Neuroscience

werner-herzog-muses-on-mysteries-of-the-brain-in-theater-of-thought

Werner Herzog muses on mysteries of the brain in Theater of Thought

brain, consciousness, culture, documentaries, film, Neuroscience, science documentaries / /

That mind is partly revealed through Herzog’s running narration, such as when he muses about collective behavior and whether fish have souls—a digression sparked by his interview with Siri co-inventor Tom Gruber. “In the background, I saw his TV screen still on, we didn’t switch it off, and I saw some very, very strange school of fish,” said Herzog. “I asked him about the school of fish, which he had filmed himself. And all of a sudden, I’m only interested in the fish and common behavior. Why do they behave in big schools, in unison? Why do they do that? Do they dream? And if they think, what are they thinking about? I immerse the audience into a very strange form of underwater landscape and behavior of fish.”

Werner Herzog’s inspiration for Theater of Thought arose from conversations with Columbia University neuroscientist Rafael Yuste, who served as science advisor on the film. Argot Pictures

We glimpse the inner workings of Herzog’s mind in the kinds of questions he asks his subjects, such as when he queries IBM’s Dario Gil, who works on quantum computing, about his passion for fishing, eliciting an enthusiastic smile in response. He agrees to interview University of Washington neuroscientist Christof Koch after Koch’s early-morning row on the Puget Sound and includes music from New York University neuroscientist Joseph LeDoux‘s band, the Amygdaloids, in the film’s soundtrack. He asks married scientists Cori Bargmann and Richard Axel about music, their dinner conversations, and the linguistic capabilities of parrots. In so doing, he brings out their innate humanity, not just their scientific expertise.

“That’s what I do. If you don’t have it in you, you shouldn’t be a filmmaker,” said Herzog. “But you see, also, the joy of getting into all of this and the joy of meeting these scientists. We are talking about speaking parrots. What if two parrots learned a language that is already extinct and they would speak to each other? What would we make of it? So I’m asking, spontaneously, because I saw it, I sensed it, there was something I should depart completely from scientific quests. And yet there’s a deep scientific background to it.”

Werner Herzog muses on mysteries of the brain in Theater of Thought Read More »

tweaking-non-neural-brain-cells-can-cause-memories-to-fade

Tweaking non-neural brain cells can cause memories to fade

astrocytes, Biology, memory, neurobiology, neurons, Neuroscience, Science / /

Neurons and a second cell type called an astrocyte collaborate to hold memories.

Astrocytes (labelled in black) sit within a field of neurons. Credit: Ed Reschke

“If we go back to the early 1900s, this is when the idea was first proposed that memories are physically stored in some location within the brain,” says Michael R. Williamson, a researcher at the Baylor College of Medicine in Houston. For a long time, neuroscientists thought that the storage of memory in the brain was the job of engrams, ensembles of neurons that activate during a learning event. But it turned out this wasn’t the whole picture.

Williamson’s research investigated the role astrocytes, non-neuron brain cells, play in the read-and-write operations that go on in our heads. “Over the last 20 years the role of astrocytes has been understood better. We’ve learned that they can activate neurons. The addition we have made to that is showing that there are subsets of astrocytes that are active and involved in storing specific memories,” Williamson says in describing a new study his lab has published.

One consequence of this finding: Astrocytes could be artificially manipulated to suppress or enhance a specific memory, leaving all other memories intact.

Marking star cells

Astrocytes, otherwise known as star cells due to their shape, play various roles in the brain, and many are focused on the health and activity of their neighboring neurons. Williamson’s team started by developing techniques that enabled them to mark chosen ensembles of astrocytes to see when they activate genes (including one named c-Fos) that help neurons reconfigure their connections and are deemed crucial for memory formation. This was based on the idea that the same pathway would be active in neurons and astrocytes.

“In simple terms, we use genetic tools that allow us to inject mice with a drug that artificially makes astrocytes express some other gene or protein of interest when they become active,” says Wookbong Kwon, a biotechnologist at Baylor College and co-author of the study.

Those proteins of interest were mainly fluorescent proteins that make cells fluoresce bright red. This way, the team could spot the astrocytes in mouse brains that became active during learning scenarios. Once the tagging system was in place, Williamson and his colleagues gave their mice a little scare.

“It’s called fear conditioning, and it’s a really simple idea. You take a mouse, put it into a new box, one it’s never seen before. While the mouse explores this new box, we just apply a series of electrical shocks through the floor,” Williamson explains. A mouse treated this way remembers this as an unpleasant experience and associates it with contextual cues like the box’s appearance, the smells and sounds present, and so on.

The tagging system lit up all astrocytes that expressed the c-Fos gene in response to fear conditioning. Williamson’s team inferred that this is where the memory is stored in the mouse’s brain. Knowing that, they could move on to the next question, which was if and how astrocytes and engram neurons interacted during this process.

