Posts tagged research
Articles and news from the latest research reports.
The sought-after equanimity of “living in the moment” may be impossible, according to neuroscientists who’ve pinpointed a brain area responsible for using past decisions and outcomes to guide future behavior. The study is the first of its kind to analyze signals associated with metacognition—a person’s ability to monitor and control cognition (a term cleverly described by researchers as “thinking about thinking.”
Why aren’t our thoughts independent of each other? Why don’t we just live in the moment? For a healthy person, it’s impossible to live in the moment. It’s a nice thing to say in terms of seizing the day and enjoying life, but our inner lives and experiences are much richer than that. With schizophrenia and Alzheimer’s disease, there is a fracturing of the thought process. It is constantly disrupted, and despite trying to keep a thought going, one is distracted very easily. Patients with these disorders have trouble sustaining a memory of past decisions to guide later behavior, suggesting a problem with metacognition. -Marc Sommer
Source: University of Pittsburgh
Opinion: Bias Is Unavoidable
By Lisa Cosgrove | August 7, 2012
It is part of the human condition to have implicit biases—and remain blissfully ignorant of them. Academic researchers, scientists, and clinicians are no exception; they are as marvelously flawed as everyone else. But it is not the cognitive bias that’s the problem. Rather, the denial that there is a problem is where the issues arise. Indeed, our capacity for self-deception was beautifully captured in the title of a recent book addressing researchers’ self-justificatory strategies, Mistakes Were Made (But Not by Me).
Illustration by Dusan Petricic
Decades of research have demonstrated that cognitive biases are commonplace and very difficult to eradicate, and more recent studies suggest that disclosure of financial conflicts of interest may actually worsen bias. This is because bias is most often manifested in subtle ways unbeknownst to the researcher or clinician, and thus is usually implicit and unintentional. For example, although there was no research misconduct or fraud, re-evaluations of liver tissue of rats exposed to the drug dioxin resulted in different conclusions about the liver cancer in those rats: compared to the original investigation, an industry-sponsored re-evaluation identified fewer tissue slides as cancerous and this finding affected policy recommendations (water quality standards were weakened). (See also Brown, Cold Spring Harbor Laboratory Press, 13–28, 1991.) This example is just one of many that points to a genericrisk that a financial conflict of interest may compromise research or undermine public trust.
Indeed, recent neuroscience investigations demonstrate that effective decision-making involves not just cognitive centers but also emotional areas such as the hippocampus and amygdala. This interplay of cognitive-emotional processing allows conflicts of interest to affect decision-making in a way that is hidden from the person making the decision.
Despite these findings, many individuals are dismissive of the idea that researchers’ financial ties to industry are problematic. For example, in a recent essay in The Scientist, Thomas Stossel of Brigham & Women’s Hospital and Harvard Medical School asked, “How could unrestricted grants, ideal for research that follows up serendipitous findings, possibly be problematic? The money leads to better research that can benefit patients.” Many argue that subjectivity in the research process and the potential for bias can be eradicated by strict adherence to the scientific method and transparency about industry relationships. Together, scientists believe, these practices can guarantee evidence-based research that leads to the discovery and dissemination of “objective” scientific truths. The assumption is that the reporting of biased results is a “bad apple” problem—a few corrupt individuals engaging in research fraud. But what we have today is a bad barrel.
Some have begun to use the analytic framework of “institutional corruption” to bring attention to the fact that the trouble is not with a few corrupt individuals hurting an organization whose integrity is basically intact. Institutional corruption refers to the systemic and usually legal—and often accepted and widely defended—practices that bring an organization or institution off course, undermine its mission and effectiveness, and weaken public trust. Although the entire field of biomedicine has come under scrutiny because of concerns about an improper dependence on industry and all medical specialties have struggled with financial conflicts of interest, psychiatry has been particularly troubled, being described by some as having a crisis of credibility.
This credibility crisis has been played out most noticeably in the public controversy surrounding the latest revision to the Diagnostic and Statistical Manual of Mental Disorders (DSM). The DSM is often referred to as the “Bible” of mental disorders, and is produced by the American Psychiatric Association (APA), a professional organization with a long history of industry ties. DSM-5, the revised edition scheduled for publication in May, 2013, has already been criticized for “disease mongering,” or pathologizing normal behavior. Concerns have been raised that because the individuals responsible for making changes and adding new disorders have strong and long-standing financial associations to pharmaceutical companies that manufacture the drugs used to treat these disorders, the revision process may be compromised by undue industry influence.
