Posts tagged psychology

April 30, 2012

(Medical Xpress) — Scientists at the UCSF-affiliated Gladstone Institutes have determined how specific circuitry in the brain controls not only body movement, but also motivation and learning, providing new insight into neurodegenerative disorders such as Parkinson’s disease — and psychiatric disorders such as addiction and depression.

Previously, researchers in the laboratory of Gladstone Investigator Anatol Kreitzer, PhD, discovered how an imbalance in the activity of a specific category of brain cells is linked to Parkinson’s.

Now, in a paper published online today in Nature Neuroscience, Kreitzer, who is also an assistant professor of physiology at UCSF, and his team used animal models to demonstrate that this imbalance may also contribute to psychiatric disorders. These findings also help explain the wide range of Parkinson’s symptoms — and mark an important step in finding new treatments for those who suffer from addiction or depression.

“The physical symptoms that affect people with Parkinson’s — including tremors and rigidity of movement — are caused by an imbalance between two types of medium spiny neurons in the brain,” said Kreitzer, whose lab studies how Parkinson’s disease affects brain functions. “In this paper we showed that psychiatric disorders — specifically addiction and depression —might be caused by this same neural imbalance.”

Normally, two types of medium spiny neurons, or MSNs, coordinate body movements. One type, called direct pathway MSNs (dMSNs), acts like a gas pedal. The other type, known as indirect pathway MSNs (iMSNs), acts as a brake. And while researchers have long known about the link between a chemical in the brain called dopamine and Parkinson’s, Gladstone researchers recently clarified that dopamine maintains the balance between these two MSN types.

But abnormal dopamine levels are implicated not only in Parkinson’s, but also in addiction and depression. Kreitzer and his team hypothesized that the same circuitry that controlled movement might also control the process of learning to repeat pleasurable experiences and avoid unpleasant ones—and that an imbalance in this process could lead to addictive or depressive behaviors.

Kreitzer and his team genetically modified two sets of mice so that they could control which specific type of MSN was activated. They placed mice one at a time in a box with two triggers — one that delivered a laser pulse to stimulate the neurons and one that did nothing. They then monitored which trigger each mouse preferred.

“The mice that had only dMSNs activated gravitated toward the laser trigger, pushing it again and again to get the stimulation — reminiscent of addictive behavior,” said Alexxai Kravitz, PhD, Gladstone postdoctoral fellow and a lead author of the paper. “But the mice that had only iMSNs activated did the opposite. Unlike their dMSN counterparts, the iMSN mice avoided the laser stimulation, which suggests that they found it unpleasant.” These findings reveal a precise relationship between the two MSN types and how behaviors are learned. They also show how an MSN imbalance can throw normal learning processes out of whack, potentially leading to addictive or depressive behavior.

“People with Parkinson’s disease often show signs of depression before the onset of significant movement problems, so it’s likely that the neural imbalance in Parkinson’s is also responsible for some behavioral changes associated with the disease,” said Kreitzer, who is also an assistant professor of physiology at UCSF.. “Future research could discover how MSNs are activated in those suffering from addiction or depression—and whether tweaking them could reduce their symptoms and improve their quality of life.

Graduate student Lynne Tye was also a lead author on this paper. Funding came from a variety of sources, including the W.M. Keck Foundation, the Pew Biomedical Scholars Program, the McKnight Foundation and the National Institutes of Health.

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Provided by University of California, San Francisco 

Source: medicalxpress.com

April 30, 2012

Children with developmental delay or autism may have unrecognized epilepsy-like brain activity during sleep, report researchers at Boston Children’s Hospital. These nighttime electrical spikes, detectable only on EEGs, occur even in some children without known epilepsy and appear to result from early strokes or other early life injuries to the developing brain, the study found. Results were published online April 25 by the journal Neurology.

“Kids can have an almost normal EEG while awake, but may show increased spikes during sleep,” says lead investigator Tobias Loddenkemper, MD, a neurologist in the Epilepsy Center at Boston Children’s. “If nighttime spiking remains undiagnosed and untreated, it may interfere with learning and development. This has been frequently overlooked in the past.”

