Source: NIH/National Institute Of Arthritis And Musculoskeletal And Skin Diseases (http://www.niams.nih.gov)

Scientists studying systemic lupus erythematosus (SLE), a chronic, inflammatory, autoimmune disease whose symptoms can include neurological damage, have discovered a possible molecular mechanism for brain dysfunction in some people with the disease.

With support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health, Betty Diamond, M.D., of Albert Einstein College of Medicine, and her colleagues have found that antibodies that attack the DNA of people with lupus can also attack molecules that bind glutamate, a neurotransmitter involved in nerve cell activity. These antibodies, they discovered, can cause neuron death, and are present in the fluid of the brain and spinal cord (cerebrospinal fluid), possibly affecting brain function.

"For people with lupus and their families, potential cognitive and neuropsychiatric symptoms can be particularly distressing," said NIAMS Director Stephen I. Katz, M.D., Ph.D. "This work will help us move ahead in our understanding of the disease's nervous system complications."

In lupus, antibodies that attack double-stranded DNA are known to contribute to kidney problems. The scientists showed that these antibodies also react with similarly structured molecules called NMDA receptors, channels that control the activity of glutamate, the neurotransmitter that stimulates nerve cells. These same antibodies, moreover, are involved in the programmed death of neurons, and the investigators demonstrated their presence in the cerebrospinal fluid of a lupus patient. These factors, they concluded, showed a possible pathway to the neurological symptoms some people with lupus experience.

"Previous studies have documented cognitive dysfunction in patients with SLE, but there has been no explanation for this symptom," said Dr. Diamond. "The excitement of identifying this potential mechanism for cognitive decline is that it suggests therapeutic possibilities."

Lupus is a rheumatic disease with a variety of symptoms and an unpredictable, individualized course. It may affect multiple organs, with common symptoms that include extreme fatigue, painful or swollen joints, unexplained fever and skin rashes. In some patients, lupus can cause headaches, dizziness, memory disturbances, vision problems, stroke, or changes in behavior.

Lupus usually occurs in young women of childbearing years, but many men and children also develop it. African Americans and Hispanics have a higher frequency of the disease than do Caucasians. Both genetic and environmental factors appear to play a role in lupus.

The study was also supported by the Systemic Lupus Erythematosus (SLE) Foundation and the American Heart Association.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the federal National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases.

For more information about NIAMS, call 1-877-22-NIAMS or visit the NIAMS Web site at http://www.niams.nih.gov.

Ritalin May Cause Long-Lasting Changes In Brain-Cell Function, University At Buffalo Researchers Find
Source: University At Buffalo (http://www.buffalo.edu/)

SAN DIEGO -- Scientists at the University at Buffalo have shown that the drug methylphenidate, the generic form of Ritalin, which physicians have considered to have only short-term effects, appears to initiate changes in brain function that remain after the therapeutic effects have dissipated.

The changes appear to be similar to those that occur with other stimulant drugs such as amphetamine and cocaine, said Joan Baizer, Ph.D., UB professor of physiology and biophysics and senior author of the study. Results of the research were presented Nov. 11, 2001 at the annual meeting of the Society for Neuroscience.

"Clinicians consider Ritalin to be short-acting," said Baizer. "When the active dose has worked its way through the system, they consider it 'all gone.' Our research with gene expression in an animal model suggests that it has the potential for causing long-lasting changes in brain cell structure and function." Ritalin is the drug of choice for the treatment of attention deficit disorder in children.

Previous work in other laboratories has shown that high doses of amphetamine and cocaine switch on certain genes called "immediate early genes" in particular brain cells and that this action causes changes in some aspects of nerve cell function. One of those genes is called "c-fos." Amphetamine and cocaine both cause c-fos activity in the striatum, a brain structure important for both movement and motivation, and the presence of c-fos activity there has been implicated in the mechanism of addiction, Baizer said. The researchers wanted to see if methylphenidate caused c-fos activation in the same parts of the brain, and at the same levels, as the other drugs.

"These data do suggest that there are effects of Ritalin on cell function that outlast the short term and we should sort that out," Baizer said. "There is no indication of tolerance, but we have no idea if there is adaptation to the effects."

