Even ON TARGET Needs a Vacation
To our over 4,400 loyal readers, this year ON TARGET is taking its 2 week annual leave in Santa Fe, NM. It is time to take a break and enjoy the mountain air, chamber music and the opera. Enjoy your summer as well.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com
Moral Judgment Fails Without Feelings
Co-senior author Antonio Damasio said the feeling of aversion normally blocks humans from harming each other. (Credit: Philip Channing: University of Southern California)
Joyce Hays and Jules Mitchel from Target Health Inc. will be attending a neuroscience conference in early August 2012, held in Santa Fe, New Mexico. One of the speakers is the internationally acclaimed neuroscientist, Antonio Damasio MD, PhD, professor at the University of Southern California and author or many books, among them, “Descartes’ Error: Emotion, Reason, and the Human Brain”. The following quiz article represents, a joint research project Professor Damasio was involved in.
Consider the following scenario: someone you know has AIDS and plans to infect others, some of whom will 1) ___. Your only options are to let it happen or to kill the person. Do you pull the trigger? Most people waver or say they could not, even if they agree that in theory they should. But according to a study in the journal Nature, subjects with damage to a part of the frontal lobe make a less personal calculation. The logical choice, they say, is to sacrifice 2) ___ life to save many. The study, conducted at the University of Southern California, Harvard University, Caltech and the University of Iowa, shows that emotion plays an important role in scenarios that pose a moral dilemma.
If certain emotions are blocked, we make decisions that — right or 3) ___ — seem unnaturally cold. The scenarios in the study are extreme, but the core dilemma is not: should one confront a co-worker, challenge a neighbor, or scold a loved one in the interest of the greater good?
A total of 30 subjects of both genders faced a set of scenarios pitting immediate harm to one person against future certain harm to 4) ___. Six had damage to the ventromedial prefrontal cortex (VMPC), a small region behind the forehead, while 12 had brain damage elsewhere, and another 12 had no damage. The subjects with VMPC 5) ___ stood out in their stated willingness to harm an individual — a prospect that usually generates strong aversion.
“Because of their 6) ___ damage, they have abnormal social emotions in real life. They lack empathy and compassion,” said Ralph Adolphs, Bren Professor of Psychology and Neuroscience at Caltech. “In those circumstances most people without this specific brain damage will be torn. But these particular subjects seem to lack that conflict,” said co-senior author Antonio Damasio, director of the Brain and Creativity Institute and holder of the David Dornsife Chair in Neuroscience at USC. “Our work provides the first causal account of the role of emotions in moral judgments,” said co-senior author Marc Hauser, professor of psychology at Harvard and Harvard College Professor. But, Hauser added, not all moral reasoning depends so strongly on 7) ___. “What is absolutely astonishing about our results is how selective the deficit is,” he said. “Damage to the frontal lobe leaves intact a suite of moral problem solving abilities, but damages judgments in which an aversive action is put into direct conflict with a strong utilitarian outcome.” It is the feeling of aversion that normally blocks 8) ___ from harming each other. Damasio described it as “a combination of rejection of the act, but combined with the social emotion of compassion for that particular person.”
“The question is, are the social emotions necessary to make these moral judgments,” Adolphs asked. The study’s answer will inform a classic philosophical debate on whether humans make moral judgments based on norms and societal rules, or based on their emotions. The study holds another implication for philosophy. By showing that humans are neurologically unfit for strict utilitarian thinking, the study suggests that neuroscience may be able to test different philosophies for compatibility with human nature.
The Nature study expands on work on emotion and decision- 9) ___ that Damasio began in the early 1990s and that caught the public eye in his first book, Descartes’ Error. Marc Hauser, whose behavioral work in animals has attempted to identify precursors to moral 10) ___, then teamed up with Damasio’s group to extend those observations.
ANSWERS: 1) die; 2) one; 3) wrong; 4) many; 5) damage; 6) brain; 7) emotion; 8) humans; 9) making; 10) behavior
Drawing by Santiago Ramón y Cajal (1899) of neurons in the pigeon cerebellum
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics, medicine and allied disciplines, philosophy, physics, and psychology. The term neurobiology is usually used interchangeably with the term neuroscience, although the former refers specifically to the biology of the nervous system, whereas the latter refers to the entire science of the nervous system.
The scope of neuroscience has broadened to include different approaches used to study the molecular, cellular, developmental, structural, functional, evolutionary, computational, and medical aspects of the nervous system. The techniques used by neuroscientists have also expanded enormously, from molecular and cellular studies of individual nerve cells to imaging of sensory and motor tasks in the brain. Recent theoretical advances in neuroscience have also been aided by the study of neural networks.
Given the increasing number of scientists who study the nervous system, several prominent neuroscience organizations have been formed to provide a forum to all neuroscientists and educators. For example, the International Brain Research Organization was founded in 1960, the International Society for Neurochemistry in 1963, the European Brain and Behaviour Society in 1968, and the Society for Neuroscience in 1969.
