Chapter 5. The Sensorimotor System
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|By Carl Erik Fisher After 22 years of failed treatments, including rehabilitation, psychotherapy and an array of psychiatric medications, a middle-aged Dutch man decided to take an extraordinary step to fight his heroin addiction. He underwent an experimental brain surgery called deep brain stimulation (DBS). At the University of Amsterdam, researchers bored small holes in his skull and guided two long, thin probes deep into his head. The ends of the probes were lined with small electrodes, which were positioned in his nucleus accumbens, a brain area near the base of the skull that is associated with addiction. The scientists ran the connecting wires under his scalp, behind his ear and down to a battery pack sewn under the skin of his chest. Once turned on, the electrodes began delivering constant electrical pulses, much like a pacemaker, with the goal of altering the brain circuits thought to be causing his drug cravings. At first the stimulation intensified his desire for heroin, and he almost doubled his drug intake. But after the researchers adjusted the pulses, the cravings diminished, and he drastically cut down his heroin use. Neurosurgeries are now being pursued for a variety of mental illnesses. Initially developed in the 1980s to treat movement disorders, including Parkinson's disease, DBS is today used to treat depression, dementia, obsessive-compulsive disorder, substance abuse and even obesity. Despite several success stories, many of these new ventures have attracted critics, and some skeptics have even called for an outright halt to this research. © 2014 Scientific American
by Douglas Heaven We have the world at our fingertips. A sense of touch can sometimes be as important as sight, helping us to avoid crushing delicate objects or ensuring that we hold on firmly when carrying hot cups of coffee. Now, for the first time, a person who lost his left hand has had a near-natural sense of touch restored thanks to a prosthesis. "I didn't realise it was possible," says Dennis Aabo Sørensen, who is so far the only person to have been fitted with the new prosthesis. "The feeling is very close to the sensation you get when you touch things with your normal hand." To restore Sørensen's sense of touch, Silvestro Micera at the Swiss Federal Institute of Technology in Lausanne and his colleagues implanted tiny electrodes inside the ulnar and median nerve bundles in Sørensen's upper arm. Between them, the ulnar nerve – which runs down to the little finger and ring finger – and the median nerve – which runs down to the index and middle fingers – carry sensations from most of the hand, including the palm. The team then connected the electrodes to pressure sensors on the fingertips and palm of a robotic prosthetic hand via cables running down the outside of Sørensen's arm. When he used the hand to grasp an object, electrical signals from the pressure pads were fired directly into the nerves, providing him with a sense of touch. Getting to grips The electrical signals were calibrated so that Sørensen could feel a range of sensation, from the slightest touch to firm pressure just below his pain threshold, depending on the strength of his grip. © Copyright Reed Business Information Ltd.
by Andy Coghlan If you flinch where others merely frown, you might want to take a look at your lifestyle. That's because environmental factors may have retuned your genes to make you more sensitive to pain. "We know that stressful life events such as diet, smoking, drinking and exposure to pollution all have effects on your genes, but we didn't know if they specifically affected pain genes," says Tim Spector of King's College London. Now, a study of identical twins suggests they do. It seems that epigenetic changes – environmentally triggered chemical alterations that affect how active your genes are – can dial your pain threshold up or down. This implies that genetic tweaks of this kind, such as the addition of one or more methyl groups to a gene, may account for some differences in how our senses operate. Spector and his colleagues assessed the ability of hundreds of pairs of twins to withstand the heat of a laser on their skin, a standard pain test. They selected 25 pairs who showed the greatest difference in the highest temperature they could bear. Since identical twins have the same genes, any variation in pain sensitivity can be attributed to epigenetic differences. Pain thermostat The researchers screened the twins' DNA for differences in methylation levels across 10 million gene regions. They found a significant difference in nine genes, most of which then turned out to have been previously implicated in pain-sensitivity in animal experiments. © Copyright Reed Business Information Ltd.