Based on their findings, the researchers suggest that sleep EEG monitoring should be considered more often in children not meeting developmental milestones, and that bedtime medications to suppress nighttime seizures may be beneficial if heightened brain electrical activity is found. In a preliminary treatment trial, such nighttime dosing before times of greatest spike or seizure activity has been found to be beneficial.

The study involved sleep EEG monitoring in 147 patients who were suspected of having excess brain electrical activity during sleep, based on loss of developmental milestones, and, in some cases, known seizures. All children had at least one brain MRI available for review. The EEGs and MRIs were read by physicians who did not know details of the patients’ history.

Of the 147 patients, seen at Boston Children’s over a 14-year period, 100 had prominent EEG spikes during sleep; the other 47 (controls) did not. Although there was no significant difference between groups in the percentage of patients with recognized seizures (78 percent of the “spike” group versus 64 percent of controls) or on most clinical measures, the “spike” group had significantly more patients with brain lesions on MRI (48 vs. 19 percent).

Children with EEG spikes were especially more likely than controls (14 vs. 2 percent) to have damage in the thalamus, the structure that relays sensory and motor signals to the cortex and regulates sleep and consciousness. The most common type of brain injury was early stroke (found in 14 vs. 0 percent, respectively).

The authors speculate that these early injuries disrupt circuit formation in the developing brain and lead to over-excitability – too much communication that is reflected in the EEG spikes and that may impinge on learning and development. “We know that children lose skills when these spikes appear,” says Loddenkemper. “These children lose out on a critical period of brain development and may never fully catch up later in life.”

Loddenkemper notes that up to 20 percent of children with heightened nighttime brain electrical activity do not have seizures or recognizable epilepsy. “Developmental delay may be the only clinical finding in some children,” he says. “Children at age 2 or 3, and sometimes older, may suddenly lose developmental milestones such as language, walking skills or fine motor movement.”

In the future, Loddenkemper and colleagues hope to conduct a prospective, multicenter trial in which they follow children with known early brain injury and monitor their nighttime EEG activity. They will then try different drugs to suppress nighttime spiking to see how the children’s long-term learning and development are affected.

Provided by Children’s Hospital Boston 

Source: medicalxpress.com

April 29, 2012

Why do some teenagers start smoking or experimenting with drugs—while others don’t?

Newly discovered networks in the brain, shown here in color, go a long way toward explaining why some teenagers are more likely to start experimenting with drugs and alcohol. Diminished activity in some of these networks, discovered by two scientists at the University of Vermont and their European colleagues, makes some teens more impulsive — and less able to inhibit urges to try alcohol, cigarettes and illegal drugs in early adolescence. Credit: Robert Whelan, University of Vermont, Nature Neuroscience, 2012

In the largest imaging study of the human brain ever conducted—involving 1,896 14-year-olds—scientists have discovered a number of previously unknown networks that go a long way toward an answer.

Robert Whelan and Hugh Garavan of the University of Vermont, along with a large group of international colleagues, report that differences in these networks provide strong evidence that some teenagers are at higher risk for drug and alcohol experimentation—simply because their brains work differently, making them more impulsive.

Their findings are presented in the journal Nature Neuroscience, published online April 29, 2012.

This discovery helps answer a long-standing chicken-or-egg question about whether certain brain patterns come before drug use—or are caused by it.

"The differences in these networks seem to precede drug use," says Garavan, Whelan’s colleague in UVM’s psychiatry department, who also served as the principal investigator of the Irish component of a large European research project, called IMAGEN, that gathered the data about the teens in the new study.

In a key finding, diminished activity in a network involving the “orbitofrontal cortex” is associated with experimentation with alcohol, cigarettes and illegal drugs in early adolescence.

"These networks are not working as well for some kids as for others," says Whelan, making them more impulsive.

Faced with a choice about smoking or drinking, the 14-year-old with a less functional impulse-regulating network will be more likely to say, “yeah, gimme, gimme, gimme!” says Garavan, “and this other kid is saying, ‘no, I’m not going to do that.’”

