start direct bear witness that infants born preterm may exist wired differently before birth.¹⁸ The fMRI images generated during pregnancy suggested a difference betwixt the brains of preterm versus term babies: An expanse on the left side of the encephalon that after forms a language-processing region had weaker connections to other brain regions in fetuses that would exist born preterm compared with fetuses carried to term.

Importantly, the was modest—merely 14 preterm and 18 term pregnancies—and the medical relevance of the findings is non still clear. Long-term studies are needed to determine whether differences detected in utero predict cognitive impairment later in life, according to Thomason.

The oldest children in Thomason'due south Detroit cohort have at present reached school age. She is working to link patterns of early brain activeness to babyhood behavioral outcomes, including speech, motor skills, and noesis. If maps of functional connectivity in the fetal brain plow out to predict health outcomes later in life, the findings will bring us closer to agreement the origins of neurodevelopmental problems.

Even so, for Thomason, her research is equally much almost finding the alterable weather in an environment that could modify a child's developmental trajectory every bit it is about understanding the genesis of illness. During home visits, she has collected data nigh each kid's environs. "Fetal brain action may predict a item consequence, but what other ecology factors buffer or exacerbate prenatal risk factors?" she asks.

Ecology Health Connections

Other researchers agree that acting on environmental risk factors may exist central to developing effective neurobehavioral interventions.⁴ For preterm infants, interventions could include irresolute the hospital surround, says Annemarie Stroustrup, a neonatologist at Mount Sinai Hospital in New York.

"The neonatal intensive intendance unit [NICU] is not designed for environmental health safety," Stroustrup says. Preterm babies face a host of unfamiliar stressors in the NICU—from vivid lights and loud sounds to stressful interventions and potentially toxic chemicals.¹⁹ For instance, plastic medical equipment may contain hormone-disrupting chemicals, such as phthalates or phenols, and intravenous feeding solutions may comprise high levels of neurotoxic metals, such as aluminum. Although such exposures may exist largely or wholly tolerable for older patients, their toxicity is amplified in the preterm babe.²⁰

Some developmental abnormalities event from disease processes that started in the womb, just others may arise from the very human action of being born prematurely and the stress of subsequent medical interventions. Annemarie Stroustrup et al. are investigating whether the NICU environs contributes to the latter category. If it does, that's 1 negative influence that could be inverse to a positive—or at least improved. Prototype: © Nenov/Getty Images.

Stroustrup leads a report designed to look at the developmental impacts of NICU exposures.^xi She plans to comprise the use of neuroimaging to assess neurodevelopment in premature infants nether NICU care and then compare early on brain connectivity to measures of exposure and childhood behavioral outcomes. "If it turns out that some morbidities are related to ecology exposures in the NICU, that information could be used to improve the NICU environment," she says.

The brain is plastic, especially during babyhood. That means information technology is able to organize its neural connections in response to its environment—including both positive and negative influences. Although toxic exposures can have a negative influence, other positive influences may help to build resilience and mitigate the negative impacts, Wright says.

"It's a misconception that if yous're exposed to a certain chemic, you're destined to get a damaged brain," he says. "Agin outcomes are by no means destiny. Positive influences tin remold the encephalon."

Lindsey Konkel is a New Jersey–based announcer who reports on scientific discipline, health, and the surround.

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