Posts tagged cerebral cortex
Articles and news from the latest research reports.
3-D map of blood vessels in cerebral cortex holds suprises
Blood vessels within a sensory area of the mammalian brain loop and connect in unexpected ways, a new map has revealed.
The study, published June 9 in the early online edition of Nature Neuroscience, describes vascular architecture within a well-known region of the cerebral cortex and explores what that structure means for functional imaging of the brain and the onset of a kind of dementia.
David Kleinfeld, professor of physics and neurobiology at the University of California, San Diego, and colleagues mapped blood vessels in an area of the mouse brain that receives sensory signals from the whiskers.
The organization of neural cells in this brain region is well-understood, as was a pattern of blood vessels that plunge from the surface of the brain and return from the depths, but the network in between was uncharted. Yet these tiny arterioles and venules deliver oxygen and nutrients to energy-hungry brain cells and carry away wastes.
The team traced this fine network by filling the vessels with a fluorescent gel. Then, using an automated system, developed by co-author Philbert Tsai, that removes thin layers of tissue with a laser while capturing a series of images to reconstructed the three-dimensional network of tiny vessels.
The project focused on a region of the cerebral cortex in which the nerve cells are so well known that they can be traced to individual whiskers. These neurons cluster in “barrels,” one per whisker, a pattern of organization seen in other sensory areas as well.
The scientists expected each whisker barrel to match up with its own blood supply, but that was not the case. The blood vessels don’t line up with the functional structure of the neurons they feed.
"This was a surprise, because the blood vessels develop in tandem with neural tissue," Kleinfeld said. Instead, microvessels beneath the surface loop and connect in patterns that don’t obviously correspond to the barrels.
To search for patterns, they turned to a branch of mathematics called graph theory, which describes systems as interconnected nodes. Using this approach, no hidden subunits emerged, demonstrating that the mesh indeed forms a continous network they call the “angiome.”
The vascular maps traced in this study raise a question of what we’re actually seeing in a widely used kind of brain imaging called functional MRI, which in one form measures brain activity by recording changes in oxygen levels in the blood. The idea is that activity will locally deplete oxygen. So they wiggled whiskers on individual mice and found that optical signals associated with depleted oxygen centered on the barrels, where electrical recordings confirmed neural activity. Thus brain mapping does not depend on a modular arrangement of blood vessels.
The researchers also went a step further to calculate patterns of blood flow based on the diameters and connections of the vessels and asked how this would change if a feeder arteriole were blocked. The map allowed them to identify “perfusion domains,” which predict the volumes of lesions that result when a clot occludes a vessel. Critically, they were able to build a physical model of how these lesions form, as may occur in cases of human dementia.
(Image: Andreas Weil)
Changes in Brain Structure Found After Childhood Abuse
Different forms of childhood abuse increase the risk for mental illness as well as sexual dysfunction in adulthood, but little has been known about how that happens. An international team of researchers, including the Miller School’s Charles B. Nemeroff, M.D., Ph.D., Leonard M. Miller Professor and Chair of Psychiatry and Behavioral Sciences, has discovered a neural basis for this association. The study, published in the June 1 issue of the American Journal of Psychiatry, shows that sexually abused and emotionally mistreated children exhibit specific and differential changes in the architecture of their brain that reflect the nature of the mistreatment.
Researchers have known that victims of childhood abuse often suffer from psychiatric disorders later in life, including sexual dysfunction following sexual abuse. The underlying mechanisms mediating this association have been poorly understood. Nemeroff and a group of scientists led by Christine Heim, Ph.D., Director of the Institute of Medical Psychology at Charité University of Medicine Berlin, and Jens Pruessner, Ph.D., Director of the McGill Center for Studies in Aging at McGill University in Montreal, hypothesized that cortical changes during segments of mistreatment played a role. To study these potential changes, the researchers used magnetic resonance imaging (MRI) to examine the brains of 51 adult women who were exposed to various forms of childhood abuse.