Testing for lower function in this and other brain networks could, perhaps, be used by researchers someday as “a risk factor or biomarker for potential drug use,” Garavan says.

The researchers were also able to show that other newly discovered networks are connected with the symptoms of attention-deficit hyperactivity disorder. These ADHD networks are distinct from those associated with early drug use.

In recent years, there has been controversy and extensive media attention about the possible connection between ADHD and drug abuse. Both ADHD and early drug use are associated with poor inhibitory control—they’re problems that plague impulsive people.

But the new research shows that these seemingly related problems are regulated by different networks in the brain—even though both groups of teens can score poorly on tests of their “stop-signal reaction time,” a standard measure of overall inhibitory control used in this study and other similar ones. This strengthens the idea that risk of ADHD is not necessarily a full-blown risk for drug use as some recent studies suggest.

The impulsivity networks—connected areas of activity in the brain revealed by increased blood flow—begin to paint a more nuanced portrait of the neurobiology underlying the patchwork of attributes and behaviors that psychologists call impulsivity—as well as the capacity to put brakes on these impulses, a set of skills sometimes called inhibitory control.

Edythe London, Professor of Addiction Studies and Director of the UCLA Laboratory of Molecular Pharmacology, who was not part of the new study, described it as “outstanding,” noting that the work by Whelan and others “substantially advances our understanding of the neural circuitry that governs inhibitory control in the adolescent brain.”

Using a complex mathematical approach called factor analysis, Whelan and colleagues were able to fish out seven networks involved when impulses were successfully inhibited and six networks involved when inhibition failed—from the vast and chaotic actions of a teenage brain at work. These networks “light up,” Whelan says, in a functional MRI scanner during trials when the teenagers were asked to perform a repetitive task that involved pushing a button on a keyboard, but then were able to successfully stop—or inhibit—the act of pushing the button in mid-action. Those teens with better inhibitory control were able to succeed at this task faster.

But the underlying networks behind these tasks could not have been detectable in a “typical fMRI study of about 16 or 20 people,” says Whelan. “This study was orders of magnitude bigger, which lets us overcome much of the randomness and noise—and find the brain regions that actually vary together.”

"The take-home message is that impulsivity can be decomposed, broken down into different brain regions," says Garavan, "and the functioning of one region is related to ADHD symptoms, while the functioning of other regions is related to drug use.

The new study draws on the multi-year work of the IMAGEN Consortium, funded by the European Union, and headed by Prof. Gunter Schumann at the Institute of Psychiatry, King’s College London. IMAGEN, lead by a team of scientists across Europe, carried out neuroimaging, genetic and behavioral analyses in 2000 teenage volunteers in Ireland, England, France, and Germany and will be following them for several years, investigating the roots of risk-taking behavior and mental health in teenagers.

That teenagers push against boundaries—and sometimes take risks—is as predictable as the sunrise. It happens in all cultures and even across all mammal species: adolescence is a time to test limits and develop independence.

But death among teenagers in the industrialized world is largely caused by preventable or self-inflicted accidents that are often launched by impulsive risky behaviors, often associated with alcohol and drug use. Additionally, “addiction in the western world is our number one health problem,” says Garavan. “Think about alcohol, cigarettes or harder drugs and all the consequences that has in society for people’s health.” Understanding brain networks that put some teenagers at higher risk for starting to use them could have large implications for public health.

Provided by University of Vermont

Source: medicalxpress.com

ScienceDaily (Apr. 27, 2012) — In a new study, scientists at the University of Copenhagen show that a specific type of carbohydrate plays an important role in the intercellular signalling that controls the growth and development of the nervous system. In particular, defects in that carbohydrate may result in the uninhibited cell growth that characterizes the genetic disease neurofibromatosis and certain types of cancer.

Egghead to the right: Changes in cellular growth. (Credit: Klaus Qvortrup)

The results have just been published in the well-reputed journal PNAS.

