These results were published in the academic journal NeuroImage on May 23, 2021.

Main Points

• The researchers showed that people who are physically active during childhood (up to 12 years of age) have higher cognitive functions in later life.
• However, they could not find a correlation between cognitive function and post-childhood physical activity.
• The positive association between childhood exercise and cognitive function was evident in the modular (*1) segregation of brain networks, strengthened inter-hemispheric connectivity, greater cortical thickness, lower levels of dendritic arborization and decreased density.
• During childhood, the formation of the brain’s network is susceptible to environmental and experience-related factors. It is thought that exercise during this period optimizes brain network development and is linked to the maintenance and promotion of cognitive function in later life.

Research Background

Research over the previous decade has shown that exercise during childhood affects the development of cognitive functions. Recent findings have indicated that these benefits of childhood exercise extend to the maintenance and promotion of cognitive functions in middle age and later life. However, the changes in brain functionality and structure related to this positive association have yet to be illuminated. This research study investigated the relationship between physical activity in childhood and cognitive function in later life, using MRI (magnetic resonance imaging) to illuminate the structural and functional changes in the brain that are behind this relationship.

Experiment Method

The research group conducted a study on 214 participants ranging in age from 26 to 69 in order to investigate the relationship between childhood exercise and cognitive function, and the underlying functional and structural neural networks and cortical structure. Childhood exercise was assessed via questionnaire. One aspect of cognitive function, response inhibition (the ability to suppress inappropriate behaviors), was measured using a Go/No-go task. The image data from the MRI was analyzed and the following were calculated: structural and functional connectivity (*2), cortical thickness, myelination, the degree of neurite orientation dispersion and density index. The brain was divided into 360 areas in accordance with the Human Connectome Project (*3), and functional and structural parameters were obtained for each area. In the statistical analysis, information obtained through the questionnaire was used as confounders. This included each participant’s educational background, parents’ educational background, number of siblings and exercise during adulthood.

Experiment Results

Firstly, the researchers analyzed the relationship between whether participants exercised during childhood and Go/No-go task performance (false alarm rate). They found that participants who exercised during childhood (up until age 12) had a lower false alarm rate than those who didn’t (Figure 1). Furthermore, this correlation was found regardless of the age of the participant. However, no such relationship was found between task performance and post-childhood exercise.

Next, the research group investigated structural and functional connectivity in the brain relating to Go/No-go task performance in participants who exercised during childhood. From these results, they confirmed that in terms of structural connectivity in the brain, there were positive associations (Figure 2A: connections indicated in red) and negative associations (Figure 2A: connections indicated in blue) between exercise during childhood and the false alarm rate in the Go/No-go task. Large-scale network connectivity was found in over half (73%) of structurally connected areas that were positively associated with the Go/No-go task false alarm rate (Figure 2B, left portion). On the other hand, inter-hemispheric connectivity was found in the majority (88%) of structurally connected areas that were negatively associated with the task’s false alarm rate (Figure 2B, right portion). In terms of connections between functional areas, connections showing positive associations (Figure 3A: connections indicated in red) with the Go/No-go task false alarm rate were identified in participants who exercised during childhood but no negatively associated connections were found. Furthermore, large-scale network connectivity was found in the majority (91%) of connected areas that were positively associated with the task’s false alarm rate (Figure 3B, left portion).

In those participants who did not exercise during childhood, there was no structural or functional connectivity identified in relation to the false alarm rate in the Go/No-go task. Lastly, the researchers investigated cortical structure parameters in relation to the Go/No-go false alarm rate for participants who exercised as children. They found that task performance was negatively associated with cortical density, and positively associated with the degree of neurite orientation dispersion and density.

The above results demonstrate that modular segregation and strengthened inter-hemispheric connections in the brain networks of people who exercised during childhood reduced the number of mistakes that they made in the Go/No-go task.

Glossary

1. Module: A single unit that combines with others to form the entire structure of a system. The human brain has a clear modular structure: it is divided into a number of large-scale networks made up of multiple areas.

2. Structural and Functional Connectivity: This refers to the structural and functional relationships between different areas of the brain. Structural connections between areas of the brain can be identified by anatomical nerve fiber connections, and functional connections are indicated by similarities in patterns of neural activity.

3. Human Connectome Project: This large scale research project began in North America in 2012 and aims to deepen understanding of brain connectivity.

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The study appears in the journal Med.

The human microbiota consists of trillions of bacteria, viruses, fungi and other microorganisms — some beneficial, some harmful — that live in and on our bodies. Women naturally provide these pioneer colonizers to their babies’ sterile bodies during labor and birth, helping their immune system to develop. But antibiotics and C-sections disturb this passing of microbes and are related to increased risks of obesity, asthma and metabolic diseases.

The researchers followed 177 babies from four countries over the first year of their lives — 98 were born vaginally and 79 were born by C-section, 30 of which were swabbed with a maternal vaginal gauze right after birth.

Lab analysis showed that the microbiota of the C-section babies swabbed with their mother’s vaginal fluids was close to that of vaginally born babies. Also, the mother’s vaginal microbiomes on the day of birth were similar to other areas of their bodies (gut, mouth and skin), showing that maternal vaginal fluids help to colonize bacteria across their babies’ bodies.

This was the first large observational study to show that restoring a C-section baby’s natural exposure to maternal vaginal microbes at birth normalizes the microbiome development during their first year of life. The researchers said the next step is conducting randomized clinical trials to determine if the microbiota normalization translates into disease protection.

“Further research is needed to determine which bacteria protect against obesity, asthma and allergies, diseases with underlying inflammation,” said senior author Maria Gloria Dominguez Bello, a professor in the Department of Biochemistry and Microbiology in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. “Our results support the hypothesis that acquiring maternal vaginal microbes normalizes microbiome development in the babies.”

According to the World Health Organization, C-section is needed in about 15 percent of births to avoid risking the life of the mother or child, but in many countries such as in Brazil, the Dominican Republic, Iran and China, C-section is performed in more than 70% of urban births.

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“The ink used in the biosensors is biocompatible and provides a user-friendly design with excellent workable time frames of more than one day,” said Kwan-Soo Lee, of Los Alamos’ Chemical Diagnostics and Engineering group.

The new biosensors allow for simultaneous recording and imaging of tissues and organs during surgical procedures.

“Simultaneous recording and imaging could be useful during heart surgery in localizing critical regions and guiding surgical interventions such as a procedure for restoring normal heart rhythms,” said Chi Hwan Lee, the Leslie A. Geddes Assistant Professor of Biomedical Engineering and Assistant Professor of Mechanical Engineering and, by courtesy, of Materials Engineering at Purdue University.

Los Alamos was responsible for formulating and synthesizing the bio-inks, with the goal of creating create an ultra-soft, thin and stretchable material for biosensors that is capable of seamlessly interfacing with the surface of organs. They did this using 3D-printing techniques.

“Silicone materials are liquid and flow like honey, which is why it is very challenging to 3D-print without sagging and flowing issues during printing,” Kwan-Soo Lee said. “It is very exciting to have found a way to create printed inks that do not have any shape deformation during the curing process.”

The bio-inks are softer than tissue, stretch without experiencing sensor degradation, and have reliable natural adhesion to the wet surface of organs without needing additional adhesives.

Craig Goergen, the Leslie A. Geddes Associate Professor of Biomedical Engineering at Purdue University, aided with the in vivo assessment of the patch via testing in both mice and pigs. The results showed the biosensor was able to reliably measure electrical signal while not impairing cardiac function.

The research was published today in Nature Communications. It was funded by Science Campaign 2.

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