Illustration from Gray’s Anatomy (1918) of a lateral view of the human brain, featuring the hippocampus among other neuroanatomical features
The study of the nervous system dates back to ancient Egypt. Evidence of trepanation, the surgical practice of either drilling or scraping a hole into the skull with the purpose of curing headaches or mental disorders or relieving cranial pressure, being performed on patients dates back to Neolithic times and has been found in various cultures throughout the world. Manuscripts dating back to 1700 BCE indicated that the Egyptians had some knowledge about symptoms of brain damage.
Early views on the function of the brain regarded it to be a “cranial stuffing” of sorts. In Egypt, from the late Middle Kingdom onwards, the brain was regularly removed in preparation for mummification. It was believed at the time that the heart was the seat of intelligence. According to Herodotus, the first step of mummification was to “take a crooked piece of iron, and with it draw out the brain through the nostrils, thus getting rid of a portion, while the skull is cleared of the rest by rinsing with drugs.”
The view that the heart was the source of consciousness was not challenged until the time of the Greek physician Hippocrates. He believed that the brain was not only involved with sensation -since most specialized organs (e.g., eyes, ears, tongue) are located in the head near the brain – but was also the seat of intelligence. Plato also speculated that the brain was the seat of the rational part of the soul. Aristotle, however, believed the heart was the center of intelligence and that the brain regulated the amount of heat from the heart. This view was generally accepted until the Roman physician Galen, a follower of Hippocrates and physician to Roman gladiators, observed that his patients lost their mental faculties when they had sustained damage to their brains.
Abulcasis, Averroes, Avenzoar, and Maimonides, active in the Medieval Muslim world, described a number of medical problems related to the brain. In Renaissance Europe, Vesalius (1514–1564) and Rene Descartes (1596–1650) also made several contributions to neuroscience.
The Golgi stain first allowed for the visualization of individual neurons.
Studies of the brain became more sophisticated after the invention of the microscope and the development of a staining procedure by Camillo Golgi during the late 1890s. The procedure used a silver chromate salt to reveal the intricate structures of individual neurons. His technique was used by Santiago Ramon y Cajal and led to the formation of the neuron doctrine, the hypothesis that the functional unit of the brain is the neuron. Golgi and Ramon y Cajal shared the Nobel Prize in Physiology or Medicine in 1906 for their extensive observations, descriptions, and categorizations of neurons throughout the brain. The neuron doctrine was supported by experiments following Luigi Galvani’s pioneering work in the electrical excitability of muscles and neurons. In the late 19th century, Emil du Bois-Reymond, Johannes Peter Muller, and Hermann von Helmholtz demonstrated that neurons were electrically excitable and that their activity predictably affected the electrical state of adjacent neurons.
In parallel with this research, work with brain-damaged patients by Paul Broca suggested that certain regions of the brain were responsible for certain functions. At the time, Broca’s findings were seen as a confirmation of Franz Joseph Gall’s theory that language was localized and that certain psychological functions were localized in specific areas of the cerebral cortex. The localization of function hypothesis was supported by observations of epileptic patients conducted by John Hughlings Jackson, who correctly inferred the organization of the motor cortex by watching the progression of seizures through the body. Carl Wernicke further developed the theory of the specialization of specific brain structures in language comprehension and production. Modern research still uses the Brodmann cerebral cytoarchitectonic map (referring to study of cell structure) anatomical definitions from this era in continuing to show that distinct areas of the cortex are activated in the execution of specific tasks.
In 1952, Alan Lloyd Hodgkin and Andrew Huxley presented a mathematical model for transmission of electrical signals in neurons of the giant axon of a squid, action potentials, and how they are initiated and propagated, known as the Hodgkin-Huxley model. In 1961-2, Richard FitzHugh and J. Nagumo simplified Hodgkin-Huxley, in what is called the FitzHugh-Nagumo model. In 1962, Bernard Katz modeled neurotransmission across the space between neurons known as synapses. In 1981 Catherine Morris and Harold Lecar combined these models in the Morris-Lecar model. In 1984, J. L. Hindmarsh and R.M. Rose further modeled neurotransmission.
Beginning in 1966, Eric Kandel and collaborators examined biochemical changes in neurons associated with learning and memory storage.
Oral Immunotherapy Shows Promise as Treatment for Egg Allergy
Children with egg allergy, one of the most common childhood food allergies, are at risk for severe reactions if they are accidentally exposed to egg-containing foods. Symptoms of allergic reactions can range from mild (hives, redness and itchiness of the skin) to severe (swelling of the back of the throat, trouble breathing, drop in blood pressure, and faintness or dizziness). Currently, the only way to prevent these reactions from occurring is to avoid foods that contain eggs.
According to an article published online in the New England Journal of Medicine (19 July 2012), giving children and adolescents with egg allergy small but increasing daily doses of egg white powder, holds the possibility of developing a way to enable some children to eat egg-containing foods without having allergic reactions.
The study is one of several federally funded trials of oral immunotherapy (OIT), an approach in which a person with food allergy consumes gradually increasing amounts of the allergenic food as a way to treat the allergy. Because OIT carries significant risk for allergic reactions, these studies are all conducted under the guidance of trained clinicians.