The results showed a correlation between specific forms of maltreatment and thinning of the cortex in precisely the regions of the brain that are involved in the perception or processing of the type of abuse. Specifically, the somatosensory cortex in the area in which the female genitals are represented was significantly thinner in women who were victims of sexual abuse in their childhood. Similarly, victims of emotional mistreatment were found to have a reduction of the thickness of the cerebral cortex in specific areas associated with self-awareness, self-evaluation and emotional regulation.
“This is one of the first studies documenting long-term alterations in specific brain areas as a consequence of child abuse and neglect,” said Nemeroff, who is also Director of the Center on Aging. “The finding that specific types of early life trauma have discrete, long lasting effects on the brain that underlie symptoms in adults is an important step in developing novel therapies to intervene to reduce the often lifelong psychiatric/psychological burden of such trauma.”
“Our data point to a precise association between experience-dependent neural plasticity and later health problems,” said Heim. Pruessner agreed that the “large effect and the regional specificity in the brain that corresponds to the type of abuse is remarkable.”
The scientists speculate that a regional thinning of the cortex may serve as a protective mechanism, immediately shielding the child from the experience of the abuse by gating or blocking the sensory experience. However, that thinning of the cortical sections may lay the groundwork for the development of behavioral problems in adulthood. The results of this study extend the literature on neural plasticity and show that cortical representation fields can be smaller when certain sensory experiences are damaging or developmentally inappropriate.
Premature birth interrupts brain development
Imaging technique shows premature birth interrupts vital brain development processes, leading to reduced cognitive abilities in infants
Researchers from King’s College London have for the first time used a novel form of MRI to identify crucial developmental processes in the brain that are vulnerable to the effects of premature birth. This new study, published today in the Proceedings of the National Academy of Sciences (PNAS), shows that disruption of these specific processes can have an impact on cognitive function.
The researchers say the new techniques developed here will enable them to explore how the disruption of key processes can also cause conditions such as autism, and will be used in future studies to test possible treatments to prevent brain damage.
Scientists from King’s College London and Imperial College London used diffusion MRI – a type of imaging which looks at the natural diffusion of water – to observe the maturation of the cerebral cortex where much of the brain’s computing power resides. By analysing the diffusion of water in the cerebral cortex of 55 premature infants and 10 babies born at full term they mapped the growing complexity and density of nerve cells across the whole of the cortex in the months before the normal time of birth.
They found that during this period maturation was most rapid in areas of the brain relating to social and emotional processing, decision making, working memory and visual-spatial processing. These functions are often impaired after premature birth, and the researchers found that cortical development was reduced in preterm compared to full term infants, with the greatest effect in the most premature infants. When they re-examined the infants at two years of age, the preterm infants with the slowest cortical development performed less well on neurodevelopmental testing, demonstrating the longer-term impact of prematurity on cortical maturation.
Professor David Edwards, Director of the Centre for the Developing Brain at King’s, based at the Evelina Children’s Hospital, said: ‘The number of babies born prematurely is increasing, so it has never been more important to improve our understanding of how preterm birth affects brain development and causes brain damage. We know that prematurity is extremely stressful for an infant, but by using a new technique we are able to track brain maturation in babies to pinpoint the exact processes that might be affected by premature birth. Here we have used innovative ways to understand how the development of the cerebral cortex is affected.
‘These findings highlight a key stage of brain development where the neurons branch out to create a complex, mature structure. We can now see that this happens in the latter stages of development that would usually take place in healthy babies when they are still in the womb. This suggests that premature birth can interrupt this vital developmental process. It may explain why we sometimes see adverse effects on brain development in those born only slightly prematurely as we now know that this process is happening right up to the normal time of birth. With this study we found that the earlier a baby is born, the less mature the cortex structure. The weeks a baby loses in the womb really matter.
‘These new techniques we’ve developed to identify these crucial processes will allow us to examine how disruption caused by premature birth can lead to conditions such as autism and learning difficulties. We will also use the technique in future studies to test new treatments to prevent brain damage. It’s an extremely exciting step forward.’
