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Beautiful Brains
02 February

People who have seen Earth from space report a "cognitive shift in awareness". Space philosopher, Frank White, calls this "the overview effect". It is often experienced as a profound feeling of awe and interconnection, and a renewed sense of responsibility for taking care of the environment.

It's important to explore and understand the mental health benefits of space flight not only to extend our knowledge of how to improve psychological well-being on space missions, but also to see if we can use positive aspects of this experience back on Earth.

My psychology doctoral research explored how the overview effect might have therapeutic value – and I interviewed seven retired NASA astronauts.

I asked them if their experience had enhanced their personal growth and promoted psychological well-being. I also asked them if they had used their experience to deal with the challenges of daily life back on Earth.

Mind expanding

All the participants said the experience was awe inspiring and helped them form a more significant, lasting and positive emotional attachment with their home planet.

The analysis revealed that the participants clustered into two groups based on the intensity of the changes they experienced in terms of both attitude and behavior. It appears that distance made the heart grow fonder – that is to say, the physical separation from "mother Earth" helped them appreciate the beauty of life and created a stronger bond to the planet.

Past research has suggested that being apart from Earth can cause separation anxiety, also known as "breakoff phenomenon". However, this state might also solidify the astronauts' attachment and dependence to Earth. From the vantage point of space, divisions and boundaries could not be seen and were pointless. Earth was seen as a "living bio-sphere" and as a "fragile oasis" harboring and cocooning life in unlikely circumstances in the void of space.

The astronauts orbited earth 16 times every 24 hours and became more familiar with its topography and landscape. Some of the participants commented how they were initially drawn to man-made structures such as bridges, roads, harbors, and cities at night. But Earth's raw beauty really came alive during daylight. Once they had bypassed the "superficial" features of the planet, they were overwhelmed by how fragile and alone Earth looked in space. They were also shocked by the sight of humankind's impact on the planet, such as deforestation and pollution.

One of the astronauts, Ronald Garan, spoke of the "sobering contradiction between the beauty of the Earth and the injustices and unfortunate realities on it". This contradiction appears to have evoked a state of tension in some of the astronauts that psychologists refer to as "cognitive dissonance" – the stress or discomfort experienced when holding contradictory beliefs, ideas, or values.

Feeling significant

Another key theme that arose was that some of the astronauts were puzzled by the fact that feelings of insignificance were not triggered. On the contrary, feelings of significance were reinforced. One explanation for this unanticipated outcome might be that the astronauts felt deeply connected to Earth and so part of something much bigger and more meaningful than their mere selves.

They thought it was extraordinary that our planet was in the "goldilocks zone" in our solar system, harbored life and existed at all. They developed what might be called a "cosmic consciousness" which appears to have strengthened their resilience when facing problems and existential challenges back on Earth.

All the participants were more reverent toward their home planet. They came back more geared towards solidarity and less towards individualism. Their inclinations to promote and act on common goals such as environmental issues were strengthened. The experience resonates with them all today and they continue, years after their return, to make sense and draw from it.

Meanwhile, back on Earth

The future mental health demands of a population that is growing rapidly, aging and increasingly feeling more detached, need to be discussed and addressed. If the view of Earth from space can induce feelings of calmness, significance and even euphoria maybe we should consider how we can recreate and use aspects of it in novel ways back on Earth.

Psychologists could use images of Earth from space, via virtual reality simulations or video footage, as a therapeutic tool to promote well-being, diminish stress, or even relieve distress at the end of life. The United Nations is already using virtual reality as a powerful empathy machine and story telling tool for fundraiser events to highlight some of the most pressing global challenges, including the Syrian refugee crisis and climate change. Counseling psychologists should follow in their footsteps.

This article first appeared on The Conversation and is republished here under a Creative Commons license.

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Beautiful Brains
12 January

From the Book: NeuroLogic by Eliezer J. Sternberg. Copyright © 2015 by Eliezer J. Sternberg, published by arrangement with Pantheon Books, an imprint of The Knopf Doubleday Publishing Group, a division of Random House LLC.

"I can figure out what things look like through other means," Amelia, who was born blind, tells me. She's describing the way she creates a mental picture of her environment.

"As I'm walking down a hallway, I can picture it. By the echoes of my heels against the ground, I know that it's a marble corridor. I can tell how long and wide it is. I sense whether the hall is congested with people or if it's empty. I'm aware of all the other footsteps. I feel the slight whoosh of air as someone passes me."

The echo of her heels against the marble changes as she enters the building's main lobby. "I can sense the grandeur of the atrium," she says. "This is clearly a fancy tower." Even in the absence of vision, Amelia can picture her surroundings by integrating her other sensations. Her brain exploits the interconnectedness of its various sensory pathways to reconstitute her vision using nonvisual means. Despite being blind, Amelia can appreciate the dimensions of a hallway, assess how crowded it is, detect the position of people around her, and even sense the elegance of the building she's in. She can navigate her environment using a nonvisual mental map.

