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The Frequencies of Top-Down and Bottom-Up Visual Processing
By Jason von Stietz, M.A.
February 12, 2016
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Recent research suggests that the visual cortex processes information in two ways: top-down and bottom-up. Utilizing magnetoencephalography, researchers found that bottom-up information flowed through gamma waves whereas top-down information flowed through alpha-beta waves. The study was discussed in a recent article in NeuroScientistNews: 

 

In the brain, the visual cortex processes visual information and passes it from lower to higher areas of the brain. However, information also flows in the opposite direction, e.g. to direct attention to particular stimuli. But how does the brain know which path the information should take? Researchers at the Ernst Strüngmann Institute (ESI) for Neuroscience in Frankfurt in Cooperation with Max Planck Society have now demonstrated that the visual cortex of human subjects uses different frequency channels depending on the direction in which information is being transported. Their findings were only possible thanks to previous research with macaque monkeys. They might help to understand the cause of psychiatric illnesses in which the two channels appear to be mixed up. 
 

The terms “bottom-up” and “top-down” refer to processes by which the human brain processes information. “In the visual system, bottom-up communication occurs when information enters through the eyes and flows from lower to higher visual areas, i.e. from bottom to top,” explains Pascal Fries from the Ernst Strüngmann Institute for Neuroscience.

 

As soon as a person observes the environment, sensory input is continuously processed using the bottom-up principle. But how do we know that one piece of information is more important than another? Fries: “The top-down principle helps us to do this. The brain uses previous experiences to organize information in the present context and to make predictions on this basis.” The top-down flow therefore influences the bottom-up flow and steers our attention towards things that are important in the current situation. This can happen automatically, for example due to the sudden appearance of a threatening stimulus, as well as through attention, for example when we are looking for something or following instructions. “Many of our cognitive capabilities can only be explained by invoking this principle,” says Fries.

 

For the top-down principle to work, the brain requires mechanisms that pass information from higher to lower areas of the brain. The anatomical connections in the top-down direction are known for a long time, but how the information is sent through these connections has remained elusive.

 

Macaque monkeys helped Fries and his colleagues to get on the right track. First, they examined the bottom-up flow in the brains of those animals and found that it uses a particular frequency band of rhythmic neuronal activity, known as the gamma band, around 60 Hertz. Information flows from bottom to top, when rhythmic oscillatory activity of lower brain areas entrains the rhythm of the next higher area.

 

Subsequently, the neuroscientists discovered the channel for top-down information flow, namely the so-called alpha and beta frequency rhythms, between 10 and 20 Hertz. Thus, in essence, the hierarchically arranged areas of visual cortex use a separate frequency channel to send information from higher to lower areas.

 

In their present work, the researchers show that a very similar principle is at work in the human brain. “We knew the rhythms and wanted to look for them in the human brain,” explains Fries. To do this, they used a technique known as magnetoencephalography (MEG). MEG uses sensors outside the head to record the magnetic fields, which result from the electric currents of active nerve cells. The measurements allow conclusions to be drawn about the activity in certain areas of the brain. “In the raw MEG data, signals from several brain areas are mixed and have to be separated as well as possible using advanced mathematical methods,” says Fries.

 

This is one of the reasons why the investigations into the macaque brain were so important. As macaques have a very similar brain to humans, scientific insights obtained on macaques can often be transferred to humans. It was thanks to the previous work on the animals that the researchers were able to interpret the MEG measurements correctly.

 

In their experiments, the researchers demonstrate that the human brain also uses different frequency ranges for bottom-up and top-down signalling. Furthermore, the neurophysiologists were able to describe the hierarchical positioning of additional areas, some of which only present in the human brain. A total of 26 areas were investigated in the human brain.

 

The new findings might help us to better understand the causes of some psychiatric illnesses to one day be able to treat them. In some mental illnesses, the top-down and bottom-up flow seem to get mixed up. There are indications that in individuals with schizophrenia, the top-down flow does not interact with the bottom-up flow in a normal way. “A healthy person can distinguish between sensory inputs and their interpretation produced in higher areas. For example, they can see facial features in a cloud without thinking that the cloud is a face. Schizophrenic patients may think the face is real, potentially taking the top-down interpretation for a bottom-up sensation,” explains Fries.

