Of Glia and Ganglion

Save your tears for Tiny Tim. A boom in sophisticated prostheses has created a most unlikely by-product: envy.

There are many advantages to having your leg amputated.

Pedicure costs drop 50% overnight. A pair of socks lasts twice as long. But Hugh Herr, the director of the Biomechatronics Group at the MIT Media Lab, goes a step further. "It's actually unfair," Herr says about amputees' advantages over the able-bodied. "As tech advancements in prosthetics come along, amputees can exploit those improvements. They can get upgrades. A person with a natural body can't." Herr lost both his legs below the knee in a Mount Washington climbing accident when he was 17, but says that shouldn't inspire pity. Instead, by donning whirring, whispering, shiny supermachines -- the robotic ankles that can propel him across the room in 400-watt bursts -- Herr has been given: Power. Allure. The strange animal magnetism of the very bad boy.

"When the prosthetic technology doesn't work," Herr says, "and the [amputee] is limping and he can't run and he's hurting, then nobody feels threatened, because that person is labeled as 'cute' and 'courageous.' " He leans forward in his office and crosses his aluminum shins with an audible clink. "But when the technology works, when it can make you stronger or faster than you were, it overnight becomes sexy and powerful and threatening. Overnight."

Anybody who hears "prosthetic" and thinks "peg leg" might wonder about Herr's sunny hubris. The thought that an artificial limb could make anybody stronger or faster, or confer social advantage, is an opinion ripe for skepticism. Wearing one is inconvenient at best. It often hurts. It can break. It is obvious proof of loss. It seems by its very nature to announce a lack of health or vitality.

Yet much of the dissonance in Herr's "prosthetics as progress" thesis stems from the undeniable fact that for years, prostheses were irredeemably ugly, off-putting, scary. Who would call a disembodied limb a "design object" to be lusted after, like an Audi or an iPhone? Who would consider herself better, or more beautiful, than a person without one?

"When I first got this job," says Stuart Mead, CEO of Touch Bionics, a prosthetics and robotics firm based in Scotland, "it struck me how depressing it all was. Prosthetics were at the back of the hospital, the downstairs office, the back room. The look of most of these devices was horrible -- half-human, half-plastic. This frightening pink color."

Just wearing one could induce shame: The Barbie doll cosmesis (a cosmetic cover), tipped with a hook, acted like social repellent, pushing the user and the observer apart. "It was like having a scarlet letter," says Marshall Young, an industrial designer for Otto Bock HealthCare, of the old-style prosthetic limbs. "It was, 'I've got this damn thing and now my life sucks.'"

All that is about to change -- not only because prostheses are being built with materials found in sports cars and jet airplanes; or because designers are giving their creations an exuberant, unapologetic carbon-fiber sparkle; or even because nerve reintegration and myoelectrics are offering some amputees the joy of normal function. The biggest reason for amputees' unlikely rise into a new, socially advantaged class comes from something much more mundane: profit. The prosthetics business is set to explode, and its products will make amputees stronger, faster, and, to some, more desirable than the rest of us.

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Not surprisingly, the money is following the market. MIT's Herr cofounded a company called iWalk, which has received $10 million in venture financing to develop the PowerFoot One -- what the company calls the "world's first actively powered prosthetic ankle and foot." Meanwhile, the Department of Veterans Affairs recently gave Brown University's Center for Restorative and Regenerative Medicine a $7 million round of funding, on top of the $7.2 million it provided in 2004. And the Defense Advanced Research Projects Administration (DARPA) has funded Manchester, New Hampshire-based DEKA Research, which is developing the Luke, a powered prosthetic arm (named after Luke Skywalker, whose hand is hacked off by his father, Darth Vader).

This influx of R&D cash, combined with breakthroughs in materials science and processor speed, has had a striking visual and social result: an emblem of hurt and loss has become a paradigm of the sleek, modern, and powerful. Which is why Michael Bailey, a 24-year-old student in Duluth, Georgia, is looking forward to the day when he can amputate the last two fingers on his left hand.

"I don't think I would have said this if it had never happened," says Bailey, referring to the accident that tore off his pinkie, ring, and middle fingers. "But I told Touch Bionics I'd cut the rest of my hand off if I could make all five of my fingers robotic."

Young, of Otto Bock HealthCare, says Bailey is far from alone. Amputees are now regularly removing healthy tissue to make room for more powerful technology. "I see it every day," he says. "People will get a second amputation -- move their amputation up their leg -- to get the prosthetic equivalent of a hotter car."

