Human brain cells put much more energy into signaling


Image of a person staring pensively, with question marks drawn on the wall behind him.

Indian elephants have larger brains than we do (obviously). Mice have a higher brain-to-body mass ratio, and long-finned pilot whales have more neurons. So what makes humans—and more specifically, human brains—special?

As far as organs go, human brains certainly consume a ton of energy—almost 50 grams of sugar, or 12 lumps, every day. This is one of the highest energy demands relative to body metabolism known among species. But what uses up all of this energy? If the human brain is the predicted size and has the predicted number of neurons for a primate of its size, and each individual neuron uses comparable amounts of energy to those in other mammals, then its energy use shouldn’t be exceptional.

The cost of signaling

A group of neuroscientists speculated that maybe the amount of signaling that takes place within the human brain accounts for its heightened energy needs. A consequence of this would be that brain regions that are more highly connected and do more signaling will use more energy.

To test their hypothesis, the scientists started by imaging the brains of 30 healthy, right-handed volunteers between 20 and 50 years old. The imaging took place at two separate institutions, and it allowed the researchers to correlate a given brain region’s energy use (as measured by glucose metabolism) with its level of signaling and connectivity. They found that energy use and signaling scaled in tandem in all 30 brains. But certain regions stuck out. Signaling pathways in certain areas of the cortex—the front of the brain—require almost 70 percent more energy than those in sensory-motor regions.

The frontal cortex is one of the regions that expanded the most during human evolution. According to Robert Sapolsky, “What the prefrontal cortex is most about is making tough decisions in the face of temptation—gratification postponement, long-term planning, impulse control, emotional regulation. The PFC is essential for getting you to do the right thing when it is the harder thing to do.” This is the stuff that humans must constantly contend with. And energetically, it is extraordinarily costly.

Increased modulation is also key for cognition

It is not only signaling that takes energy; it is modulating that signaling, ensuring that it occurs at the appropriate levels and only at the appropriate times.

Using the Allen Human Brain Atlas, these researchers looked at gene activity in the frontal cortex. They found elevated activity of neuromodulators and their receptors. The authors note that “the human brain spends excessive energy on the long-lasting regulation of (fast) neurotransmission with (slow) neuromodulators such as serotonin, dopamine, or noradrenaline.” And also endogenous opiates. “This effect is more about setting the tone of general excitability than transferring individual bits of information,” they write.

Once they correlated energy use to signaling and slow-acting neuromodulation in the cortex, the last thing the scientists did was look at the Neurosynth project, which maps cognitive functions to brain regions. Lo and behold, the energy-hogging, highly connected, strongly modulated, and evolutionarily expanded parts of the cortex are the same ones involved in complex functions like memory processing, reading, and cognitive inhibition. This supports their idea of “an expensive signaling architecture being dedicated to human cognition.”

Science Advances, 2023.  DOI: 10.1126/sciadv.adi7632


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