The goals of the study were to determine if daily egg OIT reduced or eliminated participants’ allergic responses to egg protein and if it did, whether or not the benefit persisted after therapy was stopped for four to six weeks. The Consortium of Food Allergy Research (CoFAR) study enrolled 55 children and adolescents aged 5 to 18 years who had egg allergy. Participants were randomly assigned either to the treatment group, which received egg OIT (40 participants), or to the control group, which did not (15 participants). Both groups were followed for 24 months.
Participants received a daily dose of egg white powder or cornstarch powder (placebo) at home. Authors gradually increased the dose of egg or placebo powder every two weeks until the children in the egg OIT group were eating the equivalent of about one-third of an egg every day. Participants came to the clinic to have three oral food challenges, at 10 months, 22 months and 24 months, with the maximum challenge equivalent to one egg. The challenge was deemed successful if there were either no symptoms or only transient symptoms not directly observable by a doctor, such as throat discomfort. Participants failed the challenge if they had a symptom that could be observed by a doctor, such as wheezing.
Results showed that after 10 months, none of the participants who received placebo passed the challenge, but 55% of those on egg OIT did. After 22 months of egg OIT, a second oral food challenge was given to all of the children in the treatment group. At this food challenge, 75% of those on egg OIT passed.
To determine if egg OIT had any long-term benefit on treating the children’s food allergy, the participants who passed the 22-month test were completely removed from egg OIT for four to six weeks and then rechallenged at 24 months. Eleven of the original 40 children (about 27%) passed this third food challenge. None of the children from the placebo group were retested because they had failed the prior food challenges. The 11 children who passed the third test were allowed to eat egg or egg-containing foods in their normal diets as frequently or infrequently as they chose. At a one-year follow-up, they reported no symptoms.
According to the study authors, these results indicate two types of benefits. First, the majority of the study children could be safely exposed to egg while on egg OIT. Second, a small group of children — approximately one-fourth — were able to eat egg in their regular diets even after stopping OIT for four to six weeks.
The authors noted that although these results indicate that OIT may help resolve certain food allergies, this type of therapy is still in its early experimental stages and more research is needed. The authors also emphasized that food OIT and oral food challenges should not be tried at home because of the risk of severe allergic reactions.
Study Shows Colon and Rectal Tumors Constitute a Single Type of Cancer
The National Cancer Institute (NCI) estimates that in 2012, more than 143,000 people in the US will be diagnosed with colorectal cancer and that 51,500 are likely to die. Colorectal cancer is the fourth most common cancer in men, after non-melanoma skin, prostate and lung cancer. It is also the fourth most common cancer in women, after non-melanoma skin, breast and lung cancer.
According to the Cancer Genome Atlas (TCGA) project’s large-scale study of colon and rectal cancer tissue specimens published online in the journal Nature (19 July 2012), the pattern of genomic alterations in colon and rectal tissues appear the same regardless of anatomic location or origin within the colon or the rectum, thus leading to the conclusion that these two cancer types can be grouped as one. The study also found several of the recurrent genetic errors that contribute to colorectal cancer.
There is a known negative association between aggressiveness of colorectal tumors and the phenomenon of hypermutation, in which the rate of genetic mutation is abnormally high because normal DNA repair mechanisms are disrupted. In this study, 16% of the specimens were found to be hypermutated. Three-fourths of these cases exhibited microsatellite instability (MSI), which often is an indicator for better prognosis. Microsatellites are repetitive sections of DNA in the genome. If mutations occur in the genes responsible for maintaining those regions of the genome, the microsatellites may become longer or shorter; this is called MSI.
The authors observed that in the 224 colorectal cancer specimens examined, 24 genes were mutated in a significant numbers of cases. In addition to genes found through prior research efforts (e.g., APC, ARID1A, FAM123B/WTX, TP53, SMAD4, PIK3CA and KRAS), the authors identified other genes (ARID1A, SOX9 and FAM123B/WTX) as potential drivers of this cancer when mutated. It is only through a study of this scale that these three genes could be implicated in this disease.
The research network also identified the genes ERBB2 and IGF2 as mutated or overexpressed in colorectal cancer and as potential drug targets. These genes are involved in regulating cell proliferation and were observed to be frequently overexpressed in colorectal tumors. This finding points to a potential drug therapy strategy in which inhibition of the products of these genes would slow progression of the cancer.
A key part of this study was the analysis of signaling pathways. Signaling pathways control gene activity during cell development and regulate the interactions between cells as they form organs or tissues. Among other findings, the TCGA Research Network identified new mutations in a particular signaling cascade called the WNT pathway. According to the authors, this finding will improve development of WNT signaling inhibitors, which show initial promise as a class of drugs that could benefit colorectal cancer patients.
In addition to examining the WNT pathway, the authors also identified RTK/RAS and AKT-PI3K as pathways that are altered in a substantial set of colorectal tumors, which may show promise for targeting therapies for colorectal cancer. Because of these findings, drug developers may now be able to narrow their scope of investigation with an expectation of producing more focused therapeutic approaches.
