Neuroscience

Non-invasive brain stimulation techniques aimed at mental and neurological conditions include transcranial magnetic stimulation (TMS) for depression, and transcranial direct current (electrical) stimulation (tDCS), shown to improve memory. Transcranial ultrasound stimulation (TUS) has also shown promise.

Ultrasound consists of mechanical vibrations, like sound, but with frequencies far greater than the upper limit of human hearing, around 20 thousand to 20 million cycles per second (20 kilohertz to 20 megahertz). Ultrasound vibrations penetrate bodily tissue including bone, and are widely used to image anatomical structures via echo effects, e.g. visualizing unborn babies in mothers’ wombs, and organs, blood vessels, nerves and other structures in medical procedures. Virtually every part of the body, including the brain, has been safely imaged with low to moderate intensity ultrasound.

High intensity, focused ultrasound can damage tissue by heating and cavitation, and has been used to ablate tumors and other lesions. ‘Sub-thermal’ ultrasound can safely stimulate neural tissue. In 2002 a UCLA group led by Alexander Bystritsky noticed beneficial side effects in psychiatric patients whose brains were imaged by TUS. A team led by Virginia Tech’s W. Jamie Tyler has shown TUS-induced behavioral and electrophysiological changes in animals. A Harvard group led by S-S Yoo has used focused ultrasound aimed at mouse motor cortex to wag the mouse’s tail. But clinical trials of TUS aimed at human mental states have been lacking.

Now, in an article in the journal Brain Stimulation, a group from the Departments of Anesthesiology and Radiology at the University of Arizona Medical Center in Tucson, Arizona has investigated TUS for modulating mental states in a pilot study in human volunteers suffering from chronic pain. A clinical ultrasound imaging device (General Electric LOGIQe) was used, with the ultrasound probe applied at the scalp overlying the brain’s temporal and frontal cortex (visible on the imaging screen). In random order, each subject received two 15 second exposures: sham/placebo, and 8 megahertz ultrasound (undetectable to subjects). Following exposure, subjects reported (by visual analog scales) significant improvement in mood both 10 minutes and 40 minutes after TUS, but not after sham/placebo. In a followup study (led by University of Arizona psychologists Jay Sanguineti and John JB Allen) preliminary results suggest 2 megahertz TUS (which traverses skull more readily) may be more effective in mood enhancement than 8 megahertz TUS.

The mechanism by which TUS can affect mental states is unknown (as is the mechanism by which the brain produces mental states). Tyler proposed TUS acts by vibrational stretching of neuronal membranes and/or extracellular matrix, but two recent papers from the group of Anirban Bandyopadhyay at National Institute of Material Sciences (NIMS) in Tsukuba, Japan (Sahu et al. [2013] Appl. Phys. Letts.; Sahu et al [2013] Biosensors and Bioelectronics) have suggested another possibility. The NIMS group used nanotechnology to study conductive properties of individual microtubules, protein polymers of tubulin (the brain’s most prevalent protein). Major components of the neuronal cytoskeleton, microtubules grow and extend neurons, form and regulate synapses, are disrupted in Alzheimer’s disease, and theoretically linked to information processing, memory encoding and mental states. Bandyopadhyay’s NIMS group found that microtubules have remarkable electronic conductive properties when excited at certain specific resonant frequencies, e.g. in the low megahertz, precisely the range of TUS.

Dr. Stuart Hameroff, lead author on the new TUS study, said: “This suggests TUS may stimulate natural megahertz resonances in brain microtubules, enhancing not only mood and conscious mental states, but perhaps also microtubule functions in synaptic plasticity, nerve growth and repair. We plan further studies of TUS on traumatic brain injury, Alzheimer’s disease and post-traumatic stress disorders. ‘Tuning the tubules’ may help a variety of mental states and cognitive disorders.”

The instability of “white matter” in humans may contribute to greater cognitive decline during the aging of humans compared with chimpanzees, scientists from Yerkes National Primate Research Center, Emory University have found.

Yerkes scientists have discovered that white matter — the wires connecting the computing centers of the brain — begins to deteriorate earlier in the human lifespan than in the lives of aging chimpanzees.

This was the first examination of white matter integrity in aging chimpanzees. The results were published April 24 and are available online before print in the journal Neurobiology of Aging.

"Our study demonstrates that the price we pay for greater longevity than other primates may be the unique vulnerability of humans to neurodegenerative disease," says research associate Xu (Jerry) Chen, first author of the paper. “The breakdown of white matter in later life could be part of that vulnerability.” 

Both humans’ longer life spans and distinctive metabolism could lie behind the differences in the patterns of brain aging, says co-author Todd Preuss, PhD, associate research professor in Yerkes’ Division of Neuropharmacology and Neurologic Diseases.

“White matter integrity actually peaks around the same absolute age in both chimpanzees and humans, but humans may experience more degradation because they live longer. Perhaps the need to retain brain capacity late in life is one reason increased brain size was selected for in human evolution,” Preuss says.  

The senior author is James Rilling, PhD, Yerkes researcher, associate professor of anthropology at Emory and director of the Laboratory for Darwinian Neuroscience. Collaborators at the University of Oslo also contributed to the paper.

In the brain, gray matter represents information processing centers, while white matter represents wires connecting these centers. White matter looks white because it is made up of myelin, a fatty electrical insulator that coats the axons of neurons.

If myelin deteriorates, neurons’ electrical signals are not transmitted as effectively, which contributes to cognitive decline. Myelin breakdown has been linked with cognitive decline both in healthy aging and in the context of Alzheimer’s disease.

The team’s data show that white matter integrity, as measured through a form of magnetic resonance imaging (MRI), peaks at age 31 in chimpanzees and at age 30 in humans. The average lifespan of chimpanzees is between 40 to 45 years, although in zoos or research facilities some have lived until 60. For comparison, human life expectancy in some developed countries is more than 80 years.

"The human equivalent of a 31 year old chimpanzee is about 47 years," Rilling says. "Extrapolating from chimpanzees, we could expect that human white matter integrity would peak at age 47, but instead it peaks and begins to decline at age 30."

The researchers collected MRI scans from 32 female chimpanzees and 20 female rhesus macaques and compared them with a pre-existing set of scans from human females. They used diffusion-weighted imaging (a form of MRI) to examine age-related changes in white matter integrity.

Diffusion-weighted imaging picks up microscopic changes in white matter by detecting directional differences in the ability of water molecules to diffuse. When the myelin coating of axons breaks down, water molecules in the brain can diffuse more freely, especially in directions perpendicular to axon bundles, Chen says.