Orthopedic surgeons often consider amputation the equivalent of failure, Young says, and reflexively save as much of a damaged, injured, or diseased limb as possible. But in leaving lots of human being, they create a bigger problem: There is little room left for high-performance machinery. Now, the allure of that machinery has become so powerful that amputees are routinely taking the extreme step of paying out-of-pocket for what the industry calls "revisions."

"It's very simple," Young says. "Prosthetic feet act like leaf springs on a truck -- the bigger they are, the longer the lever arms, the more energy storage and return you get. With enough clearance, you can go from a walking foot to a higher-performance running foot. So people with too much residual limb are in a position of saying, If I want to go to a knee that will let me play basketball, I will have to downgrade my foot. They'll say, Take four more inches, because I want that cool Corvette."

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As the rhetoric heats up -- as robots perform surgery and build automobiles, and as the suspicion grows that our original equipment is somehow deficient -- Herr offers some perspective. Poor eyesight, he says, is a medical condition. Eyeglasses are prosthetic. And while they were once purely medical devices, they're now expensive fashion items.

"Often people can have contact lenses, but they choose in certain social environments to wear their glasses, because it looks hot. People put glasses on to make themselves look more intelligent. To augment their appearance, not just their performance."

Herr's suggestion, of course, is that the better prostheses make us perform, and the more glamorous they look, the more beautiful they will make amputees seem, too, even though their sheen, contour, texture, and color have ceased to look human.

"What is the obsession with looking human?" he says. "You think the only beauty is human? Bridges can be beautiful. Cars can be beautiful. Cell phones can be beautiful. They don't look biological. So why do you anticipate 30 years from now that amputees will give a shit about human beauty? They won't. Their limbs will be sculptures."

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MIT professor Hugh Herr, 45, who lost his legs in a mountain-climbing accident, says 70% of amputees have hip and back problems. One reason: When walking, there is no "lift" or "push" forward from the prosthetic foot, which leads to a violent, uncushioned impact on the forward foot. For the able-bodied, that lift is "like the hand of God," he says. So Herr invented powered iWalk ankles (shown) that use hydraulics, pulleys, and batteries that can provide a 400-watt boost out of each step. "I don't walk my legs. My legs walk me." 

"Last year," says Carrie Davis, "I went down to a clinic and met this lady who saw what I could do with my arm, and she said, 'I want one like that.' She wanted to knit." Davis was born with one forearm missing and has 12 dif-ferent hands, or "terminal devices," each designed for different tasks. Her favorite: the carbon-fiber-sheathed bionic hand (shown) from Touch Bionics. "I get a lot of attention walking into a room with i-Limb. I love it. It's bad-ass looking." The limb uses a battery and a force-sensitive resistor to respond to her muscle contractions and impulses.

 

In children with ADHD, the degree of motivation when carrying out an activity is related to the immediacy with which the objectives of the activity are met. This would explain why their attention and hyperactivity levels differ depending on the tasks being carried out.

Susanna Carmona, researcher at the Cognitive Neuroscience Unit of the UAB Department of Psychiatry and Legal Medicine (URNC-IAPS-Hospital del Mar), has worked in collaboration with clinical researchers of the Vall d'Hebron University Hospital on the first research which relates the structure of the brain's reward system, the ventral striatum, with clinical symptoms in children suffering from ADHD.

Models describing the origin of ADHD tend to emphasise the relevance of attention processes and of the cognitive functions which guide our mental processes in achieving proposed objectives. Nevertheless, recent research has focused on neural gratification/pleasure circuits, which can be found in what is known as the brain's reward system, with the nucleus accumbens as the central part of this system.

The nucleus accumbens is in charge of maintaining levels of motivation when commencing a task and continues to do so until reaching what experts name the "reinforcement", the proposed objective. This motivation can be maintained throughout time, even when the gratification obtained is not immediate. However, in children with ADHD motivational levels seem to drop rapidly and there is a need for immediate reinforcements to continue persisting in their efforts.

In this study, researchers selected a sample of 84 participants aged 6 to 18 years and divided them according to presence of ADHD symptoms, with one experimental group of 42 children with ADHD and one control group of 42 children with no signs of mental or behavioural anomalies, paired by sex and age. Magnetic resonance images were taken of all participants to view the structure of their brains. Of these images, the cerebral region corresponding to the ventral striatum, which includes the nucleus accumbens, was demarcated.

Differences in the structure of the ventral striatum - particularly on the right-hand side - could be seen between those with ADHD and those without the disorder. Children with ADHD exhibited reduced volumes in this region. These differences were associated with symptoms of hyperactivity and impulsiveness.