Cognitive Changes May Be Only Sign of Fetal Alcohol Exposure – Give Kids a Chance
Fetal alcohol syndrome refers to a pattern of birth defects found in children of mothers who consumed alcohol during pregnancy. These involve a characteristic pattern of facial abnormalities, growth retardation, and brain damage. Neurological and physical differences seen in children exposed to alcohol prenatally — but who do not have the full pattern of birth defects seen in fetal alcohol syndrome — are classified as fetal alcohol spectrum disorders
According to a study published online in Alcoholism: Clinical and Experimental Research (23 July 2012), most children exposed to high levels of alcohol in the womb do not develop the distinct facial features seen in fetal alcohol syndrome, but instead show signs of abnormal intellectual or behavioral development. These abnormalities of the nervous system involved language delays, hyperactivity, attention deficits or intellectual delays. The authors used the term “s functional neurologic impairment” to describe these abnormalities. The authors documented an abnormality in one of these areas in about 44% of children whose mothers drank four or more drinks per day during pregnancy. In contrast, abnormal facial features were present in about 17% of alcohol exposed children.
The authors’ concern is that in the absence of the distinctive facial features, health care providers evaluating children with any of these functional neurological impairments might miss their history of fetal alcohol exposure and as a result, children might not be referred for appropriate treatment and services.”
The Centers for Disease Control and Prevention provides information on the treatments for FASD.
The study was conducted as part of a long-term study of heavy drinking in pregnancy known as the NICHD-University of Chile Alcohol in Pregnancy Study. To conduct the study, the authors asked over 9,000 women at a community health clinic in Santiago, Chile about their alcohol use during pregnancy. They found 101 pregnant women, who had four or more drinks per day during their pregnancies and matched them with 101 women having similar characteristics but who consumed no alcohol when they were pregnant. After these women gave birth, the authors evaluated the infants’ health and conducted regular assessments of their physical, intellectual and emotional development through age 8.
The authors documented differences in the rate of children affected in the following areas:
Abnormal facial features
— Alcohol exposed: 17%
— Unexposed: 1%
— Alcohol exposed: 27%
— Unexposed: 13%
Cognitive delays (including intellectual)
— Alcohol exposed: 35%
— Unexposed: 6%
— Alcohol exposed: 42%
— Unexposed: 24%
— Alcohol exposed: 27%
— Unexposed: 2%
Some of the women with heavy drinking habits also engaged in binge drinking (5 or more drinks at a time). Even though these women already had high levels of alcohol consumption, the authors found that this habit increased the likelihood of poor outcomes for their children.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
FDA Warns Consumers Not to Eat Shellfish From Oyster Bay Harbor, Nassau County, NY
Shellfish harvested from Oyster Bay Harbor have been linked to confirmed illnesses due to infections of the Vibrio parahaemolyticus bacterium. As a result, the FDA is warning consumers not to eat raw or partially cooked oysters and clams (shellfish) with tags listing Oyster Bay Harbor, in Nassau County, N.Y., as the harvest area, following additional illnesses reported in several states caused by the bacteria.
When ill persons reported consumption of raw or partially cooked shellfish from the affected area, the New York state Department of Environmental Conservation (DEC) closed Oyster Bay Harbor, on July 13 to shellfish harvesting. All shellfish harvesters, shippers, re-shippers, processors, restaurants, and retail food establishments are advised to check the identity tags on all containers of shellfish in their inventories. If the tag indicates the harvest area was Oyster Bay Harbor and a harvest date on or after June 1, 2012, the product should be disposed of and not be sold or served.
What are the Symptoms of Vibrio parahaemolyticus Illness?
Illness is typically characterized by nausea, vomiting, and diarrhea. The symptoms begin from a few hours to as many as five days after consumption of raw or undercooked seafood, particularly shellfish.
What do Consumers Need to Do?
Consumers possessing shellfish with tags listing Oyster Bay Harbor as the harvest area and a harvest date on or after June 1, 2012 should dispose of and not eat the shellfish. Consumers possessing shellfish for which the harvest area is not known should inquire of the retailer, restaurant or other facility about the source of shellfish. If the shellfish was already consumed and no one became ill, no action is needed. However, if you develop a diarrheal illness within a week after consuming raw or undercooked shellfish, see your health care provider and inform the provider about this exposure.
Where was the Shellfish Distributed?
Records and information obtained by the New York state DEC indicate that the shellfish from this area of Oyster Bay Harbor in New York were distributed in several states, including, but not necessarily limited to, Connecticut, Maine, Maryland, Massachusetts, Michigan, Missouri, New Jersey, New York, Pennsylvania and Rhode Island.
What is Being Done About the Problem?
The New York state DEC has prohibited the harvesting of shellfish from Oyster Bay Harbor in Nassau County, and has issued media releases advising establishments not to use shellfish from this harvest area and advising consumers not to eat the shellfish. The DEC has notified states that received implicated shellfish and the Interstate Shellfish Sanitation Conference, which has subsequently notified its membership.
The map at http://www.dec.ny.gov/outdoor/7765.html shows the area that has been closed to harvesting of shellfish. This closure will remain in effect until samples collected by the DEC indicate that shellfish from the affected area are no longer a threat to consumers.
