3-D map of blood vessels in cerebral cortex holds suprises

Blood vessels within a sensory area of the mammalian brain loop and connect in unexpected ways, a new map has revealed.

The study, published June 9 in the early online edition of Nature Neuroscience, describes vascular architecture within a well-known region of the cerebral cortex and explores what that structure means for functional imaging of the brain and the onset of a kind of dementia.

David Kleinfeld, professor of physics and neurobiology at the University of California, San Diego, and colleagues mapped blood vessels in an area of the mouse brain that receives sensory signals from the whiskers.

The organization of neural cells in this brain region is well-understood, as was a pattern of blood vessels that plunge from the surface of the brain and return from the depths, but the network in between was uncharted. Yet these tiny arterioles and venules deliver oxygen and nutrients to energy-hungry brain cells and carry away wastes.

The team traced this fine network by filling the vessels with a fluorescent gel. Then, using an automated system, developed by co-author Philbert Tsai, that removes thin layers of tissue with a laser while capturing a series of images to reconstructed the three-dimensional network of tiny vessels.

The project focused on a region of the cerebral cortex in which the nerve cells are so well known that they can be traced to individual whiskers. These neurons cluster in “barrels,” one per whisker, a pattern of organization seen in other sensory areas as well.

The scientists expected each whisker barrel to match up with its own blood supply, but that was not the case. The blood vessels don’t line up with the functional structure of the neurons they feed.

"This was a surprise, because the blood vessels develop in tandem with neural tissue," Kleinfeld said. Instead, microvessels beneath the surface loop and connect in patterns that don’t obviously correspond to the barrels.

To search for patterns, they turned to a branch of mathematics called graph theory, which describes systems as interconnected nodes. Using this approach, no hidden subunits emerged, demonstrating that the mesh indeed forms a continous network they call the “angiome.”

The vascular maps traced in this study raise a question of what we’re actually seeing in a widely used kind of brain imaging called functional MRI, which in one form measures brain activity by recording changes in oxygen levels in the blood. The idea is that activity will locally deplete oxygen. So they wiggled whiskers on individual mice and found that optical signals associated with depleted oxygen centered on the barrels, where electrical recordings confirmed neural activity. Thus brain mapping does not depend on a modular arrangement of blood vessels.

The researchers also went a step further to calculate patterns of blood flow based on the diameters and connections of the vessels and asked how this would change if a feeder arteriole were blocked. The map allowed them to identify “perfusion domains,” which predict the volumes of lesions that result when a clot occludes a vessel. Critically, they were able to build a physical model of how these lesions form, as may occur in cases of human dementia.

(Image: Andreas Weil)

Incredible Technology: How to See Inside the Mind

Human experience is defined by the brain, yet much about this 3-lb. organ remains a mystery. Even so, from brain imaging to brain-computer interfaces, scientists have made impressive strides in developing technologies to peer inside the mind.

Imaging the brain

Currently, scientists who study the brain can look at its structure or its function. In structural imaging, machines take snapshots of the brain’s large-scale anatomy that can be used to diagnose tumors or blood clots, for example. Functional imaging provides a dynamic view of the brain, showing which areas are active during thinking and perception.

Structural-imaging techniques include CAT scans, or computerized axial tomography, which takes images of slices through the brain by beaming X-rays at the head from many different angles. CAT, or CT, scans are often used to diagnose a brain injury, for example. Another method, positron emission tomography (PET), generates both 2D and 3D images of the brain: A radioactively labeled chemical injected into the blood emits gamma rays that a scanner detects. And magnetic resonance imaging (MRI) provides a view of the brain’s overall structure by measuring the magnetic spin of atoms inside a strong magnetic field.

"There’s no question that MRI is probably the best way to see the brain," said Dr. Mauricio Castillo, a radiologist at the University of North Carolina at Chapel Hill and editor-in-chief of the American Journal of Neuroradiology.

In the realm of functional imaging, the current gold standard is functional MRI (fMRI). This technique measures changes in blood flow to different brain areas as a proxy for which areas are active when someone performs a task like reading a word or viewing a picture.

