Brain scans show unusual activity in retired American football players

A new study has discovered profound abnormalities in brain activity in a group of retired American football players

Although the former players in the study were not diagnosed with any neurological condition, brain imaging tests revealed unusual activity that correlated with how many times they had left the field with a head injury during their careers.

Previous research has found that former American football players experience higher rates of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The new findings, published in Scientific Reports, suggest that players also face a risk of subtle neurological deficits that don’t show up on normal clinical tests.

Hidden problems

The study involved 13 former National Football League (NFL) professionals who believed they were suffering from neurological problems affecting their everyday lives as a consequence of their careers.

The former players and 60 healthy volunteers were given a test that involved rearranging coloured balls in a series of tubes in as few steps as possible. Their brain activity was measured using functional magnetic resonance imaging (fMRI) while they did the test.

The NFL group performed worse on the test than the healthy volunteers, but the difference was modest. More strikingly, the scans showed unusual patterns of brain activity in the frontal lobe. The difference between the two groups was so marked that a computer programme learned to distinguish NFL alumni and controls at close to 90 per cent accuracy based just on their frontal lobe activation patterns.

“The NFL alumni showed some of the most pronounced abnormalities in brain activity that I have ever seen, and I have processed a lot of patient data sets in the past,” said Dr Adam Hampshire, lead author of the study, from the Department of Medicine at Imperial College London.

The frontal lobe is responsible for executive functions: higher-order brain activity that regulates other cognitive processes. The researchers think the differences seen in this study reflect deficits in executive function that might affect the person’s ability to plan and organise their everyday lives.

“The critical fact is that the level of brain abnormality correlates strongly with the measure of head impacts of great enough severity to warrant being taken out of play. This means that it is highly likely that damage caused by blows to the head accumulate towards an executive impairment in later life.”

Early detection

Dr Hampshire and his colleagues at the University of Western Ontario, Canada suggest that fMRI could be used to reveal potential neurological problems in American football players that aren’t picked up by standard clinical tests. Brain imaging results could be useful to retired players who are negotiating compensation for neurological problems that may be related to their careers. Players could also be scanned each season to detect problems early.

The findings also highlight the inadequacy of standard cognitive tests for detecting certain types of behavioural deficit.

“Researchers have put a lot of time into developing tests to pick up on executive dysfunction, but none of them work at all well. It’s not unusual for an individual who has had a blow to the head to perform relatively well on a neuropsychological testing battery, and then go on to struggle in everyday life.

“The results tell us something very interesting about the human brain, which is that after damage, it can work harder and bring extra areas on line in order to cope with cognitive tasks. It is likely that in more complicated real world scenarios, this plasticity is insufficient and consequently, the executive impairment is no longer masked. In this respect, the results are also of relevance to other patients who suffer from multiple head injuries.

“Of course, this is a relatively preliminary study. We really need to test more players and to track players across seasons using brain imaging.”

When neurons have less to say, they say it with particular emphasis

The brain is an extremely adaptable organ – but it is also very conservative according to scientists from the Max Planck Institute of Neurobiology in Martinsried in collaboration with colleagues from the Friedrich Miescher Institute in Basel and the Ruhr Institute Bochum. The researchers succeeded in demonstrating that neurons in the brain regulate their own excitability so that the activity level in the network remains as constant as possible. Even in the event of major changes, for example the complete absence of information from a sensory organ, the almost silenced neurons re-establish levels of activity similar to their previous ones after only 48 hours. The mean activity level thus achieved is a basic prerequisite for a healthy brain and the formation of new connections between neurons – an essential capacity for regeneration following injury to the brain or a sensory organ, for example.

Neurons communicate using electrical signals. They transmit these signals to neighbouring cells via special contact points known as the synapses. When a new item of information presents for processing, the cells can develop new synaptic contacts with their neighbouring cells or strengthen existing ones. To enable forgetting, these processes are also reversible. The brain is consequently in a constant state of reorganisation, through which individual neurons are prevented from becoming either too active or too inactive. The aim is to keep the level of activity constant, as the long-term overexcitement of neurons can result in damage to the brain.

Too little activity is not good either. “The cells can only re-establish connections with their neighbours when they are ‘awake’, so to speak, that is when they display a minimum level of activity,” explains Mark Hübener, head of the recently published study. The international team of researchers succeeded in demonstrating for the first time that the brain itself compensates for massive changes in neuronal activity within a period of two days, and can return to a similar level of activity to that before the change.

Up to now, the only indication of this astonishing capacity of the brain came from cell cultures. It was also unclear as to how neurons could control their own excitability in relation to the activity of the entire network. Now, the scientists have made significant progress towards finding an answer to this question. In their study, they examined the visual cortex of mice that recently went blind. As expected, but never previously demonstrated, the activity of the neurons in this area of the brain did not fall to zero but to half of the original value. “That alone was an astonishing finding, as it shows the extent to which the visual cortex also processes information from other areas of the brain,” explains Tobias Bonhoeffer, who has been researching processes in the visual cortex at his department in the Max Planck Institute of Neurobiology for many years. “However, things really became exciting when we observed the area further over the following hours and days.”