Scientists at Washington University School of Medicine in St. Louis have helped identify many of the biomarkers for Alzheimer’s disease that could potentially predict which patients will develop the disorder later in life. Now, studying spinal fluid samples and health data from 201 research participants at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center, the researchers have shown the markers are accurate predictors of Alzheimer’s years before symptoms develop.

“We wanted to see if one marker was better than the other in predicting which of our participants would get cognitive impairment and when they would get it,” said Catherine Roe, PhD, research assistant professor of neurology. “We found no differences in the accuracy of the biomarkers.”

The study, supported in part by the National Institute on Aging, appears in Neurology.

The researchers evaluated markers such as the buildup of amyloid plaques in the brain, newly visible thanks to an imaging agent developed in the last decade; levels of various proteins in the cerebrospinal fluid, such as the amyloid fragments that are the principal ingredient of brain plaques; and the ratios of one protein to another in the cerebrospinal fluid, such as different forms of the brain cell structural protein tau.

The markers were studied in volunteers whose ages ranged from 45 to 88. On average, the data available on study participants spanned four years, with the longest recorded over 7.5 years.

The researchers found that all of the markers were equally good at identifying subjects who were likely to develop cognitive problems and at predicting how soon they would become noticeably impaired.

Next, the scientists paired the biomarkers data with demographic information, testing to see if sex, age, race, education and other factors could improve their predictions.

“Sex, age and race all helped to predict who would develop cognitive impairment,” Roe said. “Older participants, men and African Americans were more likely to become cognitively impaired than those who were younger, female and Caucasian.”

Roe described the findings as providing more evidence that scientists can detect Alzheimer’s disease years before memory loss and cognitive decline become apparent.

“We can better predict future cognitive impairment when we combine biomarkers with patient characteristics,” she said. “Knowing how accurate biomarkers are is important if we are going to some day be able to treat Alzheimer’s before symptoms and slow or prevent the disease.”

Clinical trials are already underway at Washington University and elsewhere to determine if treatments prior to symptoms can prevent or delay inherited forms of Alzheimer’s disease. Reliable biomarkers for Alzheimer’s should one day make it possible to test the most successful treatments in the much more common sporadic forms of Alzheimer’s.

Human intelligence cannot be explained by the size of the brain’s frontal lobes, say researchers.

Research into the comparative size of the frontal lobes in humans and other species has determined that they are not - as previously thought - disproportionately enlarged relative to other areas of the brain, according to the most accurate and conclusive study of this area of the brain.

It concludes that the size of our frontal lobes cannot solely account for humans’ superior cognitive abilities.

The study by Durham and Reading universities suggests that supposedly more ‘primitive’ areas, such as the cerebellum, were equally important in the expansion of the human brain. These areas may therefore play unexpectedly important roles in human cognition and its disorders, such as autism and dyslexia, say the researchers.

The study is published in the Proceedings of the National Academy of Sciences (PNAS) today.

The frontal lobes are an area in the brain of mammals located at the front of each cerebral hemisphere, and are thought to be critical for advanced intelligence.

Lead author Professor Robert Barton from the Department of Anthropology at Durham University, said: “Probably the most widespread assumption about how the human brain evolved is that size increase was concentrated in the frontal lobes.

"It has been thought that frontal lobe expansion was particularly crucial to the development of modern human behaviour, thought and language, and that it is our bulging frontal lobes that truly make us human. We show that this is untrue: human frontal lobes are exactly the size expected for a non-human brain scaled up to human size.

"This means that areas traditionally considered to be more primitive were just as important during our evolution. These other areas should now get more attention. In fact there is already some evidence that damage to the cerebellum, for example, is a factor in disorders such as autism and dyslexia."

The scientists argue that many of our high-level abilities are carried out by more extensive brain networks linking many different areas of the brain. They suggest it may be the structure of these extended networks more than the size of any isolated brain region that is critical for cognitive functioning.

Previously, various studies have been conducted to try and establish whether humans’ frontal lobes are disproportionately enlarged compared to their size in other primates such as apes and monkeys. They have resulted in a confused picture with use of different methods and measurements leading to inconsistent findings.

The Durham and Reading researchers, funded by The Leverhulme Trust, analysed data sets from previous animal and human studies using phylogenetic, or ‘evolutionary family tree’, methods, and found consistent results across all their data. They used a new method to look at the speed with which evolutionary change occurred, concluding that the frontal lobes did not evolve especially fast along the human lineage after it split from the chimpanzee lineage.

Finding of disrupted brain gene orchestration gives first direct evidence of circadian rhythm changes in depressed brains, opens door to better treatment

Every cell in our bodies runs on a 24-hour clock, tuned to the night-day, light-dark cycles that have ruled us since the dawn of humanity. The brain acts as timekeeper, keeping the cellular clock in sync with the outside world so that it can govern our appetites, sleep, moods and much more.

But new research shows that the clock may be broken in the brains of people with depression — even at the level of the gene activity inside their brain cells.

It’s the first direct evidence of altered circadian rhythms in the brain of people with depression, and shows that they operate out of sync with the usual ingrained daily cycle. The findings, in the Proceedings of the National Academy of Sciences, come from scientists from the University of Michigan Medical School and other institutions.

The discovery was made by sifting through massive amounts of data gleaned from donated brains of depressed and non-depressed people. With further research, the findings could lead to more precise diagnosis and treatment for a condition that affects more than 350 million people worldwide.

What’s more, the research also reveals a previously unknown daily rhythm to the activity of many genes across many areas of the brain – expanding the sense of how crucial our master clock is.

In a normal brain, the pattern of gene activity at a given time of the day is so distinctive that the authors could use it to accurately estimate the hour of death of the brain donor, suggesting that studying this “stopped clock” could conceivably be useful in forensics. By contrast, in severely depressed patients, the circadian clock was so disrupted that a patient’s “day” pattern of gene activity could look like a “night” pattern — and vice versa.

The work was funded in large part by the Pritzker Neuropsychiatric Disorders Research Fund, and involved researchers from the University of Michigan, University of California’s Irvine and Davis campuses, Weill Cornell Medical College, the Hudson Alpha Institute for Biotechnology, and Stanford University.

The team uses material from donated brains obtained shortly after death, along with extensive clinical information about the individual. Numerous regions of each brain are dissected by hand or even with lasers that can capture more specialized cell types, then analyzed to measure gene activity. The resulting flood of information is picked apart with advanced data-mining tools.

