brain

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Sleeping more flushes junk out of the brain

Biology, brain, Neuroscience, Science, sleep / /

Better sleep on it —

Rhythmic activity during sleep may get fluids in the brain moving.

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Abstract image of a pink brain against a blue background.

As if we didn’t have enough reasons to get at least eight hours of sleep, there is now one more. Neurons are still active during sleep. We may not realize it, but the brain takes advantage of this recharging period to get rid of junk that was accumulating during waking hours.

Sleep is something like a soft reboot. We knew that slow brainwaves had something to do with restful sleep; researchers at the Washington University School of Medicine in St. Louis have now found out why. When we are awake, our neurons require energy to fuel complex tasks such as problem-solving and committing things to memory. The problem is that debris gets left behind after they consume these nutrients. As we sleep, neurons use these rhythmic waves to help move cerebrospinal fluid through brain tissue, carrying out metabolic waste in the process.

In other words, neurons need to take out the trash so it doesn’t accumulate and potentially contribute to neurodegenerative diseases. “Neurons serve as master organizers for brain clearance,” the WUSTL research team said in a study recently published in Nature.

Built-in garbage disposal

Human brains (and those of other higher organisms) evolved to have billions of neurons in the functional tissue, or parenchyma, of the brain, which is protected by the blood-brain barrier.

Everything these neurons do creates metabolic waste, often in the form of protein fragments. Other studies have found that these fragments may contribute to neurodegenerative diseases such as Alzheimer’s.

The brain has to dispose of its garbage somehow, and it does this through what’s called the glymphatic system (no, that’s not a typo), which carries cerebrospinal fluid that moves debris out of the parenchyma through channels located near blood vessels. However, that still left the questions: What actually powers the glymphatic system to do this—and how? The WUSTL team wanted to find out.

To see what told the glymphatic system to dump the trash, scientists performed experiments on mice, inserting probes into their brains and planting electrodes in the spaces between neurons. They then anesthetized the mice with ketamine to induce sleep.

Neurons fired strong, charged currents after the animals fell asleep. While brain waves under anesthesia were mostly long and slow, they induced corresponding waves of current in the cerebrospinal fluid. The fluid would then flow through the dura mater, the outer layer of tissue between the brain and the skull, taking the junk with it.

Just flush it

The scientists wanted to be sure that neurons really were the force that pushed the glymphatic system into action. To do that, they needed to genetically engineer the brains of some mice to nearly eliminate neuronal activity while they were asleep (though not to the point of brain death) while leaving the rest of the mice untouched for comparison.

In these engineered mice, the long, slow brain waves seen before were undetectable. As a result, the fluid was no longer pushed to carry metabolic waste out of the brain. This could only mean that neurons had to be active in order for the brain’s self-cleaning cycle to work.

Furthermore, the research team found that there were fluctuations in the brain waves of the un-engineered mice, with slightly faster waves thought to be targeted at the debris that was harder to remove (at least, this is what the researchers hypothesized). It is not unlike washing a plate and then needing to scrub slightly harder in places where there is especially stubborn residue.

The researchers also found out why previous experiments produced different results. Because the flushing out of cerebrospinal fluid that carries waste relies so heavily on neural activity, the type of anesthetic used mattered—anesthetics that inhibit neural activity can interfere with the results. Other earlier experiments worked poorly because of injuries caused by older and more invasive methods of implanting the monitoring hardware into brain tissues. This also disrupted neurons.

“The experimental methodologies we used here largely avoid acute damage to the brain parenchyma, thereby providing valuable strategies for further investigations into neural dynamics and brain clearance,” the team said in the same study.

Now that neurons are known to set the glymphatic system into motion, more attention can be directed towards the intricacies of that process. Finding out more about the buildup and cleaning of metabolic waste may contribute to our understanding of neurodegenerative diseases. It’s definitely something to think about before falling asleep.

Nature, 2024.  DOI: 10.1038/s41586-024-07108-6

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Human brain cells put much more energy into signaling

Biology, brain, frontal cortex, nerve cells, neurobiology, Science, signaling / /

Being human is hard —

Signaling molecules help modulate the brain’s overall activity.

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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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Elon Musk’s Brain-chip Startup Approved by FDA for Testing on Humans

bci, bmi, brain, brain computer interface, brain machine interface, elon musk, n1 implant, Neural Interface, Neuralink, neuralink n1, News / /

Neuralink, Elon Musk’s brain-machine interface (BMI) company, has announced that it has received approval from the US Food and Drug Administration (FDA) to conduct its first tests on humans. The company is developing minimally invasive brain chips which it hopes to use to restore vision and mobility for people with disabilities.

Neuralink says it doesn’t have immediate plans to recruit participants, however the FDA approval marks a significant step forward after a previous bid was rejected on safety grounds.

In March, Reuters reported the FDA’s major safety concerns involved the device’s lithium battery, the potential for the implant’s tiny wires to migrate to other areas of the brain, and questions over whether and how the device can be removed without damaging brain tissue.

Musk’s BMI startup first revealed a wireless version of its ‘N1 Link’ implant working in pigs in 2020, which streamed neural data in order to track limb movement. It has since showcased its neural implants working in primates, notably allowing a macaque test subject to play Pong using only its thoughts.

N1 Link (left), Removable charger/transmitter (right) | Image courtesy Neuralink

Neuralink’s N1 Implant is hermetically sealed in a biocompatible enclosure which the company says is capable of withstanding harsh physiological conditions. The N1 Implant is implanted by a custom a surgical robot; Neuralink says this ensures accurate and efficient placement of its 64 flexible threads which are distrusted to 1,024 electrodes.

Powered by a small lithium battery that can be wirelessly charged using a compact, inductive charger, the implant is said to incorporate custom low-power chips and electronics that process neural signals and transmit them wirelessly to the Neuralink Application.

Neuralink is currently focused on giving people with quadriplegia the ability to control computers and mobile devices with their thoughts. In the future, the company hopes to restore capabilities such as vision, motor function, and speech, and eventually expand “how we experience the world,” the company says on its website.

That last bit is undoubtedly the company’s most ambitious goal, which the company has said will not only include reading electrical brain signals from paralyzed and neurotypical users alike, but also eventually the ability to “write” signals back to the brain.

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