Posts tagged psychology
Articles and news from the latest research reports.
Drugs that weaken traumatic memories hold promise for PTSD treatment
Memories of traumatic events often last a lifetime because they are so difficult to treat through behavioral approaches. A preclinical study in mice published by Cell Press January 16th in the journal Cell reveals that drugs known as histone deacetylase inhibitors (HDACis) can enhance the brain’s ability to permanently replace old traumatic memories with new memories, opening promising avenues for the treatment of posttraumatic stress disorder (PTSD) and other anxiety disorders.
Caption: Metabolic activity (green and red colors) in the hippocampus (white dotted line) of animals that underwent extinction training in combination with HDACis (right) is significantly higher than in animals that underwent extinction training alone (left). Metabolic activity serves to estimate the learning capacity of an animal. Credit: Cell, Gräff et al.
"Psychotherapy is often used for treating PTSD, but it doesn’t always work, especially when the traumatic events occurred many years earlier," says senior study author Li-Huei Tsai of the Massachusetts Institute of Technology. "This study provides a mechanism explaining why old memories are difficult to extinguish and shows that HDACis can facilitate psychotherapy to treat anxiety disorders such as PTSD."
One common treatment for anxiety disorders is exposure-based therapy, which involves exposing patients to fear-evoking thoughts or events in a safe environment. This process reactivates the traumatic memory, opening a short time window during which the original memory can be disrupted and replaced with new memories. Exposure-based therapy is effective when the traumatic events occurred recently, but until now, it was not clear whether it would also be effective for older traumatic memories.
To address this question, Tsai and her team used a protocol for studying fear responses associated with traumatic memories. In the first phase, the researchers exposed mice to a tone followed by an electrical footshock. Once the mice learned to associate these two events, they began to freeze in fear upon hearing the tone by itself, even when they did not receive a shock. Using an extinction protocol, which is similar to exposure-based therapy, the researchers repeatedly presented the tone without the shock to test whether the mice could unlearn the association between these two events and would stop freezing in response to the tone. The extinction protocol was successful for mice that were exposed to the tone-shock pairing just one day earlier, but it was not effective for mice that originally formed the traumatic memory one month earlier. The researchers hypothesized that epigenetic modification of genes involved in learning and memory might be responsible for the diminished response of treatment for older memories.
The researchers tested whether HDACis, which promote long-lasting activation of genes involved in learning and memory, could help replace old traumatic memories with new memories. Mice previously exposed to the tone-shock pairing received HDACis and then underwent the extinction protocol. These mice learned to stop freezing in response to the tone, even when they originally formed the traumatic memory one month earlier. “Collectively, our findings suggest that exposure-based therapy alone does not effectively weaken traumatic memories that were formed a long time ago, but that HDACis can be combined with exposure-based therapy to substantially improve treatment for the most enduring traumatic memories,” Tsai says.
(Source: eurekalert.org)
Brain interactions differ between religious and non-religious subjects
An Auburn University researcher teamed up with the National Institutes of Health to study how brain networks shape an individual’s religious belief, finding that brain interactions were different between religious and non-religious subjects.
Gopikrishna Deshpande, an assistant professor in the Department of Electrical and Computer Engineering in Auburn’s Samuel Ginn College of Engineering, and the NIH researchers recently published their results in the journal, “Brain Connectivity.”
The group found differences in brain interactions that involved the theory of mind, or ToM, brain network, which underlies the ability to relate between one’s personal beliefs, intents and desires with those of others. Individuals with stronger ToM activity were found to be more religious. Deshpande says this supports the hypothesis that development of ToM abilities in humans during evolution may have given rise to religion in human societies.
“Religious belief is a unique human attribute observed across different cultures in the world, even in those cultures which evolved independently, such as Mayans in Central America and aboriginals in Australia,” said Deshpande, who is also a researcher at Auburn’s Magnetic Resonance Imaging Research Center. “This has led scientists to speculate that there must be a biological basis for the evolution of religion in human societies.”
Deshpande and the NIH scientists were following up a study reported in the Proceedings of the National Academy of Sciences, which used functional magnetic resonance imaging, or fMRI, to scan the brains of both self-declared religious and non-religious individuals as they contemplated three psychological dimensions of religious beliefs.
The fMRI – which allows researchers to infer specific brain regions and networks that become active when a person performs a certain mental or physical task – showed that different brain networks were activated by the three psychological dimensions; however, the amount of activation was not different in religious as compared to non-religious subjects.
