Highly detailed reconstruction of human brain connectivity includes dozens of brainstem nuclei

by Ingrid Fadelli , Medical Xpress

A highly detailed reconstruction of human brain connectivity including dozens of brainstem nucleiCredit: Hansen et al.

Recent technological advances are allowing neuroscientists to map the human brain with increasing precision, highlighting connections between different regions and their function in greater depth. While the role of many brain regions has been broadly identified, the unique contribution of the brainstem to their function remains less understood.

Researchers at McGill University, Massachusetts General Hospital and Harvard Medical School and other institutes recently employed an advanced technique known as high-resolution 7-Tesla functional magnetic resonance imaging (7T MRI) to map the functional connectivity of the human brain in detail, including both the cortex and 58 brainstem nuclei. Their paper, published in Nature Neuroscience, provides one of the most detailed reconstructions of cortical functional architectures and the brainstem compiled to date.

“The brainstem is a key part of the nervous system that controls all aspects of life, including breathing, sleep, eating and conscious awareness,” Dr. Bratislav Misic and Ms. Justine Hansen, lead author of the article and graduate student in Misic’s lab, told Medical Xpress. “Its anatomy and function are taught in every introductory neuroscience and medical textbook.”

Most of what is currently known about the brainstem is derived from studies examining the brains of live animals or post-mortem human brains. As a result, the functioning of the brainstem in living humans and the processes via which it communicates with the rest of the brain remain poorly understood.

“The main challenge is that the brainstem is divided into lots of small regions (called nuclei) and resides deep in the brain, making it difficult to accurately neural activity in people,” said Misic and Hansen. “The main goal of the present study was to image the connection patterns between the brainstem and the rest of the brain, to understand how the brainstem influences human behavior.”

The Network Neuroscience Lab, led by Misic, is specialized in the study of brain connectomics, or in other words, the connections and interactions between different brain regions. While they have gathered various interesting findings so far, they had so far been unable to reliably measure brainstem activity.

“The spark for the present work was a chance encounter with Dr. Marta Bianciardi from Harvard, whose group has developed detailed atlases and sophisticated imaging techniques that make it possible to study the brainstem in living humans,” said the researchers. “Joining forces, we used high-resolution 7T MRI images to map out connections between the brainstem and the rest of the brain.”

After they mapped connections between the brainstem and the rest of the brain using 7T MRI, the researchers annotated these connections with neurochemical and cellular measurements they collected. This allowed them to better understand how these connections fit with the known biology of the brain.

Subsequently, Misic, Hansen and the rest of their team mapped patterns of brainstem connectivity to cognitive atlases (i.e., existing knowledge about the mental functions of specific brain regions). This allowed them to gather further insight about how brainstem nuclei support various psychological functions.

“First, we generated and made publicly available one of the most detailed reconstructions of human brain connectivity that involves dozens of brainstem nuclei,” said Misic and Hansen. “Second, we find that multiple brain functions that were traditionally thought to be cortical can be traced back to the brainstem, demonstrating the consistent influence that the brainstem exerts on cortical function.”

The detailed brain connectivity map created by Misic and his research lab could open new possibilities for research; for instance, enabling further investigations into the connectivity of brainstem nuclei. In addition, the imaging technique they used could be employed by other teams to closely study parts of the human nervous system that were previously deemed inaccessible.

“This work is part of our larger research program to use data science to integrate multiscale measurements of brain structure and function and build a more biologically detailed map of the human brain, kind of like a ‘Google Map’ of the brain (e.g., neuromaps),” added Misic and Hansen. “These detailed maps can then be used by neuroscientists across the globe to study healthy brain function over the lifespan as well as dysfunction in psychiatric and neurological disease.”

More information: Justine Y. Hansen et al, Integrating brainstem and cortical functional architectures, Nature Neuroscience (2024). DOI: 10.1038/s41593-024-01787-0.

Journal information:Nature Neuroscience

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