Posts tagged neuroscience

ScienceDaily (July 16, 2012) — Mayo Clinic researchers have found a novel way to monitor real-time chemical changes in the brains of patients undergoing deep brain stimulation (DBS). The groundbreaking insight will help physicians more effectively use DBS to treat brain disorders such as Parkinson’s disease, depression and Tourette syndrome.

The findings are published in the journal Mayo Clinic Proceedings.

Researchers hope to use the discovery to create a DBS system that can instantly respond to chemical changes in the brain. Parkinson’s, Tourette syndrome and depression all involve a surplus or deficiency of neurochemicals in the brain. The idea is to monitor those neurochemicals and adjust them to appropriate levels.

"We can learn what neurochemicals can be released by DBS, neurochemical stimulation, or other stimulation. We can basically learn how the brain works," says author Su-Youne Chang, Ph.D., of the Mayo Clinic Neurosurgery Department. As researchers better understand how the brain works, they can predict changes, and respond before those changes disrupt brain functioning.

Researchers observed the real-time changes of the neurotransmitter adenosine in the brains of tremor patients undergoing deep brain stimulation. Neurotransmitters such as dopamine and serotonin are chemicals that transmit signals from a neuron to a target cell across a synapse.

The team used fast scan cyclic voltammetry (FSCV) to quantify concentrations of adenosine released in patients during deep brain stimulation. The data was recorded using Wireless Instantaneous Neurotransmitter Concentration Sensing, a small wireless neurochemical sensor implanted in the patient’s brain. The sensor, combined with FSCV, scans for the neurotransmitter and translates that information onto a laptop in the operating room. The sensor has previously identified neurotransmitters serotonin and dopamine in tests in brain tissue. This was the first time researchers used this technique in patients.

Tremors are a visual cue that the technique is working; researchers suspect adenosine plays a role in reducing tremors.

Researchers also hope to learn more about conditions without such external manifestations.

"We can’t watch pain as we do tremors," says Kendall Lee, M.D., Ph.D., a Mayo Clinic neurosurgeon. "What is exciting about this electrochemical feedback is that we can monitor the brain without external feedback. So now, we can monitor neurochemicals in the brain and learn about brain processes like pain."

DBS has been used successfully worldwide to treat patients with tremors. However, physicians do not fully understand why DBS works in patients. They know that when DBS electrodes are inserted before electrical stimulation, there is an immediate tremor reduction. Known as the microthalamotomy effect, it is reported in up to 53 percent of patients and known to last as long as a year.

Researchers hope to use the study findings to create a self-contained “smart” DBS system.

"With the stimulator and detection, we can create algorithms and then raise neurotransmitters to a specified level," says Kevin Bennet, a Mayo Clinic engineer who helped create the system. "We can raise these chemicals to appropriate levels, rising and falling with each person throughout their life. Within milliseconds, we can measure, calculate and respond. From the patient’s perspective, this would be essentially instantaneous."

Source: Science Daily

FRIDAY, July 13 (HealthDay News) — Movies often stereotype people with schizophrenia as being violent and unpredictable, says a researcher who claims Hollywood dispenses misinformation about symptoms, causes and treatment of this mental illness.

Hollywood portrayals are often inaccurate, misleading, study shows.

For the study, published in the July issue of Psychiatric Services, Patricia Owen of the psychology department at St. Mary’s University in San Antonio, Texas, reviewed 41 English-language films released between 1990 and 2010 that featured at least one main character with schizophrenia.

Owen found that 83 percent of those characters were portrayed as dangerous or violent to others or themselves. Almost one-third engaged in homicidal behavior, and one-quarter committed suicide, the researcher said.

According to the U.S. National Institute of Mental Health, the risk of violence is small among people with schizophrenia. But suicide risk is higher than average. About 10 percent, mostly young men, do kill themselves, the agency notes.

Delusions, auditory and visual hallucinations, and disorganized speech or thought were displayed by most of the characters, the study author pointed out in a news release from the American Psychiatric Association.

But much more common symptoms of schizophrenia — such as flat affect, lack of speech and lack of motivation — were seen much less frequently.

Although schizophrenia incidence is nearly equal among women and men, almost 80 percent of the characters with schizophrenia were male, the study found.

The review noted, however, the movies did get some characterizations of schizophrenia right. Specifically, about half of the characters had low socioeconomic status, which is consistent with data on the illness. Moreover, about half of the movies depicted or alluded to the use of medication to treat the mental illness. Psychotherapy and group therapy were not portrayed often.

Owen suggested that more research is needed to understand how films influence public perceptions about schizophrenia, and to determine how to increase empathy and understanding.

Films featuring a character with schizophrenia include A Beautiful Mind and Donnie Darko.

Source: DoctorsLounge

ScienceDaily (July 13, 2012) — A new study by University of North Carolina School of Medicine researchers found that 31 percent of children identified as at risk for autism spectrum disorders (ASD) at 12 months received a confirmed diagnosis of ASD by age 3 years.

