A Major Cause of Age-Related Memory Loss Identified

Study points to possible treatments and confirms distinction between memory loss due to aging and that of Alzheimer’s

A team of Columbia University Medical Center (CUMC) researchers, led by Nobel laureate Eric R. Kandel, MD, has found that deficiency of a protein called RbAp48 in the hippocampus is a significant contributor to age-related memory loss and that this form of memory loss is reversible. The study, conducted in postmortem human brain cells and in mice, also offers the strongest causal evidence that age-related memory loss and Alzheimer’s disease are distinct conditions. The findings were published today in the online edition of Science Translational Medicine.

“Our study provides compelling evidence that age-related memory loss is a syndrome in its own right, apart from Alzheimer’s. In addition to the implications for the study, diagnosis, and treatment of memory disorders, these results have public health consequences,” said Dr. Kandel, who is University Professor & Kavli Professor of Brain Science, co-director of Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute, director of the Kavli Institute for Brain Science, and senior investigator, Howard Hughes Medical Institute, at CUMC. Dr. Kandel received a share of the 2000 Nobel Prize in Physiology or Medicine for his discoveries related to the molecular basis of memory.

The hippocampus, a brain region that consists of several interconnected subregions, each with a distinct neuron population, plays a vital role in memory. Studies have shown that Alzheimer’s disease hampers memory by first acting on the entorhinal cortex (EC), a brain region that provides the major input pathways to the hippocampus. It was initially thought that age-related memory loss is an early manifestation of Alzheimer’s, but mounting evidence suggests that it is a distinct process that affects the dentate gyrus (DG), a subregion of the hippocampus that receives direct input from the EC.

“Until now, however, no one has been able to identify specific molecular defects involved in age-related memory loss in humans,” said co-senior author Scott A. Small, MD, the Boris and Rose Katz Professor of Neurology and director of the Alzheimer’s Research Center at CUMC.

The current study was designed to look for more direct evidence that age-related memory loss differs from Alzheimer’s disease. The researchers began by performing microarray (gene expression) analyses of postmortem brain cells from the DG of eight people, ages 33 to 88, all of whom were free of brain disease. The team also analyzed cells from their EC, which served as controls since that brain structure is unaffected by aging. The analyses identified 17 candidate genes that might be related to aging in the DG. The most significant changes occurred in a gene called RbAp48, whoseexpressiondeclined steadily with aging across the study subjects.

To determine whether RbAp48plays an active role in age-related memory loss, the researchers turned to mouse studies. “The first question was whether RbAp48is downregulated in aged mice,” said lead author Elias Pavlopoulos, PhD, associate research scientist in neuroscience at CUMC. “And indeed, that turned out to be the case—there was a reduction of RbAp48 protein in the DG.”

When the researchers genetically inhibited RbAp48inthe brains ofhealthy young mice, they found the same memory loss as in aged mice, as measured by novel object recognition and water maze memory tests. When RbAp48inhibition was turned off, the mice’s memory returned to normal.

The researchers also did functional MRI (fMRI) studies of the mice with inhibited RbAp48 and found a selective effect in the DG, similar to that seen in fMRI studies of aged mice, monkeys, and humans. This effect of RbAp48 inhibition on the DG was accompanied by defects in molecular mechanisms similar to those found in aged mice. The fMRI profile and mechanistic defects of the mice with inhibited RbAp48 returned to normal when the inhibition was turned off.

In another experiment, the researchers used viral gene transfer and increased RbAp48expression inthe DG of aged mice. “We were astonished that not only did this improve the mice’s performance on the memory tests, but their performance was comparable to that of young mice,” said Dr. Pavlopoulos.

“The fact that we were able to reverse age-related memory loss in mice is very encouraging,” said Dr. Kandel. “Of course, it’s possible that other changes in the DG contribute to this form of memory loss. But at the very least, it shows that this protein is a major factor, and it speaks to the fact that age-related memory loss is due to a functional change in neurons of some sort. Unlike with Alzheimer’s, there is no significant loss of neurons.”