By LAUREN BRADY When I was 18 I watched my father perform what would be his final surgery. It was the summer of 2007 and I had just returned to Colorado after surviving my freshman year of film school at New York University. One day my dad invited me to observe a vitrectomy. And while I hadn’t a clue what this would entail I immediately accepted, honored by the invitation and determined not to faint. My father’s 21 years as an ophthalmologist produced over 15,000 operations, a private practice spanning three offices, and very little vacation time. While I sensed from an early age that the long hours were taxing on him I never felt an absence. In fact, my childhood was picturesque: two loving parents, a rowdy little brother whom I pushed around until he was big enough to push back, family trips in the Jeep to the Rocky Mountains. He was the dad with the Handycam at every soccer game and school play. He worked as a surgeon, but he lived for his children. The morning of the vitrectomy we left extra early because of a limp in my dad’s right leg that had appeared a few months earlier and had gradually worsened. He suspected it was a pinched nerve and had been meaning to get it checked out. In the interim, he had started using a chair during surgery. Walking toward the hospital entrance we encountered a fellow doctor who greeted me with the familiarity of someone who’d been exposed to years of my father’s wallet photos. He asked how I liked Greenwich Village, whether I had directed any films yet and if I had tried a bialy. We walked and talked until I noticed at one point that my dad was no longer part of the conversation. Turning around I realized he was a half block back pushing himself up from the ground. © 2014 The New York Times Company
Keyword: ALS-Lou Gehrig's Disease
Link ID: 19192 - Posted: 02.01.2014
By JAMES GORMAN The question of how moles move all that dirt when they tunnel just under the surface of lawns has never attracted the extensive study that other forms of locomotion — like the flight of birds and insects, or even the jet-propulsion of jellyfish — have. But scientists at the University of Massachusetts and Brown University have recently been asking exactly how, and how hard, moles dig. Yi-Fen Lin, a graduate student at the University of Massachusetts, reported at a recent meeting of the Society for Integrative and Comparative Biology that moles seem to swim through the earth, and that the stroke they use allows them to pack a lot of power behind their shovel-like paws. Ms. Lin measured the power of hairy-tailed moles that she captured in Massachusetts and found they could exert a force up to 40 times their body weight. She also analyzed and presented X-ray videos taken of moles in a laboratory enclosure tunneling their way through a material chosen for its consistency and uniform particle size: cous cous. Angela M. Horner recorded the videos while studying the movement of Eastern moles in the lab of Thomas Roberts, a professor at Brown. One reason moles have not been studied as much as some other animals may be that they are not easy to capture or keep in a laboratory. “People said, ‘You won’t be able to catch them and you won’t be able to keep them alive,’ ” said Elizabeth R. Dumont, an evolutionary biologist who is Ms. Lin’s dissertation adviser. Ms. Lin solved the first problem by camping out in mole territory, on golf courses and farms, and marking their tunnels with sticks that she would watch for hours until movement indicated a mole on the move. © 2014 The New York Times Company
Link ID: 19179 - Posted: 01.29.2014
by Kat Arney Next time you struggle to resist an itchy rash or insect bite, you could find relief in the mirror. Perception of our own bodies can be easily manipulated using tricks such as the rubber hand illusion, which fools people into thinking a rubber hand is their own. Reflecting someone's limb in a mirror has also been used to treat phantom limb pain. Now Christoph Helmchen and his colleagues at the University of Lübeck in Germany have shown that a similar mirror illusion can fool people into feeling relief from an itch, even when they scratch the wrong place. The team injected the right forearms of 26 male volunteers with itch-inducing chemical histamine. Because the injection creates a red spot, they painted a corresponding dot on the opposite arm so both looked identical. One of the researchers then scratched each arm in turn. Unsurprisingly, scratching the itchy arm produced relief, while scratching the other one did not. Next, they placed a large vertical mirror in front of the itchy arm, blocking off the subject's view of their right arm and reflecting back the non-itchy one in its place . They asked the volunteers to look only at the reflected limb in the mirror, whilst a member of the team again scratched each arm. This time the participants felt relief when the unaffected, reflected arm was scratched. © Copyright Reed Business Information Ltd.