 

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Brain Connectivity Related Ability to Learn New Language
By Jason von Stietz, M.A.
January 29, 2016
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Why do some adults find it easier to learn a second language than others do? Recent research suggests that one’s ability to learn a new language is related to brain connectivity. Researchers from McGill University found that fMRI scans showed the greater connectivity between the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA) in English speakers able to learn French more quickly than their peers. The article was discussed in a recent article of NeuroScientistNews: 

 

Learning a second language is easier for some adults than others, and innate differences in how the various parts of the brain “talk” to one another may help explain why, according to a new study published in The Journal of Neuroscience.

 

“These findings have implications for predicting language learning success and failure,” said study author Xiaoqian Chai.

 

The various regions of our brains communicate with each other even when we are resting and aren’t engaged in any specific tasks. The strength of these connections—called resting-state connectivity—varies from person to person, and differences have previously been linked to differences in behavior including language ability.

 

Led by Chai and Denise Klein, researchers at McGill University explored whether differences in resting-state connectivity relate to performance in a second language. To study this, the group at the Montreal Neurological Institute scanned the brains of 15 adult English speakers who were about to begin an intensive 12-week French course, and then tested their language abilities both before and after the course.

 

Using resting state functional magnetic resonance imaging (fMRI), the researchers examined the connectivity within the subjects’ brains prior to the start of the French course. They looked at the strength of connections between various areas in the brain and two specific language regions: an area of the brain implicated in verbal fluency, the left anterior insula/frontal operculum (AI/FO), and an area active in reading, the visual word form area (VWFA).  

 

The researchers tested the participants’ verbal fluency and reading speed both prior to the course and after its completion. To test verbal fluency, the researchers gave subjects a prompt and asked them to speak for two minutes in French. The researchers counted the number of unique words that were used correctly. To test reading speed, the researchers had participants read French passages aloud, and they calculated the number of words read per minute.

 

Participants with stronger connections between the left AI/FO and an important region of the brain’s language network called the left superior temporal gyrus showed greater improvement in the speaking test. Participants with greater connectivity between the VWFA and a different area of the left superior temporal gyrus language area in the left temporal lobe showed greater improvement in reading speed by the end of the 12-week course.

 

“The most interesting part of this finding is that the connectivity between the different areas was observed before learning,” said Arturo Hernandez, a neuroscientist at the University of Houston who studies second-language learning and was not involved in the study. “This shows that some individuals may have a particular neuronal activity pattern that may lend itself to better learning of a second language.” 

 

However, that doesn’t mean success at a second language is entirely predetermined by the brain’s wiring. The brain is very plastic, meaning that it can be shaped by learning and experience, Chai said.

 

The study is “a first step to understanding individual differences in second language learning,” she added. “In the long term it might help us to develop better methods for helping people to learn better.”

 

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Poverty Linked to Brain Connectivity and Depression
By Jason von Stietz, M.A.
January 25, 2016
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Poverty has been linked to a litany of negative outcomes. Now, altered brain connectivity is among them. Researchers at Washington University St. Louis found that that poverty was associated with reduced connectivity between the hippocampus and the amygdala and surrounding brain regions, which in turn, was associated with higher levels of depression. The study was discussed in a recent article in MedicalXpress: 

 

Many negative consequences are linked to growing up poor, and researchers at Washington University St. Louis have identified one more: altered brain connectivity.

 

Analyzing brain scans of 105 children ages 7 to 12, the researchers found that key structures in the brain are connected differently in poor children than in kids raised in more affluent settings. In particular, the brain's hippocampus—a structure key to learning, memory and regulation of stress—and the amygdala—which is linked to stress and emotion—connect to other areas of the brain differently in poor children than in kids whose families had higher incomes.

 

Those connections, viewed using functional MRI scans, were weaker, depending on the degree of poverty to which a child was exposed. The poorer the family, the more likely the hippocampus and amygdala would connect to other brain structures in ways the researchers characterized as weaker. In addition, poorer preschoolers were much more likely to have symptoms of clinical depression when they reached school age.