Scientists Find 'Nose Plug' in Brain

Johns Hopkins University School of Medicine scientists have discovered the "nose plug" of the brain - the switch that allows us to stop smelling something, even when the odor remains.

"The ability to desensitize to odors is important for our well-being," says Randall Reed, Ph.D., a Howard Hughes Medical Institute (HHMI) investigator and a molecular biologist and neuroscientist in the school's Institute for Basic Biomedical Sciences.

"Odor adaptation is important in telling whether a scent is getting stronger or going away, and it prevents sensory overload. Understanding this process should help us figure out how adaptation affects our perception of odors."

According to two papers published in the December 7th issue of Science, a protein called CNGA4 helps plug the "nose" of odor receptor cells -- neurons whose job is to detect smells and send that information to the brain as an electrical signal. The "nose" is actually a channel in the neurons' membrane that opens when an odor is presented and closes as the neuron becomes desensitized to that smell.

Reed measured the signals from these odor receptor cells in genetically engineered mice and found that mice lacking CNGA4 can't adapt to odors. Other scientists studied the molecule's behavior in laboratory-grown cells and reported that CNGA4 speeds up the "nose's" closing.

In normal mice, as well as in humans, the electrical signal from odor receptor neurons diminishes quickly over time, even when the odor is still present. In addition, the neurons usually produce a much smaller electrical signal if exposed to the same odor twice in a short period of time, says Reed.

Using mice missing CNGA4, a protein believed to be involved in odor sensitivity, Reed and his collaborators from the University of Maryland, Baltimore, found that mice without CNGA4 could sense odors but could not adapt to them. In these mice, the signal from the neurons stayed almost constant, and the response to an odor the second time was identical to that from the initial exposure.

"Adaptation and sensitivity are related, but CNGA4 clearly plays a bigger role in adaptation," says Reed. "We thought we knew what the protein did, but the gene knockout mouse showed us that we didn't. It showed us that the biggest impact of CNGA4 is on odor adaptation, not sensitivity."

Jonathan Bradley, a postdoctoral fellow in neuroscience in HHMI at Johns Hopkins, examined in a separate study the electrical behavior of CNGA4 and the odor channel in isolated cells. The channel opens in response to one molecule (cAMP), allowing charged calcium atoms inside the odor neuron. The channel closes as the calcium entering the cell turns around and inhibits it.

Bradley's experiments showed that when CNGA4 is present, the odor channel closes within a second of opening. Without CNGA4, it takes 100 times longer for enough calcium to bind and close the channel, he says. "We came by CNGA4's involvement by our interest in what the channel is doing from a biology perspective, and they came at it from the biophysical side," says Reed. "It's really nice because we can refer to their detailed work about the mechanism, and they can refer to ours because we have generated the protein's biological effects. This is what science is about."

The scientists are now determining how the lack of CNGA4 affects the mouse's normal behavior and how exactly CNGA4 facilitates calcium binding, Reed noted. Co-authors with Reed are Steven Munger, formerly of Hopkins and now at the University of Maryland, Baltimore; Andrew Lane, Trese Leinders-Zufall and Frank Zufall of the University of Maryland, Baltimore; and Haining Zhong and King-Wai Yau of Johns Hopkins.

Funding was provided by the Howard Hughes Medical Institute, the National Institute on Deafness and Other Communication Disorders, the National Institute of Neurological Disorders and Stroke, and the National Science Foundation. Co-authors with Bradley, who was at the Ecole Normale Superiere in Paris, are Dirk Reuter, now with Sophion Bioscience in Denmark, and Stephan Frings of the Institute for Biological Information Processing in Juelich, Germany. Funding was provided by the Deutsche Forschungsgemeinschaft (German Research Partnership), European Community and the Centre Nationale de la Recherche Scientifique (CNRS, National Center for Scientific Research).

Source: Johns Hopkins

The Evidence
Some of what you are about to read regarding the causes of learning disabilities and attention deficit disorder may at first appear surprising, however, all research included in this web site has been conducted by major medical universities and research agencies and should therefore, be given careful assessment. It is human nature to avoid acknowledgment of practices that may have been conducted innocently for years, but now appear responsible for contributing to neurological harm to our children. However, continued avoidance of the evidence will only allow the problem to continue, with obvious negative consequences upon our children, school systems and society as a whole.