The obtained data corroborate results from previous studies carried out with animals: the importance of the reward system, as well as the relation between nucleus accumbens, impulsive behaviour and the development of motor hyperactivity. This leads researchers to consider that ADHD is not only caused by brain alterations affecting cognitive processes, but also by anomalies which cause motivational deficiencies. This would explain the imbalance in levels of attention and hyperactivity in a child with ADHD depending on his or her motivation when engaged in a specific task and the immediacy of the gratification/pleasure while carrying it out.

via medicalnewstoday.com

Scientists have found that blocking the ability to move the body causes changes in cognition and emotion, but there were always questions. (One of the test treatments caused widespread, if temporary, paralysis.) In contrast, Havas was studying people after a pinpoint treatment to paralyze a single pair of "corrugator" muscles, which cause brow-wrinkling frowns.

To test how blocking a frown might affect comprehension of language related to emotions, Havas asked the patients to read written statements, before and then two weeks after the Botox treatment. The statements were angry ("The pushy telemarketer won't let you return to your dinner"); sad ("You open your email in-box on your birthday to find no new emails"); or happy ("The water park is refreshing on the hot summer day.")

Havas gauged the ability to understand these sentences according to how quickly the subject pressed a button to indicate they had finished reading it. "We periodically checked that the readers were understanding the sentences, not just pressing the button," says Havas.

The results showed no change in the time needed to understand the happy sentences. But after Botox treatment, the subjects took more time to read the angry and sad sentences. Although the time difference was small, it was significant, he adds. Moreover, the changes in reading time couldn't be attributed to changes in participants' mood.

The use of Botox to test how making facial expressions affect emotional centers in the brain was pioneered by, Andreas Hennenlotter of the Max Planck Institute in Leipzig, Germany.

"There is a long-standing idea in psychology, called the facial feedback hypothesis," says Havas. "Essentially, it says, when you're smiling, the whole world smiles with you. It's an old song, but it's right. Actually, this study suggests the opposite: When you're not frowning, the world seems less angry and less sad."

The Havas study broke new ground by linking the expression of emotion to the ability to understand language, says Havas's advisor, UW-Madison professor emeritus of psychology Arthur Glenberg. "Normally, the brain would be sending signals to the periphery to frown, and the extent of the frown would be sent back to the brain. But here, that loop is disrupted, and the intensity of the emotion, and of our ability to understand it when embodied in language, is disrupted."

Practically, the study "may have profound implications for the cosmetic-surgery," says Glenberg. "Even though it's a small effect, in conversation, people respond to fast, subtle cues about each other's understanding, intention and empathy. If you are slightly slower reacting as I tell you about something made me really angry, that could signal to me that you did not pick up my message."

"People with BDD are ashamed, anxious and depressed," said Dr. Jamie Feusner, an assistant professor of psychiatry and lead author of the study. "They obsess over tiny flaws on their face or body that other people would never even notice. Some refuse to leave the house, others feel the need to cover parts of their face or body, and some undergo multiple plastic surgeries. About half are hospitalized at some point in their lifetimes, and about one-fourth attempt suicide."

Despite its prevalence -- BDD affects an estimated 1 to 2 percent of the population -- and severe effects, little is known about the underlying brain abnormalities that contribute to the disease.

To better understand its neurobiology, Feusner and colleagues examined 17 patients with BDD and matched them by sex, age and education level with 16 healthy people. Participants underwent functional magnetic resonance imaging (fMRI) while viewing photographs of two faces -- their own and that of a familiar actor -- first unaltered, and then altered in two ways to parse out different elements of visual processing.

One altered version included only high-spatial frequency information, which would allow detailed analysis of facial traits, including blemishes and hairs. The other showed only low-spatial frequency information, conveying the general shape of the face and the relationship between facial features.

Compared to the control participants, individuals with BDD demonstrated abnormal brain activity in visual processing systems when viewing the unaltered and low-spatial frequency versions of their own faces. They also had unusual activation patterns in their frontostriatal systems, which help control and guide behavior and maintain emotional flexibility in responding to situations.

Brain activity in both systems correlated with the severity of symptoms. In addition, differences in activity in the frontostriatal system varied based on participant reports of how disgusting or repulsive they found each image. Basically, how ugly the individuals viewed themselves appeared to explain abnormal brain activity in these systems.

The abnormal activation patterns, especially in response to low-frequency images, suggest that individuals with body dysmorphic disorder have difficulties perceiving or processing general information about faces.

"This may account for their inability to see the big picture -- their face as a whole," Feusner said. "They become obsessed with detail and think everybody will notice any slight imperfection on their face. They just don't see their face holistically."

All our knowledge of how the brain really works has been based on taking a small sampling of all available neurons and making inferences about how the other neurons respond, Dr. Kanold explains. "This is like showing someone who wants to know how America looks, 'Here is one person from New York City and one person from California.' You don't get a very good picture of what the country looks like from that sampling," says Kanold, originally from Germany.