I closed my eyes and tried to imagine what it might be like to perceive the world as Amelia does, but visual images kept popping into my mind. I wondered whether her concept of perceiving a corridor of sound was something like the way bats sense their environments using echolocation, their biological sonar that works by detecting the reflections of sounds they emit. Apparently, I'm not the only one who noticed the parallel.

Blind since he was a baby, Daniel Kish founded World Access for the Blind, an organization aiming to help people confront and overcome their blindness by developing their other senses. Kish is particularly known for his ability to use his own form of echolocation. The technique involves rapidly clicking his tongue against the roof of his mouth and listening for how the sound reflects off walls, cars, people, or anything else in his environment.

"It is the same process bats use," Kish says. "If a person is clicking and they're listening to surfaces around them they do get an instantaneous sense of the positioning of these surfaces." By carefully listening for the echo, Kish can discern even subtle differences between materials: "For example, a wooden fence is likely to have thicker structures than a metal fence and when the area is very quiet, wood tends to reflect a warmer, duller sound than metal."

Using fMRI, researchers in Canada were able to peer into the brains of people who use this human echolocation. Two blind individuals who were trained in the technique and two sighted control subjects participated in the study. All four volunteers first sat in a chamber specially designed so that echoes do not occur. The researchers monitored their brain activity while they tried the technique in the anti-echoic chamber. The purpose of this was to determine the baseline brain activation, to map the signals triggered by the activity of just hearing one's own clicks so as to eventually subtract that from the final results. In the next phase of the experiment, the control subjects were blindfolded, and along with the blind volunteers they tried echolocating outside near trees, cars, or lampposts. All the while, tiny microphones implanted in their ears recorded the sounds they heard. In the final stage of the experiment, the participants entered the fMRI machine one by one, where they listened to the recordings of their own echolocation attempts.

To generate the results, the researchers subtracted out the effects of hearing participants' own clicks from each of their brain activity patterns measured by fMRI, leaving only the neurological response to the echoes. The brains of the sighted volunteers showed almost no additional activity. As expected, they were just hearing their own clicks. The results for the blind group, on the other hand, were astonishing. As they heard the recordings of their tongues clicking, the fMRI revealed activation in the visual cortex: They weren't just hearing echoes of clicking sounds. Their brains were listening to sounds and translating them into a visuospatial map of the environment.

Despite being unable to see, blind people don't stop using their occipital lobes. The purpose of vision is to navigate our environment. The purpose is survival. Even when visual input is cut off, the occipital lobe keeps trying to be our compass, processing spatial information through other means. The brain constructs our picture of the world by piecing together whatever information it has, even crossing sensory boundaries—and not just those of vision and hearing.

In 2013, neuroscientists in Denmark published a study looking at how the brain allows for navigation when vision is deactivated. The experiment required that the participants find their way through a virtual corridor using only their sense of touch . . . on their tongues. They used a device called the tongue display unit, which created a tactile map by stimulating the tongue whenever the user bumps into a wall of the maze. Subjects could navigate the maze using arrow keys on a computer. The challenge was to use trial and error to find their way through. Participants might first try going straight until they hit a dead end, which they could feel as a buzzing sensation, and then have to figure out which way to turn, all the while constructing a map of the maze in their minds.

The neuroscientists trained two groups of participants to use the tongue display unit: congenitally blind subjects and sighted but blindfolded controls. As neuroscientists tend to do, they watched the participants' brains with fMRI as both the blind and the blindfolded subjects maneuvered through the virtual maze.

The fMRI results looked just like those of the human echolocation study. The blind subjects, who had never perceived a photon of light in their lives, were firing all cylinders of their visual cortices during the tongue stimulation task. Their brains had translated tactile signals into a visuospatial map. The blindfolded subjects exhibited no such activity. Their visual cortices remained quiet. In fact, when the sighted subjects stripped off their blindfolds and navigated the maze with their eyes, their brain activity matched that of the blind subjects navigating with their tongues.

Whether it's from our eyes, ears, or tongue, the brain will accept whatever sensory information it can get to construct a model of the world around us. Though members of the blind community lose the ability to see with their eyes, they can still generate a picture of the world through other means. Imagine how much more prominent these intersections are in the brains of blind people, who depend on sensory cross talk to substitute for their visual deficit. Their unconscious system can reprogram the visual cortex by remodeling the sensory highway system, pixelating the world around them by interweaving their other senses. They keep their sense of navigation and spatial relationships. They can enhance their use of one sense to fill the gaps of another. They retain their ability to imagine and to dream.

By Eliezer Sternberg, from the book, Neurologic.

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Beautiful Brains
29 October 2015

Dead men don't talk, but their brains can be quite verbose. Depending on how and where one looks, dead brains hold clues to the mysteries of this complex organ in both health and disease. Here, four pathologists and anatomists tell the tales of brain preservation and dissection. Interestingly, it's not unlike cooking, they note—there's a lot of slicing and dicing involved. But whether cubed, ground, frozen or marinated in formalin, your brains can reveal a lot in their afterlife.

Fresh out of the skull

Judy Melinek, forensic pathologist and co-author of Working Stiff, says that with the exception of a scalpel and a saw, she bought all her equipment at a culinary supply store. "They gave me a trade discount after I told them what I do for a living!"