No other harvest areas have been implicated in the recent Vibrio parahaemolyticus illnesses.
Cauliflower Roasted With Balsamic & Parmesan
The recipes that will appear in this section, were created with health (low calories plus vitamins & minerals) in mind, as well as delicious taste. Another attribute, you will find, is ease of preparation. This particular recipe has wonderful flavor and is very low in calories. It’s better served warm, but any left-overs could be served as a salad.
- 8 cups 1-inch-cauliflower florets, (One large cauliflower)
- 2 Tablespoons extra-virgin olive oil
- 1 teaspoon dried marjoram
- 1/4 teaspoon Kosher salt
- Pinch fine black pepper or grind your own
- 2 Tablespoons balsamic vinegar
- 1/2 cup finely shredded Parmesan cheese
- Preheat oven to 450°F.
- Toss cauliflower, oil, marjoram, salt and pepper in a large bowl.
- Spread on a large rimmed baking sheet and roast in oven (350 F) until starting to soften and brown on the bottom, 15 to 20 minutes. Remove from oven.
- Toss the cauliflower, carefully, in a large bowl, with vinegar and sprinkle with cheese. Place in glass oven-proof baking dish.
- Return to the oven and roast until the cheese is melted and any moisture has evaporated, 5 to 10 minutes more. Serve, or cover and put in warming oven until ready to serve
This is a wonderful side dish to serve with any kind of fish
Vilayanur S. Ramachandran
Vilayanur S. Ramachandran MD, PhD
Vilayanur Subramanian Ramachandran (born 1951) is a neuroscientist known for his work in the fields of behavioral neurology and visual psychophysics. He is the Director of the Center for Brain and Cognition, and is currently a Professor in the Department of Psychology and the Neurosciences Graduate Program at the University of California, San Diego.
Ramachandran is noted for his use of experimental methods that rely relatively little on complex technologies such as neuroimaging. According to Ramachandran, “too much of the Victorian sense of adventure [in science] has been lost.” Despite the apparent simplicity of his approach, Ramachandran has generated many new ideas about the brain. He has been called “The Marco Polo of neuroscience” by Richard Dawkins and “the modern Paul Broca” by Eric Kandel. In 1997 Newsweek named him a member of “The Century Club”, one of the “hundred most prominent people to watch” in the 21st century. In 2011 Time listed him as one of “the most influential people in the world” on the “Time 100” list. Early life and education
Vilayanur Subramanian Ramachandran (in accordance with some Tamil family name traditions, his family name, Vilayanur, is placed first) was born in 1951 in Tamil Nadu, India. His father, V.M. Subramanian, was an engineer who worked for the U.N. Industrial Development Organization and served as a diplomat in Bangkok, Thailand.Ramachandran spent much of his youth moving among several different posts in India and other parts of Asia. As a young man he attended schools in Madras, Bangkok and England, and pursued many scientific interests, including conchology. Ramachandran obtained an M.B.B.S. from Stanley Medical College in Madras, India, and subsequently obtained a Ph.D. from Trinity College at the University of Cambridge. While a graduate student at Cambridge Ramachandran also collaborated on research projects with faculty at Oxford, including David Whitteridge of the Physiology Department. He then spent two years at Caltech, as a research fellow working with Jack Pettigrew. He was appointed Assistant Professor of Psychology at the University of California, San Diego in 1983, and has been a full professor there since 1998.
Ramachandran is the grandson of Sir Alladi Krishnaswamy Iyer, Advocate General of Madras and co-architect of the Constitution of India. He is married to Diane Rogers-Ramachandran and they have two boys, Mani and Jaya.
Ramachandran has studied neurological syndromes to investigate neural mechanisms underlying human mental function. Ramachandran is best known for his work on syndromes such as phantom limbs, body integrity identity disorder, and Capgras delusion. His research has also contributed to the understanding of synesthesia. More recently his work has focused on the theoretical implications of mirror neurons and the cause of autism. In addition, Ramachandran is known for the invention of the mirror box. He has published over 180 papers in scientific journals. Twenty of these have appeared in Nature, and others have appeared in Science, Nature Neuroscience, Perception and Vision Research. Ramachandran is a member of the editorial board of Medical Hypotheses (Elsevier) and has published 15 articles there.
Ramachandran’s work in behavioral neurology has been widely reported by the media. He has appeared in numerous Channel 4 and PBS documentaries. He has also been featured by the BBC, the Science Channel, Newsweek, Radio Lab, and This American Life, TED Talks, and Charlie Rose.
He is author of Phantoms in the Brain which formed the basis for a two part series on BBC Channel 4 TV (UK) and a 1-hour PBS special in the USA. He is the editor of the Encyclopedia of the Human Brain (2002), and is co-author of the bi-monthly “Illusions” column in Scientific American Mind.
Ramachandran has recently lamented that science has become too professionalized. In a 2010 interview with the British Neuroscience Association he stated: “But where I’d really like to go is back in time. I’d go to the Victorian age, before science had professionalized and become just another 9–5 job, with power-brokering and grants nightmares. Back then scientists just had fun. People like Darwin and Huxley; the whole world was their playground.”
