When the brain lights up, its blood supply doesn’t always follow

In 5 seconds Two nearly identical patterns of brain activity, two radically different blood flow responses: a discovery by UdeM researchers on mice could improve how human brain scans are interpreted.
Antoine Malescot, the study’s lead author, and Ravi Rungta, a researcher at the Institut Courtois d’innovation biomédicale and a professor in the Department of Stomatology at the Faculty of Dentistry and in the Department of Neurosciences at Université de Montréal

When the brain is stimulated, blood flow increases. For 30 years, functional magnetic resonance imaging (fMRI), one of the most powerful windows into the human brain, has operated on the basis of this connection. fMRI doesn’t actually see neurons firing; it tracks changes in blood oxygenation.

A new study on mice may force a rethink. Scientists led by Ravi Rungta, a professor in the Department of Stomatology and the Department of Neuroscience at Université de Montréal, reveal the relationship is not as straightforward as once thought.

Their findings were published in the journal Science.

Comparing responses to touch and pain

Rungta and his Ph.D. student Antoine Malescot, the study’s first author, compared how the mouse brain responded to two very different sensations: touch and pain.

In most layers of the mouse cortex, the two stimuli triggered nearly identical neural activity. Yet the blood flow told a different story—it was more than 50 percent lower for pain than for touch.

“I expected a difference, but not to that degree,” said Rungta, a researcher at the Institut Courtois d’innovation biomédicale and Canada Research Chair in Neurovascular Interactions.

“At first, I thought it stemmed from capillary regulation. It took us a while to understand what was really going on.”

Multiple networks at play

The explanation lies in the brain’s intricate plumbing. 

The cortex is fed by multiple independent networks of arterioles—tiny vessels that bridge arteries and capillaries. These networks are not created equal. They don’t all supply the same cortical layers and don’t react identically to stimulation. 

To untangle this complexity, the research eam combined advanced tools: genetic markers to track neural firing in real time, and a far-red imaging technique capable of peering a full millimeter into brain tissue—twice the depth previously achievable.

“This let us observe all six layers of the mouse cortex and we saw that the overall change in blood flow didn’t always match the brain activity,” explained Rungta. “But when we zoom in on where the blood is going, we get a much clearer picture of what kind of activity triggered it.”

A different perspective

Although the research was carried out in mice, it has much wider implications. 

The latest fMRI technologies can detect signals specific to each layer of the cerebral cortex. A better understanding of vascular architecture could therefore improve analysis of the brain imaging used in research on pain, cognition and neurological disorders.

“We need to start viewing blood vessels as an active architecture of neural circuits, not just a delivery system,” said Rungta.

His team now plans to investigate whether these distinct vascular networks are also involved in chronic pain and neurodegenerative diseases, which are often associated with reduced blood flow in the deep layers of the cortex.

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