Medicine Man

What began as an informal presentation by a clinical linguist to a group of philosophers, has led to some surprising discoveries about the communicative language abilities of people with autism.

Several years back, Robert Stainton, now a philosophy professor at The University of Western Ontario, attended a presentation by his long-time friend Jessica de Villiers, a clinical linguist now at the University of British Columbia. The topic was Autism Spectrum Disorder (ASD). De Villiers explained that many individuals with ASD have significant difficulties with what linguists call "pragmatics." That is, people with ASD often have difficulty using language appropriately in social situations. They do not make appropriate use of context or knowledge of what it would be "reasonable to say." Most glaringly, many speakers with ASD have immense trouble understanding metaphor, irony, sarcasm, and what might be intimated or presumed, but not stated.

Drawing on his philosophical training, however, Stainton noticed less-than-obvious pragmatic abilities at work in de Villiers' examples, which were drawn from transcripts of conversations with 42 speakers with ASD - abilities that had been missed by clinicians.

Thus began research to more clearly understand and define the conversational abilities and challenges of people with Autism Spectrum Disorder (ASD). Stainton and de Villiers' research, in collaboration with Peter Szatmari, a clinical psychiatrist at McMaster University, has shown that indeed, many individuals with ASD do have "a rich array of pragmatic abilities."

These researchers do not contest the well-established claim that people with ASD have difficulty with non-literal pragmatics, such as metaphors ("Juliet is the sun") or irony/sarcasm ("Boy, is that a good idea"). They have, however, found that many speakers with ASD do not show the same difficulty with literal pragmatics. An example is the phrase, "I took the subway north" from a transcript of a conversation with a research participant with ASD. The use of the word "the" could indicate there is only one subway in existence going north. "The subway" could also be referring to a subway car, a subway system or a subway tunnel. Taking account of the context and the listener's expectations, however, the individual using the phrase was able to convey the specific meaning he intended. That is, he used pragmatics effectively.

In short, Stainton and his colleagues produced surprising evidence to show that speakers with ASD use and understand pragmatics in cases of literal talk, as in the subway example.

Stainton, who is also Acting Associate Dean of Research in the Faculty of Arts and Humanities at Western, says, "It is especially gratifying and encouraging, because this is an Arts and Humanities contribution to clinical research. Without a philosophical perspective, this discovery might not have been made."

Related research allowed de Villiers and Szatmari to develop a rating scale of pragmatic abilities that can be used in the clinical assessment of people with ASD. Stainton says, "In the short term, their new tool will help identify where an individual fits on that spectrum. In the longer term, however, by making use of recent results in philosophy of language, it may contribute to our theoretical understanding of the boundary between knowledge of the meanings of words, and non-linguistic abilities - specifically pragmatics."

Stainton believes that both clinicians who work with people with ASD, and language theorists who are interested in pragmatics for philosophical reasons, will find these results striking.

http://www.uwo.ca/

Parents of children with autism are increasingly turning to sensory integration treatment to help their children deal with the disorder, and they're seeing good results. In 2007, 71 percent of parents who pursued alternatives to traditional treatment used sensory integration methods, and 91 percent found these methods helpful.

A new study from Temple University researchers, presented this month at the American Occupational Therapy Association's 2008 conference, found that children with autistic spectrum disorders who underwent sensory integration therapy exhibited fewer autistic mannerisms compared to children who received standard treatments. Such mannerisms, including repetitive hand movements or actions, making noises, jumping or having highly restricted interests, often interfere with paying attention and learning.

The children assigned to the sensory integration intervention group also reached more goals specified by their parents and therapists, said study authors Beth Pfeiffer, Ph.D., OTR/L, BCP, and Moya Kinnealey, Ph.D., OTR/L, from the Occupational Therapy Department in Temple University's College of Health Professions. The children made progress toward goals in the areas of sensory processing/regulation, social-emotional and functional motor tasks.

Sensory integration is the ability of the brain to properly integrate and adapt to the onslaught of information coming in through the senses. Dysfunction in this area makes it difficult for people with autism to adapt to and function like others in their environment. They may be hypersensitive to sound or touch, or unable to screen out distracting noise or clothing textures. Their response might be impulsive motor acts, making noises or running away.