(Source: kcl.ac.uk)
Pathway Competition Affects Early Differentiation of Higher Brain Structures
Sand-dwelling and rock-dwelling cichlids living in East Africa’s Lake Malawi share a nearly identical genome, but have very different personalities. The territorial rock-dwellers live in communities where social interactions are important, while the sand-dwellers are itinerant and less aggressive.
Those behavioral differences likely arise from a complex region of the brain known as the telencephalon, which governs communication, emotion, movement and memory in vertebrates – including humans, where a major portion of the telencephalon is known as the cerebral cortex. A study published this week in the journal Nature Communications shows how the strength and timing of competing molecular signals during brain development has generated natural and presumably adaptive differences in the telencephalon much earlier than scientists had previously believed.
In the study, researchers first identified key differences in gene expression between rock- and sand-dweller brains during development, and then used small molecules to manipulate developmental pathways to mimic natural diversity.
“We have shown that the evolutionary changes in the brains of these fishes occur really early in development,” said Todd Streelman, an associate professor in the School of Biology and the Petit Institute for Bioengineering and Biosciences at the Georgia Institute of Technology. “It’s generally been thought that early development of the brain must be strongly buffered against change. Our data suggest that rock-dweller brains differ from sand-dweller brains – before there is a brain.”
For humans, the research could lead scientists to look for subtle changes in brain structures earlier in the development process. This could provide a better understanding of how disorders such as autism and schizophrenia could arise during very early brain development.
The research was supported by the National Science Foundation and published online April 23 by the journal.
“We want to understand how the telencephalon evolves by looking at genetics and developmental pathways in closely-related species from natural populations,” said Jonathan Sylvester, a postdoctoral researcher in the Georgia Tech School of Biology and lead author of the paper. “Adult cichlids have a tremendous amount of variation within the telencephalon, and we investigated the timing and cause of these differences. Unlike many previous studies in laboratory model organisms that focus on large, qualitative effects from knocking out single genes, we demonstrated that brain diversity evolves through quantitative tuning of multiple pathways.”
In examining the fish from embryos to adulthood, the researchers found that the mbuna, or rock-dwellers, tended to exhibit a larger ventral portion of the telencephalon, called the subpallium – while the sand-dwellers tended to have a larger version of the dorsal structure known as the pallium. These structures seem to have evolved differently over time to meet the behavioral and ecological needs of the fishes. The team showed that early variation in the activity of developmental signals expressed as complementary dorsal-ventral gradients, known technically as “Wingless” and “Hedgehog,” are involved in creating those differences during the neural plate stage, as a single sheet of neural tissue folds to form the neural tube.
To specifically manipulate those two pathways, Sylvester removed clutches of between 20 and 40 eggs from brooding female cichlids, which normally incubate fertilized eggs in their mouths. At about 36 to 48 hours after fertilization, groups of eggs were exposed to small-molecule chemicals that either strengthened or weakened the Hedgehog signal, or strengthened or weakened the Wingless signal. The chemical treatment came while the structures that would become the brain were little more than a sheet of cells. After treatment, water containing the chemicals was replaced with fresh water, and the embryos were allowed to continue their development.
“We were able to artificially manipulate these pathways in a way that we think evolution might have worked to shift the process of rock-dweller telencephalon development to sand-dweller development, and vice-versa. Treatment with small molecules allows us incredible temporal and dose precision in manipulating natural development,” Sylvester explained. “We then followed the development of the embryos until we were able to measure the anatomical structures – the size of the pallium and subpallium – to see that we had transformed one to the other.”
The two different brain regions, the dorsal pallium and ventral subpallium, give rise to excitatory and inhibitory neurons in the forebrain. Altering the relative sizes of these regions might change the balance between these neuronal types, ultimately producing behavioral changes in the adult fish.
“Evolution has fine-tuned some of these developmental mechanisms to produce diversity,” Streelman said. “In this study, we have figured out which ones.”
The researchers studied six different species of East African cichlids, and also worked with collaborators at King’s College in London to apply similar techniques in the zebrafish.
As a next step, the researchers would like to follow the embryos through to adulthood to see if the changes seen in embryonic and juvenile brain structures actually do change behavior of adults. It’s possible, said Streelman, that later developmental events could compensate for the early differences.
