Posts tagged neuroscience

A team of scientists has identified the neurons used in certain types of motion detection—findings that deepen our understanding of how the visual system functions.

“Our results show how neurons in the brain work together as part of an intricate process used to detect motion,” says Claude Desplan, a professor in NYU’s Department of Biology and the study’s senior author.

The study, whose authors included Rudy Behnia, an NYU post-doctoral fellow, as well as researchers from the NYU Center for Neural Science and Yale and Stanford universities, appears in the journal Nature.

The researchers sought to explain some of the neurological underpinnings of a long-established and influential model, the Hassenstein–Reichardt correlator. It posits that motion detection relies on separate input channels that are processed in the brain in ways that coordinate these distinct inputs. The Nature study focused on neurons acting in this processing.

The researchers examined the fruit fly Drosophila, which is commonly used in biological research as a model system to decipher basic principles that direct the functions of the brain.

Previously, scientists studying Drosophila have identified two parallel pathways that respond to either moving light, or dark edges—a dynamic that underscores much of what flies see in detecting motion. For instance, a bird is an object whose dark edges flies see as it first moves across the bright light of the sky; after it passes through their field of view, flies see the light edge of the background sky.

However, the nature of the underlying neurological processing had not been clear.

In their study, the researchers analyzed the neuronal activity of particular neurons used to detect these movements. Specifically, they found that four neurons in the brain’s medulla implement two processing steps. Two neurons— Tm1 and Tm2—respond to brightness decrements (central to the detection of moving dark edges); by contrast, two other neurons— Mi1 and Tm3—respond to brightness increments (or light edges). Moreover, Tm1 responds slower than does Tm2 while Mi1 responds slower than does Tm3, a difference in kinetics that fundamental to the Hassenstein-Reichardt correlator.

In sum, these neurons process the two inputs that precede the coordination outlined by the Hassenstein–Reichardt correlator, thereby revealing elements of the long-sought neural activity of motion detection in the fly.

(Source: nyu.edu)

Johns Hopkins researchers say they have discovered a chemical alteration in a single human gene linked to stress reactions that, if confirmed in larger studies, could give doctors a simple blood test to reliably predict a person’s risk of attempting suicide.

The discovery, described online in The American Journal of Psychiatry, suggests that changes in a gene involved in the function of the brain’s response to stress hormones plays a significant role in turning what might otherwise be an unremarkable reaction to the strain of everyday life into suicidal thoughts and behaviors.

“Suicide is a major preventable public health problem, but we have been stymied in our prevention efforts because we have no consistent way to predict those who are at increased risk of killing themselves,” says study leader Zachary Kaminsky, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “With a test like ours, we may be able to stem suicide rates by identifying those people and intervening early enough to head off a catastrophe.”

For his series of experiments, Kaminsky and his colleagues focused on a genetic mutation in a gene known as SKA2. By looking at brain samples from mentally ill and healthy people, the researchers found that in samples from people who had died by suicide, levels of SKA2 were significantly reduced.

Within this common mutation, they then found in some subjects an epigenetic modification that altered the way the SKA2 gene functioned without changing the gene’s underlying DNA sequence. The modification added chemicals called methyl groups to the gene. Higher levels of methylation were then found in the same study subjects who had killed themselves. The higher levels of methylation among suicide decedents were then replicated in two independent brain cohorts.

In another part of the study, the researchers tested three different sets of blood samples, the largest one involving 325 participants in the Johns Hopkins Center for Prevention Research Study found similar methylation increases at SKA2 in individuals with suicidal thoughts or attempts. They then designed a model analysis that predicted which of the participants were experiencing suicidal thoughts or had attempted suicide with 80 percent certainty. Those with more severe risk of suicide were predicted with 90 percent accuracy. In the youngest data set, they were able to identify with 96 percent accuracy whether or not a participant had attempted suicide, based on blood test results.

The SKA2 gene is expressed in the prefrontal cortex of the brain, which is involved in inhibiting negative thoughts and controlling impulsive behavior. SKA2 is specifically responsible for chaperoning stress hormone receptors into cells’ nuclei so they can do their job. If there isn’t enough SKA2, or it is altered in some way, the stress hormone receptor is unable to suppress the release of cortisol throughout the brain. Previous research has shown that such cortisol release is abnormal in people who attempt or die by suicide.

Kaminsky says a test based on these findings might best be used to predict future suicide attempts in those who are ill, to restrict lethal means or methods among those a risk, or to make decisions regarding the intensity of intervention approaches.