 

The study is available online Friday, Jan. 15, in The American Journal of Psychiatry.

 

"Our past research has shown that the brain's anatomy can look different in poor children, with the size of the hippocampus and amygdala frequently altered in kids raised in poverty," said first author Deanna M. Barch, PhD, chair of Washington University's Department of Psychological & Brain Sciences in Arts & Sciences, and the Gregory B. Couch Professor of Psychiatry at the School of Medicine. "In this study, we found that the way those structures connect with the rest of the brain changes in ways we would consider to be less helpful in regulating emotion and stress."

 

Those changes in connectivity also are related to a risk of clinical depression. Those in the study who were poor as preschoolers were more likely to be depressed at age 9 or 10.

 

Previous research from the same group of investigators had identified differences in the volume of gray matter and white matter, and the size and volume of the hippocampus and amygdala. But they also found that many of those changes could be overcome through nurturing from parents. That wasn't true, however, regarding changes in connectivity identified in the new study.

 

"Poverty is one of the most powerful predictors of poor developmental outcomes for children," said co-investigator Joan L. Luby, MD, the Samuel and Mae S. Ludwig Professor of Child Psychiatry and director of Washington University's Early Emotional Development Program. "Previously, we've seen that there may be ways to overcome some brain changes linked to poverty, but we didn't see anything that reversed the negative changes in connectivity present in poor kids."

 

The researchers measured poverty using what's called an income-to-needs ratio that takes into account a family's size and annual income. The current federal poverty level is $24,250 for a family of four.

 

Children raised in poverty tend to have poorer cognitive and educational outcomes and are at higher risk for psychiatric illnesses, including depression and antisocial behaviors. Researchers hypothesize that factors such as stress, adverse environmental exposures—including lead, cigarette smoke and poor nutrition—along with limited educational opportunities, can contribute to problems later in life.

 

But Barch emphasized that the link between poverty and poor outcomes doesn't necessarily lock a child into a difficult life.

 

"Many things can be done to foster brain development and positive emotional development," she said. "Poverty doesn't put a child on a predetermined trajectory, but it behooves us to remember that adverse experiences early in life are influencing the development and function of the brain. And if we hope to intervene, we need to do it early so that we can help shift children onto the best possible developmental trajectories."

 

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Stories Involving Personal Values Activate Default Mode Network
By Jason von Stietz
January 21, 2016
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Stories involving infidelity, politics, war, labor strikes, or abortion often tap into our most deeply held values. Recent research found that value-laden stories activate the default mode network, previously thought to activate as the brain’s autopilot. Researchers now believe the default mode network is activated as the brain works to find meaning in narrative. The study was discussed in a recent article in MedicalXpress: 

 

Everyone has at least a few non-negotiable values. These are the things that, no matter what the circumstance, you'd never compromise for any reason - such as "I'd never hurt a child," or "I'm against the death penalty."

 

Real-time brain scans show that when people read stories that deal with these core, protected values, the "default mode network" in their brains activates.

 

This network was once thought of as just the brain's autopilot, since it has been shown to be active when you're not engaged by anything in the outside world - but studies like this one suggest that it's actually working to find meaning in the narratives.

 

"The brain is devoting a huge amount of energy to whatever that network is doing. We need to understand why," said Jonas Kaplan of the USC Dornsife Brain and Creativity Institute. Kaplan was the lead author of the study, which was published on Jan. 7 in the journal Cerebral Cortex.

 

Kaplan thinks that it's not just that the brain is presented with a moral quandary, but rather that the quandary is presented in a narrative format.

 

"Stories help us to organize information in a unique way," he said.

 

To find relevant stories, the researchers sorted through 20 million blog posts using software developed at the USC Institute for Creative Technologies.

 

"We wanted to know how people tell stories in their daily lives. It was kind of like finding stories in their natural habitat," said Kaplan, assistant research professor of psychology at the Brain and Creativity Institute at the USC Dornsife College of Letters, Arts and Sciences.

 

That 20 million was pared down to 40 stories that each contained an example of a crisis involving a potentially protected value: cheating on a spouse, having an abortion, crossing a picket line, or getting in a fight.