Ramachandran’s early research was on human visual perception using psychophysical methods to draw clear inferences about the brain mechanisms underlying visual processing.
Ramachandran is credited with discovering several new visual effects and illusions; most notably perceived slowing of motion at equiluminance (when red and green are seen as equally bright), stereoscopic “capture” using illusory contours, stereoscopic learning, shape-from-shading, and motion capture. He invented (together with Richard Gregory) filling in of “artificial scotomas” and discovered a new “dynamic noise after effect.” He also invented a class of stimuli (phantom contours) that selectively activate the magnocellular pathway in human vision and that have been used by Anne Sperling, and her colleagues, to evaluate aspects of dyslexia.
When an arm or leg is amputated, patients continue to feel vividly the presence of the missing limb as a “phantom limb”. Building on earlier work by Ronald Melzack (McGill University) and Timothy Pons (NIMH), Ramachandran theorized that there was a link between the phenomenon of phantom limbs and neural plasticity in the adult human brain. In particular, he theorized that the body image maps in the somatosensory cortex are re-mapped after the amputation of a limb. In 1993, working with T.T. Yang who was conducting MEG research at the Scripps Research Institute, Ramachandran demonstrated that there had been measurable changes in the somatosensory cortex of several patients who had undergone arm amputations. Ramachandran theorized that there was a relationship between the cortical reorganization evident in the MEG images and the referred sensations he observed in his subjects. He presented this theory in a paper titled “Perceptual correlates of massive cortical reorganization.” Although Ramachandran was one of the first scientists to emphasize the role of cortical reorganization as the basis for phantom limb sensations, subsequent research has demonstrated that referred sensations are not the perceptual correlate of cortical reorganization after amputation. The question of which neural processes are related to non-painful referred sensations has not been resolved.
Mirror visual feedback & Mirror box
Ramachandran is credited with the invention of the mirror box and the introduction of mirror visual feedback as a treatment for a variety of conditions associated with phantom limb pain, stroke, and regional pain syndrome. Several research studies using mirror therapy have produced promising results. However, mirror therapy has produced conflicting results in randomized controlled trials, and the applications of mirror therapy are still under experimental evaluation.
Synesthetes who experience color when viewing different symbols may quickly identify the presence of the “triangle” in the left-hand image.
Main article: Synesthesia
Ramachandran has studied the neural mechanisms of synesthesia, a condition in which stimulation in one sensory modality leads to experiences in a second, unstimulated modality. His initial studies focused on grapheme → color synesthesia, in which viewing black and white letters or numbers (collectively referred to as graphemes) on a page evokes the experience of seeing colors. Ramachandran (with then PhD student, Edward Hubbard) showed that some synesthetes were better able to detect “embedded figures” composed of one letter or number (for example a triangle composed of 2s) on a background of another number (for example 5s).
Based on his previous work on phantom limbs, Ramachandran suggested that synesthesia may arise from a cross-activation between brain regions. Although the idea of cross-connections dates to some of the earliest work on synesthesia, Ramachandran was the first to give this idea a specific anatomical explanation. Ramachandran suggested that grapheme-color synesthesia is the result of increased connectivity between brain areas that are responsible for the perceptual recognition of letters and numbers and colors, perhaps due to genetic factors, given that synesthesia is known to run in families. Ramachandran theorized that
Different subtypes of number–color synaesthesia…are caused by hyperconnectivity between colour and number areas at different stages in processing; lower synaesthetes may have cross-wiring (or cross-activation) within the fusiform gyrus, whereas higher synaesthetes may have cross-activation in the angular gyrus.
Consistent with this model, Ramachandran’s group found increased activity in color selective areas in synesthetes compared to non-synesthetes using fMRI. Using MEG, they also showed that differences between synesthetes and non-synesthetes begin very quickly after the grapheme is presented. However, recent research in the Netherlands (involving 19 grapheme-color synesthetes) demonstrated that synesthesia can be the result of either direct bottom-up cross-activation from grapheme processing areas within the fusiform gyrus, or indirectly via higher-order parietal areas. Tessa van Leeuwen and her colleagues concluded:
To summarize, in this first study of effective connectivity in synesthesia, we established that while the same network of regions is active in different types of synesthesia, individual differences in subjective color experience are determined by altered coupling.
Recently, Ramachandran has also begun investigations of other forms of synesthesia, including number forms and tactile → emotion synesthesia. Ramachandran has helped to advance public awareness of synesthesia by hosting two meetings of the American Synesthesia Association at UCSD in 2002 and 2011.
Ramachandran has speculated that synesthesia and conceptual metaphors may share a common basis in cortical cross-activation. In 2003 Ramachandran and Edward Hubbard published a paper in which they speculated that the angular gyrus is at least partially responsible for understanding metaphors.
Recent research by Krish Sathian (Emory University) using functional magnetic resonance imaging (fMRI) suggests that conceptual metaphors activate the texture-selective somatosensory cortex in the parietal operculum. Sathian stated that “I don’t think that there’s only one area for metaphor processing…several recent lines of research indicate that engagement with abstract concepts is distributed around the brain.” Vilayanur Ramachandran commented that “the authors have paved the way” to study how different brain regions communicate. “This is a very ingenious and elegant approach to the problem.”
