Posts tagged neuroscience
Articles and news from the latest research reports.
Study finds link between commonly prescribed statin and memory impairment
New research that looked at whether two commonly prescribed statin medicines, used to lower low-density lipoprotein (LDL) or‘bad cholesterol’ levels in the blood, can adversely affect cognitive function has found that one of the drugs tested caused memory impairment in rats.
Between six and seven million people in the UK take statins daily and the findings follow anecdotal evidence of people reporting that they feel that their newly prescribed statin is affecting their memory. Last year, the US Food and Drug Administration (FDA) insisted that all manufacturers list in their side effects that statins might affect cognitive function.
The study, led by scientists at the University of Bristol and published in the journal PLOS ONE, tested pravastatin and atorvostatin (two commonly prescribed statins) in rat learning and memory models. The findings show that while no adverse cognitive effects were observed in rat performance for simple learning and memory tasks for atorvostatin, pravastatin impaired their performance.
Rats were treated daily with pravastatin (brand name - Pravachol) or atorvostatin (brand name - Lipitor) for 18 days. The rodents were tested in a simple learning task before, during and after treatment, where they had to learn where to find a food reward. On the last day of treatment and following one week withdrawal, the rats were also tested in a task which measures their ability to recognise a previously encountered object (recognition memory).
The study’s findings showed that pravastatin tended to impair learning over the last few days of treatment although this effect was fully reversed once treatment ceased. However, in the novel object discrimination task, pravastatin impaired object recognition memory. While no effects were observed for atorvostatin in either task.
The results suggest that chronic treatment with pravastatin impairs working and recognition memory in rodents. The reversibility of the effects on stopping treatment is similar to what has been observed in patients, but the lack of effect of atorvostatin suggests that some types of statin may be more likely to cause cognitive impairment than others.
Neil Marrion, Professor of Neuroscience at Bristol’s School of Physiology and Pharmacology in the Faculty of Medical and Veterinary Sciences and the study’s lead author, said: “This finding is novel and likely reflects both the anecdotal reports and FDA advice. What is most interesting is that it is not a feature of all statins. However, in order to better understand the relationship between statin treatment and cognitive function, further studies are needed.”
(Source: bris.ac.uk)
![Maths experts are “made, not born”
A new study of the brain of a maths supremo supports Darwin’s belief that intellectual excellence is largely due to “zeal and hard work” rather than inherent ability.
University of Sussex neuroscientists took fMRI scans of champion ‘mental calculator’ Yusnier Viera during arithmetical tasks that were either familiar or unfamiliar to him and found that his brain did not behave in an extraordinary or unusual way.
The paper, published this week (23 September 2013) in PLOS ONE, provides scientific evidence that some calculation abilities are a matter of practice. Co-author Dr Natasha Sigala says: “This is a message of hope for all of us. Experts are made, not born.”
Cuban-born Yusnier holds world records for being able to name the days of the week for any dates of the past 400 years, giving his answer in less than a second. This is the kind of ability sometimes found in those with autism, although Yusnier is not on the autistic spectrum. Unlike those with autism or the related condition Asperger’s, he is able to explain exactly how he calculates his answers – and even teaches his system and has written books on the subject.
The study, carried out at the Clinical Imaging Sciences Centre on the University of Sussex campus, suggests that Yusnier has honed his ability to create short cuts to his answers by storing information in the middle part of the brain specialised for long-term working memory (the hippocampus and surrounding cortex). This type of memory helps us carry out tasks in our area of expertise with speed and efficiency.
Although the left side of his brain was activated during mathematical problems – which is normal for all brains – the scientists observed that something slightly different happened when Yusnier was presented with unfamiliar problems.
The scans showed marked connectivity of the anterior parts of the brain (prefrontal cortex), which are involved in decision making, during the unfamiliar calculations. This supports Yusnier’s report that he was building in an extra step to his mental processes to turn an unfamiliar problem into a familiar one. His answers to the unfamiliar questions had an 80 per cent degree of accuracy (compared with more than 90 per cent for familiar questions) and his responses were slightly slower.