 

Those stories were translated into Mandarin Chinese and Farsi, and then read by American, Chinese and Iranian participants in their native language while their brains were scanned by fMRI. They also answered general questions about the stories while being scanned.

 

Stories that participants said involved values that were protected to them activated the default mode network in their brain to a greater degree. In addition, the level of activation varied from culture to culture. On average, Iranians showed the greatest level of activation in the study, while the Chinese participants showed the least.

 

"Stories appear to be a fundamental way in which the brain organizes information in a practical and memorable manner. It is important to understand the neural mechanisms required to do this, and this study is a step in that direction," said Antonio Damasio, senior author of the study. Damasio is co-director of the Brain and Creativity Institute, holder of the David Dornsife Chair in Neuroscience and a professor of psychology and neurology.

 

It's not yet clear whether a value either is or is not protected, or whether the sacredness of a value is on a sliding scale. But in a nation where political beliefs are growing more polarized and entrenched, it's important to understand what biological processes lie at the root of these values, Kaplan said.

 

"People will often hold political values as protected values and protected values are at the root of many political conflicts around the world, which is why they're interesting to us," he said.

 

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Brainwaves Spread Through Mild Electrical Field
By Jason von Stietz, M.A.
January 15, 2016
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Scientists once thought that the brain’s electrical endogenous fields were too weak to propagate transmission. However, recent findings from researchers from Case Western Reserve University suggested that brainwaves spread through a mild electrical field. The study was discussed in a recent article in MedicalXpress: 

 

Researchers at Case Western Reserve University may have found a new way information is communicated throughout the brain.

 

Their discovery could lead to identifying possible new targets to investigate brain waves associated with memory and epilepsy and better understand healthy physiology.

 

They recorded neural spikes traveling at a speed too slow for known mechanisms to circulate throughout the brain. The only explanation, the scientists say, is the wave is spread by a mild electrical field they could detect. Computer modeling and in-vitro testing support their theory.

 

"Others have been working on such phenomena for decades, but no one has ever made these connections," said Steven J. Schiff, director of the Center for Neural Engineering at Penn State University, who was not involved in the study. "The implications are that such directed fields can be used to modulate both pathological activities, such as seizures, and to interact with cognitive rhythms that help regulate a variety of processes in the brain."

 

Scientists Dominique Durand, Elmer Lincoln Lindseth Professor in Biomedical Engineering at Case School of Engineering and leader of the research, former graduate student Chen Sui and current PhD students Rajat Shivacharan and Mingming Zhang, report their findings in The Journal of Neuroscience.

 

"Researchers have thought that the brain's endogenous electrical fields are too weak to propagate wave transmission," Durand said. "But it appears the brain may be using the fields to communicate without synaptic transmissions, gap junctions or diffusion."

 

How the fields may work

 

Computer modeling and testing on mouse hippocampi (the central part of the brain associated with memory and spatial navigation) in the lab indicate the field begins in one cell or group of cells.

 

Although the electrical field is of low amplitude, the field excites and activates immediate neighbors, which, in turn, excite and activate immediate neighbors, and so on across the brain at a rate of about 0.1 meter per second.

 

Blocking the endogenous electrical field in the mouse hippocampus and increasing the distance between cells in the computer model and in-vitro both slowed the speed of the wave.

 

These results, the researchers say, confirm that the propagation mechanism for the activity is consistent with the electrical field.

 

Because sleep waves and theta waves—which are associated with forming memories during sleep—and epileptic seizure waves travel at about 1 meter per second, the researchers are now investigating whether the electrical fields play a role in normal physiology and in epilepsy.

 

If so, they will try to discern what information the fields may be carrying. Durand's lab is also investigating where the endogenous spikes come from.