Getting brains out of their skulls takes some brawn. First, Melinek uses a scalpel to make a round cut in the head's flesh—from one ear to another and over the top of the head. From there, she cuts and peels off the galea, a tough thick layer of fibrous tissue attached to the skull, folding it inside-out—forward over the face and backward over the neck. Once the bone is exposed, she makes another circle cut—this time with the Stryker saw, which she describes as a "jacked-up kitchen hand blender fitted with a crescent-shaped buzz saw blade." The saw makes an "awful racket" and spews bone dust, smelling just like a dental drill (so it's a good idea to do it under a plastic cover), but when it's done, the top of the skull comes off like a lid on a pot.

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Scooping the brain out of that "pot" requires more slicing. Melinek slips her left index and middle fingers under the bone of the brow, lifts up the brain's frontal lobes, and cuts everything that still ties the brain to its former home—nerves and arteries leading to the eyes and nose, a part of the dura matter called the brain tent, and the spinal cord. Then she slowly guides the organ out. "I cradle the back of the brain with my right hand while tipping it back with the fingers of my left," she says. "Sometimes, if the skull cap has come off just the right way, I can use it as a bowl to collect the brain."

Fresh brains are squishy like Jell-O and tricky to cut. "I gently squeeze its hemispheres together so they don't splay out while I slice off half-inch-thick slabs," Melinek says. "I take a look at each piece as it falls away from the brain to my right to see if there's anything unusual." For instance, trauma results in bleeding while lack of oxygen damages the nerves and causes swelling. A hypertension stroke, in which usually a small vessel in the center of the brain bursts, leaves "a bloody mess inside the normally white and grayish tissue." In an ischemic stroke caused by lack of blood flow from blocked arteries, the brain swells, turning mottled reddish-white where the blood could no longer reach. Thermal injuries from fire or superheated water can cook the brain, leaving it swollen, firm to the touch, and smelling like bad barbecue.

(image)Damien Hirst, Autopsy with Sliced Human Brain, oil on canvas 2004

Fixed in formalin and placed under the microscope, brain slices reveal more clues. Oxygen-starved nerves appear bright pink or red. Although it's not possible to tell whether the person was strangled, had a drug overdose, or something else happened, Melinek notes. Certain poisons can also paint brains in vivid colors. Hydrogen sulfide can give it a green tinge, while carbon monoxide or cyanide can dye it a bright, cherry red shade. For a definitive diagnose, however, Melinek sends samples to forensic chemist at a toxicology lab.

Unlike fresh brains, formalin-fixed brains are firm. They are cut into shapely slices that are easy to move around on the cutting board for picture-taking. "For that I use another tool I bought at the culinary supply store," Melinek reveals. "The metal spatula a cook uses to flip burgers."

Marinated and sliced

At the Imperial College London, neuropathologist Steve Gentlemen gets his brains after they soak in formalin for four weeks and turn into hardened brownish globules. His job too has a detective element to it, although his culprits are various diseases that ruin the brain, from stroke to Alzheimer's. He begins to gather his clues the moment he holds the organ in his hands. An acute stroke leaves dead tissue on the brain surface which is soft to the touch. A past stroke makes a small cavity, because the brain will eventually clear dead cells but leave the empty spot. Meningitis, an infection of brain membranes, leaves a white pus-like substance under the arachnoid membrane. An asymmetry between the two brain hemispheres means that there may be a tumor inside shifting the midline.

(image)Gentleman cutting a brain, image via Wellcome Collection

Sometimes Gentleman gets only half a brain to work with, because the other hemisphere is frozen somewhere for research. When he receives a full brain, Gentleman scoops out the brain stem and cerebellum from under the hemispheres, not unlike how a cook cleans out the chicken guts. He then examines the blood vessels at the base of the brain for yellow patches. "They're the arteriosclerotic debris," he explains. "When the little deposits built up, they can completely block the vessels or break off and cause the stroke higher up in the brain." He also examines the midbrain for substantia nigra, a normally darker brain tissue, which loses its color in Parkinson disease. "Even before I can get to a microscope, if this coloration is lost, I'm pretty sure what I am going to find."

With a blade akin to a large bread knife, Gentleman halves the brain in two and cuts it up—except he makes his cuts horizontally, not vertically: the hemisphere lies on its freshly cut side while the knife slices it from bottom up to assure uniformity. The resulting pieces look just like slices of a bread loaf with a roundish top. At that point you can spot some atrophied and shrunk tissue, Gentleman says. "The brain folds get narrower and it begins to look like a pickled walnut." The cuts are then embedded in paraffin, sliced seven microns thin, and stained with various chemicals for research.

Gentleman says he feels terribly privileged being able to do his job. "These people have bequeathed their brains to us, and I am fulfilling their last will and testament," he says. And his wonder in the brain's inner workings never ceases. "I've been examining brains for 25 years and I am still fascinated by this kilo and a half of fat," Gentleman says.