Researchers, clinicians, and psychiatrists who served on the DSM-IV have pointed out that adding new disorders or lowering the diagnostic threshold of previously included disorders may create “false positives,” individuals incorrectly identified as having a mental disorder and prescribed psychotropic medication. For example, there was a heated debate about pathologizing the normal grieving process if DSM-5 eliminated the bereavement exclusion for major depressive disorder (MDD). The concern was that widening the diagnostic boundaries of depression to include grief as a “qualifying event,” thereby allowing for a diagnosis of MDD just 2 weeks after the loss of a loved one, would falsely identify individuals as depressed. Although it is not the APA’s intent to play handmaiden to industry, the reality is that such a change would result in more people being prescribed antidepressants following the loss of a loved one. In fact, psychiatrist Allen Frances, who chaired the DSM-IV task force, has noted that DSM-5 would be a “bonanza” for drug companies.
After receiving criticism about potential bias in the development of the DSM-IV, the APA required that DSM-5 panel members file financial disclosures. Additionally, during their tenure on the panels they were not allowed to receive more than $10,000 from pharmaceutical companies or have more than $50,000 in stock holdings in pharmaceutical companies (unrestricted research grants were excluded from this policy). The majority of diagnostic panels, however, continue to have the majority of their members with financial ties to the pharmaceutical industry. Specifically, 67 percent of the 12-person panel for mood disorders, 83 percent of the 12-person panel for psychotic disorders, and all 7 members of the sleep/wake disorders panel (which now includes ‘‘Restless Leg Syndrome’’) have ties to the pharmaceutical companies that manufacture the medications used to treat these disorders or to companies that service the pharmaceutical industry.
Clearly, the new disclosure policy has not been accompanied by any reduction in the financial conflicts of interest of DSM panel members. Moreover, Darrel Regier, speaking on behalf of the APA and in defense of DSM panel members with industry ties, told USA Today. “There’s this assumption that a tie with a company is evidence of bias. But these people can be objective.” However, as science has repeatedly shown, transparency alone cannot mitigate bias and is an insufficient solution for protecting the integrity of the revision process. Objectivity is not a product that can be easily secured by adherence to the scientific method. Rather, there is a generic risk that a conflict of interest may result in implicit, unintentional bias. Similarly, as Sinclair Lewis said, “It is difficult to get a man to understand something when his salary depends upon his not understanding it.”
Source: TheScientist
A fine-tuned combination of two existing pharmaceutical drugs has shown promise as a potential new therapy for people addicted to cocaine—a therapy that would reduce their craving for the drug and blunt their symptoms of withdrawal.
In laboratory experiments at The Scripps Research Institute, the potential therapy, which combines low doses of the drug naltrexone with the drug buprenorphine, made laboratory rats less likely to take cocaine compulsively—a standard preclinical test that generally comes before human trials.
While the two-drug combination would have to prove safe and effective for people in clinical trials before approval by the U.S. Food and Drug Administration (FDA), the work represents a significant advance in the field because there are currently no FDA-approved medications for treating cocaine addiction.
The brains of people with schizophrenia may attempt to heal from the disease
7 August 2012
New NeuRA research shows that the brains of people with schizophrenia may attempt to repair damage caused by the disease, in another example of the adult brain’s capacity to change and grow.
Prof Cyndi Shannon Weickert, Dr Dipesh Joshi and colleagues from Neuroscience Research Australia studied the brains of people with schizophrenia and focussed on one of the hardest-hit regions, the orbitofrontal cortex, which is the part of the brain involved in regulating emotional and social behaviour.
Most neurons – brain cells that transmit information – are found in tissue near the surface of the brain. However, in the brains of people with schizophrenia, the team found a high density of neurons in deeper areas.
“For over a decade we’ve known about the high density of neurons in deeper brain tissue in people with schizophrenia. Researchers thought these neurons were simply forgotten by the brain, and somehow didn’t die off like they do during development in healthy people,” says Prof Shannon Weickert.