The results could be of interest to scientists investigating human neurological disorders that result from an imbalance between excitatory and inhibitory neurons. Those disorders include autism and schizophrenia. “We think it is particularly interesting that there may be some adaptive variation in the natural proportions of excitatory versus inhibitory neurons in the species we study, correlated with their natural behavioral differences,” said Streelman.
How the brain folds to fit
During fetal development of the mammalian brain, the cerebral cortex undergoes a marked expansion in surface area in some species, which is accommodated by folding of the tissue in species with most expanded neuron numbers and surface area. Researchers have now identified a key regulator of this crucial process.
Different regions of the mammalian brain are devoted to the performance of specific tasks. This in turn imposes particular demands on their development and structural organization. In the vertebrate forebrain, for instance, the cerebral cortex – which is responsible for cognitive functions – is remarkably expanded and extensively folded exclusively in mammalian species. The greater the degree of folding and the more furrows present, the larger is the surface area available for reception and processing of neural information. In humans, the exterior of the developing brain remains smooth until about the sixth month of gestation. Only then do superficial folds begin to appear and ultimately dominate the entire brain in humans. Conversely mice, for example, have a much smaller and smooth cerebral cortex.
“The mechanisms that control the expansion and folding of the brain during fetal development have so far been mysterious,” says Professor Magdalena Götz, a professor at the Institute of Physiology at LMU and Director of the Institute for Stem Cell Research at the Helmholtz Center Munich. Götz and her team have now pinpointed a major player involved in the molecular process that drives cortical expansion in the mouse. They were able to show that a novel nuclear protein called Trnp1 triggers the enormous increase in the numbers of nerve cells which forces the cortex to undergo a complex series of folds. Indeed, although the normal mouse brain has a smooth appearance, dynamic regulation of Trnp1 results in activating all necessary processes for the formation of a much enlarged and folded cerebral cortex.
Levels of Trnp1 control expansion and folding
“Trnp1 is critical for the expansion and folding of the cerebral cortex, and its expression level is dynamically controlled during development,” says Götz. In the early embryo, Trnp1 is locally expressed in high concentrations. This promotes the proliferation of self-renewing multipotent neural stem cells and supports tangential expansion of the cerebral cortex. The subsequent fall in levels of Trnp1 is associated with an increase in the numbers of various intermediate progenitors and basal radial glial cells. This results in the ordered formation and migration of a much enlarged number of neurons forming folds in the growing cortex.
The findings are particularly striking because they imply that the same molecule – Trnp1 – controls both the expansion and the folding of the cerebral cortex and is even sufficient to induce folding in a normally smooth cerebral cortex. Trnp1 therefore serves as an ideal starting point from which to dissect the complex network of cellular and molecular interactions that underpin the whole process. Götz and her colleagues are now embarking on the next step in this exciting journey - determination of the molecular function of this novel nuclear protein Trnp1 and how it is regulated. (Cell 2013)
(Source: en.uni-muenchen.de)
Scientists probe the source of a pulsing signal in the sleeping brain
New findings clarify where and how the brain’s “slow waves” originate. These rhythmic signal pulses, which sweep through the brain during deep sleep at the rate of about one cycle per second, are assumed to play a role in processes such as consolidation of memory. For the first time, researchers have shown conclusively that slow waves start in the cerebral cortex, the part of the brain responsible for cognitive functions. They also found that such a wave can be set in motion by a tiny cluster of neurons.
"The brain is a rhythm machine, producing all kinds of rhythms all the time," says Prof. Arthur Konnerth of the Technische Universitaet Muenchen (TUM). "These are clocks that help to keep many parts of the brain on the same page." One such timekeeper produces the so-called slow waves of deep sleep, which are thought to be involved in transmuting fragments of a day’s experience and learning into lasting memory. They can be observed in very early stages of development, and they may be disrupted in diseases such as Alzheimer’s.
