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.”

Researcher Reveals the Brain Connections Underlying Accurate Introspection

The human mind is not only capable of cognition and registering experiences but also of being introspectively aware of these processes. Until now, scientists have not known if such introspection was a single skill or dependent on the object of reflection. Also unclear was whether the brain housed a single system for reflecting on experience or required multiple systems to support different types of introspection.

A new study by UC Santa Barbara graduate student Benjamin Baird and colleagues suggest that the ability to accurately reflect on perceptual experience and the ability to accurately reflect on memories were uncorrelated, suggesting that they are distinct introspective skills. The findings appear in the Journal of Neuroscience.

The researchers used classic perceptual decision and memory retrieval tasks in tandem with functional magnetic resonance imaging to determine connectivity to regions in the front tip of the brain, commonly referred to as the anterior prefrontal cortex. The study tested a person’s ability to reflect on his or her perception and memory and then examined how individual variation in each of these capacities was linked to the functional connections of the medial and lateral parts of the anterior prefrontal cortex.

"Our results suggest that metacognitive or introspective ability may not be a single thing," Baird said. "We actually find a behavioral dissociation between the two metacognitive abilities across people, which suggests that you can be good at reflecting on your memory but poor at reflecting on your perception, or vice versa."

The newly published research adds to the literature describing the role of the medial and lateral areas of the anterior prefrontal cortex in metacognition and suggests that specific subdivisions of this area may support specific types of introspection. The findings of Baird’s team demonstrate that the ability to accurately reflect on perception is associated with enhanced connectivity between the lateral region of the anterior prefrontal cortex and the anterior cingulate, a region involved in coding uncertainty and errors of performance.

In contrast, the ability to accurately reflect on memory is linked to enhanced connectivity between the medial anterior prefrontal cortex and two areas of the brain: the precuneus and the lateral parietal cortex, regions prior work has shown to be involved in coding information pertaining to memories.

The experiment assessed the metacognitive abilities of 60 participants at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, where Baird was a visiting researcher. The perceptual decision task consisted of visual displays with six circles of vertical alternating light and dark bars –– called Gabor gratings –– arranged around a focal point. Participants were asked to identify whether the first or second display featured one of the six areas with a slight tilt, not always an easy determination to make.

A classic in psychology literature, the memory retrieval task consisted of two parts. First, participants were shown a list of 145 words. They were then shown a second set of words and asked to distinguish those they had seen previously. After each stimulus in both the perceptual decision and the memory retrieval task, participants rated their confidence in the accuracy of their responses on a scale of 1 (low confidence) to 6 (high confidence).

"Part of the novelty of this study is that it is the first to examine how connections between different regions of the brain support metacognitive processes," Baird said. "Also, prior means of computing metacognitive accuracy have been shown to be confounded by all kinds of things, like how well you do the primary task or your inherent bias toward high or low confidence.

"Using these precise measures, we’re now beginning to drill down and see how different types of introspection are actually housed in the real human brain," Baird concluded. "So it’s pretty fascinating from that perspective."

Enigmatic Neurons Help Flies Get Oriented

Neurons deep in the fly’s brain tune in to some of the same basic visual features that neurons in bigger animals such as humans pick out in their surroundings. The new research is an important milestone toward understanding how the fly brain extracts relevant information about a visual scene to guide behavior.

As a tiny fruit fly navigates through its environment, it relies on visual landmarks to orient itself. Now, researchers at the Howard Hughes Medical Institute’s Janelia Farm Research Campus have identified neurons deep in the fly’s brain that tune in to some of the same basic visual features that neurons in bigger animals such as humans pick out in their surroundings. The new research is an important milestone toward understanding how the fly brain extracts relevant information about a visual scene to guide behavior.

In Vivek Jayaraman’s lab at Janelia, researchers are studying fly neural circuits with the goal of understanding fundamental principles of information processing. “Our hope is that over time we will get a clear picture of the neural transformations and algorithms involved in creating actions from sensory and motor information,” Vivek says. In a study published October 9, 2013, in the journal Nature, Vivek and postdoctoral researcher Johannes Seelig report on visual representations in a region of the fly brain thought to be important for visual learning.