Dr Sigala explains: “Although this kind of ability is seen among some people with autism, it is much rarer in those not on that spectrum. Brain scans of those with autism tend to show a variety of activity patterns, and autistic people are not able to explain how they reach their answer.
“With Yusnier, however, it is clear that his expertise is a result of long-term practice – and motivation.”
She adds: “It was beyond the scope of our paper to discuss the debate on deliberate practice vs. innate ability. But our study does not provide evidence for specific innate ability for mental calculations. As put by Charles Darwin to Francis Galton: ‘ […] I have always maintained that, excepting fools, men did not differ much in intellect, only in zeal and hard work; I still think this an eminently important difference.’”](http://40.media.tumblr.com/749a98eac0fa21f91c01da24b2bf7089/tumblr_mtqmqtOttT1rog5d1o1_500.png)
Maths experts are “made, not born”
A new study of the brain of a maths supremo supports Darwin’s belief that intellectual excellence is largely due to “zeal and hard work” rather than inherent ability.
University of Sussex neuroscientists took fMRI scans of champion ‘mental calculator’ Yusnier Viera during arithmetical tasks that were either familiar or unfamiliar to him and found that his brain did not behave in an extraordinary or unusual way.
The paper, published this week (23 September 2013) in PLOS ONE, provides scientific evidence that some calculation abilities are a matter of practice. Co-author Dr Natasha Sigala says: “This is a message of hope for all of us. Experts are made, not born.”
Cuban-born Yusnier holds world records for being able to name the days of the week for any dates of the past 400 years, giving his answer in less than a second. This is the kind of ability sometimes found in those with autism, although Yusnier is not on the autistic spectrum. Unlike those with autism or the related condition Asperger’s, he is able to explain exactly how he calculates his answers – and even teaches his system and has written books on the subject.
The study, carried out at the Clinical Imaging Sciences Centre on the University of Sussex campus, suggests that Yusnier has honed his ability to create short cuts to his answers by storing information in the middle part of the brain specialised for long-term working memory (the hippocampus and surrounding cortex). This type of memory helps us carry out tasks in our area of expertise with speed and efficiency.
Although the left side of his brain was activated during mathematical problems – which is normal for all brains – the scientists observed that something slightly different happened when Yusnier was presented with unfamiliar problems.
The scans showed marked connectivity of the anterior parts of the brain (prefrontal cortex), which are involved in decision making, during the unfamiliar calculations. This supports Yusnier’s report that he was building in an extra step to his mental processes to turn an unfamiliar problem into a familiar one. His answers to the unfamiliar questions had an 80 per cent degree of accuracy (compared with more than 90 per cent for familiar questions) and his responses were slightly slower.
Dr Sigala explains: “Although this kind of ability is seen among some people with autism, it is much rarer in those not on that spectrum. Brain scans of those with autism tend to show a variety of activity patterns, and autistic people are not able to explain how they reach their answer.
“With Yusnier, however, it is clear that his expertise is a result of long-term practice – and motivation.”
She adds: “It was beyond the scope of our paper to discuss the debate on deliberate practice vs. innate ability. But our study does not provide evidence for specific innate ability for mental calculations. As put by Charles Darwin to Francis Galton: ‘ […] I have always maintained that, excepting fools, men did not differ much in intellect, only in zeal and hard work; I still think this an eminently important difference.’”
![Stanford scientists build a ‘brain stethoscope’ to turn seizures into music
When Chris Chafe and Josef Parvizi began transforming recordings of brain activity into music, they did so with artistic aspirations. The professors soon realized, though, that the work could lead to a powerful biofeedback tool for identifying brain patterns associated with seizures.
Josef Parvizi was enjoying a performance by the Kronos Quartet when the idea struck. The musical troupe was midway through a piece in which the melodies were based on radio signals from outer space, and Parvizi, a neurologist at Stanford Medical Center, began wondering what the brain’s electrical activity might sound like set to music.
He didn’t have to look far for help. Chris Chafe, a professor of music research at Stanford, is one of the world’s foremost experts in “musification,” the process of converting natural signals into music. One of his previous works involved measuring the changing carbon dioxide levels near ripening tomatoes and converting those changing levels into electronic performances.