Carved, ground and frozen

For Jean-Paul Vonsattel, who runs the Brain Bank at Columbia University in New York, timing and precision is everything. He dissects brains fresh, as soon as they're harvested from donors. Because formalin changes tissue, certain aspects of morphological and biomolecular research require brain flesh that is still "living." Donated brains arrive at Vonsattel's laboratory inside bags and boxes filled with ice, and are immediately processed. First, they're sliced in two precisely equal halves, one to be prepared for research and the other fixed in formalin. "You can use the fixed tissue for diagnosis, but you can no longer extract proteins from it," explains Vonsattel. "So more and more researchers are asking for fresh samples to study what was in the brain while it was still alive." Because left and right hemispheres specialize at different tasks, and may be responsible for different symptoms, Vonsattel's team alternates them: On an even day, the right half gets carved, on an odd day, the left one.

The fresh half is sectioned into blocks carved from various brain areas such as the amygdala, hippocampus, motor cortex and others, yielding about 150 samples in total. Precision is important, Vonsattel notes, otherwise you can carve out the wrong part and skew months of someone's research. Sandwiched between two chilled metal plates, the slices are dipped into liquid nitrogen at around -180 degrees Celsius, which freezes the water inside the flesh so quickly that it doesn't form ice crystals that would rapture tissue and turn it to Swiss cheese. When such a block is thawed, it would retain the quality and the chemical composition of the fresh brain it had once been. From that, investigators would slice seven to 10 micrometer-thick sections for research. For the biomolecular studies of brain chemistry, Vonsattle's team manually grinds the samples into mush with a mortar and pestle, and then mixes in liquid nitrogen. When defrosted, the amalgams let researchers study the cells' genetic and biochemical make-up. "From that pulverized tissue you can isolate as many proteins as possible to see which one is toxic," says Vonsattlel, "For example the abnormal tau protein," which is implicated in Alzheimer's disease.

The blocks go into plastic bags and the liquefied mixes into vials, all of which are barcoded and catalogued akin to library materials, except they're stored in massive locked freezers at about -80 degrees Celsius. When a researcher requests tissue with a specific disorder, it takes minutes to locate the sample in a catalogue and then trace it to a freezer, shelf, rack, box, and finally the plastic bag. To date, Vonsattle's freezer library holds about three hundred thousand samples from 4,000 brains. And as the neurodegenerative research will grow, so will the hunger for his fresh brain slices.

Reassembled and digitized

Jacopo Annese, a computational neuroanatomist with The Brain Observatory at The Institute for Brain and Society, dissects brains to rebuild them once again. "There's a universe inside our heads," he says, but we know little about it. So he wants to create a digital neuroanatomical library that would store high-resolution images of hundreds of human brains.

Building digital brains requires dissecting its human predecessors into extraordinary thin slices which then can be "stacked up" to reassemble the brain as it has once been, so researchers can see its connections and structures. To get that level of finesse, the brains are frozen, embedded in gelatin, and cut using a microtome machine (from the Greek "tom," which means "to slice.") Akin to a deli meat cutter that slices prosciutto so fine you can see through it, the microtome produces nearly transparent micron-thin brain peels, each taking only a few seconds. Under the microtome's super-sharp horizontal blade, the brain is kept precisely at -35 degrees Celsius. At a higher temperature the blade may mar the slices, at a lower one, the brain turns brittle. As the knife peels off each slice into a pale mass of bunched-up tissue, Annese swipes it off with a brush and gently unfolds it inside a solution. "I like using the brush," he says. "It makes me feel like an artist."

(image)Jacopo Annese, The Brain Observatory.

Turning a brain into 2500 to 3000 peels is time-consuming and physically exhaustive, but it's the only way to gather a lot of detail about a brain that researchers really care about. A few years ago, Annese and his colleagues used their method on the brain of Henry Molaison, or Patient H.M., the man who lost his ability to form memories after a surgery and became a focus of brain research for the rest of his life. Immediately after his death, his brain was scanned and then extracted to be sliced by in Annese's microtome.

"When we sliced the famous brain we were going all night, for 50 hours without sleep," Annese says. "If I'd start to miss my timing, my assistant had to alert me with a code word 'prosciutto.'"

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Once a brain is sliced, the layers are stained with chemicals to reveal various brain parts and their connections. For example, some dyes would stain neurons a certain color while silver would reveal Alzheimer's plagues. "Brain is like a book written with magic ink so you have to use magic chemicals to reveal what's actually in it," Annese says. Then the slices are digitized and assembled into colorful three-dimensional brains, allowing researchers to traverse the entire organ, front to back. Annese's current goal is to digitize 1000 brains to help scientists with understanding neurological diseases. He also hopes to uncover how our brains define us, but for that he would need many more brains, he says. "Every brain has a different story to tell."

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Beautiful Brains
24 September 2015

In the last years of the 19th century, Santiago Ramón y Cajal looked down into his microscope and was amazed; for the first time ever, he saw the clear shape of neurons, sharply standing out from their fuzzy surrounding.

