Posts tagged neuroscience

July 19, 2012

(Medical Xpress) — When learning to master complex movements such as those required in surgery, is being physically guided by an expert more effective than learning through trial and error?

Dr. George Van Doorn and a participant in the fMRI

New research by Monash University’s Departments of Psychological Studies and Physiology challenges earlier claims that externally guided (or passive) movement is a superior learning method to self-generated (or active) movement.

In the first study of its kind, researchers discovered that different brain regions become active depending on the type of movement used. Lead researcher Dr. George Van Doorn, head of Psychological Studies, said the findings did not support the view that passive movement was a more effective way to learn.

“There has been much debate over the last 30 years about which form of movement is better,” Dr. Van Doorn said. “We found that active movements result in greater activation in brain areas implicated in higher-order processes such as monitoring and controlling goal-directed behaviour, attention, execution of movements, and error detection.

“Passive movements, in contrast, produced greater activity in areas associated with touch perception, length discrimination, tactile object recognition, and the attenuation of sensory inputs.”

People were tested while making movements themselves, and while being guided.

“Whilst inside a functional Magnetic Resonance Imaging (fMRI) machine, we had people either freely move their index finger around a two-dimensional, raised-line pattern to measure self-generated touch. Or we had an experimenter guide the person’s finger around the pattern, to measure externally generated touch. Using the fMRI, we found that different brain regions become active depending on the type of movement used,” Dr. Van Doorn said.

Dr. Van Doorn said touch was becoming a popular area of investigation, with more scientists contributing to understanding about this important, though under-acknowledged, sensory system.

All researchers involved in this study are located at Monash University’s Gippsland campus. The study findings were presented at EuroHaptics 2012, a major international conference and the primary European meeting for researchers in the field of human haptic sensing and touch-enabled computer applications.

Provided by Monash University

Source: medicalxpress.com

ScienceDaily (July 19, 2012) — By decoding brain activity, scientists were able to “see” that two monkeys were planning to approach the same reaching task differently — even before they moved a muscle.

The obstacle-avoidance task is a variation on the center-out reaching task in which an obstacle sometimes prevents the monkey from moving directly to the target. The monkey must first place a cursor (yellow) on the central target (purple). This was the starting position. After the first hold, a second target appeared (green). After the second hold an obstacle appeared (red box). After the third hold, the center target disappeared, indicating a “go” for the monkey, which then moved the cursor out and around the obstacle to the target. (Credit: Moran/Pearce)

Anyone who has looked at the jagged recording of the electrical activity of a single neuron in the brain must have wondered how any useful information could be extracted from such a frazzled signal.

But over the past 30 years, researchers have discovered that clear information can be obtained by decoding the activity of large populations of neurons.

Now, scientists at Washington University in St. Louis, who were decoding brain activity while monkeys reached around an obstacle to touch a target, have come up with two remarkable results.

Their first result was one they had designed their experiment to achieve: they demonstrated that multiple parameters can be embedded in the firing rate of a single neuron and that certain types of parameters are encoded only if they are needed to solve the task at hand.

Their second result, however, was a complete surprise. They discovered that the population vectors could reveal different planning strategies, allowing the scientists, in effect, to read the monkeys’ minds.

Read more …

ScienceDaily (July 18, 2012) — Researchers at Oregon Health & Science University School of Dentistry have discovered that TDP-43, a protein strongly linked to ALS (amyotrophic lateral sclerosis) and other neurodegenerative diseases, appears to activate a variety of different molecular pathways when genetically manipulated. The findings have implications for understanding and possibly treating ALS and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

ALS affects two in 100,000 adults in the United States annually and the prognosis for patients is grim.The new discovery is published online in G3: Genes, Genomes, Genetics (and the July 2012 print issue of G3).

Using a fruit fly model, the OHSU team genetically increased or eliminated TDP-43 to study its effect on the central nervous system. By using massively parallel sequencing methods to profile the expression of genes in the central nervous system, the team found that the loss of TDP-43 results in widespread gene activation and altered splicing, much of which is reversed by rescue of TDP-43 expression. Although previous studies have implicated both absence and over expression of TDP-43 in ALS, the OHSU study showed little overlap in the gene expression between these two manipulations, suggesting that the bulk of the genes affected are different.