Scientists from The Faculty of Health and Medical Sciences at the University of Copenhagen have put a special type of fruit fly under the microscope. The new research results turn the spotlight on a certain group of carbohydrates — the so-called glycolipids — and their influence on the cells’ complicated communication system. In the long term, this model study can shine new light on the disease neurofibromatosis for the benefit of patients the world over.

"The most important thing about our discovery right now is that we document a new function for carbohydrates in the communication between cells. We also show how disturbances in the signalling pathways cause changes in cellular growth. This is knowledge that cancer researchers can develop," says Ole Kjærulff, doctor and associate professor at the Department of Neuroscience and Pharmacology, who has conducted the study together with Dr. Katja Dahlgaard, and Hans Wandall, associate professor at the Copenhagen Center for Glycomics.

Sugar chains control cell growth

Glycolipids are compounds consisting of fats linked to long chains of sugar molecules. They are located in the cell membrane, where they serve various functions, such as protecting the cell or making it recognizable to the immune system.

"In the fruit fly model, if we prevent the sugar chains from lengthening, we can show that carbohydrate plays an important role in controlling the growth of normal cells. When the sugar chains are shortened, the tissue grows dramatically on account of increased cell division. In particular, it appears that the nervous system’s support cells — the glia cells — are influenced," explains Hans Wandall, associate professor.

Neurofibromatosis can cause deformity

The new results also influence our understanding of neurofibromatosis. This is a heritable disorder that results in unsightly tumours — so-called neurofibromas — in the nerves and skin. The disease affects approximately 20 people out of 100,000 and varies from mild to severe cases with decided deformities. The condition also affects the bones and often causes learning problems:

"When you get closer to an understanding of the mechanisms that result in a certain disease, naturally it is easier to influence the disease process in the form of drug development in the longer term. Neurofibromatosis is not a terminal disease, but it very much affects the life quality of the people who have it because the symptoms are so noticeable," explains Ole Kjærulff. Hans Wandall adds that the disease is also associated with certain types of cancer, particularly in the brain.

Source: Science Daily 

April 27, 2012

Aging may seem unavoidable, but that’s not necessarily so when it comes to the brain. So say researchers in the April 27th issue of the Cell Press journal Trends in Cognitive Sciences explaining that it is what you do in old age that matters more when it comes to maintaining a youthful brain not what you did earlier in life.

"Although some memory functions do tend to decline as we get older, several elderly show well preserved functioning and this is related to a well-preserved, youth-like brain," says Lars Nyberg of Umeå University in Sweden.

Education won’t save your brain — PhDs are as likely as high-school dropouts to experience memory loss with old age, the researchers say. Don’t count on your job either. Those with a complex or demanding career may enjoy a limited advantage, but those benefits quickly dwindle after retirement.

Engagement is the secret to success. Those who are socially, mentally and physically stimulated reliably show better cognitive performance with a brain that appears younger than its years.

"There is quite solid evidence that staying physically and mentally active is a way towards brain maintenance," Nyberg says.

The researchers say this new take on successful aging represents an important shift in focus for the field. Much attention in the past has gone instead to understanding ways in which the brain copes with or compensates for cognitive decline in aging. The research team now argues for the importance of avoiding those age-related brain changes in the first place. Genes play some role, but life choices and other environmental factors, especially in old age, are critical.

Elderly people generally do have more trouble remembering meetings or names, Nyberg says. But those memory losses often happen later than many often think, after the age of 60. Older people also continue to accumulate knowledge and to use what they know effectively, often to very old ages.

"Taken together, a wide range of findings provides converging evidence for marked heterogeneity in brain aging," the scientists write. "Critically, some older adults show little or no brain changes relative to younger adults, along with intact cognitive performance, which supports the notion of brain maintenance. In other words, maintaining a youthful brain, rather than responding to and compensating for changes, may be the key to successful memory aging."

Provided by Cell Press

Source: medicalxpress.com

April 27, 2012

(HealthDay) — Childhood socioeconomic status affects hippocampal volume in older adults, after adjusting for adult socioeconomic status, gender, education, and other factors, according to a study published in the May issue of the Annals of Neurology.