Finally, the study data suggest that RbAp48 protein mediates its effects, at least in part, through the PKA-CREB1-CBP pathway, which the team had found in earlier studies to be important for age-related memory loss in the mouse. According to the researchers, RbAp48 and the PKA-CREB1-CBP pathway are valid targets for therapeutic intervention. Agents that enhance this pathway have already been shown to improve age-related hippocampal dysfunction in rodents.

“Whether these compounds will work in humans is not known,” said Dr. Small. “But the broader point is that to develop effective interventions, you first have to find the right target. Now we have a good target, and with the mouse we’ve developed, we have a way to screen therapies that might be effective, be they pharmaceuticals, nutraceuticals, or physical and cognitive exercises.”

“There’s been a lot of handwringing over the failures of drug trials based on findings from mouse models of Alzheimer’s,” Dr. Small said. “But this is different. Alzheimer’s does not occur naturally in the mouse. Here, we’ve caused age-related memory loss in the mouse, and we’ve shown it to be relevant to human aging.”

Migraine May Permanently Change Brain Structure

Migraine may have long-lasting effects on the brain’s structure, according to a study published in the August 28, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“Traditionally, migraine has been considered a benign disorder without long-term consequences for the brain,” said study author Messoud Ashina, MD, PhD, with the University of Copenhagen in Denmark. “Our review and meta-analysis study suggests that the disorder may permanently alter brain structure in multiple ways.”

The study found that migraine raised the risk of brain lesions, white matter abnormalities and altered brain volume compared to people without the disorder. The association was even stronger in those with migraine with aura.

For the meta-analysis, researchers reviewed six population-based studies and 13 clinic-based studies to see whether people who experienced migraine or migraine with aura had an increased risk of brain lesions, silent abnormalities or brain volume changes on MRI brain scans compared to those without the conditions.

The results showed that migraine with aura increased the risk of white matter brain lesions by 68 percent and migraine with no aura increased the risk by 34 percent, compared to those without migraine. The risk for infarct-like abnormalities increased by 44 percent for those with migraine with aura compared to those without aura. Brain volume changes were more common in people with migraine and migraine with aura than those with no migraines.

“Migraine affects about 10 to 15 percent of the general population and can cause a substantial personal, occupational and social burden,” said Ashina. “We hope that through more study, we can clarify the association of brain structure changes to attack frequency and length of the disease. We also want to find out how these lesions may influence brain function.”

(Image: Getty images)

Size of personal space is affected by anxiety

The space surrounding the body (known by scientists as ‘peripersonal space’), which has previously been thought of as having a gradual boundary, has been given physical limits by new research into the relationship between anxiety and personal space.

New findings have allowed scientists to define the limit of the ‘peripersonal space’ surrounding the face as 20-40cm away. The study is published today in The Journal of Neuroscience.

As well as having numerical limits the specific distance was found to vary between individuals. Those with anxiety traits were found to have larger peripersonal space.

In an experiment, Dr Chiara Sambo and Dr Giandomenico Iannetti from UCL recorded the blink reflex - a defensive response to potentially dangerous stimuli at varying distances from subject’s face. They then compared the reflex data to the results of an anxiety test where subjects rated their levels of anxiety in various situations.

Those who scored highly on the anxiety test tended to react more strongly to stimuli 20cm from their face than subjects who got low scores on the anxiety test. Researchers classified those who reacted more strongly to further away stimuli as having a large ‘defensive peripersonal space’ (DPPS).

A larger DPPS means that those with high anxiety scores perceive threats as closer than non-anxious individuals when the stimulus is the same distance away. The research has led scientists to think that the brain controls the strength of defensive reflexes even though it cannot initiate them.

Dr Giandomenico Iannetti (UCL Neuroscience, Physiology and Pharmacology), lead author of the study, said: “This finding is the first objective measure of the size of the area surrounding the face that each individual considers at high-risk, and thus wants to protect through the most effective defensive motor responses.”

In the experiment, a group of 15 people aged 20 to 37 were chosen for study. Researchers applied an intense electrical stimulus to a specific nerve in the hand which causes the subject to blink. This is called the hand-blink reflex (HBR) which is not under conscious control of the brain.

This reflex was monitored with the subject holding their own hand at 4, 20, 40 and 60 cm away from the face. The magnitude of the reflex was used to determine how dangerous each stimulus was considered, and a larger response for stimuli further from the body indicated a larger DPPS.