Lead author Jun Li, Ph.D., an assistant professor in the U-M Department of Human Genetics, describes how this approach allowed the team to accurately back-predict the hour of the day when each non-depressed individual died – literally plotting them out on a 24-hour clock by noting which genes were active at the time they died. They looked at 12,000 gene transcripts isolated from six regions of 55 brains from people who did not have depression.

This provided a detailed understanding of how gene activity varied throughout the day in the brain regions studied. But when the team tried to do the same in the brains of 34 depressed individuals, the gene activity was off by hours. The cells looked as if it were an entirely different time of day.

“There really was a moment of discovery,” says Li, who led the analysis of the massive amount of data generated by the rest of the team and is a research assistant professor in U-M’s Department of Computational Medicine at Bioinformatics. “It was when we realized that many of the genes that show 24-hour cycles  in the normal individuals were well-known circadian rhythm genes – and when we saw that the people with depression were not synchronized to the usual solar day in terms of this gene activity. It’s as if they were living in a different time zone than the one they died in.”

Huda Akil, Ph.D., the co-director of the U-M Molecular & Behavioral Neuroscience Institute and co-director of the U-M site of the Pritzker Neuropsychiatric Disorders Research Consortium, notes that the findings go beyond previous research on circadian rhythms, using animals or human skin cells, which were more easily accessible than human brain tissues.

“Hundreds of new genes that are very sensitive to circadian rhythms emerged from this research — not just the primary clock genes that have been studied in animals or cell cultures, but other genes whose activity rises and falls throughout the day,” she says. “We were truly able to watch the daily rhythm play out in a symphony of biological activity, by studying where the clock had stopped at the time of death. And then, in depressed people, we could see how this was disrupted.”

Now, she adds, scientists must use this information to help find new ways to predict depression, fine-tune treatment for each depressed patient, and even find new medications or other types of treatment to develop and test. One possibility, she notes, could be to identify biomarkers for depression – telltale molecules that can be detected in blood, skin or hair.

And, the challenge of determining why the circadian clock is altered in depression still remains. “We can only glimpse the possibility that the disruption seen in depression may have more than one cause. We need to learn more about whether something in the nature of the clock itself is affected, because if you could fix the clock you might be able to help people get better,” Akil notes.

The team continues to mine their data for new findings, and to probe additional brains as they are donated and dissected. The high quality of the brains, and the data gathered about how their donors lived and died, is essential to the project, Akil says. Even the pH level of the tissue, which can be affected by the dying process and the time between death and freezing tissue for research, can affect the results. The team also will have access to blood and hair samples from new donors.

Researchers at Georgetown University Medical Center have used tiny doses of a leukemia drug to halt accumulation of toxic proteins linked to Parkinson’s disease in the brains of mice. This finding provides the basis to plan a clinical trial in humans to study the effects.

They say their study, published online May 10 in Human Molecular Genetics, offers a unique and exciting strategy to treat neurodegenerative diseases that feature abnormal buildup of proteins in Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Huntington disease and Lewy body dementia, among others. 

“This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell. By clearing intracellular proteins, the drug prevents their accumulation in pathological inclusions called Lewy bodies and/or tangles, and also prevents amyloid secretion into the extracellular space between neurons, so proteins do not form toxic clumps or plaques in the brain,” says the study’s senior investigator, neuroscientist Charbel E-H Moussa, MB, PhD. Moussa heads the laboratory of dementia and Parkinsonism at Georgetown.

When the drug, nilotinib, is used to treat chronic myelogenous leukemia (CML), it forces cancer cells into autophagy — a biological process that leads to death of tumor cells in cancer.

“The doses used to treat CML are high enough that the drug pushes cells to chew up their own internal organelles, causing self-cannibalization and cell death,” Moussa says. “We reasoned that small doses — for these mice, an equivalent to one percent of the dose used in humans — would turn on just enough autophagy in neurons that the cells would clear malfunctioning proteins, and nothing else.”

Moussa, who has long sought a way to force neurons to clean up their garbage, came up with the idea of using cancer drugs that push autophagy in tumors to help diseased brains. “No one has tried anything like this before,” he says.

Moussa, and his two co-authors — graduate student Michaeline Hebron and Irina Lonskaya, PhD, a postdoctoral researcher in Moussa’s lab — searched for cancer drugs that can cross the blood-brain barrier. They discovered two candidates — nilotinib and bosutinib, which is also approved to treat CML. This study discusses experiments with nilotinib, but Moussa says that use of bosutinib is also beneficial.  

The mice used in this study over-express alpha-Synuclein, the protein that builds up in Lewy bodies in Parkinson’s disease and dementia patients and which is found in many other neurodegenerative diseases. The animals were given one milligram of nilotinib every two days. (By contrast, the FDA approved use of up to 1,000 milligrams of nilotinib once a day for CML patients.)

 “We successfully tested this for several diseases models that have an accumulation of intracellular protein,” Moussa says. “It gets rid of alpha synuclein and tau in a number of movement disorders, such as Parkinson’s disease as well as Lewy body dementia.”

The team also showed that movement and functionality in the treated mice was greatly improved, compared with untreated mice.

In order for such a therapy to be as successful as possible in patients, the agent would need to be used early in neurodegenerative diseases, Moussa hypothesizes. Later use might retard further extracellular plaque formation and accumulation of intracellular proteins in inclusions such as Lewy bodies.

Moussa is planning a phase II clinical trial in participants who have been diagnosed with disorders that feature build-up of alpha Synuclein, including Lewy body dementia, Parkinson’s disease, progressive supranuclear palsy (PSP) and multiple system atrophy (MSA).

In a study recently published in IEEE Transactions on Neural Systems and Rehabilitation Engineering, neurobiologists at the University of Chicago show how an organism can sense a tactile stimulus, in real time, through an artificial sensor in a prosthetic hand.

Scientists have made tremendous advances toward building lifelike prosthetic limbs that move and function like the real thing. These are amazing accomplishments, but an important element to creating a realistic replacement for a hand is the sense of touch. Without somatosensory feedback from the fingertips about how hard you’re squeezing something or where it’s positioned relative to the hand, grasping an object is about as accurate as using one of those skill cranes to grab a stuffed animal at an arcade. Sure, you can do it, but you have to concentrate intently while watching every movement. You’re relying on your sense of vision to compensate for the lack of touch.

Sliman Bensmaia, assistant professor of organismal biology and anatomy at the University of Chicago, studies the neural basis of the sense of touch. Now, he and his colleagues are working with a robotic hand equipped with sensors that send electrical signals to electrodes implanted in the brain to recreate the same response to touch as a real hand.