Researchers have gathered compelling evidence that fruit flies recognize and remember visual features in their environment. Flies can use that information to seek out safe spaces or to avoid uncomfortable ones. Genetic studies have indicated that a region deep in the fly brain called the central complex is critical for these behaviors.

The central complex is found in the brains of insects and some crustaceans. “It’s not purely involved in visual learning, and is quite likely to be broadly important for sensory-motor integration in all these critters,” Vivek says, noting that in butterflies and locusts, the central complex may facilitate the use of polarized light for navigation during migration. Also, studies in cockroaches have found that it is important for turning in response to antennal touch. But in flies, no one had yet examined the activity of the neurons in the central complex to characterize their role. “It really was quite a mystery what was going on in this part of the fly brain,” Seelig says, adding that this study is only one step on a long road.

Technical limitations had prevented researchers from measuring neuronal activity in the fly’s central complex, where neurons are far smaller than they are in larger insects. Available techniques required flies to be immobilized, so scientists were limited to studying parts of the nervous system that detected sensory information, rather than those that processed that information or converted it into motor activity. But in 2010, Seelig and colleagues in Vivek’s lab at Janelia developed a method that enabled them to peer into the interior of a fly’s brain with a two-photon microscope, while the insect maintained the freedom to walk and move its wings. The microscope can detect genetically encoded proteins that light up when a nerve cell fires, due to the surge of calcium ions that accompanies a nerve impulse. “Once we had these tools, we really wanted to apply them to this central brain area,” Seelig says.

Using genetically modified strains of flies, Vivek and Seelig focused their experiments on specific classes of neurons and collected more comprehensive data about the activity of those populations than had been done in other species. They chose to zero in on a class of neurons known as ring neurons, on which the dendrites—the branching structures that connect to neighboring cells—were densely concentrated in specific spots within a region neighboring the central complex.

To test the ring neurons’ response to visual stimuli, Seelig placed the flies into a small virtual reality arena in which the flies could be presented with simple patterns of light. By monitoring the calcium-indicating dyes in the cells, Seelig could visualize nerve activity as each fly was exposed to different stimuli.

The researchers found that each neuron responded to visual stimuli in specific regions of the fly’s field of view. “Each cell seemed to have its receptive field in a slightly different area of that space,” Vivek explains. Further, they found that the orientation of the patterns that they projected onto the walls of the arena influenced the ring cells’ response: for example, vertical bars elicited a stronger response than horizontal bars for most cells.

Flies have an innate tendency to walk or fly toward vertically-oriented stimuli, but Vivek and Seelig were nonetheless surprised by the ring neurons’ strong bias towards detecting such patterns. Further, Seelig says, this preference for specific orientations parallels what others have found in larger animals. Neurons in the primary visual cortex of mammalian brains known as simple cells function similarly—identifying basic visual patterns and being tuned to their orientation. “A wide range of visual animals seem to use the same basic feature set when they break down the visual scene,” Vivek says, explaining that in humans, such simple features are combined by later brain regions into increasingly complex ones to eventually produce representations for faces.

He says it is not clear whether fruit flies reassemble the features in their visual field in the same way, or whether basic representations are instead converted directly into guidance for actions. “It’s an open question how complex a shape a fly needs to recognize and respond to,” he says.

The scientists also found that the ring neurons responded similarly to the visual environment regardless of whether the flies were stationary or walking. Flying diminished the response somewhat, but overall, Seelig says, visual patterns influenced the neurons’ activity far more than the insects’ behavior. “These particular neurons seem to filter out visual features, then send that information to other parts of the central complex that may transform that information into a behavioral signal. So this may be one of the major entry points for visual information to the region,” says Seelig.