 

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Prosocial Behavior Linked to Amygdala
By Jason von Stietz, M.A.
December 30, 2015
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Researchers studying social behavior of rhesus monkeys found amgydala activation linked to prosocial or charitable behavior. Findings suggested that when rhesus monkeys were faced with a task of either donating or withholding rewards to others, activation of the amgydala reflected the value of the rewards delivered. The study was discussed in a recent article in MedicalXpress:    

 

The amygdala, a small structure at the front end of the brain's temporal lobe, has long been associated with negative behaviors generally, and specifically with fear. But new research from Michael Platt, the James S. Riepe University Professor in the psychology, neuroscience and marketing departments at the University of Pennsylvania, along with Steve Chang from Yale University and collaborators from Duke, shows this collection of nuclei can also influence positive social functions like kindness and what might be called charitable giving in humans.

 

Such a link could have implications for people with autism, schizophrenia or anxiety-related disorders, Platt said.

 

"What we're trying to do is both identify and understand the basic brain mechanism that allows us to be kind to each other and to respond to the experiences of other individuals," he said. "We're also trying to use that knowledge to evaluate potential therapies that could improve the function of these neural circuits, especially for those who have difficulty connecting with others."

 

To make this discovery about the amygdala, Platt and his team looked at the social behavior of rhesus macaques, a non-human primate species he has studied for 22 years both in the lab and in the wild, on an island off of Puerto Rico called Cayo Santiago. The researchers incorporated a task they developed four years ago as a way to observe how animals make beneficial decisions, a process Platt described as a reward-donation task.

 

"We have an actor monkey and a recipient monkey. The actor monkey learns that different-colored shapes on the screen are associated with a reward that can be delivered to himself, to the monkey next to him, to both or to nobody at all," he said. "They learn that over a couple of weeks."

 

Once the researchers determine the monkeys understand the task, based on how quickly the macaques respond to the rewards, they then present the actor monkey with choices and their accompanying potential rewards. The primates can keep the reward (in this case, a squirt of juice), share it, give it away or let it go to waste.

 

"Generally our actor monkeys prefer to reward the other monkey rather than let it go unclaimed," Platt said. Relationship status matters, too. "They are more likely to give to those they're more familiar with," he added, "and also to monkeys subordinate to them. The social relationships shape how prosocial the actor monkeys are."

 

Simultaneous to watching the monkeys' behavior, Platt and his colleagues recorded the neural activity of the amygdala of each animal, to note any correlations between what's happening in the brain and their outward actions. They found that neural activity in the amygdala reflected the value of the recipient's reward in the same way it reflected the value of the reward for the actor. The scientists could predict when actors would give rewards to the recipients based on these neural responses.

 

When oxytocin was introduced, behaviors changed rapidly. Oxytocin is a hormone linked to social bonds between individuals. In animals, it's been shown to create strong ties between mother and offspring, as well as male and female partners in certain monogamous animals. Though not definitive, research on how oxytocin affects humans has, in some cases, shown to help those with autism better read and understand social cues.

 

"We don't really know how it works in people. It's very difficult to study. When people inhale oxytocin, there is a change in blood flow to the amygdala, which we think might be involved in making people kinder and more receptive to others," Platt said. In his experiment, the monkeys receiving oxytocin became more willing to give to other monkeys and paid more attention to them after offering the rewards.

 

Rhesus macaques offer a valuable comparison to humans because the animals model many of the social behaviors in which humans engage. They also live in large social groups and form what Platt described as long-term social bonds.

 

"Not only with relatives but non-relatives, too. You can think of these as friendships or alliances, and they work hard to maintain them," he said. "Just like humans, the stronger these bonds the monkeys have, the more successful they are. Monkeys with more friends and better friends live longer and have more offspring."

 

Thanks to funding from the Simons Foundation, the next phase of this research will focus on the part of the brain that identifies social context, for example, determining who is nearby, for what reason and what effect each decision will have on them.

 

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Social Decision-Making in Autism
By Jason von Stietz, M.A.
December 23, 2015
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It is widely believed that individuals with autism lack the capacity to read social cues. However, recent findings suggest autism affects not how social information is processed but how the information is used in decision making. The study was discussed in a recent article in MedicalXpress:  

 

Scientists at the Max Planck Institute of Psychiatry in Munich together with colleagues in Cologne and Zürich have used mathematical models to explain differences in social behaviour associated with autistic personality traits. They show that autistic traits do not – as previously thought – stop the individual from "reading" social cues, but instead affect how social information is used in making decisions. This new understanding provides a new basis for future research that will improve therapies for people with autism.