"Our data suggest that TDP-43 plays a role in synaptic transmission, synaptic release and endocytosis," said Dennis Hazelett, Ph.D., lead author of the study. "We also uncovered a potential novel regulation of several pathways, many targets of which appear to be conserved."

Source: Science Daily

ScienceDaily (July 18, 2012) — Researchers from the University of Medicine and Dentistry of New Jersey (UMDNJ), collaborating with scientists from Northwestern University in Illinois, have provided direct experimental evidence that diabetes is linked to the onset of Alzheimer’s disease. The study, published online this week in the Journal of Alzheimer’s Disease, used an experimental model that shows potential as an important new tool for investigations of Alzheimer’s disease and of drugs being developed to treat Alzheimer’s.

UMDNJ researchers Peter Frederikse, PhD, and Chinnaswamy Kasinathan, PhD, collaborated with William Klein, PhD, at Northwestern University, to build on prior studies from the Klein lab and others that indicated close links between Alzheimer’s disease and diabetes. Working with Claudine Bitel and Rajesh Kaswala, students at UMDNJ, the researchers tested whether untreated diabetes would provide a physiological model of Alzheimer neuropathology.

"The results were striking," Frederikse said. "Because we used diabetes as an instigator of the disease, our study shows — for the first time directly — the link between Alzheimer’s and diabetes."

The researchers found substantial increases in amyloid beta peptide pathology — a hallmark of Alzheimer’s disease — in the brain cortex and hippocampus concurrent with diabetes. They also found significant amyloid beta pathology in the retina and by contrast, when diabetes is not present, no observable pathology was detected in either the brain or the retina.

"Second, our study examined the retina, which is considered an extension of the brain, and is more accessible for diagnostic exams," Frederikse added. "Our findings indicate that scientists may be able to follow the onset and progression of Alzheimer’s disease through retinal examination, which could provide a long sought after early-warning sign of the disease."

This experimental model replicated spontaneous formation of amyloid beta “oligomer” assemblies in brain and retina which may help to explain one of the most widely recognized symptoms of Alzheimer’s. “This is exciting,” Klein said. “Oligomers are the neurotoxins now regarded as causing Alzheimer’s disease memory loss. What could cause them to appear and buildup in late-onset Alzheimer’s disease has been a mystery, so these new findings with diabetes represent an important step.”

Previous research indicated that insulin plays an important role in the formation of memories. Once attached to neurons, oligomers cause insulin receptors to be eliminated from the surface membranes, contributing to insulin resistance in the brain. This launches a vicious cycle in which diabetes induces oligomer accumulation which makes neurons even more insulin resistant.

"In light of the near epidemic increases in Alzheimer’s disease and diabetes today, developing a physiological model of Alzheimer neuropathology has been an important goal," Kasinathan added. "It allows us to identify a potential biomarker for Alzheimer’s disease and may also make important contributions to Alzheimer drug testing and development."

Source: Science Daily

7/18/2012

Metabolic syndrome, a term used to describe a combination of risk factors that often lead to heart disease and type 2 diabetes, seems to be linked to lower blood flow to the brain, according to research by the University of Wisconsin School of Medicine and Public Health.

Dr. Barbara Bendlin, researcher for the Wisconsin Alzheimer’s Disease Research Center and an assistant professor of medicine (geriatrics) at the UW School of Medicine and Public Health, said study participants with multiple risk factors connected to metabolic syndrome, including abdominal obesity, high blood pressure, high blood sugar and high cholesterol averaged 15 percent less blood flow to the brain than those in a control group, according to results of brain scans to measure cerebral blood flow.

"We thought the cerebral blood flow measurements of the metabolic syndrome group would be lower, but it was striking how much lower it was," said Bendlin.

Although lower blood flow could result in an eventual reduction in memory skills, Bendlin said it is not known if people with metabolic syndrome will get Alzheimer’s disease.