He says that it might make sense for use in the military to test whether members have the gene mutation that makes them more vulnerable. Those at risk could be more closely monitored when they returned home after deployment. A test could also be useful in a psychiatric emergency room, he says, as part of a suicide risk assessment when doctors try to assess level of suicide risk.

The test could be used in all sorts of safety assessment decisions like the need for hospitalization and closeness of monitoring. Kaminsky says another possible use that needs more study could be to inform treatment decisions, such as whether or not to give certain medications that have been linked with suicidal thoughts.

“We have found a gene that we think could be really important for consistently identifying a range of behaviors from suicidal thoughts to attempts to completions,” Kaminsky says. “We need to study this in a larger sample but we believe that we might be able to monitor the blood to identify those at risk of suicide.”

(Source: hopkinsmedicine.org)

The researchers focused on a network of brain areas they have studied before. These areas are involved in making decisions, performing social tasks and identifying relevant events in the environment to guide behavior. The team’s prior work showed that, in children with autism, activity in these areas was more tightly connected when the brain was at rest than it was in children who didn’t have autism.

The new research shows that, in autism, connectivity in these networks that can be seen on fMRI scans is fairly similar regardless of whether the brain is at rest or performing a task. In contrast, typically developing children have a larger shift in brain connectivity when they perform tasks.

The study looked at 34 kids with autism and 34 typically developing children. All of the children with autism received standard clinical evaluations to characterize the severity of their disorder. Then, the two groups were split in half: 17 children with autism and 17 typically developing children had their brains scanned with fMRI while at rest and while performing simple arithmetic problems. The remaining children had their brains scanned at rest and during a task that asked them to distinguish between different people’s faces. The facial recognition task was chosen because autism is characterized by social deficits; the math task was chosen to reflect an area in which children with autism do not usually have deficits.

Children with autism performed as well as their typically developing peers on both tasks — that is, they were as good at distinguishing between the faces and solving the math problems. However, their brain scan results were different. In addition to the reduced brain flexibility, the researchers showed a correlation between the degree of inflexibility and the severity of restrictive and repetitive behaviors, such as performing the same routine over and over or being obsessed with a favorite topic.

“This is the first study that has examined how the patterns of intrinsic brain connectivity change with a cognitive load in children with autism,” Menon said. The research is the first to demonstrate that brain connectivity in children with autism changes less, relative to rest, in response to a task than the brains of other children, he added.

Guidance for new therapies

“The findings may help researchers evaluate the effects of different autism therapies,” said Kaustubh Supekar, PhD, a research associate and the other lead author of the study. “Therapies that increase the brain’s flexibility at switching from rest to goal-directed behaviors may be a good target, for instance.”

“We’re making progress in identifying a brain basis of autism, and we’re starting to get traction in pinpointing systems and signaling mechanisms that are not functioning properly,” Menon said. “This is giving us a better handle both in thinking about treatment and in looking at change or plasticity in the brain.”

(Source: med.stanford.edu)

Some people can handle stressful situations better than others, and it’s not all in their genes: Even identical twins show differences in how they respond.

(Image: iStockphoto)

Researchers have identified a specific electrical pattern in the brains of genetically identical mice that predicts how well individual animals will fare in stressful situations.

The findings, published July 29 in Nature Communications, may eventually help researchers prevent potential consequences of chronic stress — such as post-traumatic stress disorder, depression and other psychiatric disorders — in people who are prone to these problems.

“In soldiers, we have this dramatic, major stress exposure, and in some individuals it’s leading to major issues, such as problems sleeping or being around other people,” said senior author Kafui Dzirasa, M.D., Ph.D., an assistant professor of psychiatry and behavioral sciences at Duke University Medical Center and a member of the Duke Institute for Brain Sciences. “If we can find that common trigger or common pathway and tune it, we may be able to prevent the emergence of a range of mental illnesses down the line.”

In the new study, Dzirasa’s team analyzed the interaction between two interconnected brain areas that control fear and stress responses in both mice and men: the prefrontal cortex and the amygdala. The amygdala plays a role in the ‘fight-or-flight’ response. The prefrontal cortex is involved in planning and other higher-level functions. It suppresses the amygdala’s reactivity to danger and helps people continue to function in stressful situations.

Implanting electrodes into the brains of the mice allowed the researchers to listen in on the tempo at which the prefrontal cortex and the amygdala were firing and how tightly the two areas were linked — with the ultimate goal of figuring whether the electrical pattern of cross talk could help decide how well animals would respond when faced with an acute stressor.