The beautiful, mysterious landscape before his eyes would mark the beginning of modern neuroscience and become an endless source of fascination for scientists and artists alike. "What an unexpected spectacle!" Cajal wrote of his observations. "On the perfectly translucent yellow background, sparse black filaments appeared that were smooth and thin or thorny and thick, as well as black triangular, stellate, or fusiform bodies! One would have thought that they were designs in Chinese ink on transparent Japanese paper."

In the latest of artistic explorations of the brain's inner world, Greg Dunn, a neuroscientist-turned-artist and his collaborator Brian Edwards have found a way to reflect both the beauty and sophistication of this most complex organ. Their work is on display through the end of the year at the Mütter Museum in Philadelphia.

"The brain is an incomprehensibly elegant and complex machine," Dunn said. "And despite our increased understanding over the last 30 years, its mysteries run very deep. There is a vast amount of insight yet to be gleaned from its depths."

Dunn earned a PhD in neuroscience before deciding to become a full-time artist. In his earlier works he took a minimalistic approach, often depicting a handful of neurons painted in the sumi-e (ink wash painting) style on gilded canvas. But the brain is anything but minimalistic—it's a chaotic forest of 100 billion neurons, constantly talking to each other. To capture some of that complexity and dynamism, Dunn and Edwards developed a technique called microetching: on a reflective surface, they painted the neurons by making microscopic ridges at specific angles in order to catch light from different light sources. As a result, the images change as the viewer moves around the piece.

"We wanted to see how much information we could put into a single piece and still have it be comprehensible," said Edwards, who is a physicist and engineer at the University of Pennsylvania.

(image) Chaotic Connectome, 22K gilded microetching, 2013, Greg Dunn and Brian Edwards. This is the first microetching the duo produced, and depicts an abstract neural landscape. Designed to illustrate the depth of complexity of any given region of the brain, the piece is illuminated by three colors of light embedded in the frame.

Here's another microetching that shows a mouse hippocampus:

(image)Brainbow Hippocampus, 22K gilded microetching, 2014, Greg Dunn and Brian Edwards. This microetching is of a mouse hippocampus, a region of the brain involved in learning and memory. This piece illustrates an important genetic technique called Brainbow, in which neurons are altered to express random combinations of blue, red, and yellow fluorescent proteins and as a result, stand apart from the many millions of neurons in the brain. Similarly, in this microetching, each neuron catches light from a specific angle. So when different lamps are placed around the painting, each neuron catches a unique combination of colors, which changes based on the angular perspective of the viewer.

As you walk past these pieces, you see the neurons glow yellow, blue or red. Some parts vanish and reappear, creating a sense of movement in the piece. "The lines are made of small ridges, like waves on the ocean. When your eyes are at correct angle relative to the light source, it would direct that light to your eyes," Edwards said. "To try and include more information in a piece we encode an extra dimension into it, which is the angle of the ridges."

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This way, Dunn and Edwards were able to animate some of the pieces. Edwards wrote an algorithm that calculates the precise angle necessary at any coordinate on the microetching to reflect light to the viewer standing at a given position. The microetching was then created in a way so that as the viewer walks past the piece, certain parts of the piece light up accordingly. In a piece titled Pranayama, for example, as you pass by from left to right, you can see a moving pattern of light starting from the extremities, moving into the chest, and then coming out through the mouth:

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Pranayama, 22K handmade gilded microetching.

Here's another animated microetching that merges neurons with the typical design of a circuitboard:

(image) Cortical Circuitboard, 22K gilded microetching

The true experience of viewing microetching cannot be captured in still images. Here's a video:

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Neurons and their many branches follow random trajectories. And randomness is incredibly difficult for humans to create. "Drawing each individual line by hand is a humbling insight into just how badly your brain wants to make regular patterns out of everything," Dunn said. For his previous works, he invented a technique to replicate this randomness: "I blow ink around on the canvas. The turbulence of the air, variances in the viscosity of the ink, randomness in fiber direction or absorptivity in the paper contribute random variables that impart the chaotic element that I'm looking for."

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Recently, Dunn and Edwards received a grant from the National Science Foundation to create a giant piece for the Franklin Institute. The piece, which will cover a whole wall, will depict a human brain cut down the middle, shining with its many neurons and connections drawn from neuroimaging data and literature about brain anatomy.

But the duo say they are not limited to the brain. Anything inspiring, thought-provoking and visually pleasing could be their next adventure.

"There's a lot of interesting things that happen in science and nature and unfortunately scientists are some of the few people who get to see them," Edwards said. "They might not even notice because they spend so much time looking through the microscope that they don't appreciate it anymore. But for everybody else it could be beautiful. They would say, 'this is gorgeous to look at!'"

Dunn agreed. "There is a huge amount to explore out there."

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Gray Matters
21 July 2015

Several years after being hospitalized for psychosis, an anonymous writer has described the onslaught of skewed thinking and perception that permeated every experience of their time in the emergency department:

I am thinking fast; new fears flood in at the speed of perception. I'm noticing some things you—the interviewing doctors—do not. Yes hallucinations, some of them; fight or flight is also heightening my senses. Paranoid hypotheses are disproved and discarded, others take their place.