(Source: wireeagle.auburn.edu)
How Vision Captures Sound Now Somewhat Uncertain
When listening to someone speak, we also rely on lip-reading and gestures to help us understand what the person is saying.
To link these sights and sounds, the brain has to know where each stimulus is located so it can coordinate processing of related visual and auditory aspects of the scene. That’s how we can single out a conversation when it’s one of many going on in a room.
While past research has shown that the brain creates a similar code for vision and hearing to integrate this information, Duke University researchers have found the opposite: neurons in a particular brain region respond differently, not similarly, based on whether the stimuli is visual or auditory.
The finding, which posted Jan. 15 in the journal PLOS ONE, provides insight into how vision captures the location of perceived sound.
The idea among brain researchers has been that the neurons in a brain area known as the superior colliculus employ a “zone defense” when signaling where stimuli are located. That is, each neuron monitors a particular region of an external scene and responds whenever a stimulus — either visual or auditory — appears in that location. Through teamwork, the ensemble of neurons provides coverage of the entire scene.
But the study by Duke researchers found that auditory neurons don’t behave that way. When the target was a sound, the neurons responded as if playing a game of tug-of-war, said lead author Jennifer Groh, a professor of psychology and neuroscience at Duke.
"The neurons responded to nearly all sound locations. But how vigorously they responded depended on where the sound was," Groh said. "It’s still teamwork, but a different kind. It’s pretty cool that the neurons can use two different strategies, play two different games, at the same time."
Groh said the finding opens up a mystery: if neurons respond differently to visual and auditory stimuli at similar locations in space, then the underlying mechanism of how vision captures sound is now somewhat uncertain.
"Which neurons are ‘on’ tells you where a visual stimulus is located, but how strongly they’re ‘on’ tells you where an auditory stimulus is located," said Groh, who conducted the study with co-author Jung Ah Lee, a postdoctoral fellow at Duke.
"Both of these kinds of signals can be used to control behavior, like eye movements, but it is trickier to envision how one type of signal might directly influence the other."
The study involved assessing the responses of neurons, located in the rostral superior colliculus of the midbrain, as two rhesus monkeys moved their eyes to visual and auditory targets.
The sensory targets — light-emitting diodes attached to the front of nine speakers — were placed 58 inches in front of the animals. The speakers were located from 24 degrees left to 24 degrees right of the monkey in 6-degree increments.
The researchers then measured the monkey’s responses to bursts of white noise and the illuminating of the lights.
Groh said how the brain takes raw input of one form and converts it into something else “may be broadly useful for more cognitive processes.”
"As we develop a better understanding of how those computations unfold it may help us understand a little bit more about how we think," she said.
Nearly 8 million Americans suffer from posttraumatic stress disorder (PTSD), a condition marked by severe anxiety stemming from a traumatic event such as a battle or violent attack.
Many patients undergo psychotherapy designed to help them re-experience their traumatic memory in a safe environment so as to help them make sense of the events and overcome their fear. However, such memories can be so entrenched that this therapy doesn’t always work, especially when the traumatic event occurred many years earlier.
MIT neuroscientists have now shown that they can extinguish well-established traumatic memories in mice by giving them a type of drug called an HDAC2 inhibitor, which makes the brain’s memories more malleable, under the right conditions. Giving this type of drug to human patients receiving psychotherapy may be much more effective than psychotherapy alone, says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory.
“By inhibiting HDAC2 activity, we can drive dramatic structural changes in the brain. What happens is the brain becomes more plastic, more capable of forming very strong new memories that will override the old fearful memories,” says Tsai, the senior author of a paper describing the findings in the Jan. 16 issue of Cell.
The new study also reveals the molecular mechanism explaining why older memories are harder to extinguish. Lead authors of the paper are former Picower Institute postdoc Johannes Graff and Nadine Joseph, a technical assistant at the Picower Institute.
Genes and memories
Tsai’s lab has previously shown that when memories are formed, neurons’ chromatin — DNA packaged with proteins — undergoes extensive remodeling. These chromatin modifications make it easier to activate the genes necessary to create new memories.
In this study, the researchers focused on chromatin modifications that occur when previously acquired memories are extinguished. To do this, they first trained mice to fear a particular chamber — by administering a mild foot shock — and then tried to recondition the mice so they no longer feared it, which was done by placing the mice in the chamber where they received the shock, without delivering the shock again.