By Roni Jacobson Over the past 10 years the number of overdose deaths from prescription painkillers—also known as opioid analgesics—has tripled, from 4,000 people in 1999 to more than 15,000 people every year in the U.S. today. Prescription pain medication now causes more overdose deaths than heroin and cocaine combined. In 2010 one in 20 Americans older than age 12 reported taking painkillers recreationally; some steal from pharmacies or buy them from a dealer, but most have a doctor's prescription or gain access to pills through friends and relatives. Yet millions of people legitimately rely on these medications to cope with the crippling pain they face every day. How do we make sure prescription opioids are readily available to those who depend on them for medical relief but not so available that they become easily abused? Here we break down the steps taken at various levels—and the experts' recommendations for future interventions—to curb prescription opioid addiction and overdose in the U.S. © 2014 Scientific American
By Michelle Roberts Health editor, BBC News online A magnet device can be used to treat some types of migraine, new UK guidance advises. The watchdog NICE says although there is limited evidence, transcranial magnetic stimulation (TMS) may help ease symptoms in some patients. It says that the procedure is still relatively new and that more data is needed about its long-term safety and efficacy. But it may be useful for patients for whom other treatments have failed. Migraine is common - it affects about one in four women and one in 12 men in the UK. There are several types - with and without aura and with or without headache - and several treatment options, including common painkillers, such as paracetamol. Although there is no cure for migraine, it is often possible to prevent or lessen the severity of attacks. NICE recommends various medications, as well as acupuncture, and now also TMS, under the supervision of a specialist doctor - although it has not assessed whether it would be a cost effective therapy for the NHS. TMS involves using a portable device that is placed on the scalp to deliver a brief magnetic pulse. NICE says doctors and patients might wish to try TMS, but they should be aware about the treatment's uncertainties. Reduction in migraine symptoms may be moderate, it says. Prof Peter Goadsby, chairman of the British Association for the Study of Headache, said many migraine patients stood to benefit from trying TMS. BBC © 2014
Keyword: Pain & Touch
Link ID: 19158 - Posted: 01.22.2014
Things are heating up in the world of genetics. The hot pepper (Capsicum annuum) is one of the most widely grown spice crops globally, playing an important role in many medicines, makeups, and meals worldwide. Although the plant’s so-called capsaicin chemical is well known for spicing things up, until now the genetic spark responsible for the pepper’s pungency was unknown. A team of scientists recently completed the first high-quality reference genome for the hot pepper. Comparing the pepper’s genome with that of its tame cousin, the tomato, the scientists discovered the gene responsible for fiery capsaicin production appeared in both plants. While the tomato carried four nonfunctioning copies of the gene, the hot pepper carried seven nonfunctioning copies and one functioning copy, the team reports online today in Nature Genetics. The researchers believe the pepper’s capsaicin-creating gene appeared after five mutations occurred during DNA replication, with the final mutation creating a functional copy. The mouth-burning chemicals likely protected the mutant pepper’s seeds from grazing land animals millions of years ago, giving the mutant a reproductive advantage and helping the mutant gene spread. The team says the finding could help breeders boost the pepper’s heat, nutrition, and medicinal properties. One researcher even suggests that geneticists could activate one of the tomato’s dormant genes, enabling capsaicinoid production and creating a plant that makes ready-made salsa. © 2014 American Association for the Advancement of Science.
-- Bats and other animals use ultrasound to their advantage. Now a new study of humans suggests ultrasound can alter brain activity to boost people's sensory perception. First, researchers placed an electrode on the wrist of volunteers to stimulate the nerve that runs down the arm and into the hand. Before stimulating the radial nerve, they delivered ultrasound to the head -- to an area of the cerebral cortex that processes sensory information received from the hand. The participants' brain responses were recorded using electroencephalography (EEG). The ultrasound decreased the EEG signal and weakened the brain waves responsible for processing sensory input from the hands, according to the study published online Jan. 12 in the journal Nature Neuroscience. The Virginia Tech researchers then conducted two common neurological tests. One measures a person's ability to distinguish whether two pins placed close together and touching the skin are actually two distinct contact points. The other test measures sensitivity to the frequency of a series of air puffs. The scientists were surprised to discover that when they received ultrasound, the participants showed significant improvements in their ability to distinguish pins at closer distances and to identify small differences in the frequency of successive air puffs. The ultrasound may have changed the balance of inhibition and excitation between neighboring neurons within the cerebral cortex, resulting in a boost in sensory perception, explained study leader William Tyler, an assistant professor at Virginia Tech's Carilion Research Institute. © 2014 HealthDay