Modulating engram neurons

“Astrocytes are really bushy,” Williamson says. They have a complex morphology with lots and lots of micro or nanoscale processes that infiltrate the area surrounding them. A single astrocyte can contact roughly 100,000 synapses, and not all of them will be involved in learning events. So the team looked for correlations between astrocytes activated during memory formation and the neurons that were tagged at the same time.

“When we did that, we saw that engram neurons tended to be contacting the astrocytes that are active during the formation of the same memory,” Williamson says. To see how astrocytes’ activity affects neurons, the team artificially stimulated the astrocytes by microinjecting them with a virus engineered to induce the expression of the c-Fos gene. “It directly increased the activity of engram neurons but did not increase the activity of non-engram neurons in contact with the same astrocyte,” Williamson explains.

This way his team established that at least some astrocytes could preferentially communicate with engram neurons. The researchers also noticed that astrocytes involved in memorizing the fear conditioning event had elevated levels of a protein called NFIA, which is known to regulate memory circuits in the hippocampus.

But probably the most striking discovery came when the researchers tested whether the astrocytes involved in memorizing an event also played a role in recalling it later.

Selectively forgetting

The first test to see if astrocytes were involved in recall was to artificially activate them when the mice were in a box that they were not conditioned to fear. It turned out artificial activation of astrocytes that were active during the formation of a fear memory formed in one box caused the mice to freeze even when they were in a different one.

So, the next question was, if you just killed or otherwise disabled an astrocyte ensemble active during a specific memory formation, would it just delete this memory from the brain? To get that done, the team used their genetic tools to selectively delete the NFIA protein in astrocytes that were active when the mice received their electric shocks. “We found that mice froze a lot less when we put them in the boxes they were conditioned to fear. They could not remember. But other memories were intact,” Kwon claims.

The memory was not completely deleted, though. The mice still froze in the boxes they were supposed to freeze in, but they did it for a much shorter time on average. “It looked like their memory was maybe a bit foggy. They were not sure if they were in the right place,” Williamson says.

After figuring out how to suppress a memory, the team also figured out where the “undo” button was and brought it back to normal.

“When we deleted the NFIA protein in astrocytes, the memory was impaired, but the engram neurons were intact. So, the memory was still somewhere there. The mice just couldn’t access it,” Williamson claims. The team brought the memory back by artificially stimulating the engram neurons using the same technique they employed for activating chosen astrocytes. “That caused the neurons involved in this memory trace to be activated for a few hours. This artificial activity allowed the mice to remember it again,” Williamson says.

The team’s vision is that in the distant future this technique can be used in treatments targeting neurons that are overactive in disorders such as PTSD. “We now have a new cellular target that we can evaluate and potentially develop treatments that target the astrocyte component associated with memory,” Williamson claims. But there’s lot more to learn before anything like that becomes possible. “We don’t yet know what signal is released by an astrocyte that acts on the neuron. Another thing is our study was focused on one brain region, which was the hippocampus, but we know that engrams exist throughout the brain in lots of different regions. The next step is to see if astrocytes play the same role in other brain regions that are also critical for memory,” Williamson says.

Nature, 2024.  DOI: 10.1038/s41586-024-08170-w

Photo of Jacek Krywko

Jacek Krywko is a freelance science and technology writer who covers space exploration, artificial intelligence research, computer science, and all sorts of engineering wizardry.

Tweaking non-neural brain cells can cause memories to fade Read More »

study:-cats-in-little-crocheted-hats-shed-light-on-feline-chronic-pain

Study: Cats in little crocheted hats shed light on feline chronic pain

animals, Biology, chronic pain, domestic cats, EEG, feline osteoarthitis, Neuroscience, Science / /

For the fashion-forward cat —

The custom-made caps hold electrodes in place and reduce motion artifacts during EEGs.

–

A cat wearing a crocheted hat custom-made to record brain activity

Enlarge / “When you spend more time putting electrodes back on than you do actually recording the EEGs, you get creative.”

Alienor Delsart

Our feline overlords aren’t particularly known for obeying commands from mere humans, which can make it difficult to study their behaviors in controlled laboratory settings. So a certain degree of ingenuity is required to get usable results—like crocheting adorable little hats for kitties taking part in electroencephalogram (EEG) experiments. That’s what researchers at the University of Montreal in Quebec, Canada, did to learn more about assessing chronic pain in cats—and they succeeded. According to their recent paper published in the Journal of Neuroscience Methods, it’s the first time scientists have recorded the electrical activity in the brains of conscious cats.