Parvizi, an associate professor, specializes in treating patients suffering from intractable seizures. To locate the source of a seizure, he places electrodes in patients’ brains to create electroencephalogram (EEG) recordings of both normal brain activity and a seizure state.
He shared a consenting patient’s EEG data with Chafe, who began setting the electrical spikes of the rapidly firing neurons to music. Chafe used a tone close to a human’s voice, in hopes of giving the listener an empathetic and intuitive understanding of the neural activity.
Upon a first listen, the duo realized they had done more than create an interesting piece of music. [Listen to the audio here]
"My initial interest was an artistic one at heart, but, surprisingly, we could instantly differentiate seizure activity from non-seizure states with just our ears," Chafe said. "It was like turning a radio dial from a static-filled station to a clear one."
If they could achieve the same result with real-time brain activity data, they might be able to develop a tool to allow caregivers for people with epilepsy to quickly listen to the patient’s brain waves to hear whether an undetected seizure might be occurring.
Parvizi and Chafe dubbed the device a “brain stethoscope.”
The sound of a seizure
The EEGs Parvizi conducts register brain activity from more than 100 electrodes placed inside the brain; Chafe selects certain electrode/neuron pairings and allows them to modulate notes sung by a female singer. As the electrode captures increased activity, it changes the pitch and inflection of the singer’s voice.
Before the seizure begins – during the so-called pre-ictal stage – the peeps and pops from each “singer” almost synchronize and fall into a clear rhythm, as if they’re following a conductor, Chafe said.
In the moments leading up to the seizure event, though, each of the singers begins to improvise. The notes become progressively louder and more scattered, as the full seizure event occurs (the ictal state). The way Chafe has orchestrated his singers, one can hear the electrical storm originate on one side of the brain and eventually cross over into the other hemisphere, creating a sort of sing-off between the two sides of the brain.
After about 30 seconds of full-on chaos, the singers begin to calm, trailing off into their post-ictal rhythm. Occasionally, one or two will pipe up erratically, but on the whole, the choir sounds extremely fatigued.
It’s the perfect representation of the three phases of a seizure event, Parvizi said.
Part art exhibit, part experiment
Caring for a person with seizures can be very difficult, as not all seizure activity manifests itself with behavioral cues. It’s often impossible to know whether a person with epilepsy is acting confused because they are having a seizure, or if they are experiencing the type of confusion that is a marker of the post-ictal seizure phase.
To that end, Parvizi and Chafe hope to apply their work to develop a device that listens for the telltale brain patterns of an ongoing seizure or a post-ictal fatigued brain state.
"Someone – perhaps a mother caring for a child – who hasn’t received training in interpreting visual EEGs can hear the seizure rhythms and easily appreciate that there is a pathological brain phenomenon taking place," Parvizi said.
The device can also offer biofeedback to non-epileptic patients who want to hear the music their own brain waves create.
The effort to build this device is funded by Stanford’s Bio-X Interdisciplinary Initiatives Program (Bio-X IIP), which provides money for interdisciplinary projects that have potential to improve human health in innovative ways. Bio-X seed grants have funded 141 research collaborations connecting hundreds of faculty since 2000. The proof-of-concept projects have produced hundreds of publications, dozens of patents, and more than a tenfold return on research funds to Stanford.
From a clinical perspective, the work is still very experimental.
"We’ve really just stuck our finger in there," Chafe said. "We know that the music is fascinating and that we can hear important dynamics, but there are still wonderful revelations to be made."
Next year, Chafe and Parvizi plan to unveil a version of the system at Stanford’s Cantor Arts Center. Visitors will don a headset that will transmit an EEG of their brain activity to their handheld device, which will convert it into music in real time.