Subjects also completed an anxiety test in which they self-scored their predicted level of anxiety in different situations. The results of this test were used to classify individuals as more or less anxious, and were compared to the data from the reflex experiment to determine if there was a link between the two tests.

Scientists hope that the findings can be used as a test to link defensive behaviours to levels of anxiety. This could be particularly useful determining risk assessment ability in those with jobs that encounter dangerous situations such as fire, police and military officers.

Perception of Marijuana as a “Safe Drug” Is Scientifically Inaccurate

The nature of the teenage brain makes users of cannabis amongst this population particularly at risk of developing addictive behaviors and suffering other long-term negative effects, according to researchers at the University of Montreal and New York’s Icahn School of Medicine at Mount Sinai.

“Of the illicit drugs, cannabis is most used by teenagers since it is perceived by many to be of little harm. This perception has led to a growing number of states approving its legalization and increased accessibility. Most of the debates and ensuing policies regarding cannabis were done without consideration of its impact on one of the most vulnerable population, namely teens, or without consideration of scientific data,” wrote Professor Didier Jutras-Aswad of the University of Montreal and Yasmin Hurd, MD, PhD, of Mount Sinai. “While it is clear that more systematic scientific studies are needed to understand the long-term impact of adolescent cannabis exposure on brain and behavior, the current evidence suggests that it has a far-reaching influence on adult addictive behaviors particularly for certain subsets of vulnerable individuals.”

The researchers reviewed over 120 studies that looked at different aspects of the relationship between cannabis and the adolescent brain, including the biology of the brain, chemical reaction that occurs in the brain when the drug is used, the influence of genetics and environmental factors, in addition to studies into the “gateway drug” phenomenon. “Data from epidemiological studies have repeatedly shown an association between cannabis use and subsequent addiction to heavy drugs and psychosis (i.e. schizophrenia). Interestingly, the risk to develop such disorders after cannabis exposure is not the same for all individuals and is correlated with genetic factors, the intensity of cannabis use and the age at which it occurs. When the first exposure occurs in younger versus older adolescents, the impact of cannabis seems to be worse in regard to many outcomes such as mental health, education attainment, delinquency and ability to conform to adult role,” Dr Jutras-Aswad said.

Although it is difficult to confirm in all certainty a causal link between drug consumption and the resulting behavior, the researchers note that rat models enable scientists to explore and directly observe the same chemical reactions that happen in human brains. Cannabis interacts with our brain through chemical receptors (namely cannabinoid receptors such as CB1 and CB2.) These receptors are situated in the areas of our brain that govern our learning and management of rewards, motivated behavior, decision-making, habit formation and motor function. As the structure of the brain changes rapidly during adolescence (before settling in adulthood), scientists believe that the cannabis consumption at this time greatly influences the way these parts of the user’s personality develop. In adolescent rat models, scientists have been able to observe differences in the chemical pathways that govern addiction and vulnerability – a receptor in the brain known as the dopamine D2 receptor is well known to be less present in cases of substance abuse.

Only a minority (approximately one in four) of teenage users of cannabis will develop an abusive or dependant relationship with the drug. This suggests to the researchers that specific genetic and behavioral factors influence the likelihood that the drug use will continue. Studies have also shown that cannabis dependence can be inherited through the genes that produce the cannabinoid receptors and an enzyme involved in the processing of THC. Other psychological factors are also likely involved. “Individuals who will develop cannabis dependence generally report a temperament characterized by negative affect, aggressivity and impulsivity, from an early age. Some of these traits are often exacerbated with years of cannabis use, which suggests that users become trapped in a vicious cycle of self-medication, which in turn becomes a dependence” Jutras-Aswad said.