As an explanation for the continued rise in child brain cancers over the past 20-30 years throughout the U.S., the United States EPA has only recently begun initiatives to form a research council to investigate the "combined effects" of modern chemicals as an explanation for the rising rates of brain and neurological cancers among U.S. children.

Problems in EPA's Testing Guidelines
Current chemical testing guidelines set by the E.P.A. requires a chemical company to test a chemical for health effects upon test animals only one chemical at a time. This, unfortunately, is what many scientists state is a serious flaw in judging the safety of a chemical because this is not what our children are exposed to in the real world. In fact, a child is subjected to hundreds of chemicals simultaneously from chemical flavors and preservatives in food - to chemicals in cleaning compounds - cosmetics - plastic vapors in carpeting, paints and upholstery - vehicle exhaust - fabric softeners and chlorine products on bedding while they sleep and pesticides used in schools and the home.

Because of this wide range of exposure, to determine the potential for true "real-life" effects - it would be necessary to test all these compounds simultaneously at low level exposures - and this just isn't being done.

Also, recent information has shown the unborn child is far more vulnerable to developing neurological damage during pregnancy than previously thought - the human brain is growing at over 4,000 cells per second beginning in the fourth week of pregnancy. An increasing number of neurotoxic compounds are being identified in today's modern society (not present 30-50 years ago) which can weaken or damage this brain development process. The effects of these chemical exposures can then become evident in later years as learning disabilities, attention deficit disorders, mental retardation or personality and behavior difficulties such as shyness, hyperactivity, aggression or even violent tendencies and lack of conscience.

Also receiving increased documentation is research showing exposure of the father to various chemical compounds during the 65 days prior to conception (the time required to complete sperm development in the testicles) can increase the risk for various birth defects and symptoms common in learning disability students.

The names given to the science which studies this phenomena are Pregnancy Neurotoxicology, Developmental Neurotoxicology and Behavioral Toxicology.

A study has shown that a rigorously high-fat, low-carbohydrate diet can reduce the number of seizures in children with severe seizure disorders and keep them lower for years after the diet is stopped. Conducted by neurologists at Johns Hopkins Medical Institutions (Baltimore, MD, USA), the study was published in the October 2001 issue of Pediatrics.

The study involved 150 seizure-prone children between the ages of one and 16 who did not respond to at least two different anticonvulsive drugs. They had an average minimum of two seizures per week. Of the total, 83 remained on the ketogenic diet for at least one year. Three years after the last child was enrolled in the study, the researchers gathered data on the current frequency of seizures.

One-third of the original children were either seizure-free or had greater than a 90% reduction in seizures, with 44% being entirely free of medication. The researchers are not certain why the diet works. Many experts believe that the suppression of seizures is related to the build-up and breakdown of ketones, natural metabolites that accumulate in cells programmed to conserve energy.

The ketogenic diet is an excellent alternative for children whose seizures cannot be easily controlled, say the researchers. "What we're seeing is a long-lasting effect for many children who used the diet," noted John Freeman, M.D., one of the Johns Hopkins researchers.

BRAINS REWIRE FROM EXPERIENCES: A NEW AND SUCCESSFUL APPROACH TO TREATING COGNITIVE AND DEVELOPMENTAL DISORDERS
M. L. MacAlpine, Ph.D.

Babies are born with an excess of neurons in their brain, each of which is set to respond to a particular type of sensation or experience. Each time a child interacts with their environment, the neurons that are responsive to those sensations or experiences receive stimulation and begin to make connections.

However, not every experience that a newborn is capable of perceiving will be encountered in any given environment. Some languages, for example, contain sounds that do not exist in others. The brain has a built-in maintenance system that prevents unnecessary neurons from remaining and taking up cortical space.

If the brain does not encounter a particular experience consistently, the neurons dedicated to that sensation eventually die away. The first two years of life are particularly intensive periods for this type of pruning.