Keyword: Pain & Touch
Link ID: 19147 - Posted: 01.18.2014
By Katherine Harmon Courage Unless you’ve eaten sannakji, the Korean specialty of semi-live octopus, you might never have had a squirming octopus arm in your mouth. But you’ve most likely had a very similar experience. In fact, you’re probably having one right now. Octopus arms might seem strange and mysterious, but they are remarkably similar to the human tongue. Known as muscular hydrostats, both of these appendages can easily bend, extend and change shape (remember that time you had to stretch out your tongue to lick that last bit of chocolate pudding from the bottom of the cup?). Researchers are hoping a new interdisciplinary project to look at movement in the octopus arm and the human tongue will shed light on how both of these complex structures are activated. This, in turn, could help scientists understand neurological diseases that affect speech, such as Parkinson’s. “The human tongue is a very different muscular system than the rest of the human body,” Khalil Iskarous, an assistant professor of linguistics at the University of Southern California who is helping to lead the research, said in a prepared statement. “Our bodies are vertebrate mechanisms that operate by muscle working on bone to move. The tongue is in a different muscular family, much like an invertebrate. It’s entirely muscle—it’s muscle moving muscle.” Both move by compressing fluid in one section of a muscle, creating movement in another part. But we know little about exactly how that movement is initiated and so finely controlled. © 2014 Scientific American
Keyword: Movement Disorders
Link ID: 19117 - Posted: 01.11.2014
Just in time for all those New Year’s resolutions to exercise more, scientists have a better idea of how the body turns pain into gain. Exertion stimulates muscles to release a molecule that modifies fat cells, turning them into calorie-burning machines, a research team has found. Exercise works the muscles but affects cells throughout the body, even in the brain. An important player in this process is a protein called PGC-1α. In exercising muscles, it activates genes that ramp up energy use. But its impact extends beyond these tissues. The protein somehow indirectly prompts, for example, white fat—the energy-storing variety that pads our hips and stomachs—to switch on genes that are characteristic of brown fat, a form that burns calories. PGC-1α doesn’t travel outside muscle cells, so researchers aren’t sure how its influence spreads, however. By sifting through the secretions of PGC-1α-making muscle cells, Robert Gerszten of Harvard Medical School in Boston and colleagues have nabbed one molecule that might be doing the protein’s bidding: β-aminoisobutyric acid (BAIBA). They found that BAIBA induces white fat cells to become more like brown fat cells, altering their gene activity patterns. And it stimulates other cell types, stoking fat metabolism in the liver, the team also reveals today in Cell Metabolism. These effects may translate into a healthier metabolism. When mice lapped up water laced with the molecule, the rodents lost weight and were better at absorbing glucose. © 2014 American Association for the Advancement of Science
By NICHOLAS BAKALAR Both acupuncture and sham acupuncture were effective in reducing menopausal symptoms in women being treated with aromatase inhibitors for breast cancer, a small randomized trial found. Joint and muscle pain, hot flashes and night sweats are common side effects of those estrogen-lowering drugs. The trial, published online in Cancer, randomized 47 breast cancer patients to eight weekly sessions of either real or sham acupuncture. Those assigned to real acupuncture received treatment with needles in recognized acupoints believed to be helpful in relieving menopausal symptoms. The controls got non-penetrating needles placed in sham acupuncture points. Patients and researchers did not know which patients had received which treatment. The patients kept daily diaries or filled out several questionnaires on the frequency and severity of hot flashes and other symptoms. Patient-reported symptoms, especially hot flashes, improved significantly after both sham and real treatment. There was no statistically significant difference between the two groups. The results may be attributable to a placebo effect, but the scientists suggest that the slight pricking of the skin could cause physiological changes. In any case, the lead author, Dr. Ting Bao, a medical oncologist at the University of Maryland, Baltimore, said there is no harm in trying acupuncture. “Acupuncture as a medical procedure has been practiced for thousands of years,” she said. “It has a minimal risk and potentially significant benefits.” Copyright 2013 The New York Times Company
Keyword: Pain & Touch
Link ID: 19074 - Posted: 12.28.2013