Childhood socioeconomic status affects hippocampal volume in older adults, after adjusting for adult socioeconomic status, gender, education, and other factors, according to a study published in the May issue of the Annals of Neurology.

Roger T. Staff, Ph.D., of the Aberdeen Royal Infirmary in the United Kingdom, and colleagues used magnetic resonance imaging of the brain to measure whole brain and hippocampal volume in 249 volunteers without dementia who were born in 1936. Childhood socioeconomic status history was recorded and mental ability at age 11 (recorded in 1947) was available for all participants.

After adjusting for mental ability at age 11 years, adult socioeconomic status, gender, and education, the researchers observed a significant association between childhood socioeconomic status and hippocampal volume.

"Early life socioeconomic conditions contribute to hippocampal volume in late adulthood independently of later life circumstances," the authors conclude. "These findings suggest that the capacity to compensate for age-related neuropathology (reserve) may well be established in early life."

More information: Abstract

Source: medicalxpress.com

ScienceDaily (Apr. 27, 2012) — Our genes control many aspects of who we are — from the colour of our hair to our vulnerability to certain diseases — but how are the genes, and consequently the proteins they make themselves controlled? Researchers have discovered a new group of molecules which control some of the fundamental processes behind memory function and may hold the key to developing new therapies for treating neurodegenerative diseases.

The mirror-miRNA (red) is expressed in hippocampal neurons, the nucleus is shown in blue. (Credit: Image courtesy of University of Bristol)

The research, led by academics from the University of Bristol’s Schools of Clinical Sciences, Biochemistry and Physiology & Pharmacology and published in the Journal of Biological Chemistry, has revealed a new group of molecules, called mirror-microRNAs.

MicroRNAs are non-coding genes that often reside within ‘junk DNA’ and regulate the levels and functions of multiple target proteins — responsible for controlling cellular processes in the brain. The study’s findings have shown that two microRNA genes with different functions can be produced from the same piece (sequence) of DNA — one is produced from the top strand and another from the bottom complementary ‘mirror’ strand.

Specifically, the research has shown that a single piece of human DNA gives rise to two fully processed microRNA genes that are expressed in the brain and have different and previously unknown functions. One microRNA is expressed in the parts of nerve cells that are known to control memory function and the other microRNA controls the processes that move protein cargos around nerve cells.

James Uney, Professor of Molecular Neuroscience in the University’s School of Clinical Sciences, said: “These findings are important as they show that very small changes in microRNA genes will have a dramatic effect on brain function and may influence our memory function or likelihood of developing neurodegenerative diseases. These findings also suggest that many more human mirror microRNAs will be found and that they could ultimately be used as treatments for human neurodegenerative diseases such as dementia.”

MicroRNAs can be seen as a novel regulatory layer within the genome, relying on the interaction between different RNA molecules. Through binding to messenger RNA (mRNA), they adjust the levels of proteins. Due to their small size, they are able to regulate many different RNAs. MicroRNAs have already been found throughout the double helix, lying in between genes or in areas of the code for a single gene that would normally be discarded. Such areas that were once considered “junk DNA” are now revealing a more complex and important role. In addition microRNAs can be produced in conjunction with their genes, within which they lie, or be controlled and produced entirely independently.

Helen Scott and Joanna Howarth, the lead authors on the study, added: “We have now found that both sides of the double helix can each produce a microRNA. These two microRNAs are almost a perfect mirror of each other, but due to slight differences in their sequence, they regulate different sets of protein producing RNAs, which will in turn affect different biological functions. Such mirror-miRNAs are likely to represent a new group of microRNAs with complex roles in coordinating gene expression, doubling the capacity of regulation.”

Source: Science Daily

ScienceDaily (Apr. 27, 2012) — Researchers at the Centre for Addiction and Mental Health (CAMH) led a study discovering a gene for a new form of intellectual disability, as well as how it likely affects cognitive development by disrupting neuron functioning.

CAMH Senior Scientist Dr. John Vincent and his team found a mutation in the gene NSUN2 among three sisters with intellectual disability, a finding to be published in the May issue of the American Journal of Human Genetics.