After birth (and to some degree before birth), brains are constructed through their experiences with the world. These experiences stimulate neurons to multiply, migrate, and build neural networks. These networks allow an individual to perceive their world, experience feelings, develop skills, and create thoughts. Every brain is unique because every brain encounters different experiences and builds different networks.

Anything that disrupts the brain's ability to experience its environment can affect the neural architecture of the brain. Development can be compromised by blindness or deafness, transient hearing loss related to ear infections or blocked Eustachian tubes, seizures that destroy neural circuits, traumatic brain injury, metabolic or immune disorders that disrupt the brain's ability to form connections, abnormal brain development, a lack of oxygen, prematurity, and even impoverished or neglectful environments.

Fortunately, the brain is also capable of generating new neurons (neurogenesis) and forming new neural connections throughout the lifespan. Experiences with the environment can also be manipulated to enhance neurogenesis and neurodevelopment.

Kids' drawings help doctors diagnose migraines
Reprinted from Healthy News
CHICAGO (AP)

Uncovering the cause of severe headache pain in children can be difficult because there's no definitive test. Diagnosis is normally based on the patient's symptoms and medical history.

Imagine the interest when children who drew images of their headache pain helped doctors better diagnose and treat migraines, showing that pictures sometimes speak louder than words. Pediatric neurologists who analyzed the pictures came to the same diagnoses as a doctor who did regular clinical analysis in nearly nine of 10 cases.

Children who drew images of their headache pain helped doctors better diagnose and treat migraines, showing that pictures sometimes speak louder than words, a study says.

A 10-year-old boy drew a frowning person playing the drums inside a big head, and a 9-year-old boy drew a hammer and chisel pounding crevices into the top of his head. Both were among pictures by 226 children complaining of headaches.

Pediatric neurologists who analyzed the pictures came to the same diagnoses as a doctor who did regular clinical analysis in nearly nine of 10 cases, the study found.

As many as two-thirds of children complain of headaches severe enough to seek medical attention, but diagnosing them can be difficult because there's no definitive test, said Dr. Carl Stafstrom, a University of Wisconsin neurologist who led the study. He said the diagnosis is made based on the patient's symptoms and medical history, and is subject to a doctor's training and judgment.

In addition, children of all ages often have difficulty expressing their symptoms verbally - a problem drawings can help solve.

``It's cheap ... and very valuable,'' Stafstrom said.

An accurate diagnosis is critical, because treatment differs depending on the headache cause, said Stafstrom, whose study appears in the March issue of Pediatrics.

For example, migraines often are treated with prescription drugs, but over-the-counter medication such as ibuprofen often is sufficient for tension headaches, he said.

In the study, patients aged 4 to 19 referred for headaches to a Tufts University neurology clinic drew pictures to describe their pain. Neurologists scored the drawings as migraine or non-migraine, which were then compared with a standard clinical diagnosis from a different doctor.

Pictures featuring drawings consistent with migraine pain, such as pounding hammers and sparkling halo-like auras above the eyes, matched the clinical diagnoses in 87 percent of the cases.

Drawings with nonspecific pain such as a 17-year-old girl's picture of her head being squeezed by a rope represented non-migraine pain such as tension headaches. These drawings matched the non-migraine diagnoses in nearly 91 percent of the cases.

The researchers said drawings alone shouldn't be used to diagnose, but could be done in the waiting room before headache patients are examined.

``For the vast majority of children, headache drawing is an enjoyable exercise that allows the opportunity to express their symptoms and feelings and may afford greater insight into their pain,'' they said.

Our eyes, ears and indeed all our sensory organs send information to our brains in the same way -- as electrical impulses in nerve fibers. New research now suggests that, just after birth, these signals help to wire up the parts of the brain that will decode them.

The brain's auditory cortex decodes sounds and is built differently to the visual cortex. But if signals from the eyes (intended for the visual cortex) are redirected to the auditory cortex they can remold the neurons of their unexpected destination into the shape of the visual cortex. So say Mriganka Sur and colleagues at the Massachusetts Institute of Technology, who have studied the process in new-born ferrets.

How does the brain know whether a particular burst of signaling represents sight or sound? The answer lies in the connections. The brain is wired very precisely so that signals arrive at the correct part of the cortex -- the 'higher' part of the brain that interprets sensory signals, tells the motor system what to do and controls more complex reasoning.