The researchers stress that while a lot remains unknown about the mechanics of cannabis abuse, the body of existing research has clear implications for society. “It is now clear from the scientific data that cannabis is not harmless to the adolescent brain, specifically those who are most vulnerable from a genetic or psychological standpoint. Identifying these vulnerable adolescents, including through genetic or psychological screening, may be critical for prevention and early intervention of addiction and psychiatric disorders related to cannabis use. The objective is not to fuel the debate about whether cannabis is good or bad, but instead to identify those individuals who might most suffer from its deleterious effects and provide adequate measures to prevent this risk” Jutras-Aswad said. “Continuing research should be performed to inform public policy in this area. Without such systematic, evidenced-based research to understand the long-term effects of cannabis on the developing brain, not only the legal status of cannabis will be determined on uncertain ground, but we will not be able to innovate effective treatments such as the medicinal use of cannabis plant components that might be beneficial for treating specific disorders,” Dr Hurd said.

(Image: AP)

Long-term memory in the cortex

Game changing results: Brain uses the cortex for making sensory associations, not the hippocampus

‘Where’ and ‘how’ memories are encoded in a nervous system is one of the most challenging questions in biological research. The formation and recall of associative memories is essential for an independent life. The hippocampus has long been considered a centre in the brain for the long-term storage of spatial associations. Now, Mazahir T. Hasan at the Max Planck Institute for Medical Research and José Maria Delgado-Garcìa at the University Pablo de Olavide of Seville, Spain, were able to provide first experimental evidence that a specific form of memory associations is encoded in the cerebral cortex and is not localized in the hippocampus as described in most Neuroscience textbooks. The new study is a game changer since it strongly suggests that the motor cortical circuits itself, and not the hippocampus, is used as memory storage.

Henry Molaison, known widely as H.M., is a famous name in memory research. Large parts of the American‘s hippocampus – the region of the brain that is a major element in learning and memory processes – were removed in the 1950s in an attempt to cure his epileptic seizures. He subsequently suffered severe memory lapses and was no longer able to remember virtually anything new he had learned. Most scientists thereby concluded that the hippocampus is the site of long-term memory.

However, the extent of H.M.’s brain damage was obviously underestimated, because other regions in addition to the hippocampus were also removed or damaged in the surgical procedure. The researchers from Heidelberg and Seville have therefore investigated the learning behaviour of genetically modified mice in which NMDA receptors are turned off only in the motor cerebral cortex. NMDA receptors bind the neurotransmitter glutamate to the synapses and become active when several signals feed into one synapse at the same time. They are the central molecular elements of learning processes, being involved in increasing or decreasing transmission of the signals to synapses.

As the new study shows, in the motor cortex this so-called synaptic plasticity no longer functions without the NMDA receptors. The scientists were thus able to rule out the hippocampus or other regions as the cause for their observations. Based on the new findings, it is the cerebral cortex, not the hippocampus that is the storage site for some forms of memory.

In behaviour tests, so called eyeblink conditioning, animals with and without NMDA receptors in the primary motor cortex had to learn to link a tone with a subsequent electrical stimulus of the eyelid. This association of two sensory inputs involves the cerebellum which coordinates the necessary movements, as well as the hippocampus and the cerebral cortex, which are important learning and memory centres. “After a learning phase, the animals’ reflex is to close their eye when they hear just the tone. Without NMDA receptors in the primary motor cerebral cortex, the genetically modified mice on the other hand cannot remember the connection between the tone and electrical stimulus, and therefore they keep their eyes open despite the tone”, explains Mazahir T. Hasan of the Max Planck Institute for Medical Research.

The researchers have thus complemented the findings of their Heidelberg-based colleagues that the hippocampus is not the seat of memory. In July 2012, Rolf Sprengel and Peter Seeburg from the Max Planck Institute for Medical Research discovered that mice without NMDA receptors in the hippocampus are still quite capable of learning. “We now think that the hippocampus provides the necessary environmental cues, which are transmitted to the cortex where learning-dependent associations take place. Memories are thus stored at various sites in the cerebral cortex on a long-term basis”, explains Hasan.

The findings of Hasan and Delgado-Garcìa thus represent a paradigm-shift in memory research as they make clear that the cerebral cortex is the brain region where memory associations are linked and stored – not the hippocampus. An advanced and detailed knowledge of the mechanisms for the acquisition, consolidation, and recall of associations in the brain is the prerequisite for a therapeutic treatment of the devastating effects of memory loss in various neurological diseases, such as amnesia, Alzheimer`s disease and dementia.