The scientists were able, under the microscope, to witness “live” how the neurons in the visual cortex became active again. After just a few hours, they could clearly observe how the points of contact between the affected cells and neighbouring cells increased in size. When synapses get bigger, they also become stronger and signals are transmitted faster and more effectively. As a result of this intensification of the contact between the neurons, the activity of the affected network returned to its starting value after a period of between 24 and 48 hours. “To put it simply, due to the absence of visual input, the cells had less to say – but when they did say something, they said it with particular emphasis,” explains Mark Hübener.

Due to the simultaneous strengthening of all of the synapses of the affected neurons, major reductions in the neuronal activity can be normalised again with surprising speed. The relatively stable activity level thereby achieved is an essential prerequisite for maintaining a healthy, adaptable brain.

Study creates new memories by directly changing the brain

Findings could prove helpful in understanding and resolving learning and memory disorders

By studying how memories are made, UC Irvine neurobiologists created new, specific memories by direct manipulation of the brain, which could prove key to understanding and potentially resolving learning and memory disorders.

Research led by senior author Norman M. Weinberger, a research professor of neurobiology & behavior at UC Irvine, and colleagues has shown that specific memories can be made by directly altering brain cells in the cerebral cortex, which produces the predicted specific memory. The researchers say this is the first evidence that memories can be created by direct cortical manipulation. Study results appeared in the August 29 issue of Neuroscience.

During the research, Weinberger and colleagues played a specific tone to test rodents then stimulated the nucleus basalis deep within their brains, releasing acetylcholine (ACh), a chemical involved in memory formation. This procedure increased the number of brain cells responding to the specific tone. The following day, the scientists played many sounds to the animals and found that their respiration spiked when they recognized the particular tone, showing that specific memory content was created by brain changes directly induced during the experiment. Created memories have the same features as natural memories including long-term retention.

"Disorders of learning and memory are a major issue facing many people and since we’ve found not only a way that the brain makes memories, but how to create new memories with specific content, our hope is that our research will pave the way to prevent or resolve this global issue," said Weinberger, who is also a fellow with the Center for the Neurobiology of Learning & Memory and the Center for Hearing Research at UC Irvine.

The creation of new memories by directly changing the cortex is the culmination of several years of research in Weinberger’s lab implicating the nucleus basalis and ACh in brain plasticity and specific memory formation. Previously, the authors had also shown that the strength of memory is controlled by the number of cells in the auditory cortex that process a sound.

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)

Researchers discover how inhibitory neurons behave during critical periods of learning

We’ve all heard the saying “you can’t teach an old dog new tricks.” Now neuroscientists are beginning to explain the science behind the adage.

For years, neuroscientists have struggled to understand how the microcircuitry of the brain makes learning easier for the young, and more difficult for the old. New findings published in the journal Nature by Carnegie Mellon University, the University of California, Los Angeles and the University of California, Irvine show how one component of the brain’s circuitry — inhibitory neurons — behave during critical periods of learning.

The brain is made up of two types of cells — inhibitory and excitatory neurons. Networks of these two kinds of neurons are responsible for processing sensory information like images, sounds and smells, and for cognitive functioning. About 80 percent of neurons are excitatory. Traditional scientific tools only allowed scientists to study the excitatory neurons.

"We knew from previous studies that excitatory cells propagate information. We also knew that inhibitory neurons played a critical role in setting up heightened plasticity in the young, but ideas about what exactly those cells were doing were controversial. Since we couldn’t study the cells, we could only hypothesize how they were behaving during critical learning periods," said Sandra J. Kuhlman, assistant professor of biological sciences at Carnegie Mellon and member of the joint Carnegie Mellon/University of Pittsburgh Center for the Neural Basis of Cognition.

The prevailing theory on inhibitory neurons was that, as they mature, they reach an increased level of activity that fosters optimal periods of learning. But as the brain ages into adulthood and the inhibitory neurons continue to mature, they become even stronger to the point where they impede learning.

Newly developed genetic and imaging technologies are now allowing researchers to visualize inhibitory neurons in the brain and record their activity in response to a variety of stimuli. As a postdoctoral student at UCLA in the laboratory of Associate Professor of Neurobiology Joshua T. Trachtenberg, Kuhlman and her colleagues used these new techniques to record the activity of inhibitory neurons during critical learning periods. They found that, during heightened periods of learning, the inhibitory neurons didn’t fire more as had been expected. They fired much less frequently — up to half as often.

"When you’re young you haven’t experienced much, so your brain needs to be a sponge that soaks up all types of information. It seems that the brain turns off the inhibitory cells in order to allow this to happen," Kuhlman said. "As adults we’ve already learned a great number of things, so our brains don’t necessarily need to soak up every piece of information. This doesn’t mean that adults can’t learn, it just means when they learn, their neurons need to behave differently."