"This is what I like about Stanford," Parvizi said. "It nurtures collaboration between fields that are seemingly light-years apart – we’re neurology and music professors! – and our work together will hopefully make a positive impact on the world we live in."](http://40.media.tumblr.com/9065dbf8f11ead256e3e5a55b5d20b2e/tumblr_mtqn9mjEW61rog5d1o1_400.jpg)
Stanford scientists build a ‘brain stethoscope’ to turn seizures into music
When Chris Chafe and Josef Parvizi began transforming recordings of brain activity into music, they did so with artistic aspirations. The professors soon realized, though, that the work could lead to a powerful biofeedback tool for identifying brain patterns associated with seizures.
Josef Parvizi was enjoying a performance by the Kronos Quartet when the idea struck. The musical troupe was midway through a piece in which the melodies were based on radio signals from outer space, and Parvizi, a neurologist at Stanford Medical Center, began wondering what the brain’s electrical activity might sound like set to music.
He didn’t have to look far for help. Chris Chafe, a professor of music research at Stanford, is one of the world’s foremost experts in “musification,” the process of converting natural signals into music. One of his previous works involved measuring the changing carbon dioxide levels near ripening tomatoes and converting those changing levels into electronic performances.
Parvizi, an associate professor, specializes in treating patients suffering from intractable seizures. To locate the source of a seizure, he places electrodes in patients’ brains to create electroencephalogram (EEG) recordings of both normal brain activity and a seizure state.
He shared a consenting patient’s EEG data with Chafe, who began setting the electrical spikes of the rapidly firing neurons to music. Chafe used a tone close to a human’s voice, in hopes of giving the listener an empathetic and intuitive understanding of the neural activity.
Upon a first listen, the duo realized they had done more than create an interesting piece of music. [Listen to the audio here]
"My initial interest was an artistic one at heart, but, surprisingly, we could instantly differentiate seizure activity from non-seizure states with just our ears," Chafe said. "It was like turning a radio dial from a static-filled station to a clear one."
If they could achieve the same result with real-time brain activity data, they might be able to develop a tool to allow caregivers for people with epilepsy to quickly listen to the patient’s brain waves to hear whether an undetected seizure might be occurring.
Parvizi and Chafe dubbed the device a “brain stethoscope.”
The sound of a seizure
The EEGs Parvizi conducts register brain activity from more than 100 electrodes placed inside the brain; Chafe selects certain electrode/neuron pairings and allows them to modulate notes sung by a female singer. As the electrode captures increased activity, it changes the pitch and inflection of the singer’s voice.
Before the seizure begins – during the so-called pre-ictal stage – the peeps and pops from each “singer” almost synchronize and fall into a clear rhythm, as if they’re following a conductor, Chafe said.
In the moments leading up to the seizure event, though, each of the singers begins to improvise. The notes become progressively louder and more scattered, as the full seizure event occurs (the ictal state). The way Chafe has orchestrated his singers, one can hear the electrical storm originate on one side of the brain and eventually cross over into the other hemisphere, creating a sort of sing-off between the two sides of the brain.
After about 30 seconds of full-on chaos, the singers begin to calm, trailing off into their post-ictal rhythm. Occasionally, one or two will pipe up erratically, but on the whole, the choir sounds extremely fatigued.
It’s the perfect representation of the three phases of a seizure event, Parvizi said.
Part art exhibit, part experiment
Caring for a person with seizures can be very difficult, as not all seizure activity manifests itself with behavioral cues. It’s often impossible to know whether a person with epilepsy is acting confused because they are having a seizure, or if they are experiencing the type of confusion that is a marker of the post-ictal seizure phase.
To that end, Parvizi and Chafe hope to apply their work to develop a device that listens for the telltale brain patterns of an ongoing seizure or a post-ictal fatigued brain state.
"Someone – perhaps a mother caring for a child – who hasn’t received training in interpreting visual EEGs can hear the seizure rhythms and easily appreciate that there is a pathological brain phenomenon taking place," Parvizi said.
The device can also offer biofeedback to non-epileptic patients who want to hear the music their own brain waves create.
The effort to build this device is funded by Stanford’s Bio-X Interdisciplinary Initiatives Program (Bio-X IIP), which provides money for interdisciplinary projects that have potential to improve human health in innovative ways. Bio-X seed grants have funded 141 research collaborations connecting hundreds of faculty since 2000. The proof-of-concept projects have produced hundreds of publications, dozens of patents, and more than a tenfold return on research funds to Stanford.