The writer shared the experience in an article published in a patient-authored series in the British Medical Journal. In addition to describing what it feels like to undergo a psychotic episode, the writer offers tips for doctors about how they can avoid making patients with psychosis even more panicked:

If a doctor asks questions in a blank, detached way, it feels very frightening. A person with psychosis has not lost all ability to recognize and respond to social cues: intrusion, blankness, kindness. For example, if a doctor sits behind a desk, making eye contact but using deliberate silence to elicit my next move—and my normal civil rights hang in the balance—I will find this threatening, disorienting. It wouldn't look out of place in a police drama.

Doctors can also help their patients by shielding them from unnecessary noises and other sensory experiences, the author suggests.

This narrative, published July 16, comes two months after a paper in The Psychiatric Quarterly urged neuroscientists studying mental illness to listen more to the view of people who have actually experienced the conditions. (However, as Neuroskeptic has pointed out, scientists and patients are not always distinct groups.)

Whether or not experience begets understanding, patients will benefit if physicians don't become so entrenched in their role that they forget to, in the words of the BMJ author, "remain human" and "treat the distressed person as a person."

h/t Science of Us

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Odd Brains
20 July 2015

One year ago, a 24-year-old Chinese woman walked into a hospital complaining of dizziness and nausea. A brain scan revealed she was missing her entire cerebellum, a part of the brain involved in motor control and balance. The empty space where it should have been was filled with cerebrospinal fluid.

How can someone not realize a huge chunk of their brain is missing? In fact, surviving, and even thriving, without major parts of the brain is possible. The woman's doctors believe that other parts of her brain, like the cortex, took over the cerebellum's usual responsibilities as her incomplete brain developed.

Stories like these, of people born with brain regions missing or who have had large portions of their brains removed surgically, reveal a lot about how the brain works and compensates for missing parts.

"The little brain"

Although the Chinese woman with no cerebellum started walking late (at age 7) and walks unsteadily as an adult, it's remarkable that she can walk at all.

The cerebellum, also known as the "little brain," looks like a cauliflower hanging off the back of the brain's two cerebral hemispheres. It takes up about 10 percent of the brain's total volume, but contains nearly half of the brain's neurons.

The cerebellum's main job is to control voluntary movements, coordination, and balance, although recent research also points to a role in language, emotion, memory, and attention. People who suffer illnesses or injuries to the cerebellum as adults usually have severe impairments in movement and speech.

But the Chinese woman, one of just nine people who are known to have lived without their entire cerebellums, had only mild to moderate motor problems and slightly slurred speech. Her case highlights the amazing capacity of the brain to rewire itself to cope with new demands — a feature called neuroplasticity.

Removing half the brain

There are a number of cases of people missing half of their brains. A teenage girl in Germany, for instance, was born without the right hemisphere. The issue wasn't discovered until she was three years old. According to her doctors, the girl has normal psychological function and is living a normal life.

Sometimes, to treat seizures or remove a tumor, doctors have to remove brain hemisphere in an operation known as hemispherectomy. The surgery was first performed on a dog in 1888 by German physiologist Friedrich Goltz as proof of concept. Walter Dandy pioneered the surgery on a human patient in 1923 to remove a brain tumor. Fifteen years later, neurosurgeon Kenneth McKenzie performed a hemispherectomy on a 16-year-old girl, resulting in the elimination of her seizures.

Today, hemispherectomy is a last resort for children who suffer intractable seizures. Persistent seizures can damage the developing brain if not treated, and surgery is an option for those patients with severe seizures that don't respond to medications.

Gary Mathern, a neurosurgeon at the University of California, Los Angeles, says surgery is usually performed on children younger than ten years old, and sometimes as young as a few months old.

"It's a fairly rare procedure, but in the U.S. there are probably in the neighborhood of a few hundred that are done every year," he says.

The surgery can be very successful, with 75-80 percent of children becoming seizure-free after the operation. Incredibly, memory and personality develop normally after hemispherectomies, and children's academic performances often improve after the surgery.

Patients with hemispherectomies are left with some disabilities. "Primarily, they have a loss of sensory and motor function on the opposite side of the body, often walking with a limp or experiencing loss of use of the hand opposite of the hemisphere that was removed," Mathern says.

"But if you perform the operation at a young age, the remaining side of the brain takes over many functions, compensating for the loss through neuroplasticity. You'd be surprised at how effective these kids are over time."

Missing more than half a brain

It happens rarely, but as a recent case shows, even people missing the majority of their brains can live normal lives.

A 44-year-old man in France went to the doctor because of weakness in his left leg. Doctors were shocked when they looked at MRI scans of the man's head. Most of his skull cavity was filled with cerebrospinal fluid, with just a thin sheet of brain tissue lining the inside of the skull.

The man's IQ was below average, but he was not mentally disabled. He was a married father of two and worked as a civil servant in a local tax office.