“What we now have is evidence that suggests these neurons are derived from the part of the brain that produces new neurons, and that they may be in the process of moving. We can’t be sure where they are moving to, but given their location it is likely they are on their way to the surface of the brain, the area most affected by schizophrenia,” Prof Shannon Weickert concluded.
How was this study done?
- Brain tissue from the orbitofrontal cortex from 38 people with schizophrenia and 38 people without the disease were used in this study.
- The density of interstitial neurons in the white matter, and the density of GABAergic neurons in the grey matter were measured.
- An increased density of interstitial white matter neurons in the white matter, and decreased density of GABAergic neurons in the grey matter was found.
- This pattern suggests that the migration of interstitial white matter neurons towards an area where they are lacking, because of schizophrenia, is a response to the disease.
The Algorithm That Finds Connections Scientists Never See
Here’s a thought experiment for you: If someone told you you had to drink just one kind of alcoholic beverage for the rest of your life, and you wanted that life to be long and healthy, what would you pick? Wine, right? After all, you’ve probably heard about the scientific studies showing that drinking wine is associated with better health in general, and a longer life span in particular. Give jocks their beer and lushes their hard liquor; the drink of robust, long-lived people is wine.
But you have probably not heard about another study, released during the media dead zone just after Christmas last year, that questioned wine’s reputed health effects. Researchers at Stanford University and the University of Texas at Austin examined a group of Americans aged 55 to 65 and compared their drinking habits with how they fared over the course of 20 years. The scientists found that moderate drinkers lived longer than abstainers, and that wine drinkers did indeed live longer on average than people who consumed other kinds of alcohol. But they also found that wine drinkers were less likely to smoke, to be male, and to be sedentary; all of these are factors associated with dying earlier.
The Stanford-Texas team concluded that drinking wine might be an indicator of a healthy lifestyle rather than the cause of that good health. If so, wine is the drink of the healthy, all right—the already healthy.
That finding highlights what is arguably science’s greatest enemy, the confounder. Science is at heart a reductionist process: Take a complicated system, identify various factors that affect the system, and measure the effect of each factor one at a time. Confounders are devilish hidden connections that make it more difficult to isolate the factors you want to measure, like the fact that wine drinkers tend also to be nonsmokers…
In the journal Experimental Neurology, the scientists report the beneficial effects of so-called astrocytes, a certain type of glial cells. They get their name from the Greek word for glue, as it was long thought that these cells simply hold the nerve cells together and provided them with nutrients. In the case of epilepsy, the prevalent opinion was that their reaction to a seizure would actually damage the brain. The researchers from Freiburg disagree. In fact, they say, astrocytes help to reduce long-term damage brought upon by epileptic fits.
The team discovered the positive effects of astrocytes in mice, in which epileptic states can be selectively triggered. If the scientists injected mice with a specific protein to activate the astrocytes prior to an epilepsy-inducing insult, fewer nerve cells died in the wake of the seizure. Other pathological changes that would usually occur in the brain were likewise significantly reduced. The astrocytes’ protective effect lasted for many days after their activation. When the researchers measured the rodents’ brain activity, they likewise found fewer signs that are typical for a brain suffering from epilepsy. However, the authors report that the astrocytes had to be already activated before seizures were elicited. Activating them afterwards, on the other hand, did not lead to a protective effect.
Further studies will have to demonstrate that astrocytes have this protective influence all over the brain. According to Haas, who is also a member of Freiburg’s new cluster of excellence BrainLinks-BrainTools, their findings suggest that a timely activation of astrocytes could offer an effective protection from long-term damage to the brain.
Cannabis-based medications have been proved to relieve pain. This is the conclusion drawn by Franjo Grotenhermen and Kirsten Müller-Vahl in issue 29–30 of Deutsches Ärzteblatt International.
Cannabis medications can be used in patients whose symptoms are not adequately alleviated by conventional treatment. The indications are muscle spasms, nausea and vomiting as a result of chemotherapy, loss of appetite in HIV/Aids, and neuropathic pain.