Bensmaia spoke about how important the sense of touch is to creating a lifelike experience with a prosthetic limb.

“If you lose your somatosensory system it almost looks like your motor system is impaired,” he said. “If you really want to create an arm that can actually be used dexterously without the enormous amount of concentration it takes without sensory feedback, you need to restore the somatosensory feedback.”

The researchers performed a series of experiments with rhesus macaques that were trained to respond to stimulation of the hand. In one setting, they were gently poked on the hand with a physical probe at varying levels of pressure. In a second setting, some of the animals had electrodes implanted into the area of the brain that responds to touch. These animals were given electrical pulses to simulate the sensation of touch, and their hands were hidden so they wouldn’t see that they weren’t actually being touched.

Using data from the animals’ responses to each type of stimulus, the researchers were able to create a function, or equation, that described the requisite electrical pulse to go with each physical poke of the hand. Then, they repeated the experiments with a prosthetic hand that was wired to the brain implants. They touched the prosthetic hand with the physical probe, which in turn sent electrical signals to the brain.

Bensmaia said that the animals performed identically whether poked on their own hand or on the prosthetic one.

“This is the first time as far as I know where an animal or organism actually perceives a tactile stimulus through an artificial transducer,” Bensmaia said. “It’s an engineering milestone. But from a neuroengineering standpoint, this validates this function. You can use this function to have an animal perform this very precise task, precisely identically.”

The FDA is in the process of approving similar devices for human trials, and Bensmaia said he hopes such a system is implemented within the next year. Producing a lifelike sense of touch would go a long way toward improving the dexterity and performance of prosthetic hands, but he said it would also help bridge a mental divide for amputees or people who have lost the use of a limb. Until now, prosthetics and robotic arms feel more like tools than real replacements because they don’t produce the expected sensations.

“If every time you see your robotic arm touching something, you get a sensation that is projected to it, I think it’s very possible that in fact, you will consider this new thing as being part of your body,” he said.

Different brain areas are activated when we choose to suppress an emotion, compared to when we are instructed to inhibit an emotion, according a new study from the UCL Institute of Cognitive Neuroscience and Ghent University.

In this study, published in Brain Structure and Function, the researchers scanned the brains of healthy participants and found that key brain systems were activated when choosing for oneself to suppress an emotion. They had previously linked this brain area to deciding to inhibit movement.

"This result shows that emotional self-control involves a quite different brain system from simply being told how to respond emotionally," said lead author Dr Simone Kuhn (Ghent University).

In most previous studies, participants were instructed to feel or inhibit an emotional response. However, in everyday life we are rarely told to suppress our emotions, and usually have to decide ourselves whether to feel or control our emotions.

In this new study the researchers showed fifteen healthy women unpleasant or frightening pictures. The participants were given a choice to feel the emotion elicited by the image, or alternatively to inhibit the emotion, by distancing themselves through an act of self-control.

The researchers used functional magnetic resonance imaging (fMRI) to scan the brains of the participants. They compared this brain activity to another experiment where the participants were instructed to feel or inhibit their emotions, rather than choose for themselves.

Different parts of the brain were activated in the two situations. When participants decided for themselves to inhibit negative emotions, the scientists found activation in the dorso-medial prefrontal area of the brain. They had previously linked this brain area to deciding to inhibit movement.

In contrast, when participants were instructed by the experimenter to inhibit the emotion, a second, more lateral area was activated.

"We think controlling one’s emotions and controlling one’s behaviour involve overlapping mechanisms," said Dr Kuhn.

"We should distinguish between voluntary and instructed control of emotions, in the same way as we can distinguish between making up our own mind about what do, versus following instructions."

Regulating emotions is part of our daily life, and is important for our mental health. For example, many people have to conquer fear of speaking in public, while some professionals such as health-care workers and firemen have to maintain an emotional distance from unpleasant or distressing scenes that occur in their jobs.

Professor Patrick Haggard (UCL Institute of Cognitive Neuroscience) co-author of the paper said the brain mechanism identified in this study could be a potential target for therapies.

"The ability to manage one’s own emotions is affected in many mental health conditions, so identifying this mechanism opens interesting possibilities for future research.

"Most studies of emotion processing in the brain simply assume that people passively receive emotional stimuli, and automatically feel the corresponding emotion. In contrast, the area we have identified may contribute to some individuals’ ability to rise above particular emotional situations.

"This kind of self-control mechanism may have positive aspects, for example making people less vulnerable to excessive emotion. But altered function of this brain area could also potentially lead to difficulties in responding appropriately to emotional situations."

When brain cells are overwhelmed by an influx of too many calcium molecules, they shut down the channels through which these molecules enter the cells. Until now, the “stop” signal mechanism that cells use to control the molecular traffic was unknown.

In the new issue of the journal Neuron, UC Davis Health System scientists report that they have identified the mechanism. Their findings are relevant to understanding the molecular causes of the disruption of brain functioning that occurs in stroke and other neurological disorders.

"Too much calcium influx clearly is part of the neuronal dysfunction in Alzheimer’s disease and causes the neuronal damage during and after a stroke. It also contributes to chronic pain," said Johannes W. Hell, professor of pharmacology at UC Davis. Hell headed the research team that identified the mechanism that stops the flow of calcium molecules, which are also called ions, into the specialized brain cells known as neurons.

Hell explained that each day millions of molecules of calcium enter and exit each of the 100 billion neurons of the human brain. These calcium ions move in and out of neurons through pore-like structures, known as channels, that are located in the outer surface, or “skin,” of each cell.

The flow of calcium ions into brain cells generates the electrical impulses needed to stimulate such actions as the movement of muscles in our legs and the creation of new memories in the brain. The movement of calcium ions also plays a role in gene expression and affects the flexibility of the structures, called synapses, that are located between neurons and transmit electrical or chemical signals of various strengths from one cell to a second cell.

Neurons employ an unexpected and highly complex mechanism to down regulate, or reduce, the activity of channels that are permitting too many calcium ions to enter neurons, Hell and his colleagues discovered. The mechanism, which leads to the elimination of the overly permissive ion channel employs two proteins, α-actinin and the calcium-binding messenger protein calmodulin.

Located on the neuron’s outer surface, referred to as the plasma membrane, α-actinin stabilizes the type of ion channels that constitute a major source of calcium ion influx into brain cells, Hell explained. This protein is a component of the cytoskeleton, the scaffolding of cells. The ion channels that are a major source of calcium ions are referred to as Cav1.2 (L type voltage-dependent calcium channels).