Previous studies, relying mainly on electrical measurements, have lacked the spatial resolution to map the initiation and propagation of slow waves precisely. But using light, Konnerth’s Munich-based team – in collaboration with researchers at Stanford and the University of Mainz – could both stimulate slow waves and observe them in unprecedented detail. One key result confirmed that the slow waves originate only in the cortex, ruling out other long-standing hypotheses. “The second major finding,” Konnerth says, “was that out of the billions of cells in the brain, it takes not more than a local cluster of fifty to one hundred neurons in a deep layer of the cortex, called layer 5, to make a wave that extends over the entire brain.”
New light on a fundamental neural mechanism
Despite considerable investigation of the brain’s slow waves, definitive answers about the underlying circuit mechanism have remained elusive. Where is the pacemaker for this rhythm? Where do the waves start, and where do they stop? This study – based on optical probing of intact brains of live mice under anesthesia – now provides the basis for a detailed, comprehensive view.
"We implemented an optogenetic approach combined with optical detection of neuronal activity to explore causal features of these slow oscillations, or Up-Down state transitions, that represent the dominating network rhythm in sleep," explains Prof. Albrecht Stroh of the Johannes Gutenberg University Mainz. Optogenetics is a novel technique that enabled the researchers to insert light-sensitive channels into specific kinds of neurons, to make them responsive to light stimulation. This allowed for selective and spatially defined stimulation of small numbers of cortical and thalamic neurons.
Access to the brain via optical fibers allowed for both microscopic recording and direct stimulation of neurons. Flashes of light near the mouse’s eyes were also used to stimulate neurons in the visual cortex. By recording the flux of calcium ions, a chemical signal that can serve as a more spatially precise readout of the electric activity, the researchers made the slow waves visible. They also correlated optical recordings with more conventional electrical measurements. As a result, it was possible to watch individual wave fronts spread – like ripples from a rock thrown into a quiet lake – first through the cortex and then through other brain structures.
A new picture begins to emerge: Not only is it possible for a tiny local cluster of neurons to initiate a slow wave that will spread far and wide, recruiting multiple regions of the brain into a single event – this appears to be typical. “In spontaneous conditions,” Konnerth says, “as it happens with you and me and everyone else every night in deep sleep, every part of the cortex can be an initiation site.” Furthermore, a surprisingly simple communication protocol can be seen in the slow wave rhythm. During each one-second cycle a single neuron cluster sends its signal and all others are silenced, as if they are taking turns bathing the brain in fragments of experience or learning, building blocks of memory. The researchers view these findings as a step toward a better understanding of learning and memory formation, a topic Konnerth’s group is investigating with funding from the European Research Council. They also are testing how the slow waves behave during disease.
Going Places: Rat Brain ‘GPS’ Maps Routes to Rewards
Research has implications for understanding memory and imagination
While studying rats’ ability to navigate familiar territory, Johns Hopkins scientists found that one particular brain structure uses remembered spatial information to imagine routes the rats then follow. Their discovery has implications for understanding why damage to that structure, called the hippocampus, disrupts specific types of memory and learning in people with Alzheimer’s disease and age-related cognitive decline. And because these mental trajectories guide the rats’ behavior, the research model the scientists developed may be useful in future studies on higher-level tasks, such as decision-making.
The details of their work were published online in the journal Nature on April 17.
“For the first time, we believe we have evidence that before a rat returns to an important place, it actually plans out its path,” says David Foster, Ph.D., assistant professor of neuroscience at the Johns Hopkins University School of Medicine. “The rat finds that location in its mind’s eye and knows how to get there.”
Foster and his team found that, at least for the purposes of navigation, the “mind’s eye” is located in the hippocampus, which is composed of two banana-shaped segments under the cerebral cortex on both sides of the brain. It is best known for creating memories. In people with Alzheimer’s, it is one of the first parts of the brain to sustain damage.
The Foster lab experiments focused on a group of neurons in the hippocampus called place cells because they are known to fire when animals are at a given location within a given environment. What was not known, Foster says, was how and when the brain uses that information.
By miniaturizing an existing technology, Foster and a postdoc in his lab, Brad Pfeiffer, Ph.D., were able to implant 20 microwires into each side of the hippocampus of four rats. The tiny wires let them record electrical activity from as many as 250 individual place cells at the same time, more than ever achieved before.
