In the late 1800s, Italian physiologist Angelo Mosso made a curious observation while studying a patient with a skull defect that left part of the brain exposed. He noticed that when the patient became angry, the exposed area visibly swelled with blood. This led Mosso to explore the idea that changes in cerebral blood flow could reflect mental activity.
He had already observed that in newborns, the fontanelles—the soft spots where the skull has not yet fully fused—pulsate with the heartbeat, and noted similar pulsations in adults attending his clinic. Mosso devised a graphic recorder to document these pulsations and demonstrate that blood pressure changes in the brain caused by mental exertion occur independently of pressure changes elsewhere in the body.
Mosso’s groundbreaking observations would, nearly a century later, lay the foundation for the development of functional magnetic resonance imaging (fMRI), a brain scan that measures blood flow to different regions as a proxy for neural activity during various tasks.
Notably, the brain is one of the body’s most energy-hungry organs. Though it makes up just 2 per cent of body weight, it consumes nearly 20 per cent of the body’s energy. To meet this demand efficiently, the brain must direct blood flow to the regions that need it most. This targeted delivery of blood in real time is an evolutionary adaptation. It has been observed that this mechanism is impaired in cases of neurodegeneration.
Interestingly, the precise mechanism behind this dynamic distribution of blood remained a mystery for a long time. Now, researchers at Harvard Medical School have uncovered key details of how the brain directs blood to active areas as they work. Their findings are published in Cell.
The researchers conducted a series of experiments in mice, revealing a cellular signalling highway that supports this mechanism, involving a couple of key genes. They found that the brain rapidly signals the need for more blood in specific areas via endothelial cells, which line blood vessels in the brain. These endothelial cells then communicate quickly through “gap junctions”—tiny channels connecting neighbouring cells.
Using this wide-reaching and coordinated signalling system, which runs through the inner linings of blood vessels, the brain instructs the vessels when to dilate or contract, depending on need. The researchers note that since the brain’s vascular network is similar across mammals, the same system likely operates in humans. The Harvard team suggests that if these findings hold true in humans, they could significantly improve the interpretation of fMRI scans, potentially offering new insights into the relationship between blood flow and neural activity.