Pfeiffer and Kinnealey are part of a group of researchers seeking to bring more scientific understanding to occupational therapy using a sensory integration approach.

"It's been heavily documented that children on the autistic spectrum have differences in the way they process sensory information and respond motorically," Pfeiffer said. "While more families are seeking out the sensory integration approach because of its positive results, more research is needed to scientifically establish its effectiveness."

Children receiving sensory integration therapy typically participate in sensory-based activities to enable them to better regulate their behavioral responses to sensations and situations that they find disturbing or painful. A child who is oversensitive to light touch may enjoy rolling and playing in a giant foam pillow, after which he might be more able to calmly explore, touch and play with other textures. This in turn makes self-care such as dressing and washing and classroom activities that require touch more manageable.

Interpreting the child's behavior as intentional and controllable and not recognizing the underlying cause and hypersensitivities is common in educational and home settings, but is an approach that Kinnealey discourages as stressful for the child.

The study took place this past summer at a camp near Allentown, Pa., for children with autism. Participants were between the ages of 6 and 12 years old and diagnosed with autism or Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS).

One group (17) received traditional fine motor therapy and the other group (20) received sensory integration therapy. Each child received 18 treatment sessions over a period of six weeks.

A statistician randomly assigned the participants to groups; this information was provided to the project coordinator at the site. The primary researchers were blinded to group assignment and served as evaluators before and after the study.

Parents were also blinded to the interventions that their children were assigned to and were not on site. However, there was the potential for the verbal children to talk about the activities that they participated in, which may have influenced the blinding for the parents.

For their outcome data, researchers used a series of scales that measure behavior. While both groups showed significant improvements, the children in the sensory integration group showed more progress in specific areas at the end of the study.

"This pilot study provided a foundation for how we should design randomized control trials for sensory integration interventions with larger sample sizes," Pfeiffer said. "Specifically, it identified issues with measurement such as the sensitivity of evaluation tools to measure changes in this population.

"Sensory integration treatment is a widely used intervention in occupational therapy. There is a real need for research such as randomized control trials to validate what we are doing with sensory integration in the profession," she added.

http://www.temple.edu/

Shape matters, even in hearing. Specifically, it is the shape of the cochlea - the snail-shell-shaped organ in the inner ear that converts sound waves into nerve impulses that the brain deciphers - which proves to be surprisingly important.

A research published online last week in the Proceedings of the National Academy of Sciences establishes a direct link between the cochlea's curvature and the low-frequency hearing limit of more than a dozen different mammals.

The relationship will be useful in conservation to estimate the impact that the noises of human activities are having on animals like Siberian tigers, polar bears and marine mammals that won't sit still for hearing tests. It also can provide new information about the hearing of extinct mammals, like mammoths and saber-toothed tigers, and, in so doing, may contribute new insights into how the sense of hearing evolved.

"It turns out that it is the curvature of the cochlea, not its size, that is highly correlated to the low-frequency hearing limit," says Daphne Manoussaki, assistant professor of mathematics at Vanderbilt University, who headed the new study with Richard S. Chadwick, a section chief at the National Institute on Deafness and Other Communication Disorders (one of the National Institutes of Health, or NIH).

Spiral-shaped cochleae are exclusive to mammals. Birds and reptiles generally have plate-like or slightly curved versions of this critical organ, limiting the span of octaves that they can hear. Animals with tightly coiled cochleae tend to have greater hearing ranges, but previous attempts to associate these auditory effects with the physical characteristics of the cochlea have proven unsatisfactory because they did not take a critical acoustic effect into account.

In 2006 Manoussaki and her NIH collaborators published a paper proposing that the helical shape of the cochlea enhances low-frequency sounds through an effect analogous to the well-known "whispering gallery effect" in which soft sounds that travel along curved walls in a large chamber remain loud enough that they can be heard clearly on the opposite side of the room.