"The emphasis nowadays is to try to merge how the brain is wired with the activation of the cortex [the brain’s outermost layer]," Castillo said.

Several methods can be combined to merge brain structure and function. For example, MRI and PET scanning can be performed simultaneously, and the images can be combined to show physiological activity superimposed on an anatomical map of the brain. The end result can be used to tell a surgeon the location of a brain lesion so it can be removed, Castillo said.

Recently, a new technique has been developed to literally see inside the brain. Called CLARITY (originally for Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue-hYdrogel), it can make a (nonliving) brain transparent to light while keeping its structure intact. The technique has already been used to visualize the neurological wiring of an adult mouse brain.

Decoding thoughts

Some scientists want to see inside the brain more figuratively. Enter brain-computer interfaces (BCIs or BMIs, brain-machine interfaces), devices that connect brain signals to an external device, such as a computer or prosthetic limb. BCIs range from noninvasive systems that consist of electrodes placed on the scalp, to more invasive ones that require the electrodes to be implanted in the brain itself.

Noninvasive BCIs include scalp-based electroencephalography (EEG), which records the activity of many neurons over large brain areas. The advantage of EEG-based systems is that they don’t require surgery. On the other hand, these systems can only detect generalized brain activity, so the user must focus his or her thoughts on just a single task.

More invasive systems include electrocorticography (ECoG), in which electrodes are implanted on the surface of the brain to record EEG signals from the cortex. Since Wilder Penfield and Herbert Jasper pioneered the technique in the early 1950s, it has been used, among other purposes, to identify brain regions where epileptic seizures begin.

Some BCIs use electrodes implanted inside the brain’s cortex. Although these systems are more invasive, they have much better resolution and can pick up the signals sent by individual neurons. BCIs can now even allow humans with paraplegia (paralysis of all four limbs) to control a robotic arm through thought alone, or allow users to spell out words on a computer screen using just their mind.

Despite many advances, a lot remains unknown about the brain. To bridge this gap, American scientists are embarking on a new project to map the human brain, announced by President Barack Obama in April, called the BRAIN initiative (Brain Research through Advancing Innovative Neurotechnologies).

But neuroscientists have their work cut out for them. “The brain is probably the most complex machine in the universe,” Castillo said. “We’re still a long way from understanding it.”

Scientists Map Process by Which Brain Cells Form Long-Term Memories

Scientists at the Gladstone Institutes have deciphered how a protein called Arc regulates the activity of neurons – providing much-needed clues into the brain’s ability to form long-lasting memories.

These findings, reported Sunday in Nature Neuroscience, also offer newfound understanding as to what goes on at the molecular level when this process becomes disrupted.

Led by Gladstone senior investigator Steve Finkbeiner, MD, PhD, this research delved deep into the inner workings of synapses. Synapses are the highly specialized junctions that process and transmit information between neurons. Most of the synapses our brain will ever have are formed during early brain development, but throughout our lifetimes these synapses can be made, broken and strengthened. Synapses that are more active become stronger, a process that is essential for forming new memories.

However, this process is also dangerous, as it can overstimulate the neurons and lead to epileptic seizures. It must therefore be kept in check.

Neuroscientists recently discovered one important mechanism that the brain uses to maintain this important balance: a process called “homeostatic scaling.” Homeostatic scaling allows individual neurons to strengthen the new synaptic connections they’ve made to form memories, while at the same time protecting the neurons from becoming overly excited. Exactly how the neurons pull this off has eluded researchers, but they suspected that the Arc protein played a key role.

“Scientists knew that Arc was involved in long-term memory, because mice lacking the Arc protein could learn new tasks, but failed to remember them the next day,” said Finkbeiner, who is also a professor of neurology and physiology at UC San Francisco, with which Gladstone is affiliated. “Because initial observations showed Arc accumulating at the synapses during learning, researchers thought that Arc’s presence at these synapses was driving the formation of long-lasting memories.”

But Finkbeiner and his team thought there was something else in play.

The Role of Arc in Homeostatic Scaling

In laboratory experiments, first in animal models and then in greater detail in the petri dish, the researchers tracked Arc’s movements. And what they found was surprising.