This training proved successful in mice that had experienced the traumatic event only 24 hours before the reconditioning. However, in mice whose memories were 30 days old, it was impossible to eliminate the fearful memory.
The researchers also found that in the brains of mice with 24-hour-old memories, extensive chromatin remodeling occurred during the reconditioning. For several hours after the mice were placed back in the feared chamber, there was a dramatic increase in histone acetylation of memory-related genes, caused by inactivation of the protein HDAC2. That histone acetylation makes genes more accessible, turning on the processes needed to form new memories or overwrite old ones.
In mice with 30-day-old memories, however, there was no change in histone acetylation. This suggests that re-exposure to a fearful memory opens a window of opportunity during which the memory can be altered, but only if the memory has recently been formed, Tsai says.
“If you do something within this window of time, then you have the possibility of modifying the memory or forming a new trace of memory that actually instructs the animal that this is not such a dangerous place,” she says. “However, the older the memory is, the harder it is to really change that memory.”
Based on this finding, the researchers decided to treat mice with 30-day-old memories with an HDAC2 inhibitor shortly after re-exposure to the feared chamber. Following this treatment, the traumatic memories were extinguished just as easily as in the mice with 24-hour-old memories.
The researchers also found that HDAC2 inhibitor treatment turns on a group of key genes known as immediate early genes, which then activate other genes necessary for memory formation. They also saw an increase in the number of connections among neurons in the hippocampus, where memories are formed, and in the strength of communication among these neurons.
“Our experiments really strongly argue that either the old memories are permanently being modified, or a new much more potent memory is formed that completely overwrites the old memory,” Tsai says.
“This could be a very promising way to bring older memories back, process them in the hippocampus, and then extinguish them with the correct paradigm,” says Jelena Radulovic, a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine who was not part of the research team.
Treating anxiety
Some HDAC2 inhibitors have been approved to treat cancer, and Tsai says she believes it is worth trying such drugs to treat PTSD. “I hope this will convince people to seriously think about taking this into clinical trials and seeing how well it works,” she says.
Such drugs might also be useful in treating people who suffer from phobias and other anxiety disorders, she adds.
Tsai’s lab is now studying what happens to memory traces when re-exposure to traumatic memories occurs at different times. It is already known that memories are formed in the hippocampus and then transferred to the cortex for longer-term storage. It appears that the HDAC2 inhibitor treatment may somehow restore the memory to the hippocampus so it can be extinguished, Tsai says.
Heavy Drinking in Middle Age May Speed Memory Loss by up to Six Years in Men
Middle-aged men who drink more than 36 grams of alcohol, or two and a half US drinks per day, may speed their memory loss by up to six years later on, according to a study published in the January 15, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology. On the other hand, the study found no differences in memory and executive function in men who do not drink, former drinkers and light or moderate drinkers. Executive function deals with attention and reasoning skills in achieving a goal.
“Much of the research evidence about drinking and a relationship to memory and executive function is based on older populations,” said study author Séverine Sabia, PhD, of the University College London in the United Kingdom. “Our study focused on middle-aged participants and suggests that heavy drinking is associated with faster decline in all areas of cognitive function in men.”
The study involved 5,054 men and 2,099 women whose drinking habits were assessed three times over 10 years. A drink was considered wine, beer or liquor. Then, when the participants were an average age of 56, they took their first memory and executive function test. The tests were repeated twice over the next 10 years.
The study found that there were no differences in memory and executive function decline between men who did not drink and those who were light or moderate drinkers—those who drank less than 20 grams, or less than two US drinks per day. Heavy drinkers showed memory and executive function declines between one-and-a-half to six years faster than those who had fewer drinks per day.
More Than Meets the Eye
Many studies suggest that pushing your brain to multitask — writing emails, for instance, while watching the day’s latest news and eating breakfast — leads to poorer performance and lower productivity. But for at least one everyday task — visual sampling (the act of picking up bits of visual information through short glances) — multitasking is not a problem for the brain. A collaboration between researchers at the UC Santa Barbara and the University of Bristol in the UK has shown that during visual sampling, the brain can handle various visual functions simultaneously.
“We might not realize it, but human vision is rather limited,” said Miguel Eckstein, professor in the Department of Psychological and Brain Sciences at UCSB. “We only see clearly in a small region around our specific focus.” Eckstein’s study, “Foveal analysis and peripheral selection during active visual sampling,” appears in the early Proceedings of the National Academy of Sciences Plus edition.