Don’t worry about watching all those cat videos on the Internet. You’re not wasting time when you are at your computer—you’re honing your fine-motor skills. A study of people’s ability to translate training that involves clicking and twiddling a computer mouse reveals that the brain can apply that expertise to other fine-motor tasks requiring the hands. We know that computers are altering the way that people think. For example, using the Internet changes the way that you remember information. But what about use of the computer itself? You probably got to this story by using a computer mouse, for example, and that is a bizarre task compared with the activities that we’ve encountered in our evolutionary history. You made tiny movements of your hand in a horizontal plane to cause tiny movements of a cursor in a completely disconnected vertical plane. But with daily practice—the average computer user makes more than 1000 mouse clicks per day—you have become such an expert that you don’t even think about this amazing feat of dexterity. Scientists would love to know if that practice affects other aspects of your brain’s control of your body. The problem is finding people with no computer experience. So Konrad Kording, a psychologist at Northwestern University’s Rehabilitation Institute of Chicago in Illinois, and his former postdoc Kunlin Wei, now at Peking University in Beijing, turned to migrant Chinese workers. The country’s vast population covers the whole socioeconomic spectrum, from elite computer hackers to agricultural laborers whose lifestyles have changed little over the past century. The country’s economic boom is bringing people in waves from the countryside to cities in search of employment. © 2013 American Association for the Advancement of Science
Keyword: Learning & Memory
Link ID: 19060 - Posted: 12.21.2013
by Ashley Yeager With a little help from implanted electrodes, Parkinson's patients make fewer driving errors, at least on a computer. When steering a simulator, patients with active brain stimulators averaged 3.8 driving errors, compared with 7.5 for healthy people and 11.4 for those with Parkinson's disease who did not have implants. The Parkinson’s patients’ driving skills were also more accurate when receiving deep brain stimulation than when taking levodopa, a common treatment for the disease, researchers report December 18 in Neurology. © Society for Science & the Public 2000 - 2013
Link ID: 19054 - Posted: 12.19.2013
By Dana Smith Daniel Tammet has memorized Pi to the 22,514th digit. He speaks ten different languages, including one of his own invention, and he can multiply enormous sums in his head within a matter of seconds. However, he is unable to hold down a standard 9-to-5 job, in part due to his obsessive adherence to ritual, down to the precise times he has his tea every day. Daniel is a savant. He is also autistic. And he is a synesthete. Daniel experiences numbers as having color, as well as shape and texture. This helps him perform amazing mathematical feats seemingly without effort, the answer simply materializing to him rather than having to calculate it out. In an interview he gave with The Guardian, Daniel explained, “When I multiply numbers together, I see two shapes. The image starts to change and evolve, and a third shape emerges. That’s the answer. It’s mental imagery. It’s like maths without having to think.” Clearly this man has an extraordinary brain. However, Daniel is perhaps not entirely unique, and it appears that the link between autism and synesthesia is more common than originally thought. This suggests that there is a potential common mechanism between these two conditions, which may even help to explain some of Daniel’s special savant abilities. A new study published in the journal Molecular Autism from a team of researchers at the University of Cambridge now empirically shows that there is an almost three-fold higher occurrence of synesthesia in individuals with autism (18.9%), compared with that of the general population (7.2%). This increased prevalence implies that there is indeed a significant link between autism and synesthesia. © 2013 Scientific American
Link ID: 19008 - Posted: 12.06.2013
People with dementia who exercise improve their thinking abilities and everyday life, a body of medical research concludes. The Cochrane Collaboration carried out a systematic review of eight exercise trials involving more than 300 patients living at home or in care. Exercise did little for patients' moods, the research concluded. But it did help them carry out daily activities such as rising from a chair, and boosted their cognitive skills. Whether these benefits improve quality of life is still unclear, but the study authors say the findings are reason for optimism. Dementia affects some 800,000 people in the UK. And the number of people with the condition is steadily increasing because people are living longer. It is estimated that by 2021, the number of people with dementia in the UK will have increased to around one million. With no cure, ways to improve the lives of those living with the condition are vital. Researcher Dorothy Forbes, of the University of Alberta, and colleagues who carried out the Cochrane review, said: "Clearly, further research is needed to be able to develop best practice guidelines to enable healthcare providers to advise people with dementia living at home or in institutions. "We also need to understand what level and intensity of exercise is beneficial for someone with dementia." BBC © 2013
Link ID: 18999 - Posted: 12.05.2013