From a clinical perspective, the work is still very experimental.
"We’ve really just stuck our finger in there," Chafe said. "We know that the music is fascinating and that we can hear important dynamics, but there are still wonderful revelations to be made."
Next year, Chafe and Parvizi plan to unveil a version of the system at Stanford’s Cantor Arts Center. Visitors will don a headset that will transmit an EEG of their brain activity to their handheld device, which will convert it into music in real time.
"This is what I like about Stanford," Parvizi said. "It nurtures collaboration between fields that are seemingly light-years apart – we’re neurology and music professors! – and our work together will hopefully make a positive impact on the world we live in."
New approach helps those with traumatic brain injury
Greg Noack was 24 when he moved from Ontario to Victoria, B.C. He had just graduated from college and was looking forward to a fresh start.
One early morning in 1996, as he was returning home from his graveyard shift at the hotel, Noack was attacked from behind by a group of men.
He doesn’t remember being struck on the head. He does remember waking from a 15-day coma to learn he had suffered a traumatic brain injury (TBI).
Noack, through the care of his health-care team, relearned how to walk, write, and feel particular emotions.
“I was enamoured by what my therapists were able to do for me,” said Noack. “I was lucky that I got back most of my function.”
Three years post-injury, Noack enrolled in Sault College’s Occupational Therapist Assistant/Physical Therapist Assistant Program and graduated with honours.
Shortly after, Noack was hired by the Toronto Rehab Acquired Brain Injury Rehab team as an occupational therapist assistant and later became a rehab therapist.
Most recently, he was seconded to Dr. Robin Green’s traumatic brain injury research team.
Dr. Green, Senior Scientist and Neuropsychologist, Toronto Rehab and Canada Research Chair in Traumatic Brain Injury, and her Toronto Rehab team have been studying impediments to brain injury recovery as well as treatments to offset the impediments.
Dr. Green’s work suggests that moderate-severe TBI may be a progressive neurological disorder –a whole new way of perceiving the condition.
“What may be occurring after a serious brain injury,” said Dr. Green, “is that damaged tissue is leaving healthy areas of the brain disconnected and under stimulated. Over time, healthy areas may deteriorate.”
Importantly, they discovered that in people with chronic moderate-severe TBI, environmental enrichment – increased physical, social and cognitive stimulation - can offset this deterioration.
Her research paper, entitled “Environmental enrichment may protect against hippocampal atrophy in the chronic stages of traumatic brain injury,” was published September 24 in Frontiers in Human Neuroscience.
In their study of 25 patients with moderate-severe TBI, her team found a positive reaction to environmental enrichment.
Those who reported greater amounts of environmental enrichment – for example, reading, problem solving exercises, puzzles, physical activity, socializing – at 5 months after their injury showed less shrinkage of the hippocampus (associated with memory functioning) from 5 to 28 months post-injury.
“People with moderate-severe TBI are commonly unable to return to the same level of engagement in their work, school or social lives as before the injury,” said Dr. Green. “However, those with greater environmental enrichment may be keeping vulnerable areas stimulated. Environmental enrichment is also known to increase production of neurons in the hippocampus and to promote their integration into existing brain networks.”
Based on the findings from their study, Green’s team is now engaged in research designed to proactively offset deterioration, which includes the delivery of environmental enrichment to patients. Noack is instrumental in delivering enriched therapy for TBI patients who are enrolled in one of Dr. Green’s research studies.
“One thing I loved about this study is that it facilitated greater customization of a patient’s care,” said Noack. “I could see how my patients benefited from the increased amount of stimulation through extended therapy.”
“Although the brains of patients are showing negative changes, patients are still showing recovery of their functioning in spite of it,” said Dr. Green. “If we are able to offset the negative brain changes through the treatments we are developing, we may be able to very significantly improve patients’ recovery and the quality of their aging with a brain injury.”