Drug blocks light sensors in eye that may trigger migraine attacks

New compound by Salk scientists offers a way to treat migraine and potentially other disorders of the central nervous system

For many migraine sufferers, bright lights are a surefire way to exacerbate their headaches. And for some night-shift workers, just a stroll through a brightly lit parking lot during the morning commute home can be enough to throw off their body’s daily rhythms and make daytime sleep nearly impossible. But a new molecule that selectively blocks specialized light-sensitive receptors in the eyes could help both these groups of people, without affecting normal vision according to a study published August 25, 2013 in Nature Chemical Biology.

"It took almost ten years to find and test a molecule that fit all the properties and acted in vivo as we wanted," says senior study author Satchidananda Panda, an associate professor in Salk’s Regulatory Biology Laboratory.

Scientists have known for nearly a century that humans and animals can sense light even when they can’t see. Before they’ve opened their eyes, and even before cells that allow vision have matured, newborn mice still scurry away from bright lights, and set their sleep-wake cycles based on the patterns of light and dark throughout the day. The same is true of many blind people-though they can’t see what’s in front of them, their bodies still follow daily circadian rhythms, and the pupils of their eyes constrict in response to light.

More than ten years ago, Panda’s lab group discovered that melanopsin, a receptor found in neurons connecting the eyes and brain, is responsible for sensing light independently of normal vision. Since then, researchers have determined that the receptor is vital for maintaining sleep cycles and other circadian rhythms in those with healthy vision, constricting the pupil of the eye in bright light, and potentially exacerbating the light-sensitivity associated with migraine headaches. While melanopsin senses light for these non-vision purposes in the body, closely related receptors-rhodopsin and cone opsins-provide vision-forming information to the brain.

Panda figured that if he could find a compound that blocked melanopsin, but not rhodopsin or cone opsins, it could pave the way toward treating migraines or circadian rhythm imbalances. Scientists already know of one class of compounds, retinoids, which interact with opsins, but they’re non-specific and so bind to melanopsin, rhodopsin, cone opsins, and a whole handful of other receptors in the body, causing widespread side effects. Panda wanted something more specific. So for ten years, his lab group, in collaboration with scientists at the pharmaceutical company Lundbeck, has attempted to find chemical compounds that specifically shut off melanopsin in animals.

In their latest search, Panda and his collaborators turned to the Lundbeck library of diverse compounds. In hundreds of 384-well plates, a team led by Ken Jones at Lundbeck tested whether each chemical from the library turned off melanopsin by measuring the calcium levels after the plate was exposed to light. When melanopsin is functioning, calcium levels increase after light exposure indicating that light has been sensed and a signal is being generated. Several compounds from the chemical library stopped this calcium increase from happening, suggesting that they were blocking the function of melanopsin.

None of these compounds looked like retinoids, so it was an exciting breakthrough, Panda says. The chemicals, dubbed opsinamides, also showed no interaction with rhodopsin or other opsins. “We wanted to make sure they were specific to melanopsin,” says Panda. To find out whether the opsinamides would have a physiological response in addition to binding to melanopsin in bench experiments, Megumi Hatori and Ludovic Mure from Panda’s Salk lab group next looked at whether the drug affected the pupillary constriction in mice. Normally, in extremely bright light, the pupil of the eye shrinks to its smallest size. But when the mice were treated with one of the opsinamides, their pupils didn’t shrink as usual. Most importantly, the drug had no detectable effect in mice lacking melanopsin, further showing its specificity for melanopsin. Finally, newborn mice treated with the compound no longer avoided bright lights. The results, Panda says, show that the drug is stopping melanopsin from signaling the brain when the eyes are exposed to bright light.

"So far, everything known about melanopsin has been discovered using knock-out mice that completely lack the receptor," says Panda. "So this offers a new way to study the protein." Kenneth Jones, the former project head at Lundbeck, notes that "the two compounds require further optimization in anticipation of clinical testing but are extraordinarily useful for research purposes and as leads in the discovery process." Co-author Jeffrey Sprouse has co-founded a start-up company, Cyanaptic, to do just that.

Once more effective compounds are developed, Panda expects that they could eventually have utility in a variety of clinical settings. “There are many people who would like to work when they have migraine pain exacerbated by light,” he says. “If these drugs could stop the light-sensitivity associated with the headaches, it would enable them to be much more productive.”