This means that the brain has only to 'know' where a signal came from to interpret it correctly as, say, seeing a banana, rather than hearing a police siren. The different parts of the cortex contain different patterns of neurons. Those in the visual cortex sort images, identify colors, movement, and so on, while neurons in the auditory cortex might be 'tuned' to a particular frequency of sound.

How do these neuronal differences develop? We might expect a cortical 'master plan' to map out the various neural connections needed in each area. But there is another possibility -- the neural fibers arriving at an area of cortex during its development may somehow 'tell' the cortex what to become. Sur's team now show that this second mechanism is particularly important.

New-born ferrets have relatively undeveloped brains, and this offers a window of opportunity to study how the cortex is wired up. Sur's team changed the connections in the ferrets' brains, redirecting visual inputs from the retina to the auditory rather than the visual cortex, as they explain in Nature1. They find that the auditory cortex then takes on many of the properties of the normal visual cortex.

For example, many neurons in the normal visual cortex respond to lines at particular orientations. Neurons that are sensitive to similar orientations sit next to each other, but there are also areas called 'pinwheels' that contain neurons that respond to all orientations.

Sur and colleagues now show that when the auditory cortex receives visual input, it too develops the same kind of orientation map -- complete with pinwheels. So, they deduce that this kind of cortical patterning must depend on sensory inputs, rather than on intrinsic 'programming'.

But what do these ferrets experience? Do they perceive visual signals in the auditory cortex as sights, or as sounds?

Sur's team trained the rewired ferrets to press one of two levers when they saw a light, and the other when they heard a sound. Ferrets shown a light that was only visible by the part of their retina sending signals to the rewired auditory cortex still perceived it as a sight. They did not register it as sound, even though the signal was processed by part of the brain that would normally perceive sounds.

Eight 5-year-old children and 8 young adults repeated a 6-syllable phrase in isolation (baseline condition) and embedded in sentences of low and high syntactic complexity. Lower lip movements for the target phrase were analyzed to produce the spatiotemporal index (STI), an index that reflects the stability of lip movement over 10 repetitions of the phrase.

It was predicted that movement stability would be lower (reflected by higher values of the STI) for the phrase when it was spoken embedded in complex sentences and that, compared to adults, children's movement output would be more negatively affected by increased processing demands. The STI was significantly increased for the phrase spoken in the complex sentences compared to the baseline condition, and STIs of the children were consistently higher than those of the adults across conditions.

These findings provide novel evidence that speech motor planning, execution, or both are affected by processes often considered to be relatively remote from the motor output stage.



Dyslexia and Language Brain Areas
Society for Neuroscience

The learning disability dyslexia, which centers on difficulties in reading, once stumped scientists. Since dyslexics often have good intelligence and even may be gifted in some areas, it was thought that a little motivation could get them on the right track. Now researchers not only know that dyslexia is born of biology, but they also are getting closer to confirming the key brain areas that are affected. New insights will help pinpoint therapies and improve treatment.

The fact that the reading disability, dyslexia - often marked by deficits in the decoding of words - can affect smart people, even some famously knowledgeable, once perplexed scientists. Many assumed that laziness was the cause.

Now research confirms that more than a kick in the butt is needed to jumpstart dyslexics' stall in reading. Studies show a biological basis for this disability that affects millions of American children and adults. One line of research indicates that dyslexics use the brain regions that process written language differently than those without the disorder.

New advances are leading to:
* Earlier diagnosis and treatment of dyslexia.
* Fine-tuning of therapies.
* A better understanding of the nature of dyslexia.

For decades after researchers first described dyslexia, many people contended that it stemmed from a "slacker" attitude. Then, almost a century later, scientists began to unearth hints that the disorder was backed by biology.

In 1979 a report indicated that anatomical abnormalities existed in a dyslexic patient. The left side of the brain of the 20-year-old who died accidentally depicted disorganization in the cells that control language areas.

The finding caused researchers to investigate the brain's involvement in dyslexia.

Many scientists have identified brain regions related to dyslexia with high-tech imaging techniques that photograph the brain in action. The tools have helped them link the disability to speech sound processing, vision and language brain systems.