The researchers also found that the calcium-binding messenger protein calmodulin, which is the cell’s main sensor for calcium ions, induces internalization, or endocytosis, of Cav1.2 to remove this channel from the cell surface, thus providing an important negative feedback mechanism for excessive calcium ion influx into a neuron, Hell explained.

The discovery that α-actinin and calmodulin play a role in controlling calcium ion influx expands upon Hell’s previous research on the molecular mechanisms that regulate the activity of various ion channels at the synapse.

One previous study proved relevant to understanding the biological mechanisms that underlie the body’s fight-or-flight response during stress.

In work published in the journal Science in 2001, Hell and colleagues reported that the regulation of Cav1.2 by adrenergic signaling during stress is performed by one of the adrenergic receptors (beta 2 adrenergic receptor) directly linked to Cav1.2.

"This protein-protein interaction ensures that the adrenergic regulation is fast, efficient and precisely targets this channel," Hell said.

"We showed that Cav1.2 is regulated by adrenergic signaling on a time scale of a few seconds, and this is mainly increasing its activity when needed, for example during danger, to make our brain work faster and better. The same channel is in the heart, where adrenergic stimulation increases channel/Ca influx activity, increasing the pacing and strength of our heart beat to meet the increased physical demands during danger."

In many neurodegenerative diseases the neurons of the brain are over-stimulated and this leads to their destruction. After many failed attempts and much scepticism this process was finally shown last year to be a possible basis for treatment in some patients with stroke. But very few targets for drugs to block this process are known.

In a new highly detailed study, researchers have discovered a previously missing link between over-stimulation and destruction of brain tissue, and shown that this might be a target for future drugs. This research, led by the A. I. Virtanen Institute at the University of Eastern Finland in collaboration with scientists from Lausanne University Hospital, University of Lausanne and the company Xigen Pharma AG, was published in the Journal of Neuroscience. Research was funded mainly by the Academy of Finland.

What is this missing link? We have known for years that over-stimulated neurons produce nitric oxide molecules. Although this can activate a signal for destruction of cells, the small amount of nitric oxide produced cannot alone explain the damage to the brain. The team now show that a protein called NOS1AP links the nitric oxide that is produced to the damage that results. NOS1AP binds an initiator of cell destruction called MKK3 and also moves within the cell to the source of nitric oxide when cells are over-activated. The location of these proteins in cells causes them to convert the over-stimulation signal into a cell destruction response. The team designed a chemical that prevents NOS1AP from binding the source of nitric oxide. This reduces the cell destruction response in cells of the brain and as a result it limits brain lesions in rodents.

Other funders are the European Union and the University of Eastern Finland. Researchers used the recently developed high-throughput imaging facilities at the A. I. Virtanen Institute. The researchers hope that continuation of their work could lead to improved treatments for diseases such as stroke, epilepsy and chronic conditions like Alzheimer’s disease. As NOS1AP is associated with schizophrenia, diabetes and sudden cardiac death, future research in this area may assist the treatment of a wider range of diseases.

Many medical issues affect nerves, from injuries in car accidents and side effects of chemotherapy to glaucoma and multiple sclerosis. The common theme in these scenarios is destruction of nerve axons, the long wires that transmit signals to other parts of the body, allowing movement, sight and sense of touch, among other vital functions.

Now, researchers at Washington University School of Medicine in St. Louis have found a way the body can remove injured axons, identifying a potential target for new drugs that could prevent the inappropriate loss of axons and maintain nerve function.

“Treating axonal degeneration could potentially help a lot of patients because there are so many diseases and conditions where axons are inappropriately lost,” says Aaron DiAntonio, MD, PhD, professor of developmental biology. “While this would not be a cure for any of them, the hope is that we could slow the progression of a whole range of diseases by keeping axons healthy.”

DiAntonio is senior author of the study that appears online May 9 in the journal Cell Reports.

While axonal degeneration appears to be a major culprit in diseases like multiple sclerosis, it also paradoxically plays an important role in properly wiring the nervous systems of developing embryos.

“When an embryo is building its nervous system, there can be inappropriate or excessive axonal sprouts, or axons that are only needed at one time in development and not later,” DiAntonio says. “These axons degenerate, and that’s very important for wiring the nervous system. And in adult organisms, it might be useful to have a clean and quick way to remove a damaged axon from a healthy nerve, instead of letting it decay and potentially damage its neighboring axons.”

DiAntonio compares the process to programmed cell death, or apoptosis, which is also important in embryonic development. Apoptosis culls unnecessary or damaged cells from the body. If cell death programs become overactive, they can kill healthy cells that should remain. And if apoptosis fails to destroy damaged cells in adults, it can lead to cancer.

The new discovery also underscores the relatively recent understanding that loss of axons is not a passive decay process resulting from injury. Just as apoptosis actively destroys cells, axonal degeneration results from a cellular program that actively removes the damaged axon. In certain diseases, the program may be inappropriately triggered.

“We want to understand axonal degeneration at the same level that we understand programmed cell death, in the hopes of developing drugs to block the process when it becomes overactive,” DiAntonio says.

DiAntonio’s major collaborators in this project include Jeffrey D. Milbrandt, MD, PhD, the James S. McDonnell Professor and head of the Department of Genetics, and first author Elisabetta Babetto, PhD, postdoctoral research scholar.

Studying mice, the researchers found that a gene called Phr1 plays a major role in governing the self-destruction of injured axons. When they removed Phr1 from adult mice, the severed portion of the axons remained intact for much longer than in genetically normal mice.

In the normal mice, a severed axon degenerated entirely after two days. In mice without Phr1, they found that about 75 percent of the severed axons remained at five days, with a quarter persisting at least 10 days after being cut. The mice showed no side effects and suffered no obvious problems due to the missing Phr1.

The findings raise the possibility that blocking the Phr1 protein with a drug could keep damaged axons alive and functional when the body would normally cause the axons to self-destruct.

DiAntonio emphasizes that he is not trying to save axons that have no connection to the rest of the nerve. The paradigm is simply a good way to model nerve injury. In many instances, such as a crush injury or disease processes in which the axon is not severed, blocking the Phr1 protein could potentially preserve an attached axon that would otherwise self-destruct.

Importantly, the research team also looked at optic nerves of the central nervous system, which are damaged in glaucoma, and found similar protective effects from the loss of Phr1.

“This is not the first gene identified whose loss protects mammalian axons from degeneration,” DiAntonio says. “But it is the first one that shows evidence of working in the central nervous system. So it could be important in conditions like glaucoma, multiple sclerosis and other neurodegenerative diseases where the central nervous system is the primary problem.”