Head injuries triple long-term risk of early death
Survivors of traumatic brain injuries (TBI) are three times more likely to die prematurely than the general population, often from suicide or fatal injuries, finds an Oxford University-led study.
A TBI is a blow to the head that leads to a skull fracture, internal bleeding, loss of consciousness for longer than an hour or a combination of these symptoms. Michael Schumacher’s recent skiing injury is an example of a TBI. Concussions, sometimes called mild TBIs, do not present with these symptoms and were analysed separately in this study.
Researchers examined Swedish medical records going back 41 years covering 218,300 TBI survivors, 150,513 siblings of TBI survivors and over two million control cases matched by sex and age from the general population. The work was carried out by researchers at Oxford University and the Karolinska Institute in Stockholm.
'We found that people who survive six months after TBI remain three times more likely to die prematurely than the control population and 2.6 times more likely to die than unaffected siblings,' said study leader Dr Seena Fazel, a Wellcome Trust Senior Research Fellow in Oxford University's Department of Psychiatry. 'Looking at siblings who did not suffer TBIs allows us to control for genetic factors and early upbringing, so it is striking to see that the effect remains strong even after controlling for these.'
The results, published in the journal JAMA Psychiatry, show that TBI survivors who also have a history of substance abuse or psychiatric disorders are at highest risk of premature death. Premature deaths were defined as before age 56. The main causes of premature death in TBI survivors are suicide and fatal injuries such as car accidents and falls.
'TBI survivors are more than twice as likely to kill themselves as unaffected siblings, many of whom were diagnosed with psychiatric disorders after their TBI,' said Dr Fazel. 'Current guidelines do not recommend assessments of mental health or suicide risk in TBI patients, instead focusing on short-term survival. Looking at these findings, it may make more sense to treat some TBI patients as suffering from a chronic problem requiring longer term management just like epilepsy or diabetes. TBI survivors should be monitored carefully for signs of depression, substance abuse and other psychiatric disorders, which are all treatable conditions.'
The exact reasons for the increased risk of premature death are unknown but may involve damage to the parts of the brain responsible for judgement, decision making and risk taking. TBI survivors are three times more likely to die from fatal injuries which may be a result of impaired judgement or reactions.
'This study highlights the important and as yet unanswered question of why TBI survivors are more likely to die young, but it may be that serious brain trauma has lasting effects on people's judgement,' suggests Dr Fazel. 'People who have survived the acute effects of TBI should be more informed about these risks and how to reduce their impact.'
'When treating traumatic brain injuries focus is placed on immediate treatment and recovery of patients,' says Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust. 'This new finding offers important insight into the longer-term impact of TBIs on the brain and their effect on survival later in life. We hope that further research into understanding which parts of the brain are responsible will help improve future management programmes and reduce the potential for premature death.'
Even relatively minor brain injuries, concussions, had a significant impact on early mortality. People with concussion were found to be twice as likely to die prematurely as the control population, with suicide and fatal injuries as the main causes of death. This raises issues surrounding concussions in a wide range of sports, from American football, rugby and soccer to baseball and cricket.
(Source: ox.ac.uk)
Recall of stressful events caught in pictures
The study is of patients with conversion disorder (what Freud would have called Hysteria), which is still a very common disorder though rarely discussed or researched today.
“Freud started his whole theory by arguing that patients with hysteria repressed their memories of traumatic events and that this led to their developing their symptoms (of paralysis, for example) - what he called ‘conversion,” said Professor Richard Kanaan from the Department of Psychiatry, University of Melbourne and Austin Health.
“The world has pretty much given up on that theory largely because they thought it couldn’t be tested,” he said.
Published recently in the Journal of the American Medical Association, Psychiatry, the fMRI findings support Freud’s theories for the first time in over a century.
Researchers first painstakingly identified what they thought were the traumatic events that led to them becoming sick using the Life Events and Difficulties Schedule (LEDS) as a guide. This is a well-known psychological measurement for assessing life stress levels and experience.
“We got our patients to remember the traumatic events while we scanned their brains. Results showed something that looked like it could be them repressing their memories and possibly what could be them developing symptoms in response.”
“While it is still a preliminary study, in the history of psychiatry as a science it is potentially a significant breakthrough,” he said.