Indeed, in mice that had been subjected to a chronically stressful situation — daily exposure to an aggressive male mouse for about two weeks — the degree to which the prefrontal cortex seemed to control amygdala activity was related to how well the animals coped with the stress, the group found.

Next the group looked at how the brain reacted to the first instance of stress, before the mice were put in a chronically stressful situation. The mice more sensitive to chronic stress showed greater activation of their prefrontal cortex-amygdala circuit, compared with resilient mice.

“We were really both surprised and excited to find that this signature was present in the animals before they were chronically stressed,” Dzirasa said. “You can find this signature the very first time they were ever exposed to this aggressive dangerous experience.”

Dzirasa hopes to use the signatures to come up with potential treatments for stress. “If we pair the signatures and treatments together, can we prevent symptoms from emerging, even when an animal is stressed? That’s the first question,” he said.

The group also hopes to delve further into the brain, to see whether the circuit-level patterns can interact with genetic variations that confer risk for psychiatric disorders such as schizophrenia. The new study will enable Dzirasa and other basic researchers to segregate stress-susceptible and resilient animals before they are subjected to stress and look at their molecular, cellular and systemic differences.

(Source: today.duke.edu)

By studying the injuries and aptitudes of Vietnam War veterans who suffered penetrating head wounds during the war, scientists are tackling — and beginning to answer — longstanding questions about how the brain works.

The researchers found that brain regions that contribute to optimal social functioning also are vital to general intelligence and to emotional intelligence. This finding bolsters the view that general intelligence emerges from the emotional and social context of one’s life.

The findings are reported in the journal Brain.

“We are trying to understand the nature of general intelligence and to what extent our intellectual abilities are grounded in social cognitive abilities,” said Aron Barbey, a University of Illinois professor of neuroscience, of psychology, and of speech and hearing science. Barbey (bar-BAY), an affiliate of the Beckman Institute and of the Institute for Genomic Biology at the U. of I., led the new study with an international team of collaborators.

Studies in social psychology indicate that human intellectual functions originate from the social context of everyday life, Barbey said.

“We depend at an early stage of our development on social relationships — those who love us care for us when we would otherwise be helpless,” he said.

Social interdependence continues into adulthood and remains important throughout the lifespan, Barbey said.

“Our friends and family tell us when we could make bad mistakes and sometimes rescue us when we do,” he said. “And so the idea is that the ability to establish social relationships and to navigate the social world is not secondary to a more general cognitive capacity for intellectual function, but that it may be the other way around. Intelligence may originate from the central role of relationships in human life and therefore may be tied to social and emotional capacities.”

The study involved 144 Vietnam veterans injured by shrapnel or bullets that penetrated the skull, damaging distinct brain tissues while leaving neighboring tissues intact. Using CT scans, the scientists painstakingly mapped the affected brain regions of each participant, then pooled the data to build a collective map of the brain.

The researchers used a battery of carefully designed tests to assess participants’ intellectual, emotional and social capabilities. They then looked for patterns that tied damage to specific brain regions to deficits in the participants’ ability to navigate the intellectual, emotional or social realms. Social problem solving in this analysis primarily involved conflict resolution with friends, family and peers at work.

As in their earlier studies of general intelligence and emotional intelligence, the researchers found that regions of the frontal cortex (at the front of the brain), the parietal cortex (further back near the top of the head) and the temporal lobes (on the sides of the head behind the ears) are all implicated in social problem solving. The regions that contributed to social functioning in the parietal and temporal lobes were located only in the brain’s left hemisphere, while both left and right frontal lobes were involved.

The brain networks found to be important to social adeptness were not identical to those that contribute to general intelligence or emotional intelligence, but there was significant overlap, Barbey said.

“The evidence suggests that there’s an integrated information-processing architecture in the brain, that social problem solving depends upon mechanisms that are engaged for general intelligence and emotional intelligence,” he said. “This is consistent with the idea that intelligence depends to a large extent on social and emotional abilities, and we should think about intelligence in an integrated fashion rather than making a clear distinction between cognition and emotion and social processing. This makes sense because our lives are fundamentally social — we direct most of our efforts to understanding others and resolving social conflict. And our study suggests that the architecture of intelligence in the brain may be fundamentally social, too.”

(Source: news.illinois.edu)

U of T researchers have found a missing link that helps to explain how ALS, one of the world’s most feared diseases, paralyses and ultimately kills its victims. The breakthrough is helping them trace a path to a treatment or even a cure.