DiAntonio also points out possible ways to help cancer patients. Many chemotherapy drugs cause damage to peripheral axons, which may limit the doses a patient can tolerate.

As part of the new study, the researchers showed that intact axons without Phr1 were protected from the damage caused by vincristine, a chemotherapy drug used to treat leukemia, neuroblastoma, Hodgkin’s disease and non-Hodgkin’s lymphoma, among other cancers.

“In this case, the loss of axons is not caused by disease,” DiAntonio says. “It’s caused by the drug doctors are giving. You know the date it will start. You know the date it will stop. This is probably where I am most optimistic that we could make an impact.”

By monitoring the behavior of a class of cells in the brains of living mice, neuroscientists at Johns Hopkins discovered that these cells remain highly dynamic in the adult brain, where they transform into cells that insulate nerve fibers and help form scars that aid in tissue repair.

Published online April 28 in the journal Nature Neuroscience, their work sheds light on how these multipurpose cells communicate with each other to maintain a highly regular, grid-like distribution throughout the brain and spinal cord. The disappearance of one of these so-called progenitor cells causes a neighbor to quickly divide to form a replacement, ensuring that cell loss and cell addition are kept in balance.

“There is a widely held misconception that the adult nervous system is static or fixed, and has a limited capacity for repair and regeneration,” says Dwight Bergles, Ph.D., professor of neuroscience and otolaryngology at the Johns Hopkins University School of Medicine. “But we found that these progenitor cells, called oligodendrocyte precursor cells (OPCs), are remarkably dynamic. Unlike most other adult brain cells, they are able to respond to the repair needs around them while maintaining their numbers.”

OPCs can mature to become oligodendrocytes — support cells in the brain and spinal cord responsible for wrapping nerve fibers to create insulation known as myelin. Without myelin, the electrical signals sent by neurons travel poorly and some cells die due to the lack of metabolic support from oligodendrocytes. It is the death of oligodendrocytes and the subsequent loss of myelin that leads to neurological disability in diseases such as multiple sclerosis.

During brain development, OPCs spread throughout the central nervous system and make large numbers of oligodendrocytes. Scientists know that few new oligodendrocytes are born in the healthy adult brain, yet the brain is flush with OPCs. However, the function of OPCs in the adult brain wasn’t clear.

To find out, Bergles and his team genetically modified mice so that their OPCs contained a fluorescent protein along their edges, giving crisp definition to their many fine branches that extend in every direction. Using special microscopes that allow imaging deep inside the brain, the team watched the activity of individual cells in living mice for over a month.

The researchers discovered that, far from being static, the OPCs were continuously moving through the brain tissue, extending their “tentacles” and repositioning themselves. Even though these progenitors are dynamic, each cell maintains its own area by repelling other OPCs when they come in contact.

“The cells seem to sense each other’s presence and know how to control the number of cells in their population,” says Bergles. “It looks like this process goes wrong in multiple sclerosis lesions, where there are reduced numbers of OPCs, a loss that may impair the cells’ ability to sense whether demyelination has occurred. We don’t yet know what molecules are involved in this process, but it’s something we’re actively working on.”

To see if OPCs do more than form new oligodendrocytes in the adult brain, the team tested their response to injury by using a laser to create a small wound in the brain. Surprisingly, OPCs migrated to the injury site and contributed to scar formation, a previously unsuspected role. The empty space in the OPC grid, created by the loss of the scar-forming OPCs, was then filled by cell division of neighboring OPCs, providing an explanation for why brain injury is often accompanied by proliferation of these cells.

“Scar cells are not oligodendrocytes, so the term ‘oligodendrocyte precursor cell’ may now be outdated,” says Bergles. “These cells are likely to have a broader role in tissue regeneration and repair than we thought. Because traumatic brain injuries, multiple sclerosis and other neurodegenerative diseases require tissue regeneration, we are eager to learn more about the functions of these enigmatic cells.”

Research opens door to new drug therapies for Parkinson’s disease

McGill University researchers have unlocked a new door to developing drugs to slow the progression of Parkinson’s disease. Collaborating teams led by Dr. Edward A. Fon at the Montreal Neurological Institute and Hospital -The Neuro, and Dr. Kalle Gehring  in the Department of Biochemistry at the Faculty of Medicine, have discovered the three-dimensional structure of the protein Parkin. Mutations in Parkin cause a rare hereditary form of Parkinson’s disease and are likely to also be involved in more commonly occurring forms of Parkinson’s disease. The Parkin protein protects neurons from cell death due to an accumulation of defective mitochondria. Mitochondria are the batteries in cells, providing the power for cell functions. This new knowledge of Parkin’s structure has allowed the scientists to design mutations in Parkin that make it better at recognizing damaged mitochondria and therefore possibly provide better protection for nerve cells. The research will be published online May 9 in the leading journal Science.

VIDEO: Parkin protein

“The majority of Parkinson’s patients suffer from a sporadic form of the disease that occurs from a complex interplay of genetic and environmental factors which are still not fully understood, explains Dr. Fon, neurologist at The Neuro and head of the McGill Parkinson Program, a National Parkinson Foundation Centre of Excellence. “A minority of patients have genetic mutations in genes such as Parkin that cause the disease. Although there are differences between the genetic and sporadic forms, there is good reason to believe that understanding one will inform us about the other. It’s known that toxins that poison mitochondria can lead to Parkinson’s-like symptoms in humans and animals. Recently, Parkin was shown to be a key player in the cell’s system for identifying and removing damaged mitochondria.”

Dr. Gehring, head of McGill’s structural biology centre, GRASP, likens Parkin to a watchdog for damaged mitochondria. “Our structural studies show that Parkin is normally kept in check by a part of the protein that acts as a leash to restrict Parkin activity. When we made mutations in this specific ‘leash’ region in the protein, we found that Parkin recognized damaged mitochondria more quickly. If we can reproduce this response with a drug rather than mutations, we might be able to slow the progression of disease in Parkinson’s patients.”

Parkin is an enzyme in cells that attaches a small protein, ubiquitin, to other proteins to mark them for degradation. For example, when mitochondria are damaged, Parkin is switched on which leads to the clearing of the dysfunctional mitochondria. This is an important process because damaged mitochondria are a major source of cellular stress and thought to play a central role in the death of neurons in neurodegenerative diseases.