Moreover, Panda says, the drugs could help shift-workers set their sleep schedules without exposure to sunlight interfering with their circadian rhythms. His lab group doesn’t yet have results on how the drugs affect circadian rhythms, but based on the known mechanisms of melanopsin, Panda says that it is likely the new opsinamides alter sleep.

Researcher controls colleague’s motions in 1st human brain-to-brain interface

University of Washington researchers have performed what they believe is the first noninvasive human-to-human brain interface, with one researcher able to send a brain signal via the Internet to control the hand motions of a fellow researcher.

Using electrical brain recordings and a form of magnetic stimulation, Rajesh Rao sent a brain signal to Andrea Stocco on the other side of the UW campus, causing Stocco’s finger to move on a keyboard.

While researchers at Duke University have demonstrated brain-to-brain communication between two rats, and Harvard researchers have demonstrated it between a human and a rat, Rao and Stocco believe this is the first demonstration of human-to-human brain interfacing.

“The Internet was a way to connect computers, and now it can be a way to connect brains,” Stocco said. “We want to take the knowledge of a brain and transmit it directly from brain to brain.”

The researchers captured the full demonstration on video recorded in both labs.

Rao, a UW professor of computer science and engineering, has been working on brain-computer interfacing in his lab for more than 10 years and just published a textbook on the subject. In 2011, spurred by the rapid advances in technology, he believed he could demonstrate the concept of human brain-to-brain interfacing. So he partnered with Stocco, a UW research assistant professor in psychology at the UW’s Institute for Learning & Brain Sciences.

On Aug. 12, Rao sat in his lab wearing a cap with electrodes hooked up to an electroencephalography machine, which reads electrical activity in the brain. Stocco was in his lab across campus wearing a purple swim cap marked with the stimulation site for the transcranial magnetic stimulation coil that was placed directly over his left motor cortex, which controls hand movement.

The team had a Skype connection set up so the two labs could coordinate, though neither Rao nor Stocco could see the Skype screens.

Rao looked at a computer screen and played a simple video game with his mind. When he was supposed to fire a cannon at a target, he imagined moving his right hand (being careful not to actually move his hand), causing a cursor to hit the “fire” button. Almost instantaneously, Stocco, who wore noise-canceling earbuds and wasn’t looking at a computer screen, involuntarily moved his right index finger to push the space bar on the keyboard in front of him, as if firing the cannon. Stocco compared the feeling of his hand moving involuntarily to that of a nervous tic.

“It was both exciting and eerie to watch an imagined action from my brain get translated into actual action by another brain,” Rao said. “This was basically a one-way flow of information from my brain to his. The next step is having a more equitable two-way conversation directly between the two brains.”

The technologies used by the researchers for recording and stimulating the brain are both well-known. Electroencephalography, or EEG, is routinely used by clinicians and researchers to record brain activity noninvasively from the scalp. Transcranial magnetic stimulation is a noninvasive way of delivering stimulation to the brain to elicit a response. Its effect depends on where the coil is placed; in this case, it was placed directly over the brain region that controls a person’s right hand. By activating these neurons, the stimulation convinced the brain that it needed to move the right hand.

Computer science and engineering undergraduates Matthew Bryan, Bryan Djunaedi, Joseph Wu and Alex Dadgar, along with bioengineering graduate student Dev Sarma, wrote the computer code for the project, translating Rao’s brain signals into a command for Stocco’s brain.

“Brain-computer interface is something people have been talking about for a long, long time,” said Chantel Prat, assistant professor in psychology at the UW’s Institute for Learning & Brain Sciences, and Stocco’s wife and research partner who helped conduct the experiment. “We plugged a brain into the most complex computer anyone has ever studied, and that is another brain.”

At first blush, this breakthrough brings to mind all kinds of science fiction scenarios. Stocco jokingly referred to it as a “Vulcan mind meld.” But Rao cautioned this technology only reads certain kinds of simple brain signals, not a person’s thoughts. And it doesn’t give anyone the ability to control your actions against your will.

Both researchers were in the lab wearing highly specialized equipment and under ideal conditions. They also had to obtain and follow a stringent set of international human-subject testing rules to conduct the demonstration.