“When individual neurons are stimulated during learning, Arc begins to accumulate at the synapses – but what we discovered was that soon after, the majority of Arc gets shuttled into the nucleus,” said Erica Korb, PhD, the paper’s lead author who completed her graduate work at Gladstone and UCSF.

“A closer look revealed three regions within the Arc protein itself that direct its movements: one exports Arc from the nucleus, a second transports it into the nucleus, and a third keeps it there,” she said. “The presence of this complex and tightly regulated system is strong evidence that this process is biologically important.”

In fact, the team’s experiments revealed that Arc acted as a master regulator of the entire homeostatic scaling process. During memory formation, certain genes must be switched on and off at very specific times in order to generate proteins that help neurons lay down new memories.  From inside the nucleus, the authors found that it was Arc that directed this process required for homeostatic scaling to occur. This strengthened the synaptic connections without overstimulating them – thus translating learning into long-term memories. 

Implications for a Variety of Neurological Diseases

“This discovery is important not only because it solves a long-standing mystery on the role of Arc in long-term memory formation, but also gives new insight into the homeostatic scaling process itself – disruptions in which have already been implicated in a whole host of neurological diseases,” said Finkbeiner. “For example, scientists recently discovered that Arc is depleted in the hippocampus, the brain’s memory center, in Alzheimer’s disease patients. It’s possible that disruptions to the homeostatic scaling process may contribute to the learning and memory deficits seen in Alzheimer’s.”

Dysfunctions in Arc production and transport may also be a vital player in autism. For example, the genetic disorder Fragile X syndrome – a common cause of both mental retardation and autism, directly affects the production of Arc in neurons.

“In the future,” added Dr. Korb, “we hope further research into Arc’s role in human health and disease can provide even deeper insight into these and other disorders, and also lay the groundwork for new therapeutic strategies to fight them.”

(Image: Wikimedia)

Why Music Makes Our Brain Sing

MUSIC is not tangible. You can’t eat it, drink it or mate with it. It doesn’t protect against the rain, wind or cold. It doesn’t vanquish predators or mend broken bones. And yet humans have always prized music — or well beyond prized, loved it.

In the modern age we spend great sums of money to attend concerts, download music files, play instruments and listen to our favorite artists whether we’re in a subway or salon. But even in Paleolithic times, people invested significant time and effort to create music, as the discovery of flutes carved from animal bones would suggest.

So why does this thingless “thing” — at its core, a mere sequence of sounds — hold such potentially enormous intrinsic value?

The quick and easy explanation is that music brings a unique pleasure to humans. Of course, that still leaves the question of why. But for that, neuroscience is starting to provide some answers.

More than a decade ago, our research team used brain imaging to show that music that people described as highly emotional engaged the reward system deep in their brains — activating subcortical nuclei known to be important in reward, motivation and emotion. Subsequently we found that listening to what might be called “peak emotional moments” in music — that moment when you feel a “chill” of pleasure to a musical passage — causes the release of the neurotransmitter dopamine, an essential signaling molecule in the brain.

When pleasurable music is heard, dopamine is released in the striatum — an ancient part of the brain found in other vertebrates as well — which is known to respond to naturally rewarding stimuli like food and sex and which is artificially targeted by drugs like cocaine and amphetamine.

But what may be most interesting here is when this neurotransmitter is released: not only when the music rises to a peak emotional moment, but also several seconds before, during what we might call the anticipation phase.

The idea that reward is partly related to anticipation (or the prediction of a desired outcome) has a long history in neuroscience. Making good predictions about the outcome of one’s actions would seem to be essential in the context of survival, after all. And dopamine neurons, both in humans and other animals, play a role in recording which of our predictions turn out to be correct.

To dig deeper into how music engages the brain’s reward system, we designed a study to mimic online music purchasing. Our goal was to determine what goes on in the brain when someone hears a new piece of music and decides he likes it enough to buy it.

We used music-recommendation programs to customize the selections to our listeners’ preferences, which turned out to be indie and electronic music, matching Montreal’s hip music scene. And we found that neural activity within the striatum — the reward-related structure — was directly proportional to the amount of money people were willing to spend.