At the Society for Neuroscience meeting earlier this month in San Diego, California, Science sat down with Geoffrey Ling, deputy director of the Defense Sciences Office at the Defense Advanced Research Projects Agency (DARPA), to discuss the agency’s plans for the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, a neuroscience research effort put forth by President Barack Obama earlier this year. So far, DARPA has released two calls for grant applications, with at least one more likely: The first, called SUBNETS (Systems-Based Neurotechnology for Emerging Therapies), asks researchers to develop novel, wireless devices, such as deep brain stimulators, that can cure neurological disorders such as posttraumatic stress (PTS), major depression, and chronic pain. The second, RAM (Restoring Active Memory), calls for a separate wireless device that repairs brain damage and restores memory loss. Below is an extended version of a Q&A that appears in the 29 November issue of Science. Q: Why did DARPA get involved in the BRAIN project? G.L.: It’s really focused on our injured warfighters, but it has a use for civilians who have stress disorders and civilians who also have memory disorders from dementia and the like. But at the end of the day, it is still meeting [President Obama’s] directive. Of all the things he could have chosen—global warming, alternative fuels—he chose this, so in my mind the neuroscience community should be as excited as all get-up. Q: Why does SUBNETS focus on deep brain stimulation (DBS)? G.L.: We’ve opened the possibility of using DBS but we haven’t exclusively said that. We’re challenging people to go after neuropsychiatric disorders like PTS [and] depression. We’re challenging the community to come up with something in 5 years that’s clinically feasible. DBS is an area that has really been traditionally underfunded, so we thought what the heck, let’s give it a go—in this new BRAIN Initiative the whole idea is to go after the things that there aren’t 400 R01 grants for—and let’s be bold, and boy, if it works, fabulous. © 2013 American Association for the Advancement of Science
Scientists at the National Institutes of Health have used RNA interference (RNAi) technology to reveal dozens of genes which may represent new therapeutic targets for treating Parkinson’s disease. The findings also may be relevant to several diseases caused by damage to mitochondria, the biological power plants found in cells throughout the body. “We discovered a network of genes that may regulate the disposal of dysfunctional mitochondria, opening the door to new drug targets for Parkinson’s disease and other disorders,” said Richard Youle, Ph.D., an investigator at the National Institute of Neurological Disorders and Stroke (NINDS) and a leader of the study. The findings were published online in Nature. Dr. Youle collaborated with researchers from the National Center for Advancing Translational Sciences (NCATS). Mitochondria are tubular structures with rounded ends that use oxygen to convert many chemical fuels into adenosine triphosphate, the main energy source that powers cells. Multiple neurological disorders are linked to genes that help regulate the health of mitochondria, including Parkinson’s, and movement diseases such as Charcot-Marie Tooth Syndrome and the ataxias. Some cases of Parkinson’s disease have been linked to mutations in the gene that codes for parkin, a protein that normally roams inside cells, and tags damaged mitochondria as waste. The damaged mitochondria are then degraded by cells’ lysosomes, which serve as a biological trash disposal system. Known mutations in parkin prevent tagging, resulting in accumulation of unhealthy mitochondria in the body.
By RONI CARYN RABIN Women are more likely than men to die after a heart attack, and some researchers have suggested a reason: Doctors may be misdiagnosing women more often because their symptoms differ from those experienced by men. But a study published Monday indicates that too much has been made of gender differences in chest pain, the hallmark symptom of heart disease. Although the researchers found some distinctions, no pattern was clearly more characteristic of women or could be used to improve heart attack diagnosis in women, the authors concluded. “We should stop treating women differently at the emergency room when they present with chest pain and discomfort,” said Dr. Maria Rubini Gimenez, a cardiologist at University Hospital Basel and lead author of the new study, published in JAMA Internal Medicine. Instead, she said, all patients with acute chest pain must be evaluated for heart attack with appropriate diagnostics, including an electrocardiogram and blood tests. Roughly 80 percent of people who have chest pain and discomfort are suffering from indigestion, acid reflux or another relatively benign condition, said Dr. John G. Canto, director of the chest pain center at Lakeland Regional Medical Center in Lakeland, Fla., who has researched heart attack diagnosis. “The trick is, how do you figure out the 15 to 20 percent actually having a heart attack?” he said. The new research confirms “that there is a lot of overlap in symptoms between patients who are having a heart attack and those who aren’t, and there is a lot of overlap in symptoms between men and women.” The new study examined 2,475 patients, including 796 women, who reported to emergency rooms at nine hospitals in Switzerland, Spain and Italy complaining of acute chest pain between April 21, 2006, and Aug. 12, 2012. Copyright 2013 The New York Times Company