Scientists Develop Promising Drug Candidates for Pain, Addiction
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have described a pair of drug candidates that advance the search for new treatments for pain, addiction and other disorders.
The two new drug scaffolds, described in a recent edition of The Journal of Biological Chemistry, offer researchers novel tools that act on a demonstrated therapeutic target, the kappa opioid receptor (KOR), which is located on nerve cells and plays a role in the release of the neurotransmitter dopamine. While compounds that activate KOR are associated with positive therapeutic effects, they often also recruit a molecule known as βarrestin2 (beta arrestin), which is associated with depressed mood and severely limits any therapeutic potential.
“Compounds that act at kappa receptors may provide a means for treating addiction and for treating pain; however, there is the potential for the development of depression or dysphoria associated with this receptor target,” said Laura Bohn, a TSRI associate professor who led the study. “There is evidence that the negative feelings caused by kappa receptor drugs may be, in part, due to receptor actions through proteins called beta arrestins. Developing compounds that activate the receptors without recruiting beta arrestin function may serve as a means to improve the therapeutic potential and limit side effects.”
The new compounds are called “biased agonists,” activating the receptor without engaging the beta arrestins.
Research Associate Lei Zhou, first author of the study with Research Associate Kimberly M. Lovell, added, “The importance of these biased agonists is that we can manipulate the activation of one particular signaling cascade that produces analgesia, but not the other one that could lead to dysphoria or depression.”
The researchers note that the avoidance of depression is particularly important in addiction treatment, where depressed mood can play a role in relapse.
The two drug candidates also have a high affinity and selectivity for KOR over other opioid receptors and are able to pass through the blood-brain barrier. Given these promising attributes, the scientists plan to continue developing the compounds.
(Source: scripps.edu)
Scientific study suggests an association between physical doping and brain doping
Physical doping and brain doping apparently often go hand in hand. A study from Johannes Gutenberg University Mainz (JGU) and Eberhard Karls University in Tubingen revealed that people who engage in physical doping often also take drugs for brain doping. The study was the first of its kind to survey simultaneously the two categories of doping and brain doping. Around 3,000 hobby triathletes were anonymously surveyed using a questionnaire at sporting events in Frankfurt, Regensburg, and Wiesbaden. “The results correlated with earlier findings about doping in leisure and popular sports and brain doping in society as a whole. The findings also illustrated for the first time that physical doping and brain doping often go together, at least for recreational triathletes,” said Mainz University Professor of Sports Medicine Dr. Dr. Perikles Simon.
The study was carried out using the randomized response technique (RRT), which allows for better estimates of unknown cases in response to sensitive questions. It suggested that 13.0 percent of the athletes surveyed had used illegal and banned substances in the twelve months prior to the survey; 15.1 percent were believed to have engaged in brain doping.
When talking about doping substances, a distinction is made between illicit drugs such as cocaine or heroin and banned substances for physical performance enhancement such as anabolic steroids, EPO, or growth hormones. Brain doping is the use of illegal substances and pharmaceuticals such as illegal amphetamines, modafinil or Ritalin to improve mental performance.
The findings indicate that the estimated proportion of men who dope (13.7 percent) is higher than the proportion of women (8.0 percent). The prevalence of doping also seemed to be higher at the European Championships in Frankfurt than at the other triathlons in Regensburg and Wiesbaden. The competitions involved participants taking part in either a classic Ironman with a 4 kilometer swim, 180 kilometer cycle ride, and 42 kilometer marathon or tackling half of the actual Ironman distance.
In their survey carried out during the 2011 season, the scientists interviewed a total of 2,997 triathlon participants. 2,987 questionnaires (99.7 percent) were returned. The study also examined whether there was a correlation between the use of legal and freely available substances for improving physical and mental performance and the use of illegal and banned substances. This would appear to be the case, as athletes who use legal substances to improve their performance also tend to use illegal substances as well.
Finally, another important finding of the study was the sign of a correlation between physical doping and brain doping, which can be found with both legal and illicit substances. The use of legal substances to enhance physical performance is thus relatively often associated with the consumption of substances to improve mental performance, just as there is a correlation between the use of illicit substances for both doping and brain doping. “This indicates that athletes do not actually take the substances to achieve a specific goal, but may show a certain propensity towards performance enhancing substances,” explained Simon. The findings are important to better understand why people take such substances and to be able to provide targeted prevention.