Determining what happens next to the information received by ring neurons is an important question for Vivek and Seelig, who say they will expand their studies by testing the activity of other neurons in the central complex. “By marching through these networks, we hope to begin to understand how sensory information is integrated to make motor decisions,” Vivek explains.

Brain anatomy and language in young children

Language ability is usually located in the left side of the brain. Researchers studying brain development in young children who were acquiring language expected to see increasing levels of myelin, a nerve fiber insulator, on the left side. They didn’t: The larger myelin structure was already there. Their study underscores the importance of environment in language development.

Researchers from Brown University and King’s College London have gained surprising new insights into how brain anatomy influences language acquisition in young children.

Their study, published in the Journal of Neuroscience, found that the explosion of language acquisition that typically occurs in children between 2 and 4 years old is not reflected in substantial changes in brain asymmetry. Structures that support language ability tend to be localized on the left side of the brain. For that reason, the researchers expected to see more myelin — the fatty material that insulates nerve fibers and helps electrical signals zip around the brain — developing on the left side in children entering the critical period of language acquisition. But that is not what the research showed.

“What we actually saw was that the asymmetry of myelin was there right from the beginning, even in the youngest children in the study, around the age of 1,” said the study’s lead author, Jonathan O’Muircheartaigh, the Sir Henry Wellcome Postdoctoral Fellow at King’s College London. “Rather than increasing, those asymmetries remained pretty constant over time.”

That finding, the researchers say, underscores the importance of environment during this critical period for language.

O’Muircheartaigh is currently working in Brown University’s Advanced Baby Imaging Lab. The lab uses a specialized MRI technique to look at the formation of myelin in babies and toddlers. Babies are born with little myelin, but its growth accelerates rapidly in the first few years of life.

The researchers imaged the brains of 108 children between ages 1 and 6, looking for myelin growth in and around areas of the brain known to support language.

While asymmetry in myelin remained constant over time, the relationship between specific asymmetries and language ability did change, the study found. To investigate that relationship, the researchers compared the brain scans to a battery of language tests given to each child in the study. The comparison showed that asymmetries in different parts of the brain appear to predict language ability at different ages.

“Regions of the brain that weren’t important to successful language in toddlers became more important in older children, about the time they start school,” O’Muircheartaigh said. “As language becomes more complex and children become more proficient, it seems as if they use different regions of the brain to support it.”

Interestingly, the association between asymmetry and language was generally weakest during the critical language period.

“We found that between the ages of 2 and 4, myelin asymmetry doesn’t predict language very well,” O’Muircheartaigh said. “So if it’s not a child’s brain anatomy predicting their language skills, it suggests their environment might be more influential.”

The researchers hope this study will provide a helpful baseline for future research aimed at pinpointing brain structures that might predict developmental disorders.

“Disorders like autism, dyslexia, and ADHD all have specific deficits in language ability,” O’Muircheartaigh said. “Before we do studies looking at abnormalities we need to know how typical children develop. That’s what this study is about.”

“This work is important, as it is the first to investigate the relationship between brain structure and language across early childhood and demonstrate how this relationship changes with age,” said Sean Deoni, assistant professor of engineering, who oversees the Advanced Baby Imaging Lab. “The study highlights the advantage of collaborative work, combining expertise in pediatric imaging at Brown and neuropsychology from the King’s College London Institute of Psychiatry, making this work possible.”

What evolved first - a dexterous hand or an agile foot?

Resolving a long-standing mystery in human evolution, new research from the RIKEN Brain Science Institute indicates that early hominids developed finger dexterity and tool use ability before the development of bipedal locomotion.

Combining monkey and human behavior, brain imaging, and fossil evidence, a research team led by neurobiologist Dr. Atsushi Iriki and including Dr. Gen Suwa, an anthropologist from the University of Tokyo Museum, have overturned the common assumption that manual dexterity evolved after the development of bipedal locomotion freed hominid hands to use fingers for tool manipulation.