In contrast, Kanold and colleagues were able to look at the activity of all the neurons in a large region of the auditory cortex simultaneously. To get the highest resolution picture to date of how auditory cortex neurons are organized, the researchers used a technique to fill neurons in living mice with a dye that glows brightly when calcium levels rise, a key signal that neurons are firing. They then selectively illuminated specific regions of the cortex with a laser and measured the neuronal activity of hundreds of neurons in response to stimulation by simple tones of different frequencies.

This "in vivo 2-photon calcium imaging" technique was developed by German researchers and advanced by Harvard scientists who used it to study the visual cortex in the mid-2000s. Kanold's study is the first to apply this technique to the auditory cortex and provides an unprecedented amount of detail about how hearing happens. Dr. Andrew King, Professor of Neurophysiology at the University of Oxford, explains that "The functional organization of the auditory cortex has remained unclear and a matter of some controversy, despite the efforts of many labs over a number of years. The approach used by Dr. Kanold and colleagues is an important advance in this field."

"We discovered that the organization of the cortex does not look as pretty as it does in the textbooks, which surprised us," explains Kanold. "Things are a lot messier than expected." And we don't see evidence of the maps previously proposed using less precise techniques." But the disorder they found could indicate that the brain is far more adaptable than previously thought. "These results may rewrite our classical views of how cortical circuits are organized and what functions they serve," suggests Dr. Shihab Shamma, whose previous research has involved mapping responses in the auditory cortex using traditional microelectrodes.

By using different dyes, this study measured differences in how the neurons receive sound information (the inputs), and how they process that sound (the outputs). It was previously assumed that neighboring neurons receiving the same inputs would also produce the same outputs, but Kanold's research found something very different. "Neighboring neurons do their own thing by creating different outputs," Kanold explains. "You can imagine that you and your neighbor both receive water to your houses from the same pipe, but you do different things with it -- you might cook with it while your neighbor waters the lawn. You can't assume that they are doing the same thing just because they are neighbors."

This is the first time that this level of individuality has been observed in neighboring neurons. Dr. Kanold, who is an expert in neuroplasticity, the brain's ability to reorganize neural pathways, believes that there is a tremendous advantage in this apparent disorder. "Each individual neuron is getting inputs from a wide range of frequencies, and by selecting which frequencies they are strongly responding to, they might be very easily able to shift their function," he says. For example, it is well known that we can quickly listen in on a variety of conversations around us, the so-called "cocktail party effect." It may be that neurons having access to a large range of inputs might be able to quickly change which inputs they are responding to.

This suggests that there is very little redundancy in the function of cells in the auditory cortex, which differs notably from the visual cortex, in which neighboring neurons perform the same function as one another. This could be because our acoustic environment, such as the speech we hear, changes much faster than our visual environment, so we have to constantly adapt to new situations.

Kanold continues to study the mechanisms of brain circuitry involved in early development to gain a better understanding of why we can learn so well in early development but lose some of this ability as we age. For example, why can children easily learn new languages, while adults often struggle? Kanold's work has been focusing on identifying circuits in the young brain that mediate this remarkable ability. He is also working to apply his knowledge of developmental brain circuitry to the prevention and treatment of diseases such as cerebral palsy and epilepsy, which can be caused by early brain injuries. With his collaborator Shihab Shamma, who is studying mechanisms of adult plasticity and hearing, he is exploring how brain circuitry and learning changes over time.

The left shows thousands of dye-loaded cells in the mouse auditory cortex over a large area. The right shows the preferred frequency of many cells, and shows that neighboring cells can have dramatically different frequency preference.

Drug addiction researcher Nora Volkow walks us through the singular chemical that drives substance abuse.

"Our initial hypothesis was that feelings of guilt are more intense among females, not only among adolescents but also among young and adult women, and they also show the highest scores for interpersonal sensitivity," says Itziar Etxebarria, lead author of the study and a researcher at the University of the Basque Country (UPV/EHU).

The research, published in the Spanish Journal of Psychology, was carried out using a sample from three age groups (156 teenagers, 96 young people and 108 adults) equally divided between males and females. The team of psychologists asked them what situations most often caused them to feel guilt. They also carried out interpersonal sensitivity tests -- the Davis Empathetic Concern Scale, and a questionnaire on Interpersonal Guilt, created purposely for this study.

When it came to comparing the measurements of intensity of habitual guilt of these groups, the researchers saw that this score was significantly higher for women, in all three age groups. "This difference is particularly stark in the 40-50-year-old age group," points out Etxebarria.

Your finger is farther from your nose than your brain. So when your finger touches your nose, why do both organs feel the sensation at the same time?