It turns out that as an infant, the man had a condition called hydrocephalus — water in the brain — and had a shunt inserted into his head to drain the fluid. The shunt was removed when he was 14 years old, but it seems that the excess fluid accumulated and squished his brain toward his skull. So much fluid built up that the ventricles, usually small chambers that hold cerebrospinal fluid, greatly expanded and pushed his brain aside.

Until the problem with his leg popped up, the man had no idea that his head was essentially filled with fluid. A doctor inserted another shunt and within weeks the man's neurological problems subsided and he was back at work.

Plasticity and redundancy

The French man's case, like the others, reveals the enormous potential of the brain to reorganize and adapt to early brain damage. If parts of the brain are missing from birth, or removed at an early age, different parts can take up the functions that would normally be done by the missing parts.

Besides brain's plasticity, the good outcomes in these cases are also due to another factor: the ability of multiple different brain structures to support a single function, a phenomenon known as degeneracy. Many of the important functions of our brains are not the sole province of single, distinct brain regions, but are supported by multiple regions working together. If one region can't perform, the others can pick up the slack.

The brain's capacity to make up for lost parts is good news for hemispherectomy patients and people born without certain brain structures. With seemingly even the bare minimum amount of brain, some people are still able to live normal, fulfilling lives — sometimes without even realizing what is missing.

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Beautiful Brains
20 May 2015

Black and white photographs of some of the earliest people to have brain surgery were unveiled to the public this year by the Cushing Center at the Yale School of Medicine. The photographs represent patients treated from 1900 to 1933 by Harvey Cushing, the father of neurosurgery and a pioneer in neuroscience.

(slideshow) Images via Atlas Obscura. Credit: Cushing Tumor Registry - Cushing/Whitney Medical Library/Yale University

Scroll down for more eye-opening images below.

The pictures, recently digitized and published this week on Atlas Obscura, are part of a collection of 10,000 that had sat in the basement of a medical school dorm since 1967. The collection is part of an extensive documentation of neurological cases and brain specimens kept by Cushing during his career. While Cushing's brain collection was well-known, the photographs were discovered unexpectedly in the early 1990s when a student named Christopher John Wahl took an interest in the collection. Most photographs were in form of glass plate negatives. Some negative films were found as well, but they were damaged after spending three decades in the wet and hot conditions of the basement.

"They are amazing not because they were shot to be amazing. They were shot to be documentary, shot as the history of neuroscience was being born," Cushing Center coordinator Terry Dagradi told Reyhan Harmanci of Atlas Obscura.

Cushing turned the practice of operating on the brain into modern neurosurgery, an independent surgery discipline. During his career, he cut the mortality rate of brain surgery down from 80 or 90 percent to around 10 percent. He developed many of the basic surgical techniques for operating on the brain. He used X-rays to diagnose brain tumors, zapped the brain to study the sensory cortex, and was the first to describe Cushing's disease.

Cushing was also a leading teacher for other neurosurgeons and the photographs likely served to teach doctors how to diagnose various neurological illnesses.

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Images via Atlas Obscura and BBC. Credit: Cushing Tumor Registry - Cushing/Whitney Medical Library/Yale University

Featured
Beautiful Brains
13 April 2015

The fatty mass of the brain has been cut, sliced and picked apart to shreds by curious scientists for centuries, but only relatively recently was it finally dissected down to its most interesting components: the neurons.

These cells are not only incredibly small, but also blend in perfectly with their neighbors, as if they are individual noodles compressed in a larger bowl of spaghetti. But with their discovery also came a rapid progression in methods developed to visualize and study them.

A century ago neurons appeared only in drawings. Now, they are revealed in amazing detail, in living brains and in real time.

First visible neurons

Powerful microscopes developed in mid-nineteenth century allowed scientists to observe the tiny cells that make up the many tissues of the body. But for nerve cells, microscopic images were a blur. The neuron's cell bodies and their threadlike extensions formed a tangled, indecipherable yellow mess.

One neuroanatomist, Otto Friedrich Karl Deiters, who was trained as a surgeon, managed to isolate the neurons with his skilled hands. Deiters obtained a complete picture of the cells and showed that most nerve cells have one long fiber, which later became known as the axon, branching out, as well as a group of shorter, tree-like branches, which would later become known as dendrites.

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Otto Deiters' drawing of a neuron, published in 1865.

Isolating neurons by hand is an extremely difficult process, and Deiters died young, leaving his method a mystery. What eventually advanced the study of neurons was the development of a special staining technique by Camillo Golgi in 1873. Golgi discovered that bathing the brain tissue in potassium dichromate, and then in silver nitrate, dyes the neurons, but mysteriously, only a few of them. Those few black neurons stand out from the yellow background of their unstained neighboring neurons.

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Camillo Golgi's drawing of a dog's olfactory bulb, 1875.

Each neuron is an individual unit

Golgi's method, initially called the black reaction, helped start a revolution in our understanding of the brain. It eased the studying of individual neurons and revealed the patterns of neural organization inside brain tissue.

However, Golgi's method was largely neglected for 14 years, until another scientist, Santiago Ramón y Cajal, learned about it in 1887.