In addition, 85 percent of the children found to be at risk for ASD based on results from the First Year Inventory (FYI), a 63-item questionnaire filled out by their parents, had some other developmental disability or concern by age three, said Grace Baranek, PhD, senior author of the study and an autism researcher with the Program for Early Autism, Research, Leadership and Service (PEARLS) in the Department of Allied Health Sciences at the UNC School of Medicine.

"These results indicate that an overwhelming majority of children who screen positive on the FYI indeed experience some delay in development by age three that may warrant early intervention," she said.

Lead author of the study, Lauren Turner-Brown, PhD, also a researcher with PEARLS and the Carolina Institute for Developmental Disabilities said, “Identification of children at risk for ASD at 12 months could provide a substantial number of children and their families with access to intervention services months or years before they would otherwise receive a traditional diagnosis.”

The First Year Inventory was developed by Grace Baranek, PhD, Linda Watson, EdD, Elizabeth Crais, PhD and J. Steven Reznick, PhD, who are all researchers with PEARLS. All are also co-authors of the study with Turner-Brown, published online ahead of print on July 10, 2012 by Autism: The International Journal of Research & Practice.

In the study, parents of 699 children who had completed the FYI when their child was 12 months old completed additional screening questionnaires when their child reached age 3. In addition, children who were found to be at risk for ASD based on these measures were invited for in-person diagnostic evaluations.

"These findings are encouraging and suggest promise in the approach of using parent report of infant behaviors as a tool for identifying 12-month-olds who are at risk for an eventual diagnosis of ASD," Turner-Brown said.

Source: Science Daily

ScienceDaily (July 12, 2012) — Negative suggestion can induce symptoms of illness. Nocebo effects are the adverse events that occur during sham treatment and/or as a result of negative expectations. While the positive counterpart — the placebo effect — has been intensively studied in recent years, the scientific literature contains few studies on nocebo phenomena. In the latest issue of Deutsches Ärzteblatt International, Winfried Häuser of the Technical University of Munich and his co-authors present the underlying neurobiological mechanisms and highlight the relevance of the nocebo effect in everyday clinical practice.

Nocebo responses can, for instance, be brought about by unintended negative suggestion on the part of doctors or nurses, e.g., when informing the patient about the possible complications of a proposed treatment. It is also assumed that a certain proportion of the undesired effects of drugs can be attributed to nocebo effects. The mechanisms behind this phenomenon are — as with placebo effects — learning by Pavlovian conditioning and reaction to induced expectations.

What are the consequences for clinical practice? Doctors find themselves in an ethical dilemma between their obligation to tell the patient about the possible side effects of a treatment and their duty to minimize the risk of a medical intervention and thus to avoid triggering nocebo effects. As one possible strategy to solve this dilemma, Häuser et al. suggest emphasizing the tolerability of therapeutic measures. Another option, with the patient’s permission, would be to desist from discussing undesired effects during the patient briefing.

Source: Science Daily

ScienceDaily (July 12, 2012) — University of Kansas researchers have found larger resting pupil size and lower levels of a salivary enzyme associated with the neurotransmitter norepinephrine in children with autism spectrum disorder.

However, even though the levels of the enzyme, salivary alpha-amylase (sAA), were lower than those of typically-developing children in samples taken in the afternoon in the lab, samples taken at home throughout the day showed that sAA levels were higher in general across the day and much less variable for children with ASD.

"What this says is that the autonomic system of children with ASD is always on the same level," Christa Anderson, assistant research professor, said. "They are in overdrive."

The sAA levels of typically-developing children gradually rise and fall over the day, said Anderson, who co-directed the study with John Colombo, professor of psychology.

Norepinephrine (NE) has been found in the blood plasma levels of individuals with ASD but some researchers have questioned whether these levels were just related to the stress from blood draws.

The KU study addressed this by collecting salivary measures by simply placing a highly absorbent sponge swab under the child’s tongue and confirmed that this method of collection did not stress the children by assessing their stress levels through cortisol, another hormone.

Collecting sAA levels has the potential for physicians to screen children for ASD much earlier, noninvasively and relatively inexpensively, said Anderson.

But Anderson and Colombo also see pupil size and sAA levels as biomarkers that could be the physiological signatures of a possible dysfunction in the autonomic nervous system.

"Many theories of autism propose that the disorder is due to deficits in higher-order brain areas," said Colombo. "Our findings, however, suggest that the core deficits may lie in areas of the brain typically associated with more fundamental, vital functions."

The study, published online in the May 29, 2012 Developmental Psychobiology compared children between the ages of 20 and 72 months of age diagnosed with ASD to a group of typically developing children and a third group of children with Down Syndrome.

Both findings address the Centers for Disease Control’s urgent public health priority goals for ASD: to find biological indicators that can both help screen children earlier and lead to better understanding of how the nervous system develops and functions in the disorder.