Husband and wife team, Drs. Jean-François Trempe and Véronique Sauvé, are lead authors on the paper. Dr. Sauvé led the Gehring team that used X-ray crystallography to determine the structure of Parkin. Dr. Trempe in the Fon laboratory directed the functional studies of Parkin.

Scientists have identified a set of tests that could help identify whether and how Huntington’s disease (HD) is progressing in groups of people who are not yet showing symptoms. The latest findings from the TRACK-HD study*, published Online First in The Lancet Neurology, could be used to assess whether potential new treatments are slowing the disease up to 10 years before the development of noticeable symptoms.

“Currently, the effectiveness of a new drug is decided by its ability to treat symptoms. These new tests could be used in future preventative drug trials in individuals who are gene positive for HD but are not yet showing overt motor symptoms. These people have the most to gain by initiating treatment early to delay the start of these overt symptoms and give them a high quality of life for a longer period of time”, explains lead author Sarah Tabrizi from University College London’s Institute of Neurology.

The TRACK-HD investigators have previously reported a range of tests that could be used in clinical trials to assess the effectiveness of potential disease-modifying drugs in people who already show signs of the disease. But in individuals without noticeable symptoms there was little evidence of a decline in function over two years, limiting the ability to test new drugs early in the disease course.

HD is caused by the mutation of a single gene on chromosome 4, which causes a part of the DNA (known as a CAG motif) to repeat many more times than it is supposed to. The length of the CAG repeat is known to be a major determinant of the age at which symptoms of the disease are likely to start, but its contribution to progression is unclear.

Here the TRACK-HD investigators extend the study to a third year with the aim of identifying some of the earliest biological changes in individuals with presymptomatic HD, giving additional power to predict how the disease may progress beyond that already expected from age and CAG length.

Over 3 years, baseline measures derived from brain imaging were the clearest markers of disease progression and future diagnosis, above and beyond the effect of age and CAG count, in gene carriers up to 20 years before they were expected to show symptoms.

In particular, the investigators suggest that measuring volume change in white matter and the caudate and putamen regions might be future endpoints for treatment trials.

In individuals up to 10 years away from developing symptoms, there was also significant deterioration in performance on a number of motor (movement) and cognitive (intellectual function) tasks compared with controls, and the frequency of apathy increased. Finger tapping was the most sensitive of the motor assessments, while the symbol digit modality test proved to be the most sensitive of the cognitive measures.

According to Tabrizi, “A new generation of drugs will be ready for human trials in the very near future. Diagnosis in HD is something of an artificial construct at onset of motor symptoms, and this study now gives us a number of other, more well-defined parameters that correlate with disease progression. Something that suggests we’re moving towards a more biological, as opposed to physical, definition of disease progression that reduces the importance of an ‘onset event’ is great news. By extending the reach of clinical trials to include individuals who are currently free of overt symptoms there is a realistic future possibility that treatments in the pipeline can significantly improve the quality of life for patients and families.”**

Writing in a linked Comment, Francis O. Walker, M.D., from Wake Forest School of Medicine in the USA says that the TRACK-HD investigators have set the standard for observational studies in other neurodegenerative diseases, adding that, “Virtual roadmaps of disease in the minds of practitioners are good for care in the framework of the traditional patient encounter, but it takes substantial effort, teamwork, and genius to turn them into rigorous, quantifiable timelines that can be used to test efficacy in future therapeutic trials.”

* The Track-HD study was established to identify differences between people carrying the HD mutation at different stages and healthy controls that could be used to accurately predict the progression of HD using a variety of techniques to assess changes in brain function, motor function, behaviour, and cognition. 366 individuals from Canada, France, the Netherlands and the UK were enrolled: 120 presymptomatic carriers of the HD gene mutation, 123 patients with early symptomatic HD, and 123 healthy controls.

How does San Francisco Giants slugger Pablo Sandoval swat a 95 mph fastball, or tennis icon Venus Williams see the oncoming ball, let alone return her sister Serena’s 120 mph serves? For the first time, vision scientists at the University of California, Berkeley, have pinpointed how the brain tracks fast-moving objects.

The discovery advances our understanding of how humans predict the trajectory of moving objects when it can take one-tenth of a second for the brain to process what the eye sees.

That 100-millisecond holdup means that in real time, a tennis ball moving at 120 mph would have already advanced 15 feet before the brain registers the ball’s location. If our brains couldn’t make up for this visual processing delay, we’d be constantly hit by balls, cars and more.

Thankfully, the brain “pushes” forward moving objects so we perceive them as further along in their trajectory than the eye can see, researchers said.

“For the first time, we can see this sophisticated prediction mechanism at work in the human brain,” said Gerrit Maus, a postdoctoral fellow in psychology at UC Berkeley and lead author of the paper published today (May 8) in the journal, Neuron.

A clearer understanding of how the brain processes visual input – in this case life in motion – can eventually help in diagnosing and treating myriad disorders, including those that impair motion perception. People who cannot perceive motion cannot predict locations of objects and therefore cannot perform tasks as simple as pouring a cup of coffee or crossing a road, researchers said.

This study is also likely to have a major impact on other studies of the brain. Its findings come just as the Obama Administration initiates its push to create a Brain Activity Map Initiative, which will further pave the way for scientists to create a roadmap of human brain circuits, as was done for the Human Genome Project.

Using functional Magnetic Resonance Imaging (fMRI) Gerrit and fellow UC Berkeley researchers Jason Fischer and David Whitney located the part of the visual cortex that makes calculations to compensate for our sluggish visual processing abilities. They saw this prediction mechanism in action, and their findings suggest that the middle temporal region of the visual cortex known as V5 is computing where moving objects are most likely to end up.

For the experiment, six volunteers had their brains scanned, via fMRI, as they viewed the “flash-drag effect,”(a, b) a visual illusion in which we see brief flashes shifting in the direction of the motion.

“The brain interprets the flashes as part of the moving background, and therefore engages its prediction mechanism to compensate for processing delays,” Maus said.

The researchers found that the illusion – flashes perceived in their predicted locations against a moving background and flashes actually shown in their predicted location against a still background – created the same neural activity patterns in the V5 region of the brain. This established that V5 is where this prediction mechanism takes place, they said.

In a study published earlier this year, Maus and his fellow researchers pinpointed the V5 region of the brain as the most likely location of this motion prediction process by successfully using transcranial magnetic stimulation, a non-invasive brain stimulation technique, to interfere with neural activity in the V5 region of the brain, and disrupt this visual position-shifting mechanism.

“Now not only can we see the outcome of prediction in area V5,” Maus said. “But we can also show that it is causally involved in enabling us to see objects accurately in predicted positions.”