In a study published today in Philosophical Transactions of the Royal Society B, the researchers employed functional magnetic resonance imaging in humans and electrical recording from monkeys to locate the brain areas responsible for touch awareness in individual fingers and toes, called somatotopic maps. With these maps, the researchers confirmed previous studies showing that single digits in the hand and foot have discrete neural locations in both humans and monkeys.

However, the researchers found new evidence that monkey toes are combined into a single map, while human toes are also fused into a single map, but with the prominent exception of the big toe, which has its own map not seen in monkeys. These findings suggest that early hominids evolved dexterous fingers when they were still quadrupeds. Manual dexterity was not further expanded in monkeys, but humans gained fine finger control and a big toe to aid bipedal locomotion.

“In early quadruped hominids, finger control and tool use were feasible, while an independent adaptation involving the use of the big toe for functions like balance and walking occurred with bipedality,” the authors explained.

The brain study was supported by analysis of the well-preserved hand and feet bones of a 4.4 million year-old skeleton of the quadruped hominid Ardipithecus ramidus, a species with hand dexterity that preceded the human-monkey lineage split.

The findings suggest that the parallel evolution of two-legged locomotion and manual dexterity in hands and fingers in the human lineage were a consequence of adaptive pressures on ancestral quadrupeds for balance control by foot digits while retaining the critical capability for fine finger specialization.

“Evolution is not usually thought of as being accessible to study in the laboratory”, stated Dr. Iriki, “but our new method of using comparative brain physiology to decipher ancestral traces of adaptation may allow us to re-examine Darwin’s theories”.

How neurons enable us to know smells we like and dislike, whether to approach or retreat

Think of the smell of freshly baking bread. There is something in that smell, without any other cues – visual or tactile – that steers you toward the bakery.  On the flip side, there may be a smell, for instance that of fresh fish, that may not appeal to you. If you haven’t eaten a morsel of food in three days, of course, a fishy odor might seem a good deal more attractive.

How, then, does this work? What underlying biological mechanisms account for our seemingly instant, almost unconscious ability to determine how attractive (or repulsive) a particular smell is?  It’s a very important question for scientists who are trying to address the increasingly acute problem of obesity: we need to understand much better than we now do the biological processes underlying food selection and preferences.

New research by neuroscientists at Cold Spring Harbor Laboratory (CSHL), published in The Journal of Neuroscience, reveals a set of cells in the fruit fly brain that respond specifically to food odors. Remarkably, the team finds that the degree to which these neurons respond when the fly is presented different food odors – apple, mango, banana – predicts “incredibly well how much the flies will ‘like’ a given odor,” says the lead author of the research paper, Jennifer Beshel, Ph.D., a postdoctoral investigator in the laboratory of CSHL Professor Yi Zhong, Ph.D.

“We all know that we behave differently to different foods – have different preferences. And we also all know that we behave differently to foods when we are hungry,” explains Dr. Beshel. “Dr. Zhong and I wanted to find the part of the brain that might be responsible for these types of behavior. Is there somewhere in the brain that deals with food odors in particular? How does brain activity change when we are hungry? Can we manipulate such a brain area and change behavior?”

When Beshel and Zhong examined the response of neurons expressing a peptide called dNPF to a range of odors, they saw that they only responded to food odors. (dNPF is the fly analog of appetite-inducing Neuropeptide Y, found in people.) Moreover, the neurons responded more to these same food odors when flies were hungry. The amplitude of their response could in fact predict with great accuracy how much the flies would like a given food odor – i.e., move toward it; the scientists needed simply to look at the responses of the dNPF-expressing neurons. 

When they “switched off” these neurons, the researchers were able to make flies treat their most favored odor as if it were just air. Conversely, if they remotely turned these neurons “on,” they could make flies suddenly approach odors they previously had tried to avoid. 

As Dr. Beshel explains: “The more general idea is that there are areas in the brain that might be specifically involved in saying: ‘This is great, I should really approach this.’ The activity of neurons in other areas in the brain might only take note of what something is – is it apple? fish? — without registering or ascribing to it any particular value, whether about its intrinsic desirability or its attractiveness at a given moment.