The clinical effect of the various cannabis-based medications rests primarily on activation of endogenous cannabinoid receptors. Consumption of therapeutic amounts by adults does not lead to irreversible cognitive impairment. The risk is much greater, however, in children and adolescents (particularly before puberty), even at therapeutic doses.
Over 100 controlled trials of the effects of cannabinoids in various indications have been carried out since 1975. The positive results have led to official licensing of cannabis-based medications in many countries. In Germany, a cannabis extract was approved in 2011 for treatment of spasticity in multiple sclerosis. In June 2012 the Federal Joint Committee (the highest decision-making body for the joint self-government of physicians, dentists, hospitals and health insurance funds in Germany) pronounced that the cannabis extract showed a slight additional benefit for this indication and granted a temporary license until 2015.
More Kids Taking Antipsychotics for ADHD: Study
Use of powerful antipsychotic medications such as Abilify and Risperdal to control youngsters with attention-deficit/hyperactivity disorder (ADHD) and other behavior problems has skyrocketed in recent years, a new study finds.
Antipsychotics are approved to treat bipolar disorder, schizophrenia, other serious mental problems and irritability related to autism. But they don’t have U.S. Food and Drug Administration approval for ADHD or other childhood behavior problems, and their use for this purpose is considered “off label.”
"Only a small proportion of antipsychotic treatment of children (6 percent) and adolescents (13 percent) is for FDA-approved clinical indications," said lead researcher Dr. Mark Olfson, a professor of clinical psychiatry at Columbia University Medical Center in New York City.
Brain might not stand in the way of free will
Advocates of free will can rest easy, for now. A 30-year-old classic experiment that is often used to argue against free will might have been misinterpreted.
Our decision-making process remains hazy (Image: Jannes Glas/Getty)
In the early 1980s, Benjamin Libet, a neuroscientist at the University of California in San Francisco, used electroencephalography (EEG) to record the brain activity of volunteers who had been told to make a spontaneous movement. With the help of a precise timer that the volunteers were asked to read at the moment they became aware of the urge to act, Libet found there was a 200 millisecond delay, on average, between this urge and the movement itself.
But the EEG recordings also revealed a signal that appeared in the brain even earlier, 550 milliseconds, on average, before the action. Called the readiness potential, this has been interpreted as a blow to free will, as it suggests that the brain prepares to act well before we are conscious of the urge to move.
This conclusion assumes that the readiness potential is the signature of the brain planning and preparing to move. “Even people who have been critical of Libet’s work, by and large, haven’t challenged that assumption,” says Aaron Schurger of the National Institute of Health and Medical Research in Saclay, France.
One attempt to do so came in 2009. Judy Trevena and Jeff Miller of the University of Otago in Dunedin, New Zealand, asked volunteers to decide, after hearing a tone, whether or not to tap on a keyboard. The readiness potential was present regardless of their decision, suggesting that it did not represent the brain preparing to move. Exactly what it did mean, though, still wasn’t clear.
Crossing a threshold
Now, Schurger and colleagues have an explanation. They began by posing a question: how does the brain decide to make a spontaneous movement? They looked to other decision-making scenarios for clues. Previous studies have shown that when we have to make a decision based on visual input, for example, assemblies of neurons start accumulating visual evidence in favour of the various possible outcomes. A decision is triggered when the evidence favouring one particular outcome becomes strong enough to tip its associated assembly of neurons across a threshold.
Schurger’s team hypothesised that something similar happens in the brain during the Libet experiment. Volunteers, however, are specifically asked to ignore any external signals before they make a spontaneous movement, so the signal must be internal.
There are random fluctuations of neural activity in the brain. Schurger’s team reasoned that movement is triggered when this neural noise accumulates and crosses a threshold.
To probe the idea, the team first built a computer model of such a neural accumulator. In the model, each time the neural noise crossed a threshold it signified a decision to move. They found that when they ran the model numerous times and looked at the pattern of the neural noise that led up to the decision it looked like a readiness potential.
Next, the team repeated Libet’s experiment, but this time if, while waiting to act spontaneously, the volunteers heard a click they had to act immediately. The researchers predicted that the fastest response to the click would be seen in those in whom the accumulation of neural noise had neared the threshold – something that would show up in their EEG as a readiness potential.