But more interesting still was the cross talk between this structure and the auditory cortex, which also increased for songs that were ultimately purchased compared with those that were not.

Why the auditory cortex? Some 50 years ago, Wilder Penfield, the famed neurosurgeon and the founder of the Montreal Neurological Institute, reported that when neurosurgical patients received electrical stimulation to the auditory cortex while they were awake, they would sometimes report hearing music. Dr. Penfield’s observations, along with those of many others, suggest that musical information is likely to be represented in these brain regions.

The auditory cortex is also active when we imagine a tune: think of the first four notes of Beethoven’s Fifth Symphony — your cortex is abuzz! This ability allows us not only to experience music even when it’s physically absent, but also to invent new compositions and to reimagine how a piece might sound with a different tempo or instrumentation.

We also know that these areas of the brain encode the abstract relationships between sounds — for instance, the particular sound pattern that makes a major chord major, regardless of the key or instrument. Other studies show distinctive neural responses from similar regions when there is an unexpected break in a repetitive pattern of sounds, or in a chord progression. This is akin to what happens if you hear someone play a wrong note — easily noticeable even in an unfamiliar piece of music.

These cortical circuits allow us to make predictions about coming events on the basis of past events. They are thought to accumulate musical information over our lifetime, creating templates of the statistical regularities that are present in the music of our culture and enabling us to understand the music we hear in relation to our stored mental representations of the music we’ve heard.

So each act of listening to music may be thought of as both recapitulating the past and predicting the future. When we listen to music, these brain networks actively create expectations based on our stored knowledge.

Composers and performers intuitively understand this: they manipulate these prediction mechanisms to give us what we want — or to surprise us, perhaps even with something better.

In the cross talk between our cortical systems, which analyze patterns and yield expectations, and our ancient reward and motivational systems, may lie the answer to the question: does a particular piece of music move us?

When that answer is yes, there is little — in those moments of listening, at least — that we value more.

Bionic eye prototype unveiled by Victorian scientists and designers

A team of Australian industrial designers and scientists have unveiled their prototype for the world’s first bionic eye.

It is hoped the device, which involves a microchip implanted in the skull and a digital camera attached to a pair of glasses, will allow recipients to see the outlines of their surroundings.

If successful, the bionic eye has the potential to help over 85 per cent of those people classified as legally blind. With trials beginning next year, Monash University’s Professor Mark Armstrong says the bionic eye should give recipients a degree of extra mobility.

"There’s a camera at the front and the camera is actually very similar to an iPhone camera, so it takes live action for colour," he told PM. "And then that imagery is then distilled via a very sophisticated processor down to, let’s say, a distilled signal.

"That signal is then transmitted wirelessly from what’s called a coil, which is mounted at the back of the head and inside the brain there is an implant which consists of a series of little ceramic tiles and in each tile are microscopic electrodes which actually are embedded in the visual cortex of the brain."

Professor Armstrong says is it is hoped the technology will help those who completely blind, enabling them to navigate their way around.

"What we believe the recipient will see is a sort of a low resolution dot image, but enough… [to] see, for example, the edge of a table or the silhouette of a loved one or a step into the gutter or something like that," he said.

"So the wonderful thing, if our interpretation of this is correct - because we don’t know until the first human trial - [is] it’ll of course enable people that are blind to be reconnected with their world in a way.

"There’s a number of different settings … so you could set it to floor mapping for example and it creates a silhouette around objects on the floor so that you can see where you’re going."

A challenge the designers have had to overcome is ensuring the product was lightweight, adjustable and enabled users to feel good about themselves.

"We want to make it comfortable and light weight and adjustable so that different sized heads and shapes will still manage it well and have those sort of nice aspects," Professor Armstrong said.

"We don’t want a Heath Robinson wire springs affair on somebody’s head.

"It needs to look sophisticated and appropriate, probably less like a prosthetic and more like a cool Bluetooth device."

The first implant is scheduled to go ahead next year which is expected to be followed by clinical trials, research and user feedback to the team.

The development of a bionic eye was one of the key aspirations out of the 2020 summit that was held in 2008.