“ALS research has been taking baby steps for decades, but this has recently started changing to giant leaps,” said Karim Mekhail, professor in the Faculty of Medicine’s Department of Laboratory Medicine and Pathobiology.  “The disease is linked to a large number of genes, and previously, every time someone studied one of them, it took them off in a different direction. Nobody could figure out how they were all connected.”

Mekhail and his team discovered the function of a crucial gene called PBP1 or ATAXIN2 that’s often missing in ALS, also known as Lou Gehrig’s Disease.  Learning how this gene functions has helped them connect a lot of dots.

“This is an extremely important finding that may help us to better understand and target the pathways involved in neurodegenerative disease,” said Lorne Zinman, professor of medicine at U of T and medical director of the ALS/Neuromuscular Clinic at Sunnybrook Health Sciences Centre. “The next step will be to determine if this finding is applicable to patients with ALS.”

The key lies in a peculiarity of the human genome. It starts with the DNA, the blueprint that contains all our genetic information. The DNA passes its information to the RNA, which floats off to make proteins that help run our bodies. However, without ATAXIN2, the RNA fails to float away. It becomes glued to the DNA and forms RNA-DNA hybrids, said Mekhail. These hybrids gum up the works and stop other RNA from fully forming. Pieces of half-created RNA debris clutter the cell, and cause more hybrids.

“We think the debris and hybrids are on the same team in a never-ending Olympic relay race,” said Mekhail. “Over time there’s a vicious cycle building up. If we can find a way to disrupt that cycle, theoretically we can control or reverse the disease.”

On that front, Mekhail made a very surprising discovery: reducing calories to the minimum necessary amount stops the hybrids from forming in cells missing ATAXIN2. He and his team are studying whether a simple, non-toxic dietary restriction could be used with ALS patients, especially in the early stages or for those at risk of ALS.

Mekhail discovered the hybrids and missing genes in yeast cells and his results were published as the cover article for the July 28 edition of the journal Developmental Cell. Now his team is replicating this research on tissue from ALS patients – with very encouraging preliminary results.

“Within the next decade or two, I think there’s going to be a revolution in treatment for ALS and all kinds of brain disease,” he said. “These hybrids are going to play a role not just in ALS but in a lot of disease.”

(Source: media.utoronto.ca)

Babies can learn what to fear in the first days of life just by smelling the odor of their distressed mothers, new research suggests. And not just “natural” fears: If a mother experienced something before pregnancy that made her fear something specific, her baby will quickly learn to fear it too — through the odor she gives off when she feels fear.

In the first direct observation of this kind of fear transmission, a team of University of Michigan Medical School and New York University studied mother rats who had learned to fear the smell of peppermint – and showed how they “taught” this fear to their babies in their first days of life through their alarm odor released during distress.

In a new paper in the Proceedings of the National Academy of Sciences, the team reports how they pinpointed the specific area of the brain where this fear transmission takes root in the earliest days of life.

Their findings in animals may help explain a phenomenon that has puzzled mental health experts for generations: how a mother’s traumatic experience can affect her children in profound ways, even when it happened long before they were born. 

The researchers also hope their work will lead to better understanding of why not all children of traumatized mothers, or of mothers with major phobias, other anxiety disorders or major depression, experience the same effects.

“During the early days of an infant rat’s life, they are immune to learning information about environmental dangers. But if their mother is the source of threat information, we have shown they can learn from her and produce lasting memories,” says Jacek Debiec, M.D., Ph.D., the U-M psychiatrist and neuroscientist who led the research.  

“Our research demonstrates that infants can learn from maternal expression of fear, very early in life,” he adds. “Before they can even make their own experiences, they basically acquire their mothers’ experiences. Most importantly, these maternally-transmitted memories are long-lived, whereas other types of infant learning, if not repeated, rapidly perish.”

Peering inside the fearful brain

Debiec, who treats children and mothers with anxiety and other conditions in the U-M Department of Psychiatry, notes that the research on rats allows scientists to see what’s going on inside the brain during fear transmission, in ways they could never do in humans.

He began the research during his fellowship at NYU with Regina Marie Sullivan, Ph.D., senior author of the new paper, and continues it in his new lab at U-M’s Molecular and Behavioral Neuroscience Institute.

The researchers taught female rats to fear the smell of peppermint by exposing them to mild, unpleasant electric shocks while they smelled the scent, before they were pregnant. Then after they gave birth, the team exposed the mothers to just the minty smell, without the shocks, to provoke the fear response. They also used a comparison group of female rats that didn’t fear peppermint.