Over a two-week training period, the rats became familiar with the testing area which was surrounded by a variety of objects, so that the rats could tell where they were in relation to the objects outside. The space was 2 meters square with 36 tiny “dishes” placed at regular intervals in a grid. A single dish at a time would be filled with the rats’ reward: liquid chocolate.
The rats’ navigation tests involved as many as 40 sets of alternating “odd” and “even” trials per day. The odd trials required the rats to “forage” through the arena to find a chocolate-filled dish in a random location; the even trials required the rats to return each time to a “home” dish to receive their reward. While the rats fulfilled their tasks, the researchers recorded the firing of their place cells.
They found that as a rat travels randomly through the box without knowing where it needs to go, different combinations of place cells fire at each location along its path. The same set of cells fires every time the rat travels the same spot. These unique combinations of firings “mark” each spot in the rat’s brain and can be reconstructed into what seems like a virtual map, when needed.
When a rat is about to go to a specific location, e.g., “home,” place cells in its hippocampus fire in a sequence that creates a predictive path, which the rat then follows, somewhat like Hansel and Gretel following an imagined bread crumb trail.
Foster says that “unlike a Hansel and Gretel bread crumb trail, which only allows you to leave by the same route by which you entered, the rats’ memories of their surroundings are flexible and can be reconstructed in a way that allows them to ‘picture’ how to quickly get from point A to point B.” In order to do this, he says, the rats must already be familiar with the terrain between point A and point B, but, like a GPS, they don’t have to have previously started at point A with the goal of reaching point B.
Foster says the elderly can get lost easily, and research on aged mice shows that their place cells can fail to distinguish between different environments. His team’s research suggests that defective place cells would also affect a person’s ability to “look ahead” in their imaginations to predict a way home. Similarly, he says, higher-order brain functions, like problem solving, also require people to “look ahead” and imagine themselves in a different scenario.
“The hippocampus seems to be directing the movement of the rats, making decisions for them in real time,” says Foster. “Our model allows us to see this happening in a way that’s not been possible before. Our next question is, what will these place cells do when we put obstacles in the rats’ paths?”
Intuition results from training
A game of Japanese chess reveals how experts develop their capacity for rapid problem-solving
The superior capability of experts to rapidly solve problems depends largely on their intuition, and it has long been known that this is related to experience and training. Although many psychological models relating to the development of intuition have been proposed to explain this phenomenon, none have been validated, and the underlying neural mechanisms remain a mystery.
Keiji Tanaka and colleagues from the Cognitive Brain Mapping Laboratory and Support Unit for Functional Magnetic Resonance Imaging at the RIKEN Brain Science Institute have now shown that activity in the basal ganglia of the brain, which is related to the automatic, rapid information processing or intuition characteristic of experts, develops during the course of training. The work provides a first insight into the neural response of the brain to extended training and hints at ways to improve the efficiency of training experts in industry.
In earlier work, another research team led by Tanaka showed that amateur players of the Japanese chess-like game of shogi plotted their best next-moves consciously using the human brain’s highly developed cerebral cortex. In contrast, they found that in professional players an important part of this process was unconscious or intuitive and had shifted to the head of the caudate nucleus in the basal ganglia, a much older part of the brain. This would leave the cortex free for higher-level strategy, the researchers suggested. Yet it remained unclear as to whether this shift of neural activity was entirely due to training, or dependent to some extent on pre-existing ability.
Tanaka’s most recent experiments involved training 20 novices for 15 weeks in mini-shogi, a simplified version of shogi. After about two weeks and again at the end of the 15-week program, the intuition of the volunteers was tested through their ability to come up with the best next-move to end-phase patterns of mini-shogi games. To ensure the answers were intuitive, each problem was presented for just two seconds and participants had to respond within three seconds. During this process, brain activity was recorded using functional magnetic resonance imaging (fMRI). The researchers found that activity in the caudate nucleus developed over the training period, whereas activity in the cortex remained unchanged.