When sound waves enter the ear, they strike the eardrum and cause it to vibrate. Tiny bones in the ear amplify and transmit these vibrations to the fluid in the cochlea, creating pressure waves that travel along a narrowing canal in the coiled tube-like organ. The canal is one of two main chambers that are created by an elastic membrane that runs the length of the cochlea. The mechanical properties of this "basilar" membrane vary from very stiff at the broad, outer end to increasingly flexible toward the inner end as the chambers narrow. The basilar membrane's graded properties cause the waves to grow and then die away. Different frequencies peak at different positions along the membrane.

Sensory cells are attached to the basilar membrane and have tufts of tiny hairs called stereocilia that stick up into adjacent structures in the canal. As the basilar membrane moves it tilts the sensory cells, causing the stereocilia to bend. The motion generates electric signals that travel along the auditory nerve to the brain. As a result, the sensory cells near the outer end of the cochlea detect high-pitched sounds, like the notes of a piccolo, while those at the inner end of the spiral detect lower-frequency sounds, like the booming of a bass drum.

This mechanical ordering of response from high to low frequencies works in the same fashion whether the cochlear tube is laid out straight or coiled in a spiral. But Manoussaki's calculations predicted that the spiral shape causes the energy in the low-frequency waves to accumulate against the outside edge of the chamber. This uneven energy distribution, in turn, causes the membrane to move more toward the outer wall of the chamber, enhancing the bending of the stereocilia. The enhancement is strongest at the apex of the spiral, where the lowest frequencies are detected. Manoussaki and her collaborators calculated that the increase in the sound pressure level can be as much as 20 decibels, equivalent to the difference between the aural ambience of a quiet restaurant and a busy street.

"The idea that the cochlea's curvature has a significant effect on hearing has been quite controversial for many years," says Darlene R. Ketten, a senior scientist at Woods Hole Oceanographic Institution and assistant professor at the Harvard Medical School, who participated in the current study. "Curvature was often dismissed or, when examined, the theories were not entirely satisfactory. Now we have a theory that we have confirmed with a number of concrete examples using real ear shapes and hearing abilities."

Ketten provided Manoussaki and her collaborators with high-resolution CT scans of the cochleae of a number of different species of land and marine mammals. Together with her biophysicist colleagues, Manoussaki analyzed these shapes and found that low- frequency hearing limits of species ranging from mice to cats to cows to whales varied in step with the ratio of the radii of curvatures at their cochlea's base to that of its apex. This ratio varies from about two to nine: The larger it is the lower the frequencies that the animal can hear.

"This makes sense because the bigger the ratio, the tighter the spiral is wound and more of the sound wave energy in the low-frequency waves is forced against the cochlea's walls," Manoussaki says.

Animals like mice, which have a radii ratio of about two, can't hear much below 1000 hertz (Hz). Species like cows and elephants, which have a ratio of about nine, hear sounds as low as 20 Hz. The power of this approach is illustrated by the cat, guinea pig and sea lion. The cochlea of the cat is longer than that of the guinea pig, but the guinea pig has a ratio of 7.2 and can hear down to 47 Hz, while the cat, with a smaller ratio of 6.2, has a higher threshold of 55 Hz. Similarly, the sea lion has a basilar membrane three times as long as that of the guinea pig. But its radii ratio is 5.2, lower than either the cat or the guinea pig, and it cannot make out sounds below 180 Hz. (This limit is for the sea lion's hearing in air; under water it can hear down to 200 Hz.)

"What I like about this is that a macroscopic feature of the ear has such a major effect on our hearing," says Manoussaki. "As colleagues have pointed out, so much research today is done at the genetic and cellular level that you don't often see cases like this where simple geometry proves to be so important."

http://www.vanderbilt.edu/

Advance directives, or living wills, may not effectively honor end-of-life wishes because life-sustaining treatment preferences often change without people being aware of the changes, according to a new study co-authored by UC Irvine researchers Peter Ditto and Elizabeth Loftus.

False memories can play a significant role in the discrepancy between an individual's true preferences for end-of-life treatment and what is instructed in their living will. Life-sustaining treatment preferences often change as people age or experience new health problems, and advance directive forms typically remind people of their right to update their directives if their wishes change. This assumes that people recognize when their wishes about end-of-life treatment have changed, and remember that their current wishes are different from those documented in their living will.