Professor Armstrong says it is “amazing” that a prototype for the technology has already been achieved.

"To be honest when I heard about that 2020 conference and all of the people there, I thought it was a little bit of a hot air fest if you know what I mean," he said.

"But I’ve been proven completely wrong.

"Some of the initiatives from that, this is a major one for sure, have been brought to fruition and it’s wonderful for Australia and equally wonderful for Monash University."

Gestures of Human and Ape Infants Are More Similar Than You Might Expect

Thirteen years after the release of On the Origin of Species, Charles Darwin published another report on the evolution of mankind. In the 1872 book The Expression of the Emotions in Man and Animals, the naturalist argued that people from different cultures exhibit any given emotion through the same facial expression. This hypothesis didn’t quite pan out—last year, researchers poked a hole in the idea by showing that the expression of emotions such as anger, happiness and fear wasn’t universal (PDF). Nonetheless, certain basic things—such as the urge to cry out in pain, an increase in blood pressure when feeling anger, even shrugging when we don’t understand something—cross cultures.

A new study, published today in the journal Frontiers in Psychology, compares such involuntary responses, but with an added twist: Some observable behaviors aren’t only universal to the human species, but to our closest relatives too—chimpanzees and bonobos.

Using video analysis, a team of UCLA researchers found that human, chimpanzee and bonobo babies make similar gestures when interacting with caregivers. Members of all three species reach with their arms and hands for objects or people, and point with their fingers or heads. They also raise their arms up, a motion indicating that they want to be picked up, in the same manner. Such gestures, which seemed to be innate in all three species, precede and eventually lead to the development of language in humans, the researchers say.

To pick up on these behaviors, the team studied three babies of differing species through videos taken over a number of months. The child stars of these videos included a chimpanzee named Panpanzee, a bonobo called Panbanisha and a human girl, identified as GN. The apes were raised together at the Georgia State University Language Research Center in Atlanta, where researchers study language and cognitive processes in chimps, monkeys and humans. There, Panpanzee and Panbanisha were taught to communicate with their human caregivers using gestures, noises and lexigrams, abstract symbols that represent words. The human child grew up in her family’s home, where her parents facilitated her learning.

Researchers filmed the child’s development for seven months, starting when she was 11 months old, while the apes were taped from 12 months of age to 26 months. In the early stages of the study, the observed gestures were of a communicative nature: all three infants engaged in the behavior with the intention of conveying how their emotions and needs. They made eye contact with their caregivers, added non-verbal vocalizations to their movements or exerted physical effort to elicit a response.

By the second half of the experiment, the production of communicative symbols—visual ones for the apes, vocal ones for the human—increased. As she grew older, the human child began using more spoken words, while the chimpanzee and bonobo learned and used more lexigrams. Eventually, the child began speaking to convey what she felt, rather than only gesturing. The apes, on the other hand, continued to rely on gestures. The study calls this divergence in behavior “the first indication of a distinctive human pathway to language.”

The researchers speculate that the matching behaviors can be traced to the last shared ancestor of humans, chimps and bobonos, who lived between four and seven million years ago. That ancestor probably exhibited the same early gestures, which all three species then inherited. When the species diverged, humans managed to build on this communicative capacity by eventually graduating to speech.

Hints of this can be seen in how the human child paired her gestures with non-speech vocalizations, the precursors to words, far more than the apes did. It’s this successful combinationof gestures and words that may have led to the birth of human language.

What The Human Face Might Look Like 100,000 Years From Now

The human face might look very different in the future.

Artist and researcher Nickolay Lamm from U.K. discount site MyVoucherCodes.co.uk collaborated with a genomics expert to create pictures that show the evolution of the human face 20,000, 60,000, and 100,000 years from now.

In one possible future scenario, humans will have full control of human genome engineering. That is, they will be able to eliminate hereditary genetic disorders, or select desirable genetic traits like straight teeth and natural blonde hair.

Natural human evolution is still at work — the head will get bigger to make room for a larger brain — but most facial features will be molded to reflect what the majority of us perceive as attractive: big eyes, a straight nose, and facial symmetry.