(Source: uhn.ca)
New Study Shows How ICU Ventilation May Trigger Mental Decline
Researchers from Penn Medicine and University of Oviedo Identify Molecular Pathway Linking ICU Ventilation to Brain Damage
At least 30 percent of patients in intensive care units (ICUs) suffer some form of mental dysfunction as reflected in anxiety, depression, and especially delirium. In mechanically-ventilated ICU patients, the incidence of delirium is particularly high, about 80 percent, and may be due in part to damage in the hippocampus, though how ventilation is increasing the risk of damage and mental impairment has remained elusive.
Now, a new study published in the American Journal of Respiratory and Critical Care Medicine fromresearchers at the University of Oviedo in Spain, St. Michael’s Hospital in Toronto, Canada, and the Perelman School of Medicine at the University Pennsylvaniafound a molecular mechanism that may explain the connection between mechanical ventilation and hippocampal damage in ICU patients.
The investigators, including Adrian González-López, PhD, in the laboratory of Guillermo M. Albaiceta, MD, PhD at the University of Oviedo , and co-authored by Konrad Talbot, PhD, an assistant research professor in Neurobiology in the Department of Psychiatry at Penn Medicine, began by studying the hippocampus in control mice and in mice on low or high-pressure mechanical ventilation for 90 minutes. Compared to the controls, those on either low- or high-pressure ventilation showed evidence of neuronal cell death in the hippocampus, as a result of a cell suicide program called apoptosis.
Searching for the molecular cause of the ventilation-induced apoptosis, the team discovered that a well-known apoptosis trigger had been set off in the hippocampus of the ventilated animals. That trigger is dopamine-induced suppression of a molecule known as Akt, which normally acts to prevent neuronal apoptosis. Akt suppression was clearly evident in the hippocampus of the ventilated mice and was associated with a hyperdopaminergic state (increased levels of dopamine) in that brain area. The ventilated mice had elevated gene expression of the enzyme tyrosine hydroxylase, which is critical in synthesizing dopamine. The resulting rise in dopamine increases the strength of dopamine receptor activation in the hippocampus.
The investigators hypothesized that ventilation-induced apoptosis in the hippocampus was at least partly mediated by elevated activation of dopamine receptors in that brain area. This was confirmed by showing that pretreatment of mice with type 2 (D2) dopamine receptor blockers injected into the ventricles of the brain significantly reduced ventilation-induced apoptosis in the hippocampus.
How mechanical ventilation manages to affect the hippocampus was answered by experiments on mice in which the vagus cranial nerve connecting the lungs with the brain was severed. In these mice, mechanical ventilation had virtually no effect on levels of the dopamine-synthesizing enzyme or on apoptosis in the hippocampus.
The investigators then studied the consequences of ventilation and elevated hippocampal dopamine on dysbindin-1, a protein known to affect levels of cell surface D2 dopamine receptors, cognition, and possibly the risk of psychosis. High-pressure ventilation in mice caused an increase in gene expression of dysbindin-1C, and later, in protein levels of dysbindin-1C. Dopamine alone had similar effects on dysbindin-1C in hippocampal slice preparations, effects that were inhibited by D2 receptor blockers.
Since dysbindin-1 can lower cell-surface D2 receptors and protect against apoptosis, the authors speculate that increased dysbindin-1C expression in the ventilated mice may reflect compensatory responses to ventilation-induced hippocampal apoptosis. That possibility applies to ICU cases given the additional finding by the authors that total dysbindin-1 was increased in hippocampal neurons of ventilated compared to non-ventilated humans who died in the ICU.
The findings could lead to new therapeutic uses of established drugs and targets for new drugs that activate a molecular pathway mediating adverse effects of ICU ventilation on brain function.
“The results prove the existence of a pathogenic mechanism of lung stretch-induced hippocampal apoptosis that could explain the development of neurobehavioral disorders in patients exposed to mechanical ventilation,” the authors write. One of the coauthors, Dr. Talbot, adds: “The study indicates the need to reevaluate use of D2 receptor antagonists in minimizing the negative cognitive effects of mechanical ventilation in ICU patients and to evaluate the novel possibility that elevation in dysbindin-1C expression can also reduce those effects.”