On a more evolutionary level, the latest findings reinforce that it is actually advantageous not to see everything exactly as it is. In fact, it’s necessary to our survival:

“The image that hits the eye and then is processed by the brain is not in sync with the real world, but the brain is clever enough to compensate for that,” Maus said. “What we perceive doesn’t necessarily have that much to do with the real world, but it is what we need to know to interact with the real world.”

With a goal of helping patients with spinal cord injuries, Jason Gallivan and a team of researchers at Queen’s University’s Department of Psychology and Centre for Neuroscience Studies are probing deep into the human brain to learn how it manages basic daily tasks.

The team’s most recent research, in collaboration with a group at Western University, investigated how the human brain supports tool use. The researchers were especially interested in determining the extent to which brain regions involved in planning actions with the hand alone would also be involved in planning actions with a tool. They found that although some brain regions were involved in planning actions with either the hand or tool alone, the vast majority were involved in planning both hand- and tool-related movements. In a subset of these latter brain areas the researchers further determined that the tool was in fact being represented as an extension of the hand.

“Tool use represents a defining characteristic of high-level cognition and behaviour across the animal kingdom but studying how the brain – and the human brain in particular – supports tool use remains a significant challenge for neuroscientists” says Dr. Gallivan. “This work is a considerable step forward in our understanding of how tool-related actions are planned in humans.”

Over the course of one year, human participants had their brain activity scanned using functional magnetic resonance imaging (fMRI) as they reached towards and grasped objects using either their hand or a set of plastic tongs. The tongs had been designed so they opened whenever participants closed their grip, requiring the participants to perform a different set of movements to use the tongs as opposed to when using their hand alone.

The team found that mere seconds before the action began, that the neural activity in some brain regions was predictive of the type of action to be performed upon the object, regardless of whether the hand or tool was to be used (and despite the different movements being required). By contrast, the predictive neural activity in other brain regions was shown to represent hand and tool actions separately. Specifically, some brain regions only coded actions with the hand whereas others only coded actions with the tool.

“Being able to decode desired tool use behaviours from brain signals takes us one step closer to using those signals to control those same types of actions with prosthetic limbs,” says Dr. Gallivan. “This work uncovers the brain organization underlying the planning of movements with the hand and hand-operated tools and this knowledge could help people suffering from spinal cord injuries.”

The research was recently published in eLife.

Adding captivating visuals to a textbook lesson to attract children’s interest may sometimes make it harder for them to learn, a new study suggests.

Researchers found that 6- to 8-year-old children best learned how to read simple bar graphs when the graphs were plain and a single color.

Children who were taught using graphs with images (like shoes or flowers) on the bars didn’t learn the lesson as well and sometimes tried counting the images rather than relying on the height of the bars.

“Graphs with pictures may be more visually appealing and engaging to children than those without pictures. However, engagement in the task does not guarantee that children are focusing their attention on the information and procedures they need to learn. Instead, they may be focusing on superficial features,” said Jennifer Kaminski, co-author of the study and research scientist in psychology at The Ohio State University.

Kaminski conducted the study with Vladimir Sloutsky, professor of psychology at Ohio State.

The problem of distracting visuals is not just an academic issue. In the study, the authors cite real-life examples of colorful, engaging – and possibly confusing - bar graphs in educational materials aimed at children, as well as in the popular media.

And when the authors asked 16 kindergarten and elementary school teachers whether they would use the visually appealing graphs featured in this study, all of them said they would. Intuitively, most of these teachers felt that the graphs with the pictures would be more effective for instruction than the graphs without, according to the researchers.

The findings apply beyond learning graphs and mathematics, the authors said.

“When designing instructional material, we need to consider children’s developing ability to focus their attention and make sure that the material helps them focus on the right things,” Kaminski said.

“Any unnecessary visual information may distract children from the very procedures we want them to learn.”

The study appears online in the Journal of Educational Psychology and will appear in a future print edition.

The main study involved 122 students in kindergarten, first and second grade. All were tested individually.

The experiment began with a training phase where a researcher showed each child a graph on a computer screen and taught him or her how to read it. The children were then tested on three graphs to see if they could accurately interpret them.

The graphs in the training phase involved how many shoes were in a lost and found for each of five weeks. Half the students were presented with graphs in which the bars were a solid color. The other students were shown graphs in which the bars contained pictures of shoes. The number of shoes in the bars was equal to the corresponding y-value on the graph. In other words, if there were five shoes in the lost and found, there were five shoes pictured in the bar.

After the training phase, the children were tested on new graphs in which the bars were either solid-colored or contained pictures of objects such as flowers. However, the number of objects pictured did not equal the correct y-value for the bar. In other words, the bar value could equal 14 flowers, but only seven flowers were pictured.

“This allowed us to clearly identify which students learned the correct way to read a bar graph from those who simply counted the number of objects in each bar,” Sloutsky said.

Sure enough, children who trained with the pictures on the graph were more likely than others to get the answers wrong by simply counting the objects in each bar.

All of the first- and second-graders and 75 percent of the kindergarten children who learned on the solid-bar graphs appropriately read the new graphs.

However, those who learned with the more visually appealing shoe graphs did not do nearly as well. In this case, 90 percent of kindergarteners and 72 percent of first-graders responded by counting the number of flowers pictured. Second-graders did better, but still about 30 percent responded by counting.

All the children were then tested again with graphs that featured patterned bars, with either stripes or polka dots within each bar.

Again, those who learned from the more visually appealing graphs did worse at interpreting these patterned graphs.

“To our surprise, some children tried to count all the tiny polka dots or stripes in the bars. They clearly didn’t learn the correct way to read the graphs,” Kaminski said.

The researchers conducted several other related experiments to confirm the results and make sure there weren’t other explanations for the findings. In one experiment, some children were trained on graphs with pictures of objects. But in this case, the number of objects pictured was not even close to the correct value of the bar, so the students could not use counting as a strategy.

Still, these children did not do as well on subsequent tests as did those who learned on the graphs with single-colored bars.

“When teaching children new math concepts, keeping material simple is very important,” Sloutsky said.

“Any extraneous information we provide, even with the best of intentions, to make the lesson more interesting may actually hurt learning because it may be misinterpreted,” he said.

The researchers said these results don’t mean that textbook authors or others can never use interesting visuals or other techniques to capture the interest of students.

“But they need to study how such material will affect students’ attention. You can’t assume that it is beneficial just because it is colorful; in can affect learning by distracting attention from what is relevant,” Sloutsky said.