Evolution of language
Following Lakoff and Johnson, Ramachandran argues that metaphors are non-arbitrary. Ramachandran and Hubbard suggest that “these rules [of metaphor production] are a result of strong anatomical constraints that permit certain types of cross-activation, but not others.” Ramachandran has suggested that the evolution of language is the result of three types of non-arbitrary mappings: between sounds and visual shapes (the bouba-kiki effect), sensory-to-motor synesthesia, and motor-to-motor synesthesia (or “synkinesia”).
Ramachandran is known for advocating the importance of mirror neurons. Ramachandran has stated that the discovery of mirror neurons is the most important unreported story of the last decade. (Mirror neurons were first reported in a paper published in 1992 by a team of researchers led by Giacomo Rizzolatti at the University of Parma.) Ramachandran has speculated that research into the role of mirror neurons will help explain a variety of human mental capacities ranging from empathy, imitation learning, and the evolution of language. Ramachandran has also theorized that mirror neurons may be the key to understanding the neurological basis of human self awareness.
Ramchandran has theorized that in addition to motor command mirror neurons there are mirror neurons that are activated when a person observes someone else being touched. In 2008 Ramachandran conducted an experiment in which several phantom arm patients reported feeling touch signals on their phantom arms when they observed the arm of a student being touched. In a 2009 discussion of this theory Ramachandran and Althschuler called these mirror neurons “touch mirror neurons.”
In 1999, Ramachandran, in collaboration with then post-doctoral fellow Eric Altschuler and colleague Jaime Pineda, was one of the first to suggest that a loss of mirror neurons might be the key deficit that explains many of the symptoms and signs of autism spectrum disorders. Between 2000 and 2006 Ramachandran and his colleagues at UC San Diego published a number of articles in support of this theory, which became known as the “Broken Mirrors” theory of autism. Ramachandran and his colleagues did not measure mirror neuron activity directly; rather they demonstrated that children with ASD showed abnormal EEG responses (known as Mu wave suppression) when they observed the activities of other people. In 2008 Oberman, Ramachandran and Pineda conducted an experiment in which children with ASD showed both normal and abnormal EEG responses depending on their familiarity with people whose actions they were observing. Oberman and Ramachanran concluded that “The study revealed that mu suppression was sensitive to degree of familiarity. Both typically developing participants and those with ASD showed greater suppression to familiar hands compared to those of strangers. These findings suggest that the Mirror Neuron Systmen responds to observed actions in individuals with ASD, but only when individuals can identify in some personal way with the stimuli.”
Ramachandran’s theory that dysfunctional mirror neuron systems(MNS) play an important role in autism remains controversial. In his 2011 review of The Tell-Tale Brain, Simon Baron-Cohen, Director of the Autism Research Center at Cambridge University, states that “As an explanation of autism, the [Broken Mirrors] theory offers some tantalizing clues; however, some problematic counter-evidence challenges the theory and particularly its scope.”
Recognizing that dysfunctional mirror neuron systems cannot account for the wide range of symptoms that are included in autism spectrum disorder (ASD), Ramachandran has theorized that childhood temporal lobe epilepsy and olfactory bulb dysgenesis may also play a role in creating the symptoms of ASD. In 2010 Ramachandran stated that “The olfactory bulb hypothesis has important clinical implications” and announced that his group would undertake a study “comparing olfactory bulb volumes in individuals with autism with those of normal controls.”
Rare neurological syndromes
In 2008 Ramachandran, along with David Brang and Paul McGeoch, published the first paper to theorize that apotemnophilia is a neurological disorder caused by damage to the right parietal lobe of the brain. This rare disorder, in which a person desires the amputation of a limb, was first identified by John Money in 1977. Building on Ramachandran’s previous work identifying representations of body image in the brain, they argued that this disorder stems from a neural body image that is incomplete. Hence the person sees their limb as a foreign appendage that is outside their body. Ramachandran has extended this theory to suggest that anorexia nervosa may be a body image disorder that has its basis in neurological representations of the body, rather than an appetite disorder of the hypothalamus.
In collaboration with then post-doctoral fellow, William Hirstein, Ramachandran published a paper in 1997 in which he presented a theory describing the neural basis of Capgras delusion, a delusion in which family members and other loved ones are thought to be replaced by impostors. Previously, Capgras delusion was attributed to a disconnection between facial recognition and emotional arousal. Ramachandran and Hirstein presented a more specific structural explanation that argued that Capgras delusion might be the result of a disconnection between the “fusiform face area”, a region of the fusiform gyrus involved in face perception, and the amygdala, which is involved in the emotional responses to familiar faces. Additionally, based on their model and the specific responses of the patient they examined (a Brazilian man who had sustained a head injury in a traffic accident), Ramachandran and Hirstein proposed a general theory of memory formation. They speculated that a person suffering from Capgras delusion loses the ability to form a taxonomy of memories and hence they can no longer manage memories effectively. Instead of a continuum of memories that constitute a unified sense of self, each memory takes on its own categorical sense of self.