 

Autism spectrum disorder is a common psychiatric disorder that is characterized from childhood onwards by major impairments in social interaction and communication. About one half of autistic individuals are "high-functioning" as they have no intellectual impairment. However, all are severely limited in their social and professional life, which is why so many people with autism also suffer from depression. It has been suggested that autistic individuals may not "read" social cues and as a result do not respond to them properly. Alternatively, it has been suggested they are unable to empathize, thereby leading to social problems.

 

Leonhard Schilbach, consultant psychiatrist and Research Group leader at the Max Planck Institute of Psychiatry, explains "we have shown in this study that autistic trait-related differences in social behaviour are not due to a general inability to process social cues, but are related to the way social information is taken into account during decision-making".

 

It is thought that reading cues and making decisions involve an interplay between "expectations" generated in higher brain areas and signals from lower sensory brain areas. Normally, the behaviour of others that causes the sensory signal is interpreted in comparison to such "expectations". This allows individuals to regulate their behaviour in a context-sensitive and socially adequate way. In contrast to this, autism might be the result of an imbalance in this interplay, with a stronger reliance on sensory signals.

 

Computational modeling uses mathematical descriptions to characterize the variables that underlie social behaviour. Previous research has shown that humans do not only "read" the overt behaviour of others, but also the intentions that underlie and motivate the behaviour and use this information when making. Lead scientist Leonhard Schilbach explains, "we used a computational approach to investigate whether differences in social decision-making observed in people who are high or low in autistic traits are related to an inability to monitor others' intentions".

 

Schilbach and colleagues found that higher autistic traits do not impair the ability to process social information per se, but rather how this information influences decision-making. Furthermore, it was observed that individuals high in autistic traits found it harder to optimally use social information during unpredictable situations. It is hoped that this new insight into the autism spectrum will provide improved interventions for patients. Furthermore, the computational approach used in this study could also help to characterize social difficulties in other psychiatric disorders.

 

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Enhancing Experience-Dependent Neuroplasticity
By Jason von Stietz, M.A.
December 19, 2015
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Experience-dependent neuroplasticity, the brain’s capacity to change in response to environmental stimuli and learning, is a fundamental property of the brain. The impairment of this function in the brain is related to many psychiatric disorders including depression and bipolar disorder. Researchers recently studied the effect of D-cycloserine on the brain’s capacity for experience-dependent neuroplasticity (measured by EEG). The study was recently discussed in an article in MedicalXpress: 

 

In a recent study published in the Proceedings of the National Academy of Sciences, a group of researchers from various U.S. colleges have collaborated to determine if augmenting the signaling of a particular brain receptor would boost neuroplasticity in adults. During early development, experience-dependent neuroplasticity actually interacts with genetic programming in order to establish the neuronal organization and functionally connected circuits that characterize the mature brain.

 

This basic circuitry is well established by early adulthood, but throughout the lifespan, adult brains depend on experience-dependent neuroplasticity to enable new behavior patterns. Given the general acceptance of the relatively new idea that neuroplasticity endures in adults, the ability to augment its mechanisms could yield new approaches to associated psychiatric disorders. Here, the researchers sought to determine if augmenting N-methyl-D-aspartate receptor (NMDAR) signaling would promote experience-dependent plasticity. They tested a drug called D-cycloserine (DCS) on a group of participants who were monitored via a recently developed EEG paradigm for changes in plasticity.

 

The participants, divided into groups that received either DCS or placebo, engaged in three cognitive tasks: A weather prediction task, an information integration task and an n-back task, once before administration of DCS or placebo, and again 31 hours later. They determined that participants who received DCS showed greater potentiation of plasticity following the high-frequency visual stimuli of the tests than did those who received placebo. "Our findings of enhanced acquisition of the weather prediction task and the information integration task are consistent with other findings of enhanced incremental learning following DCS administration, including on category learning, motor learning, and mental rotation learning tasks," the authors write.