According to the authors, one-quarter of adult cats suffer from osteoarthritis and chronic pain that worsens with age. There are currently limited treatment options, namely, non-steroidal anti-inflammatory drugs, which can have significant side effects for the cats. An injectable monoclonal antibody tailored for cats has recently been developed to neutralize excessive nerve growth factor, but other alternative treatment options like supplements and regenerative medicine have yet to be tested. Nor has the effectiveness of certain smells or lighting in altering pain perception in felines been tested.

That was the Montreal team’s primary objective for their experiments. Initially, they tried to place electrodes on the heads of 11 awake adult cats with osteoarthritis, but the cats kept shaking off the electrodes.

“When you spend more time putting electrodes back on than you do actually recording the EEGs, you get creative,” co-author Aliénor Delsart of the University of Montreal told New Scientist. So he and his co-authors tapped a graduate student with crocheting skills to make the little hats. Not only did the hats hold the electrodes in place, but the cats also stopped trying to chew the wires.

With that problem solved, the real experiments could begin, designed to record brain activity of cats in response to smelling certain substances or seeing different wavelengths of colored light. The kitty subjects were housed as a group in an environment with lighting, temperature, and humidity controls, along with perches, beds, scratching posts, and cat toys.

Electrodes were attached with no need to shave the cats’ hair, thanks to a conductive paste to improve electrode/skin contact. First they recorded the basal activity before moving to exposure to sensory stimuli: a grapefruit smell for olfactory stimulation, and red, blue, and green lighting in a darkened room for visual stimulation.

Granted, there were still a few motion artifacts in that data; two cats were excluded from the data analysis for that reason. And the authors acknowledged the small sample size and largely descriptive nature of their analysis, which they deemed appropriate for what is essentially a test of the feasibility of their approach. The study met the group’s primary objectives: to assess whether the EEG method was feasible with conscious cats and whether the resulting analytical methods were an efficient means to characterize how the cats responded to specific sensory stimuli. “This opens new avenues for investigating chronic pain mechanisms and developing novel therapeutic strategies,” the authors concluded.

Journal of Neuroscience Methods, 2024. DOI: 10.1016/j.jneumeth.2024.110254  (About DOIs).

Study: Cats in little crocheted hats shed light on feline chronic pain Read More »

ars-chats-with-precision,-the-brain-chip-maker-taking-the-road-less-invasive

Ars chats with Precision, the brain-chip maker taking the road less invasive

brain computer interface, health, musk, Neuralink, Neuroscience, neurosurgery, Precision, Science / /

Brain-chip buzz —

Precision tested its BCI on 14 people so far. Two more are scheduled this month.

–

Precision’s Layer 7 Cortical Interface array.

Enlarge / Precision’s Layer 7 Cortical Interface array.

Work toward brain-computer interfaces has never been more charged. Though neuroscientists have toiled for decades to tap directly into human thoughts, recent advances have the field buzzing with anticipation—and the involvement of one polarizing billionaire has drawn a new level of attention.

With competition amping up in this space, Ars spoke with Ben Rapoport, who is a neurosurgeon, electrical engineer, and co-founder of the brain-computer interface (BCI) company Precision Neuroscience. Precision is at the forefront of the field, having placed its BCI on the brains of 14 human patients so far, with two more scheduled this month. Rapoport says he hopes to at least double that number of human participants by the end of this year. In fact, the 3-year-old company expects to have its first BCI on the market next year.

In addition to the swift progress, Precision is notable for its divergence from its competitor’s strategies, namely Neuralink, the most high-profile BCI company and headed by Elon Musk. In 2016, Rapoport co-founded Neuralink alongside Musk and other scientists. But he didn’t stay long and went on to co-found Precision in 2021. In previous interviews, Rapoport suggested his split from Neuralink related to the issues of safety and invasiveness of the BCI design. While Neuralink’s device is going deeper into the brain—trying to eavesdrop on neuron signals with electrodes at close range to decode thoughts and intended motions and speech—Precision is staying at the surface, where there is little to no risk of damaging brain tissue.

Shallow signals

“It used to be thought that you needed to put needle-like electrodes into the brain surface in order to listen to signals of adequate quality,” Rapoport told Ars. Early BCIs developed decades ago used electrode arrays with tiny needles that sink up to 1.5 millimeters into brain tissue. Competitors such as Blackrock Neurotech and Paradromics are still developing such designs. (Another competitor, Synchron, is developing a stent-like device threaded into a major blood vessel in the brain.) Meanwhile, Neuralink is going deeper, using a robot to surgically implant electrodes into brain tissue, reportedly between 3 mm and 8 mm deep.

However, Rapoport eschews this approach. Anytime something essentially cuts into the brain, there’s damage, he notes. Scar tissue and fibrous tissue can form—which is bad for the patient and the BCI’s functioning. “So, there’s not infinite scalability [to such designs],” Rapoport notes, “because when you try to scale that up to making lots of little penetrations into the brain, at some point you can run into a limitation to how many times you can penetrate the brain without causing irreversible and undetectable damage.”