Alternating gender incongruity (AGI)
In 2012, Case and Ramachandran reported the results of a survey of bigendered individuals who experience involuntary alternation between male and female states. Case and Ramachandran hypothesized that gender alternation may reflect an unusual degree (or depth) of hemispheric switching, and the corresponding suppression of sex appropriate body maps in the parietal cortex. They stated that “we hypothesize that tracking the nasal cycle, rate of binocular rivalry, and other markers of hemispheric switching will reveal a physiological basis for AGI individuals’ subjective reports of gender switches… We base our hypotheses on ancient and modern associations between the left and right hemispheres and the male and female genders.”
Awards and honors
Ramachandran was elected to a visiting fellowship at All Souls College, Oxford (1998–1999). In addition he was a Hilgard visiting professor at Stanford University in 2005. He has received honorary doctorates from Connecticut College (2001) and the Indian Institute of Technology, Madras (2004). Ramachandran received the annual Ramon y Cajal award (2004) from the International Neuropsychiatry Society, and the Ariens-Kappers medal from the Royal Netherlands Academy of Sciences for his contributions to Neuroscience (1999). He shared the 2005 Henry Dale Prize with Michael Brady of Oxford, and, as part of the award was elected an honorary life member of the Royal institution for “outstanding research of an interdisciplinary nature”. In 2007, the President of India conferred on him the third highest civilian award and honorific title in India, the Padma Bhushan. In 2008, he was listed as number 50 in the Top 100 Public Intellectuals Poll.
Invited plenary lectures
Ramachandran has presented numerous plenary lectures around the world. He gave the Decade of the Brain lecture at the 25th annual meeting of the Society for Neuroscience in 1995, the D.O. Hebb Lecture in 1997 (McGill University), and the Keynote Lecture at the 1999 Decade of the Brain meeting before the NIH and the Library of Congress, as well as the Rabindranath Tagore lecture at the Centre for Philosophy and Foundations of Science in New Delhi. In 2003 he gave the annual BBC Reith Lectures. In 2007 he gave a public lecture that was part of a series sponsored by the Templeton Foundation at the Royal Society in London. He gave the 2010 IAS Distinguished Lecture at the University of Bristol‘s Institute of Advanced Studies dedicated to the memory of his longtime friend and collaborator, Richard Gregory. In October 2011, Ramachandran delivered a lecture titled “The Neurology of Human Nature” at the 47th Nobel Conference at Gustavus Adolphus College in Saint Peter, Minnesota. In 2012, he gave the Gifford Lectures (May 28, 2012 – May 30, 2012) at the University of Glasgow.
Testimony as an expert witness
Ramachandran has served as an expert witness on the delusions associated with pseudocyesis (false pregnancy). At the 2007 trial of Lisa M. Montgomery he testified that Montgomery suffered from severe pseudocyesis disorder and that she was unable to appreciate the nature and quality of her acts.
An interest in paleontology led him to purchase a fossil dinosaur skull from the Gobi desert, which was named after him as Minotaurasaurus ramachandrani in 2009.A controversy has surfaced around the provenance of this skull. Some paleontologists claim that this fossil was removed from the Gobi desert without the permission of the Chinese government and sold without proper documentation. V.S. Ramachandran, who purchased the fossil in Tucson, Arizona, says that he would be happy to repatriate the fossil to the appropriate nation, if someone shows him “evidence it was exported without permit”. For now, the specimen rests at the Victor Valley Museum, an hour’s drive east of Los Angeles.
VS Ramachandran on your mind
Posted on February 9, 2012
This week’s TED talk comes from VS Ramachandran, who is Director of the Center for Brain and Cognition and Distinguished Professor with the Psychology Department and Neurosciences Program at UC San Diego. I first became aware of Dr. Ramachandran, as I’m sure many others did, when I read his fascinating book Phantoms in the Brain: Probing the Mysteries of the Human Mind. He has written several other books as well and I am particularly interested in his most latest work, The Tell-Tale Brain: A Neuroscientist’s Quest for What Makes Us Human, Ramachandran is an MD, PhD who’s research is focused on using patients with neurological disorders to understand normal brain function. In this TED talk, he talks about three patients with different syndromes (Capgras delusion, phantom pain, synesthesia) and how understanding them has either led to therapy or a better understanding of mental connections. (I’m not a neurologist, but I would gather that calling synesthesia a disorder or disease would be a no-no, from the few people I know who have it, but that’s for others to debate).
I enjoyed the talk immensely. Ramachandran is a great speaker and his work is on a clearly fascinating subject manner. In addition, the way he goes about discovery is akin to solving a murder mystery and often involves cheap or non-modern equipment (which gives him a sort of MacGyver feel, I suppose). His path of discovery makes for good and informative story-telling.
My only beef was one statement he made early on in the talk when he called neurons “little wisps of protoplasm.” Not quite. The molecular and cellular biologist within me cringed at that description. Yes, there’s brilliant and beautiful complexity at the level of the brain that he studies, but neurons themselves are pretty darn complex too. This can only add to the story.
Issues at the interface of science and religion
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