“I think some people will be unnerved by this because they will overestimate the technology,” Prat said. “There’s no possible way the technology that we have could be used on a person unknowingly or without their willing participation.”

Stocco said years from now the technology could be used, for example, by someone on the ground to help a flight attendant or passenger land an airplane if the pilot becomes incapacitated. Or a person with disabilities could communicate his or her wish, say, for food or water. The brain signals from one person to another would work even if they didn’t speak the same language.

Rao and Stocco next plan to conduct an experiment that would transmit more complex information from one brain to the other. If that works, they then will conduct the experiment on a larger pool of subjects.

Touch and Movement Neurons Shape the Brain’s Internal Image of the Body

The brain’s tactile and motor neurons, which perceive touch and control movement, may also respond to visual cues, according to researchers at Duke Medicine.

The study in monkeys, which appears online Aug. 26, 2013, in the journal Proceedings of the National Academy of Sciences, provides new information on how different areas of the brain may work together in continuously shaping the brain’s internal image of the body, also known as the body schema.

The findings have implications for paralyzed individuals using neuroprosthetic limbs, since they suggest that the brain may assimilate neuroprostheses as part of the patient’s own body image.

“The study shows for the first time that the somatosensory or touch cortex may be influenced by vision, which goes against everything written in neuroscience textbooks,” said senior author Miguel Nicolelis, M.D., PhD, professor of neurobiology at Duke University School of Medicine. “The findings support our theory that the cortex isn’t strictly segregated into areas dealing with one function alone, like touch or vision.”

Earlier research has shown that the brain has an internal spatial image of the body, which is continuously updated based on touch, pain, temperature and pressure – known as the somatosensory system – received from skin, joints and muscles, as well as from visual and auditory signals.

An example of this dynamic process is the “rubber hand illusion,” a phenomenon in which people develop a sense of ownership of a fake hand when they view it being touched at the same time that something touches their own hand.

In an effort to find a physiological explanation for the “rubber hand illusion,” Duke researchers focused on brain activity in the somatosensory and motor cortices of monkeys. These two areas of the brain do not directly receive visual input, but previous work in rats, conducted at the Edmond and Lily Safra International Institute of Neuroscience of Natal in Brazil, theorized that the somatosensory cortex could respond to visual cues.

In the Duke experiment, the two monkeys observed a realistic, computer-generated image of a monkey arm on a screen being touched by a virtual ball. At the same time, the monkeys’ arms were touched, triggering a response in their somatosensory and motor cortical areas.

The monkeys then observed the ball touching the virtual arm without anything physically touching their own arms. Within a matter of minutes, the researchers saw the neurons located in the somatosensory and motor cortical areas begin to respond to the virtual arm alone being touched.

The responses to virtual touch occurred 50 to 70 milliseconds later than physical touch, which is consistent with the timing involved in the pathways linking the areas of the brain responsible for processing visual input to the somatosensory and motor cortices. Demonstrating that somatosensory and motor cortical neurons can respond to visual stimuli suggests that cross-functional processing occurs throughout the primate cortex through a highly distributed and dynamic process.

“These findings support our notion that the brain works like a grid or network that is continuously interacting,” Nicolelis said. “The cortical areas of the brain are processing multiple streams of information at the same time instead of being segregated as we previously thought.”

The research has implications for the future design of neuroprosthetic devices controlled by brain-machine interfaces, which hold promise for restoring motor and somatosensory function to millions of people who suffer from severe levels of body paralysis. Creating neuroprostheses that become fully incorporated in the brain’s sensory and motor circuitry could allow the devices to be integrated into the brain’s internal image of the body. Nicolelis said he is incorporating the findings into the Walk Again Project, an international collaboration working to build a brain-controlled neuroprosthetic device. The Walk Again Project plans to demonstrate its first brain-controlled exoskeleton during the opening ceremony of the 2014 FIFA Football World Cup.

“As we become proficient in using tools – a violin, tennis racquet, computer mouse, or prosthetic limb – our brain is likely changing its internal image of our bodies to incorporate the tools as extensions of ourselves,” Nicolelis said.

(Image: Getty images)