"Living wills are a noble idea and can often be very helpful in decisions that must be made near the end of life. But the notion that you can just fill out a document and all your troubles will be solved, a notion that is frequently reinforced in the popular media, is seriously misguided," said Peter Ditto, professor of psychology and social behavior at UCI.

In research reported in the current issue of the American Psychological Association journal Health Psychology, a sample of 401 adults older than 65 were interviewed about which life-sustaining treatments they would want if they were seriously ill. They were interviewed again 12 months later to test their recall of earlier decisions. About one-third of participants changed their wishes regarding medical treatment such as CPR and "tube feeding" over the course of the year, and in 75 percent of these cases, participants falsely remembered that their original views on the issues matched their new ones.

Interviewers also talked to individuals empowered to make medical decisions if the study subjects were no longer able. These potential surrogate decision makers were even less sensitive to changes in their loved one's wishes, showing false memories in 86 percent of cases.

"On a policy level, these results suggest that living wills should have an 'expiration date.' People can't be counted upon to update their directives as their wishes change because they often have no awareness that their wishes have changed," Ditto said. "On a more personal level, our research stresses the importance of maintaining an ongoing dialogue among individuals, their families and their physicians about end-of-life treatment options," he continued.

http://www.uci.edu/

Scientists from deCODE genetics report the discovery of two common single-letter variants (SNPs) on chromosome 5 of the human genome that are associated with risk of estrogen receptor-positive (ER+) breast cancer.

More than 60% of the general population carry at least one copy of the risk variant of the most important SNP, called rs4415084, and women who have inherited the variant from both parents are at approximately 50% greater risk of developing ER+ breast cancer than women who have not inherited the variant. The second variant is located nearby and occurs only in tandem with the first, adding slight risk of the disease. Although these variants confer modest risk, they are so common that they are estimated to account for approximately 11% of breast cancers overall. The paper, 'Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer,' is published today in the online edition of Nature genetics, at www.nature.com/ng.

With this latest discovery, the genetic factors underpinning a very significant proportion of inherited risk of ER+ breast cancer have now been elucidated. Common variants previously discovered by deCODE on chromosomes 2q35 and 16q12 are together involved in an estimated 25% of ER+ breast cancers. The analysis in today's paper also reveals that a fourth known set of variants, located on chromosome 10q26 and accounting for approximately 16% of breast cancers, appear to confer risk exclusively of ER+ tumors. deCODE is applying these variants as the basis for a DNA-based reference laboratory risk-assessment test the company plans to launch in the coming months. Such a test will allow for the identification of women who may benefit from regular screening with standard as well as new, high-resolution technologies. The American Cancer Society now recommends that women who are at a 20-50% above- average risk of breast cancer should consider undergoing annual magnetic- resonance imaging (MRI) scans as well as mammograms.

"Within the past two years we have identified specific sequence variants that underlie much of the inherited risk of the common forms of breast cancer, the most frequently diagnosed cancer in women. And we have now reached a long awaited tipping point in this progress: the ability to identify, through a simple genetic test, a large proportion of women who are at a clinically- meaningful risk of the disease. The rationale for such testing is all the more compelling in ER+ cancers, since drugs such as tamoxifen have been shown to be successful in preventing as well as treating these cancers, and other drugs now in development may prove to be safe as long-term prophylactic therapy as well. deCODE's pioneering work in this field has also demonstrated that ER+ and ER- breast cancer appear to have distinct genetic bases, a phenomenon which may open the way to a better understanding of the nature, treatment and prevention of breast cancer in general. One of the most pressing next steps in this research is to analyze these results in large cohorts of women of non- European descent," said Kari Stefansson, CEO of deCODE.

deCODE made today's discovery through the analysis of genotypic data from a total of nearly 40,000 patients and control subjects from five countries. The deCODE team analyzed both genome-wide data on some 300,000 SNPs, supplemented by data on a much smaller number of SNPs on chromosome 5p12.

http://www.decode.com