 

They note that the performance of DCS participants on the n-back test, which was a spatial working memorytask, did not differ measurably from the performance of those receiving placebo. They note that this result is consistent with a growing body of evidence that the transient memory underlying working memory is modulated in a fundamentally different way than experience-dependent neuroplasticity.

 

While noting the limitation that the study was restricted to healthy young adults, the authors conclude that their results strongly suggest that enhancing NMDAR signaling augments experience-dependent plasticity in adult brains across a variety of tasks that leverage that ability. "These findings suggest exciting possibilities for using NMDAR agonists to help ameliorate plasticity deficits in neurodegenerative and psychiatric disorders. Our results complement a growing literature that suggests that DCS can enhance new learning during cognitive behavioral therapy interventions and cognitive training programs."

 

The researchers suggest that parallel studies in older adults and patient groups are an obligatory next step in assessing DCS as a therapeutic intervention for psychiatric disorders.

 

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Surgical Treatment of TBI in Older Adults
By Jason von Stietz, M.A.
November 30, 2015
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Researches at the Helsinki University Hospital Department of Neurosurgery investigated these use of surgery to treat acute subdural hemotomas in patients over the age of 75. Previously, older adult patients were not treated surgically, as the rates of patents who survived and recovered successfully were low. However, new findings show that older adult patients who lived independently before the accident, were not taking anticoagulants, and who arrived at the hospital conscious received were treated successfully through surgery. The study was discussed in a recent article in NeuroScientistNews: 

 

According to a study completed at the Helsinki University Hospital Department of Neurosurgery, even patients over the age of 75 may recover from severe traumatic brain injury. This is the first study to describe the results of surgically treated elderly patients with acute subdural hematomas.

 

It is generally accepted that elderly patients who suffer from an acute subdural hematoma should not be treated surgically, as few survive and even fewer recover to an independent life. However, the world's population is rapidly aging leading to an increased rate of fall accidents. In the worst case, falling may result in brain hemorrhage.

 

Age is one of the most significant outcome predictors in patients with traumatic brain injury. If the patient is young, an acute subdural hematoma is normally treated through a neurosurgical operation. However, even among young patients, mortality and significant morbidity are highly common, despite surgical treatment. In older patients, the success rate of the surgery are made worse by the fact that many patients are typically using oral anticoagulant medications to treat other cardiovascular diseases.

 

The Neurosurgical Department in Helsinki University Hospital has been an exception in its policy to also treat elderly patients with acute subdural hematomas surgically. Researchers from the University of Helsinki and Helsinki University Hospital have now determined how the patients' functional status before the injury and the use of oral anticoagulant medications influence the prognosis of patients 75 years or older operated on for an acute subdural hematoma.

 

The study showed that no patients who had been brought to hospital unconscious, who had not been independent before the trauma, or who had used anticoagulants were alive at one year after the surgery.

 

"What was surprising, however, was that patients who were conscious at presentation, who were not using anticoagulants or were independent before the operation, recovered quite well. The expected lifespan of these patients was comparable to their age-matched peers," says MD, PhD Rahul Raj, one of the main authors.

 

"One should be careful to make to strong conclusions from such a small number of patients," Raj points out, "but it seems that in approximately half of all cases, even elderly patients may benefit from surgery and recover to an independent life. It is important to note that included patients had an isolated acute subdural hematoma with no injuries to the brain tissue itself. This means that the results cannot be applied to patients with contusions or other intracranial injuries, whose treatment and prognosis are different."

 

The decision to operate should not be based on age alone

 

According to Raj, the study throws new light on the old assumption that surgical treatment of the elderly is not a sensible course of action: "The decision to treat through surgery should not be based on age alone, even though this is common."

 

Surgery of an acute subdural hematoma followed by intensive care and rehabilitation involve major costs and can cause significant suffering to patients and relatives. Thus, it is important to perform surgery on only the patients who are likely to benefit from it.

 

"But how do you define a bad prognosis? If only one in ten patients recovers sufficiently to live at home, is the treatment worthwhile? If half of the treated patients die within the year, is the treatment worthwhile? This is not a medical decision," the researchers emphasize. They believe that in the future, surgical treatment will be increasingly restricted to patients with the highest likelihood of recovering.

