How big is the brain of a normally developing six year old? When in life do certain brain regions develop particularly strongly? And to what extent does brain mass decrease with age? For the first time, such questions can now be answered on the basis of a large database. Using over 100,000 brain scans from people of all ages, researchers have created standardized reference charts. These provide information about the typical development of our brain over the course of life and also allow insights into pathological changes. The publicly accessible database is intended to be an important research resource in the future and, with further additions, could become a standard tool in clinical practice.
Growth curves have been standard in pediatrics for more than 200 years. They can be used to quickly and easily see whether, for example, a child’s height, head circumference and weight are within the range that can be expected for that age. Our brain also goes through serious developments in the course of our lives. How and when exactly these typically take place was unclear until now. Although magnetic resonance tomography images allow insights into the living brain, the database has so far been too small to derive general standards from it.
Data from over 100 studies
A team led by Richard Bethlehem from the University of Cambridge has now closed this research gap. To do this, the scientists used a complex process to collect brain scans from more than 100,000 people worldwide that had been published in over 100 studies. The subjects’ ages ranged from unborn fetuses 115 days after conception to 100-year-old seniors. “In this way, we were able to document the very early, rapid developmental steps of the brain as well as the slow decline with age,” says Bethlehem.
A challenge for the researchers was the large methodological variability of the different studies. “With brain imaging data, things are a bit more complicated than just taking a tape measure and measuring someone’s height or head circumference,” says co-author Jakob Seidlitz of the University of Pennsylvania. First, the researchers had to standardize the data. They started with simple properties like gray matter and white matter volume, and then expanded their work to finer details like the thickness of the cortex and the volume of specific brain regions.
Milestones in brain development
In doing so, they documented important milestones in brain development, some of which had already been suspected and some of which were newly discovered. The data show that the brain grows particularly quickly from mid-pregnancy to the third year of life – from ten percent of its later size to 80 percent. The gray matter, which is made up of brain cells, reaches its maximum volume at the age of six and decreases thereafter. The white matter, which is made up of connections between brain cells, continues to grow until just before the age of 29. After that, the brain begins to shrink again very slowly, with the decline in volume accelerating somewhat from around the age of 50.
Since the dataset also includes numerous recordings of diseased brains, the researchers were also able to see how diseases such as Alzheimer’s dementia affect our thinking organ. For example, the brain volume in Alzheimer’s patients decreases much faster than would actually be typical for the respective age of those affected. “In the future, our frame of reference may be used to assess patients being screened for diseases like Alzheimer’s,” says Bethlehem. “By comparing how quickly a patient’s brain volume has changed compared to their peers, physicians could identify possible signs of pathological neurodegeneration.”
Growing database
According to the researchers, however, before the newly created reference diagrams can actually be used in clinical practice, they must be supplemented with further data. For example, it would be helpful to include more brain scans from non-Western individuals, as these have so far been underrepresented in the dataset. “We’re still in the very early stages of our brain diagrams,” Bethlehem explains. “But our work shows that it is possible to create these tools by merging large datasets.”
To enable other researchers to contribute their data to the project, his team has made all data freely accessible on a website and provides a tool with which further datasets can be adapted and integrated. “We expect to keep updating the charts and building on these models as new data becomes available,” says Seidlitz. “By creating a common language for brain imaging, we have provided the necessary bridge that will help bring insights from imaging to clinical practice.”
Source: Richard Bethlehem (University of Cambridge) et al., Nature, doi: 10.1038/s41586-022-04554-y