This is exactly what the team found. In those with slower responses to the click, the readiness potential was absent in the EEG recordings.
Spontaneous brain activity
"Libet argued that our brain has already decided to move well before we have a conscious intention to move," says Schurger. "We argue that what looks like a pre-conscious decision process may not in fact reflect a decision at all. It only looks that way because of the nature of spontaneous brain activity."
So what does this say about free will? “If we are correct, then the Libet experiment does not count as evidence against the possibility of conscious will,” says Schurger.
Cognitive neuroscientist Anil Seth of the University of Sussex in Brighton, UK, is impressed by the work, but also circumspect about what it says about free will. “It’s a more satisfying mechanistic explanation of the readiness potential. But it doesn’t bounce conscious free will suddenly back into the picture,” he says. “Showing that one aspect of the Libet experiment can be open to interpretation does not mean that all arguments against conscious free will need to be ejected.”
According to Seth, when the volunteers in Libet’s experiment said they felt an urge to act, that urge is an experience, similar to an experience of smell or taste. The new model is “opening the door towards a richer understanding of the neural basis of the conscious experience of volition”, he says.
Source: NewScientist
Brain signal ID’s responders to fast-acting antidepressant
August 3, 2012
Scientists have discovered a biological marker that may help to identify which depressed patients will respond to an experimental, rapid-acting antidepressant. The brain signal, detectable by noninvasive imaging, also holds clues to the agent’s underlying mechanism, which are vital for drug development, say National Institutes of Health researchers.
Dr. Zarate views subject in MEG scanner from scanner control room.
The signal is among the latest of several such markers, including factors detectable in blood, genetic markers, and a sleep-specific brain wave, recently uncovered by the NIH team and grantee collaborators. They illuminate the workings of the agent, called ketamine, and may hold promise for more personalized treatment.
"These clues help focus the search for the molecular targets of a future generation of medications that will lift depression within hours instead of weeks," explained Carlos Zarate, M.D., of the NIH’s National Institute of Mental Health (NIMH). "The more precisely we understand how this mechanism works, the more narrowly treatment can be targeted to achieve rapid antidepressant effects and avoid undesirable side effects."
Zarate, Brian Cornwell, Ph.D., and NIMH colleagues report on their brain imaging study online in the journal Biological Psychiatry.
Previous research had shown that ketamine can lift symptoms of depression within hours in many patients. But side effects hamper its use as a first-line medication. So researchers are studying its mechanism of action in hopes of developing a safer agent that works similarly.
Ketamine works through a different brain chemical system than conventional antidepressants. It initially blocks a protein on brain neurons, called the NMDA receptor, to which the chemical messenger glutamate binds. However, it is not known if the drug’s rapid antidepressant effects are a direct result of this blockage or of downstream effects triggered by the blockage, as suggested by animal studies.
To tease apart ketamine’s workings, the NIMH team imaged depressed patients’ brain electrical activity with magnetoencephalography (MEG). They monitored spontaneous activity while subjects were at rest, and activity evoked by gentle stimulation of a finger, before and 6.5 hours after an infusion of ketamine.
It was known that by blocking NMDA receptors, ketamine causes an increase in spontaneous electrical signals, or waves, in a particular frequency range in the brain’s cortex, or outer mantle. Hours after ketamine administration— in the timeframe in which ketamine relieves depression — spontaneous electrical activity in people at rest was the same whether or not the drug lifted their depression.
Electrical activity evoked by stimulating a finger, however, was different in the two groups. MEG imaging made it possible to monitor excitability of the somatosensory cortex, the part of the cortex that registers sensory stimulation. Those who responded to ketamine showed an increased response to the finger stimulation, a greater excitability of the neurons in this part of the cortex.
Such a change in excitability is likely to result, not from the immediate effects of blocking the receptor, but from other processes downstream, in the cascade of effects set in motion by NMDA blockade, say the researchers. Evidence points to changes in another type of glutamate receptor, the AMPA receptor, raising questions about whether the blocking of NMDA receptors is even necessary for ketamine’s antidepressant effect. If NMDA blockade is just a trigger, then targeting AMPA receptors may prove a more direct way to effect a lifting of depression.