Unseen details of human brain structure revealed

 

Unseen details of human brain structure revealed

 

Unseen details of human brain structure revealed

At a Glance

• Researchers have created a high-resolution map of all the cells and connections within one cubic millimeter of the human brain.
•  The results reveal previously unknown details of brain structure and provide a source of information for further research.

 

To fully understand how the human brain works, we need to understand the relationships between the various cells that make up the brain. To do this, we need to visualize the brain's structure at the nanometer scale and see the connections between neurons.

A research team led by Dr.Jeff Lichtman of Harvard University and Viren Jain of Google Research used an electron microscope (EM) to image at high resolution a cubic millimeter-sized piece of human brain tissue. The tissue was excised from a patient's cerebral cortex as part of epilepsy surgery.

The research team first cut the tissue into more than 5,000 slices, or sections, and imaged each one using EM. This produced about 1.4 petabytes, or 1,400 terabytes, of data. The researchers used this data to create a 3D reconstruction of nearly every cell in the sample. The results of the NIH-funded study were published in the journal Science on May 10, 2024.

Analysis of individual cells in the sample revealed a total of more than 57,000 cells. Most of these were either neurons, which send electrical signals, or glia, which provide various support functions to neurons. Glial cells outnumbered neurons by a ratio of 2:1. The most abundant glial cells were oligodendrocytes, which provide structural support and electrical insulation to neurons. A cubic millimeter sample also contained approximately 230 mm of blood vessels.

 

The reconstruction revealed previously unseen structural details. The researchers analyzed a type of neuron called triangular cells, located in the deepest layer of the cerebral cortex. Many of these cells adopted one of two orientations that are mirror images of each other. The significance of this organization is still unclear.

The research team used machine learning to identify synapses, the connections through which signals pass from cell to cell. They found about 150 million synapses. Nearly every neuron formed only one synapse with a particular target cell. However, some formed two or more synapses to the same target. In at least one case, more than 50 synapses connected a pair of cells. Although rare, connections of seven or more synapses between cells were much more common than would be expected by chance. This suggests that these strong connections have some functional significance.

The results show how complex the brain is at the cellular level. They also demonstrate the value of connectomics, the science of creating comprehensive maps of the connections between brain cells, in understanding brain function.

"The word 'fragment' is ironic," says Lichtman. "Terabytes are huge for most people, but a human brain fragment -- a tiny part of a human brain -- is still thousands of terabytes in size."

The team has made its dataset publicly available. They also provide a range of software tools to examine the brain maps. Further study of the data by this team and others is expected to provide new insights into how the human brain works.

"This incredible advance, being able to acquire and process over 1,000 terabytes of data from the brain, would not have been possible without the generous donations by study participants and the critical partnerships between neuroscientists, computer scientists, and engineers," says Dr. John Guy, Director of the NIH BRAIN Initiative. "This collaboration is central to our goal of creating a complete map of the human brain and bringing it closer to the clinic."

– By Brian Doctorow, PhD