 

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Brain's Stress Circuitry Involved in Alzheimer's Disease Treatment
By Jason von Stietz, M.A.
November 27, 2015
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Researchers at the University of San Diego School of Medicine investigated the use of a small molecule drug in preventing and treating Alzheimer’s disease in mice. Researchers found that the drug significantly reduces activity of the stress circuitry in the brains of the mice and resulted in the prevention of neurodegeneration and cognitive impairment. The study was discussed in a recent article of NeuroScientistNews:

 

The findings are described in the current online issue of the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

 

The results underscore the complexity and diversity of AD, whose causes appear to be a mix of genetic, lifestyle and environmental factors. Previous research has shown a link between the brain’s stress signaling pathways and AD. Specifically, the release of a stress-coping hormone called corticotropin-releasing factor (CRF), which is widely found in the brain and acts as a neurotransmitter/neuromodulator, is dysregulated in AD and is associated with impaired cognition and with detrimental changes in tau protein and increased production of amyloid-beta—protein fragments that clump together and trigger the neurodegeneration characteristic of AD.

 

“Our work and that of our colleagues on stress and CRF have been mechanistically implicated in Alzheimer’s disease, but agents that impact CRF signaling have not been carefully tested for therapeutic efficacy or long-term safety in animal models,” said the study’s principal investigator and corresponding author Robert Rissman, PhD, assistant professor in the Department of Neurosciences and Biomarker Core Director for the Alzheimer’s Disease Cooperative Study (ADCS).

 

“The novelty of this study is two-fold: We used a preclinical prevention paradigm of a CRF-antagonist (a drug that blocks the CRF receptor in brain cells) called R121919 in a well-established AD model – and we did so in a way that draws upon our experience in human trials. We found that R121919 antagonism of CRF-receptor-1 prevented onset of cognitive impairment and synaptic/dendritic loss in AD mice.”

 

In other words, the researchers determined that modulating the mouse brain’s stress circuitry (without actually changing the normal response) mitigated generation and accumulation of amyloid plaques widely attributed with causing neuronal damage and death. As a consequence, behavioral indicators of AD were prevented and cellular damage was reduced.  The mice began treatment at 30-days-old – before any pathological or cognitive signs of AD were present – and continued until six months of age.

 

One particular challenge, Rissman noted, is limiting exposure of the drug to the brain so that it does not impact the body’s ability to response to stress. “This can be accomplished because one advantage of these types of small molecule drugs is that they readily cross the blood-brain barrier and actually prefer to act in the brain,” Rissman said. Drugs like R121919 were originally designed to treat generalized anxiety disorder, irritable bowel syndrome and other diseases, but failed to be effective in treating those disorders.

 

“Rissman’s prior work demonstrated that CRF and its receptors are integrally involved in changes in another AD hallmark, tau phosphorylation,” said William Mobley, MD, PhD, chair of the Department of Neurosciences and interim co-director of the Alzheimer’s Disease Cooperative Study at UC San Diego. “This new study extends those original mechanistic findings to the amyloid pathway and preservation of cellular and synaptic connections.  Work like this is an excellent example of UC San Diego’s bench-to-bedside legacy, whereby we can quickly move our basic science findings into the clinic for testing,” said Mobley.

 

Rissman said R121919 was well-tolerated by AD mice (no significant adverse effects) and deemed safe, suggesting CRF-antagonism is a viable, disease-modifying therapy for AD.  Rissman noted that repurposing R121919 for human use was likely not possible at this point. He and colleagues are collaborating with the Sanford Burnham Prebys Medical Discovery Institute to design new assays to discover the next generation of CRF receptor-1 antagonists for testing in early phase human safety trials.

 

“More work remains to be done, but this is the kind of basic research that is fundamental to ultimately finding a way to cure – or even prevent – Alzheimer’s disease,” said David Brenner, MD, vice chancellor, UC San Diego Health Sciences and dean of UC San Diego School of Medicine. “These findings by Dr. Rissman and his colleagues at UC San Diego and at collaborating institutions on the Mesa suggest we are on the cusp of creating truly effective therapies.”

 

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