The discovery was made after mapping genes in a Pakistani family, in which three of seven siblings had intellectual disability as well as muscle weakness and walking difficulties, says Dr. Vincent, who heads the Molecular Neuropsychiatry and Development Laboratory in the Campbell Family Mental Health Research Institute at CAMH.

Intellectual disability is a condition in which individuals have limitations in their mental abilities and in functioning in daily life. It affects one to three per cent of the population, and is often caused by genetic mutations.

Another study in the same journal, submitted together with the CAMH-led research, also identified NSUN2 gene mutations in Iranian and Kurdish families with intellectual disability. As with the Pakistani family, first cousin marriages in these families carrying the mutations increased the likelihood of intellectual disability among their children, and enabled researchers to focus on areas to map genes.

"The combined results from these two studies mean that NSUN2 is among the most common causes of intellectual disability resulting from recessive genes," says Dr. Vincent.

As a recessive disorder, a child must inherit one defective NSUN2 gene from each parent to develop intellectual disability. This gene, located on chromosome 5p, encodes a type of protein called an RNA methyltransferase.

At the cellular level, the researchers found that the mutated protein was prevented from reaching its target area within the nucleus of a cell. As a result, it was unable to perform its normal role in cell division and/or RNA methylation.

Collaborators from the Wellcome Trust Centre for Stem Cell Research in Cambridge, U.K., showed which type of brain cells were likely to be most affected by this mutation. They are called Purkinje cells, a type of neuron that responds to the neurotransmitter GABA. Purkinje cells also control motor coordination, which were affected in the Pakistani family.

"We speculate that the muscle effects may result from the accumulation of the NSUN2 protein outside its target area in the nucleus," says Dr. Vincent.

To date, Dr. Vincent’s lab has identified five genes causing different forms of recessive intellectual disability.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — A new University of British Columbia study finds that analytic thinking can decrease religious belief, even in devout believers.

The statue “The Thinker,” by Auguste Rodin. (Credit: © Ignatius Wooster / Fotolia)

The study, which is published in the April 27 issue of Science, finds that thinking analytically increases disbelief among believers and skeptics alike, shedding important new light on the psychology of religious belief.

“Our goal was to explore the fundamental question of why people believe in a God to different degrees,” says lead author Will Gervais, a PhD student in UBC’s Dept. of Psychology. “A combination of complex factors influence matters of personal spirituality, and these new findings suggest that the cognitive system related to analytic thoughts is one factor that can influence disbelief.”

Researchers used problem-solving tasks and subtle experimental priming – including showing participants Rodin’s sculpture The Thinker or asking participants to complete questionnaires in hard-to-read fonts – to successfully produce “analytic” thinking. The researchers, who assessed participants’ belief levels using a variety of self-reported measures, found that religious belief decreased when participants engaged in analytic tasks, compared to participants who engaged in tasks that did not involve analytic thinking.

The findings, Gervais says, are based on a longstanding human psychology model of two distinct, but related cognitive systems to process information: an “intuitive” system that relies on mental shortcuts to yield fast and efficient responses, and a more “analytic” system that yields more deliberate, reasoned responses.

“Our study builds on previous research that links religious beliefs to ‘intuitive’ thinking,” says study co-author and Associate Prof. Ara Norenzayan, UBC Dept. of Psychology. “Our findings suggest that activating the ‘analytic’ cognitive system in the brain can undermine the ‘intuitive’ support for religious belief, at least temporarily.”

The study involved more than 650 participants in the U.S. and Canada. Gervais says future studies will explore whether the increase in religious disbelief is temporary or long-lasting, and how the findings apply to non-Western cultures.

Recent figures suggest that the majority of the world’s population believes in a God, however atheists and agnostics number in the hundreds of millions, says Norenzayan, a co-director of UBC’s Centre for Human Evolution, Cognition and Culture. Religious convictions are shaped by psychological and cultural factors and fluctuate across time and situations, he says.

Source: Science Daily