They exposed the pups of both groups of mothers to the peppermint smell, under many different conditions with and without their mothers present.

Using special brain imaging, and studies of genetic activity in individual brain cells and cortisol in the blood, they zeroed in on a brain structure called the lateral amygdala as the key location for learning fears. During later life, this area is key to detecting and planning response to threats – so it makes sense that it would also be the hub for learning new fears.

But the fact that these fears could be learned in a way that lasted, during a time when the baby rat’s ability to learn any fears directly was naturally suppressed, is what makes the new findings so interesting, says Debiec.

The team even showed that the newborns could learn their mothers’ fears even when the mothers weren’t present. Just the piped-in scent of their mother reacting to the peppermint odor she feared was enough to make them fear the same thing.

Even when just the odor of the frightened mother was piped in to a chamber where baby rats were exposed to peppermint smell, the babies developed a fear of the same smell, and their blood cortisol levels rose when they smelled it.

And when the researchers gave the baby rats a substance that blocked activity in the amygdala, they failed to learn the fear of peppermint smell from their mothers. This suggests, Debiec says, that there may be ways to intervene to prevent children from learning irrational or harmful fear responses from their mothers, or reduce their impact.

 From animals to humans: next steps

The new research builds on what scientists have learned over time about the fear circuitry in the brain, and what can go wrong with it. That work has helped psychiatrists develop new treatments for human patients with phobias and other anxiety disorders – for instance, exposure therapy that helps them overcome fears by gradually confronting the thing or experience that causes their fear.

In much the same way, Debiec hopes that exploring the roots of fear in infancy, and how maternal trauma can affect subsequent generations, could help human patients. While it’s too soon to know if the same odor-based effect happens between human mothers and babies, the role of a mother’s scent in calming human babies has been shown.

Debiec, who hails from Poland, recalls working with the grown children of Holocaust survivors, who experienced nightmares, avoidance instincts and even flashbacks related to traumatic experiences they never had themselves. While they would have learned about the Holocaust from their parents, this deeply ingrained fear suggests something more at work, he says.

(Source: uofmhealth.org)

An evolutionarily ancient and tiny part of the brain tracks expectations about nasty events, finds new UCL research.

The study, published in Proceedings of the National Academy of Sciences, demonstrates for the first time that the human habenula, half the size of a pea, tracks predictions about negative events, like painful electric shocks, suggesting a role in learning from bad experiences.

Brain scans from 23 healthy volunteers showed that the habenula activates in response to pictures associated with painful electric shocks, with the opposite occurring for pictures that predicted winning money.

Previous studies in animals have found that habenula activity leads to avoidance as it suppresses dopamine, a brain chemical that drives motivation. In animals, habenula cells have been found to fire when bad things happen or are anticipated.

"The habenula tracks our experiences, responding more the worse something is expected to be," says senior author Dr Jonathan Roiser of the UCL Institute of Cognitive Neuroscience. "For example, the habenula responds much more strongly when an electric shock is almost certain than when it is unlikely. In this study we showed that the habenula doesn’t just express whether something leads to negative events or not; it signals quite how much bad outcomes are expected."

During the experiment, healthy volunteers were placed inside a functional magnetic resonance imaging (fMRI) scanner, and brain images were collected at high resolution because the habenula is so small. Volunteers were shown a random sequence of pictures each followed by a set chance of a good or bad outcome, occasionally pressing a button simply to show they were paying attention. Habenula activation tracked the changing expectation of bad and good events.

"Fascinatingly, people were slower to press the button when the picture was associated with getting shocked, even though their response had no bearing on the outcome." says lead author Dr Rebecca Lawson, also at the UCL Institute of Cognitive Neuroscience. "Furthermore, the slower people responded, the more reliably their habenula tracked associations with shocks. This demonstrates a crucial link between the habenula and motivated behaviour, which may be the result of dopamine suppression."

The habenula has previously been linked to depression, and this study shows how it could be involved in causing symptoms such low motivation, pessimism and a focus on negative experiences. A hyperactive habenula could cause people to make disproportionately negative predictions.

"Other work shows that ketamine, which has profound and immediate benefits in patients who failed to respond to standard antidepressant medication, specifically dampens down habenula activity," says Dr Roiser. "Therefore, understanding the habenula could help us to develop better treatments for treatment-resistant depression."

(Source: eurekalert.org)