“This work should open a fruitful interaction between the cognitive psychology of expertise development and biological studies of the basal ganglia,” says Tanaka. “We now would like to elucidate what computations the caudate nucleus conducts in generating the best next-move.”
‘Brain waves’ challenge area-specific view of brain activity
Our understanding of brain activity has traditionally been linked to brain areas – when we speak, the speech area of the brain is active. New research by an international team of psychologists led by David Alexander and Cees van Leeuwen (Laboratory for Perceptual Dynamics) shows that this view may be overly rigid. The entire cortex, not just the area responsible for a certain function, is activated when a given task is initiated. Furthermore, activity occurs in a pattern: waves of activity roll from one side of the brain to the other.
The brain can be studied on various scales, researcher David Alexander explains: “You have the neurons, the circuits between the neurons, the Brodmann areas – brain areas that correspond to a certain function – and the entire cortex. Traditionally, scientists looked at local activity when studying brain activity, for example, activity in the Brodmann areas. To do this, you take EEG’s (electroencephalograms) to measure the brain’s electrical activity while a subject performs a task and then you try to trace that activity back to one or more brain areas.”
Activity waves
In this study, the psychologists explore uncharted territory: “We are examining the activity in the cerebral cortex as a whole. The brain is a non-stop, always-active system. When we perceive something, the information does not end up in a specific part of our brain. Rather, it is added to the brain’s existing activity. If we measure the electrochemical activity of the whole cortex, we find wave-like patterns. This shows that brain activity is not local but rather that activity constantly moves from one part of the brain to another. The local activity in the Brodmann areas only appears when you average over many such waves.”
Each activity wave in the cerebral cortex is unique. “When someone repeats the same action, such as drumming their fingers, the motor centre in the brain is stimulated. But with each individual action, you still get a different wave across the cortex as a whole. Perhaps the person was more engaged in the action the first time than he was the second time, or perhaps he had something else on his mind or had a different intention for the action. The direction of the waves is also meaningful. It is already clear, for example, that activity waves related to orienting move differently in children – more prominently from back to front – than in adults. With further research, we hope to unravel what these different wave trajectories mean.”
Some brain cells are better virus fighters
Viruses often spread through the brain in patchwork patterns, infecting some cells but missing others. New research at Washington University School of Medicine in St. Louis helps explain why. The scientists showed that natural immune defenses that resist viral infection are turned on in some brain cells but switched off in others.
“The cells that a pathogen infects can be a major determinant of the seriousness of brain infections,” says senior author Michael Diamond, MD, PhD, professor of medicine. “To understand the basis of disease, it is important to understand which brain regions are more susceptible and why.”
While some brain infections are caused by bacteria, fungi or parasites, often the cause is a virus, such as West Nile virus, herpesvirus or enteroviruses.
For their study, now available online in Nature Medicine, the researchers focused on granule cell neurons, a cell type that rarely becomes infected. They compared gene profiles in granule cells from the cerebellum with the activity in cortical neurons in the cerebral cortex, which are more vulnerable to infection.
The comparison revealed many differences, including a number of genes in cortical neurons that were less well-expressed—meaning that for those specific genes there were fewer copies of mRNA, the molecules that relay genetic information from DNA to the cell’s protein-making mechanisms.
Next, the researchers transferred individually 40 of those genes into cortical neurons and screened the cells for susceptibility to viral infection. The test highlighted three antiviral genes that are induced by interferon, an important immune system protein. When the expression level of these genes increased in cortical neurons, the cells’ susceptibility to viral infection decreased.
The researchers also identified mechanisms that make some of these changes in genetic programming happen: regulatory factors known as microRNA, and differences in the way DNA is modified in the cell nucleus, both of which can affect gene expression levels.
Some of the genetic changes are only helpful against specific viral families, while others are effective against a broader spectrum of viruses and bacteria. The scientists can’t say yet if the differences in infection susceptibility are driven by the need to prevent infection or if they are a byproduct of changes that help neurons in particular brain regions perform essential functions.
To learn more about how these innate immune genes help cells resist infection, Diamond and his colleagues are disabling them in the brains of mice.