"Having metabolic syndrome at middle age does have an effect on the brain, and there is some suggestion that if you have lower blood flow, certain types of memory functions are reduced," she said. "The key will be to follow these people over time, because we want to know if lower blood flow will lead to a gradual loss of memory and cognitive skills. But it’s too early to say if these people will develop Alzheimer’s."

The study, presented today at the Alzheimer’s Association International Conference in Vancouver, British Columbia, involved 71 middle-aged people recruited from the Wisconsin Registry for Alzheimer’s Prevention (WRAP). Of this group, 29 met the criteria for metabolic syndrome and 42 did not.

Bendlin said the next steps will be to conduct additional brain scans on people with metabolic syndrome to get more specifics on why they have reduced cerebral blood flow.

"By comparing people with metabolic syndrome with those who don’t, we don’t know which of the risk factors are worst," she said. "Is having a high blood-glucose level worse than having high blood pressure or is it different than having abdominal obesity? All of these risk factors have been linked to increased risk for dementia, but they are clustered together. If we knew which ones were the worst, those would be the ones to target with specific treatments."

Source: Bio-Medicine

July 18, 2012

Drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD) do not appear to have long-term effects on the brain, according to new animal research from Wake Forest Baptist Medical Center.

As many as five to seven percent of elementary school children are diagnosed with ADHD, a behavioral disorder that causes problems with inattentiveness, over-activity, impulsivity, or a combination of these traits. Many of these children are treated with psychostimulant drugs, and while doctors and scientists know a lot about how these drugs work and their effectiveness, little is known about their long-term effects.

Linda Porrino, Ph.D., professor and chair of the Department of Physiology and Pharmacology, along with fellow professor Michael A. Nader, Ph.D., both of Wake Forest Baptist, and colleagues conducted an animal study to determine what the long-lasting effects may be. Their findings were surprising, said Porrino. “We know that the drugs used to treat ADHD are very effective, but there have always been concerns about the long-lasting effects of these drugs,” Porrino said.

"We didn’t know whether taking these drugs over a long period could harm brain development in some way or possibly lead to abuse of drugs later in adolescence."

Findings from the Wake Forest Baptist research are published online this month in the journal Neuropsychopharmacology.

The researchers studied 16 juvenile non-human primates, whose ages were equivalent to 6-to 10-year-old humans. Eight animals were in the control group that did not receive any drug treatment and the other eight were treated with a therapeutic-level dose of an extended-release form of Ritalin, or methylphenidate (MPH), for over a year, which is equivalent to about four years in children. Imaging of the animals’ brains, both before and after the study, was conducted on both groups to measure brain chemistry and structure. The researchers also looked at developmental milestones to address concerns that ADHD drugs adversely affect physical growth.

Once the MPH treatment and imaging studies were concluded, the animals were given the opportunity to self administer cocaine over several months. Nader measured their propensity to acquire the drug and looked at how rapidly and in what amounts, to provide an index of vulnerability to substance abuse in adolescence. As reported in the research paper, they found no differences between groups – monkeys treated with Ritalin during adolescence were not more vulnerable to later drug use than the control animals.

"After one year of drug therapy, we found no long-lasting effects on the neurochemistry of the brain, no changes in the structure of the developing brain. There was also no increase in the susceptibility for drug abuse later in adolescence," Porrino said. "We were very careful to give the drugs in the same doses that would be given to children. That’s one of the great advantages of our study is that it’s directly translatable to children."

Porrino said non-human primates provide exceptional models for developmental research because they undergo relatively long childhood and adolescent periods marked by hormonal and physiological maturation much like humans.

"Our study showed that long-term therapeutic use of drugs to treat ADHD does not cause long-term negative effects on the developing brain, and importantly, it doesn’t put children at risk for substance abuse later in adolescence," she said.

One of the exciting things about this research, Porrino said, is that a “sister” study was conducted simultaneously at John Hopkins with slightly older aged animals and different drugs and their findings were similar. “We feel very confident of the results because we have replicated each other’s studies within the same time frame and gotten similar results,” she said. “We think that’s pretty powerful and reassuring.”

Provided by Wake Forest University Baptist Medical Center

Source: medicalxpress.com