(Image credit)

Novel ‘top-down’ mechanism repatterns developing brain regions

Dennis O’Leary of the Salk Institute was the first scientist to show that the basic functional architecture of the cortex, the largest part of the human brain, was genetically determined during development. But as it so often does in science, answering one question opened up many others. O’Leary wondered what if the layout of the cortex wasn’t fixed? What would happen if it were changed?

In the August issue of Nature Neuroscience, O’Leary, holder of the Vincent J. Coates Chair of Molecular Neurobiology at Salk, and Andreas Zembrzycki, a postdoctoral researcher in his lab, demonstrate that altering the cortical layout is possible, and that this alteration produces significant changes in parts of the brain that connect with the cortex and define its functional properties. These mechanisms may lay at the heart of neural developmental problems, such as autism spectrum disorders (ASD).

The human cortex is involved in higher functions such as sensory perception, spatial reasoning, conscious thought and language. All mammals have areas in the cortex that process the senses, but they have them in different proportions. Mice, the favorite laboratory animal, are nocturnal, so they have a large somatosensory area (S1) in the cortex, responsible for somatosensation, or feelings of the body that include touch, pain, temperature and proprioception.

"The area layout of the cortex directly relates to the lifestyle of an animal," says Zembrzycki. "Areas are bigger or smaller according to the functional needs of the animal, not the physical size of the body parts from which they receive input."

Even with relative sizes to other species set in place, areas in the cortex of humans may differ greatly across individuals. Such variations may underlie why some people appear to be naturally better at certain perceptual tasks, such as hitting a baseball or detecting the details of visual illusions. In patients with neurological disorders, there is an even wider range of differences.

The neurons in S1 are arranged in functional groups called body maps according to the density of nerve endings in the skin; thus, there’s a larger group of neurons dedicated to the skin on the face, than the skin on the legs. Neurosurgeon Wilder Penfield famously illustrated this idea as a “sensory homunculus,” a cartoon of disproportionately sized body parts arching over the cortex. Mice have a similar “mouseunculus” in their cortex in which the body map of the facial whiskers is highly enlarged.

These perceptual maps are not set for life. For example, if innervation of a body part is diminished early in life during a critical period, its map may shrink, while other parts of the body map may grow in compensation. This is a version of “bottom-up plasticity,” in which external experience affects body maps in the brain.

In order to study cortical layout, O’Leary’s team altered a regulatory gene, Pax6, in the cortex in mice. In response, S1 became much smaller, demonstrating that Pax6 regulates its development. They found that the shrinkage in S1 subsequently affected other regions of the brain that feed sensory information into the cortex, but more interestingly, it also altered the body maps in these subcortical brain regions, overturning the idea that once established, these brain regions could only be changed by external experience. They dubbed this previously unknown phenomenon “top down plasticity.”

"Top-down plasticity complements in a reverse fashion the well-known bottom-up plasticity induced by sensory deprivation," says O’Leary.

Normally, the body map in S1 cortex mirrors similar body maps in the thalamus, the main switching station for sensory information, which transmits somatosensation from the body periphery to the S1 cortex through outgoing neural “wires” known as axons. In the newly discovered top-down plasticity, when S1 was made smaller, the sensory thalamus that feeds into it is also subsequently reduced in size.

But the story has a more intriguing twist. “According to our present knowledge about the development of sensory circuits, we anticipated that all body representations in S1 would be equally affected when S1 was made smaller,” says O’Leary. “It was a surprise to us that not only was the body map smaller, but some parts of it were completely missing. The specific deletion of parts of the body map is controlled by exaggerated competition for cortical resources dictated by S1 size and played out between the connections from thalamic neurons that form these maps in the cortex.”

"To put it in lay terms, ‘If you snooze, you lose,’" adds Zembrzycki. "Axons that differentiate later are preferentially excluded from the smaller S1 leading to the specific deletion of the body parts that they represent."

"The essential point about top-down plasticity is that altering the size and patterning of sensory cortex results in matching alterations in sensory thalamus through the selective death of thalamic neurons that normally would represent body parts absent from S1," Zembrzycki adds. "Therefore, a downstream part of the brain is repatterned to match the architecture in S1, resulting in aberrant wiring of the brain that has important implications for sensory perception and function. For example, autistics have very robust abnormalities in touching and other features of somatosensation."

O’Leary and Zembrzycki believe that this process provides significant insights into the development of autism and other neural disorders. “One of the hallmarks of the autistic brain early in development is the area profile seems to be abnormal, with for example, the frontal cortex being enlarged, while the overall cortex keeps its normal size,” says O’Leary. “It is implicit then that other cortical areas positioned behind the frontal areas, such as S1, would be reduced in size, and thalamus would exhibit defects that match those in sensory cortex, as has been shown to be the case in autistic patients.”