Impressed with the power of Golgi's method, Cajal helped gain the attention of other scientists who often had their own preferred staining methods. Cajal improved Golgi's method, and studied the neural tissue of different brain regions and the nervous systems of many animals. He noticed that the dendrites and axons of neurons are not connected to other neurons. In other words, he found compelling evidence that a neuron is an individual unit, rather than part of a web, which was what many scientists thought at the time.

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Cajal's drawing of cells in a pigeon's cerebellum, 1899. Label A shows Purkinje cells, and label B shows granule cells. Image from Instituto Santiago Ramón y Cajal, Madrid via Wikimedia.

From black and white to rainbows

The Golgi's method had its limits. First, it could only be applied to brain tissue taken from dead animals, and second, staining the neurons with one color could only render a few of them visible. If there was a way to use more than one color to paint them, scientists would be able to see a fuller picture and better trace the cells and their connections to one another.

This time, nature's bioluminant creatures lent a hand to neuroscience. In the 1960s, marine biologist Osamu Shimomura discovered a special glowing protein in jellyfish Aequorea victoria that would become an important part of biological research. The protein, called Green Fluorescent Protein, or GFP, shines bright fluorescent green when exposed to blue light.

In the 1990s, neurobiologist Martin Chalfie inserted a piece of DNA that coded for the GFP into the neurons of a worm, causing the cells to produce the glowing protein and lit up under the blue light.

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Glowing C. Elegans, Chalfie et al. (1994)

This development meant that scientists could now "stain" neurons in the living brain. Subsequently, the DNA codes for the glowing protein were inserted into the genome of laboratory mice, giving rise to generations of animals with glowing, traceable neurons in their heads.

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Sagittal section from an adult transgenic thy1 mouse brain. The green protein is bound to the thy1 gene, resulting in glowing neurons. Image via Frontiers in Neural Circuits

In attempts to provide more than one green color to paint the neurons, researchers modified the gene sequences to code for red, yellow, and blue derivatives of the green protein. In 2007, neuroscientist Jean Livet, working at Harvard University with Joshua Sanes and Jeff Lichtman, found a clever way to use those three or four fluorescent colors and turn them into about a hundred different hues.

Livet inserted multiple copies of genes coding for the primary colors in the genome, in a way that for each cell, a random section of the gene constructs gets turned on, resulting in different ratios of the primary color proteins. The technique, dubbed Brainbow, allowed researchers to visualize fine neural circuitry and even label and track nerve cells during development.

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Dentate gyrus, part of the hippocampus, in mice. Jeff Lichtman via Center for Brain Science

Brainbow has been used to study the nervous systems of mice, fruit flies and zebrafish, and has been fine-tuned to a variety of scientific inquiries. For example, Flybow or dBrainbow are variations of the method developed in order to study fruit fly Drosophila.

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A cross-section of Drosophila's brain. Julie Simpson, Howard Hughes Medical Institute, Janelia.

Neuronal cooperation

There are a number of other methods that researchers can use to visualize and track neurons. Two examples are antibody staining and use of viruses to trace neuronal circuits.

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In this image, scientists used a modified rabies virus to reveal the connections of various parts of the brain to dopamine neurons. Green dots represent neurons providing inputs to one group of dopamine neurons in the ventral tegmental area and red dots are the neurons providing inputs to another set of dopamine neurons in the substantia nigra region of the brain. Mitsuko Watabe-Uchida and Sachie Ogawa

To understand the brain as a whole, it is important to understand the connections between neurons, but it's also crucial to know how they work together during a given task. A modified version of the light sheet microscopy technique now allows scientists to look at the activity of thousands of neurons at the same time.

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Here's a larval zebrafish, with its head shown in gray. In (a), each color represents neural activity at a different time point. Panel (b) shows activity at a single time point. Panel (c) is a computational map of correlated activity across the same brain as in b. Shared colors indicate common patterns of activity. Scale bars are 50 μm. Credit: Philipp J Keller, Misha B Ahrens & Jeremy Freeman

The transparent head of larval zebrafish makes it ideal for neuroimaging. But in 2013, scientists developed CLARITY, a process to render a mouse brain transparent. Using the see-through brains, scientists can look at the glowing neurons in the whole, three-dimensional brain of the animals.

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CLARITY allows imaging through the entire intact brain without sectioning. The image shows fluorescent protein labeling of chiefly projection (Thy1) neurons in an entire intact mouse brain. Deisseroth lab, Stanford University

Beyond visualizing neurons, numerous technologies such as magnetic resonance imaging and optogenetics have been developed to study the brain in different scales and from various angles. Neuroscience has certainly come a long way from the days of Golgi and Cajal, and their beautiful but preliminary drawings. Now, even the art has gotten better — the following image is a slice of transparent mouse brain by neuroscientist Luis de la Torre-Ubieta of UCLA, who has painstakingly taken images of every 5.3 micrometers before combining them into one. The green-glowing neurons are color-coded by their depth from red (top) to orange, yellow, purple, blue and green (bottom).

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Luis de la Torre-Ubieta, Geschwind Laboratory, UCLA, CC BY-NC-ND 4.0, Wellcome Images