Source: Science Daily

ScienceDaily (July 12, 2012) — Researchers at Emory University School of Medicine have identified five rare mutations in a single gene that appear to increase the chances that a boy will develop an autism spectrum disorder (ASD).

Mutations in the AFF2 gene, and other genes like it on the X chromosome, may explain why autism spectrum disorders affect four times as many boys as girls.

The mutations in AFF2 appeared in 2.5 percent (5 out of 202) boys with an ASD. Mutations in X chromosome genes only affect boys, who have one X chromosome. Girls have a second copy of the gene that can compensate.

The results were published July 5 in the journal Human Molecular Genetics.

"Our data suggest that AFF2 could be one of the major X-linked risk factors for ASD’s," says senior author Michael Zwick, PhD, assistant professor of human genetics at Emory University School of Medicine.

The finding bolsters a growing consensus among geneticists that rare variants in many different genes contribute significantly to risk for autism spectrum disorders.

The mutations in the AFF2 gene probably do not cause ASDs all by themselves, Zwick says.

"We do not think that the variants we have identified are monogenic causes of autism," he says. "Our data does support the idea that this is an autism susceptibility gene."

In some situations, mutations in a single gene are enough by themselves to lead to a neurodevelopmental disorder with autistic features, such as fragile X syndrome or tuberous sclerosis complex. But these types of mutations are thought to account for a small number of ASD cases.

Recent large-scale genetic studies of autism spectrum disorders have identified several “rare variants” that sharply increase ASD risk. Scientists believe rare variants could explain up to 15 or 20 percent of ASD cases. However, until now no single variant has been found in more than one percent of ASD cases.

Working with Zwick, postdoctoral fellow Kajari Mondal and her colleagues read the sequence of the AFF2 gene in DNA from 202 boys diagnosed with autism spectrum disorders. The patient samples came from the Autism Genetic Resource Exchange and the Simons Simplex Collection.

Tests showed that in four cases, the affected boys had inherited the risk-conferring mutations from their mothers. One boy had a “de novo” (not coming from the parents) mutation. Compared with X-linked genes in unaffected people, mutations in AFF2 were five times more abundant in the boys with ASDs.

The AFF2 gene had already been identified as responsible for a rare inherited form of intellectual disability with autistic features. This effect is seen when the AFF2 gene is deleted or silenced completely.

AFF2 has some similarity to FMR1, the gene responsible for fragile X syndrome. Like FMR1, it can be silenced by a triplet repeat. In these cases, the presence of the triplet repeat (three genetic bases repeated dozens of times) triggers a change in chromosomal structure that prevents the gene from being turned on.

In contrast, the mutations Zwick’s team found are more subtle, slightly changing the sequence of the protein AFF2 encodes. Little is known about the precise function of the AFF2 protein. A related gene in fruit flies called lilliputian also appears to regulate the development of neurons.

Zwick says one of his laboratory’s projects is to learn more about the function of the AFF2 gene, and to probe how the mutations identified by his team affect the function. His team is also working on gauging the extent to which other genes on the X chromosome contribute to autism risk.

Source: Science Daily

ScienceDaily (July 12, 2012) — Diagnosing multiple sclerosis (MS) is a challenge even for experienced neurologists. This autoimmune disease has many symptoms and rarely presents a uniform clinical picture. New scientific findings on the immune response involved in MS could now help improve the diagnosis of this illness. Scientists analyzing the blood of MS patients have discovered antibodies that attack a specific potassium channel in the cell membrane. Potassium channels play an important role in transmitting impulses to muscle and nerve cells and it is exactly these processes that are inhibited in MS patients.

Right: The autoantibody can be seen binding to the membrane of glial cells in the MS serum. By comparison, the image on the left shows a blood sample from a patient with another neurological disease. (Credit: KKNMS)

The results are published in the current issue of the New England Journal of Medicine.

For the first time, scientists in Germany’s multiple sclerosis competence network have been able to identify an antibody that bonds with the potassium channel KIR4.1. “We found this autoantibody in almost half of the MS patients in our study,” explains Bernhard Hemmer, Professor of Neurology at the Klinikum rechts der Isar hospital at Technische Universität München (TUM). The biomarker was not present in healthy patients. The findings could therefore indicate that KIR4.1 is one of the targets of the autoimmune response in MS. Humans and animals without the KIR4.1 channel experience neurological failure and cannot coordinate their movements properly. Furthermore, their bodies do not create sufficient amounts of myelin, a layer of insulation that protects the nerve cells.

KIR4.1 is primarily present in the membrane of glial cells, which are responsible for controlling metabolism in the brain and forming myelin. The neurologists will now be conducting follow-up studies into how KIR4.1 antibodies influence the development of MS. This autoantibody is extremely rare in people with other neurological diseases, making it an important potential diagnostic marker for MS in the future. “This autoantibody could improve diagnosis of MS and help us differentiate it more clearly from other neurological diseases,” continues Hemmer. This will also be the focus of further research.

Source: Science Daily