Further, he says, penetrating the brain is just unnecessary. Rapoport says there is no fundamental data that suggests that penetration is necessary for BCIs advances. Rather, the idea was based on the state of knowledge and technology from decades ago. “It was just that it was an accident that that’s how the field got started,” he said. But, since the 1970s, when centimeter-scale electrodes were first being used to capture brain activity, the technology has advanced from the macroscopic to microscopic range, creating more powerful devices.

“All of conscious thought—movement, sensation, intention, vision, etc.—all of that is coordinated at the level of the neocortex, which is the outermost two millimeters of the brain,” Rapoport said. “So, everything, all of the signals of interest—the cognitive processing signals that are interesting to the brain-computer interface world—that’s all happening within millimeters of the brain surface … we’re talking about very small spatial scales.” With the more potent technology of today, Precision thinks it can collect the data it needs without physically traversing those tiny distances.

Ars chats with Precision, the brain-chip maker taking the road less invasive Read More »

the-nature-of-consciousness,-and-how-to-enjoy-it-while-you-can

The nature of consciousness, and how to enjoy it while you can

altered, consciousness, Neuroscience, psychedelics, psychology, Science / /

Remaining aware —

In his new book, Christof Koch views consciousness as a theorist and an aficionado.

–

A black background with multicolored swirls filling the shape of a human brain.

Unraveling how consciousness arises out of particular configurations of organic matter is a quest that has absorbed scientists and philosophers for ages. Now, with AI systems behaving in strikingly conscious-looking ways, it is more important than ever to get a handle on who and what is capable of experiencing life on a conscious level. As Christof Koch writes in Then I Am Myself the World, “That you are intimately acquainted with the way life feels is a brute fact about the world that cries out for an explanation.” His explanation—bounded by the limits of current research and framed through Koch’s preferred theory of consciousness—is what he eloquently attempts to deliver.

Koch, a physicist, neuroscientist, and former president of the Allen Institute for Brain Science, has spent his career hunting for the seat of consciousness, scouring the brain for physical footprints of subjective experience. It turns out that the posterior hot zone, a region in the back of the neocortex, is intricately connected to self-awareness and experiences of sound, sight, and touch. Dense networks of neocortical neurons in this area connect in a looped configuration; output signals feedback into input neurons, allowing the posterior hot zone to influence its own behavior. And herein, Koch claims, lies the key to consciousness.

In the hot zone

According to integrated information theory (IIT)—which Koch strongly favors over a multitude of contending theories of consciousness—the Rosetta Stone of subjective experience is the ability of a system to influence itself: to use its past state to affect its present state and its present state to influence its future state.

Billions of neurons exist in the cerebellum, but they are wired “with nonoverlapping inputs and outputs … in a feed-forward manner,” writes Koch. He argues that a structure designed in this way, with limited influence over its own future, is not likely to produce consciousness. Similarly, the prefrontal cortex might allow us to perform complex calculations and exhibit advanced reasoning skills, but such traits do not equate to a capacity to experience life. It is the “reverberatory, self-sustaining excitatory loops prevalent in the neocortex,” Koch tells us, that set the stage for subjective experience to arise.

This declaration matches the experimental evidence Koch presents in Chapter 6: Injuries to the cerebellum do not eliminate a person’s awareness of themselves in relation to the outside world. Consciousness remains, even in a person who can no longer move their body with ease. Yet injuries to the posterior hot zone within the neocortex significantly change a person’s perception of auditory, visual, and tactile information, altering what they subjectively experience and how they describe these experiences to themselves and others.

Does this mean that artificial computer systems, wired appropriately, can be conscious? Not necessarily, Koch says. This might one day be possible with the advent of new technology, but we are not there yet. He writes. “The high connectivity [in a human brain] is very different from that found in the central processing unit of any digital computer, where one transistor typically connects to a handful of other transistors.” For the foreseeable future, AI systems will remain unconscious despite appearances to the contrary.

Koch’s eloquent overview of IIT and the melodic ease of his neuroscientific explanations are undeniably compelling, even for die-hard physicalists who flinch at terms like “self-influence.” His impeccably written descriptions are peppered with references to philosophers, writers, musicians, and psychologists—Albert Camus, Viktor Frankl, Richard Wagner, and Lewis Carroll all make appearances, adding richness and relatability to the narrative. For example, as an introduction to phenomenology—the way an experience feels or appears—he aptly quotes Eminem: “I can’t tell you what it really is, I can only tell you what it feels like.”

The nature of consciousness, and how to enjoy it while you can Read More »

sleeping-more-flushes-junk-out-of-the-brain

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.

–

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

Sleeping more flushes junk out of the brain Read More »