Today researchers are systematically scrutinizing large numbers of dyslexics to determine which areas of the brain are the most involved and to understand how they relate to each other and contribute to different degrees and varieties of the disability.

Dyslexia's symptoms, which may include deficits in spelling, in recognizing sounds in words, in processing rapid visual information and in saying words quickly when put on the spot, have made it difficult for researchers to tease apart the key brain regions involved.

While the areas most central to the disability are still uncertain, many researchers suspect that the brain areas that control language play a critical role. One of these areas that keeps coming up in studies is the angular gyrus (AG). Located toward the back of the brain, the AG translates the mass of words and letters we encounter in day-to-day life into language.

Some researchers believe the area, which is known to be involved in normal reading, is a key component of an overall "reading pathway" in the brain. Recent studies of a variety of reading and language tasks in dyslexic individuals showed less activity in the AG than those without the disability. The researchers suspect that this part of the brain does not function normally in dyslexics.

Some scientists speculate that dyslexics use the area inadequately and may compensate by using other brain areas, such as the inferior frontal gyrus, which is located in the front of the brain, and is associated with spoken language. For example, dyslexics who say the words they are reading under their breath may rely heavily on this area to get through a passage of text, according to one theory.

Many researchers also are using imaging techniques to see if the behavioral interventions sometimes used to treat those with dyslexia actually modify brain activity. One group is reviewing three separate interventions thought to target either the brain system that processes written language, the speech sound processing system or the visual system.

The results could help confirm the brain areas that are common to the many forms of the disability and lead to a fine-tuning of interventions.


Copyright © 1999 Society for Neuroscience. All rights reserved.

The drugs traditional medicine use to treat hypertension must be taken daily and have side effects. Now, in the most rigorous study of its kind, patients with high blood pressure are being given a series of 12 acupuncture treatments. The study is not yet complete, but initial results show a substantial number of patients have responded with significant reductions in blood pressure. Perhaps most amazing, acupuncture's benefit can be long lasting. Some patients who received the acupuncture treatment nine months ago still have normal blood pressure.

By his own account, Dr. Randal Zusman, Director of blood-pressure medicine at the Massachusetts General Hospital, is a pill pusher. "I am very aggressive in the treatment of high blood pressure using drugs, using pills," he says.

High blood pressure, or hypertension, is a major risk factor for heart attack and stroke. Middle-aged Americans face a staggering 90 percent chance of developing the condition, according to a new report in the Journal of the American Medical Association .

But the drugs used to treat it must be taken daily, usually for a lifetime. And they may have side effects, such as fatigue, depression and dizziness.

So Zusman is looking for alternatives for relieving hypertension. He thinks he may have found one in the ancient Chinese technique of acupuncture. "There is an extensive literature from Asian and Russian communities that acupuncture does indeed lower blood pressure," he says.

American researchers have already shown that special acupuncture needles, when gently inserted into specific points on the skin, can stimulate nerves that reach up into the brain and to cells in the brain that control blood pressure. "There's evidence from our laboratory and many other laboratories to suggest that the cells quiet down after acupuncture," says Dr. John Longhurst professor of medicine at the University of California, Irvine.

When those cells "quiet down," or become less active, blood vessels relax. Clinical Trials Continue

Now, in the most rigorous study of its kind, patients with high blood pressure -- 140 (systolic) over 90 (diastolic) or higher -- are being given a series of 12 acupuncture treatments.

The study is not yet complete, but Zusman is already enthusiastic. "A substantial number of our patients have responded with significant reductions in blood pressure," he says.

Patients like Rip Reeves are also impressed: "In my late 30s, I was probably 145/95; with medication, I got it down to 130/80. And since I've been on acupuncture and not taking medication, I've been averaging 125/75."

Perhaps most amazing, acupuncture's benefit can be long lasting. Some patients who received the acupuncture treatment nine months ago still have normal blood pressure. "The implication," says Zusman, "is that 12 acupuncture treatments over a six-week period will produce a cure."

In this case, the doctors defined "cure" as maintaining normal blood pressure for one year without medication. And that, for some patients, may now be within their reach.