The corresponding author, Dr. Albaiceta, offered a look at future research on this topic: “Now that we have established the mouse model, we are mainly looking for therapeutic approaches aimed at avoiding the vagal activation caused by mechanical ventilation and therefore prevent the deleterious effects observed in the hippocampus,” he said. “We are also interested in studying the relationship between the different described gene polymorphisms of dysbindin, Akt, and type 2 dopamine receptor versus the incidence of neurological disorders in patients on ventilation in ICUs. This could help us to identify susceptible individuals to in which a preventive treatment could be effective.”
(Source: uphs.upenn.edu)
A neurological basis for the lack of empathy in psychopaths
When individuals with psychopathy imagine others in pain, brain areas necessary for feeling empathy and concern for others fail to become active and be connected to other important regions involved in affective processing and decision-making, reports a study published in the open-access journal Frontiers in Human Neuroscience.
Psychopathy is a personality disorder characterized by a lack of empathy and remorse, shallow affect, glibness, manipulation and callousness. Previous research indicates that the rate of psychopathy in prisons is around 23%, greater than the average population which is around 1%.
To better understand the neurological basis of empathy dysfunction in psychopaths, neuroscientists used functional magnetic resonance imaging (fMRI) on the brains of 121 inmates of a medium-security prison in the USA.
Participants were shown visual scenarios illustrating physical pain, such as a finger caught between a door, or a toe caught under a heavy object. They were by turns invited to imagine that this accident happened to themselves, or somebody else. They were also shown control images that did not depict any painful situation, for example a hand on a doorknob.
Participants were assessed with the widely used PCL-R, a diagnostic tool to identify their degree of psychopathic tendencies. Based on this assessment, the participants were then divided in three groups of approximately 40 individuals each: highly, moderately, and weakly psychopathic.
When highly psychopathic participants imagined pain to themselves, they showed a typical neural response within the brain regions involved in empathy for pain, including the anterior insula, the anterior midcingulate cortex, somatosensory cortex, and the right amygdala. The increase in brain activity in these regions was unusually pronounced, suggesting that psychopathic people are sensitive to the thought of pain.
But when participants imagined pain to others, these regions failed to become active in high psychopaths. Moreover, psychopaths showed an increased response in the ventral striatum, an area known to be involved in pleasure, when imagining others in pain.
This atypical activation combined with a negative functional connectivity between the insula and the ventromedial prefrontal cortex may suggest that individuals with high scores on psychopathy actually enjoyed imagining pain inflicted on others and did not care for them. The ventromedial prefrontal cortex is a region that plays a critical role in empathetic decision-making, such as caring for the wellbeing of others.
Taken together, this atypical pattern of activation and effective connectivity associated with perspective taking manipulations may inform intervention programs in a domain where therapeutic pessimism is more the rule than the exception. Altered connectivity may constitute novel targets for intervention. Imagining oneself in pain or in distress may trigger a stronger affective reaction than imagining what another person would feel, and this could be used with some psychopaths in cognitive-behavior therapies as a kick-starting technique, write the authors.
A shot of anxiety and the world stinks
In evolutionary terms, smell is among the oldest of the senses. In animals ranging from invertebrates to humans, olfaction exerts a primal influence as the brain continuously and subconsciously processes the steady stream of scent molecules that waft under our noses.
And while odors — whether the aroma of stinky socks or the sweet smell of baking bread — are known to stir the emotions, how they exert their influence biologically on the emotional centers of the human brain, evoking passion or disgust, has been a black box.
Now, however, researchers using powerful new brain imaging technologies are peeling back some of the mystery, revealing how anxiety or stress can rewire the brain, linking centers of emotion and olfactory processing, to make typically benign smells malodorous.
Writing today (Sept. 24, 2013) in the Journal of Neuroscience, a team led by Wen Li, a professor of psychology at the UW-Madison Waisman Center, reports that the brains of human subjects experience anxiety induced by disturbing pictures and text of things like car crashes and war transform neutral odors to distasteful ones, fueling a feedback loop that could heighten distress and lead to clinical issues like anxiety and depression.
The finding is important because it may help scientists understand the dynamic nature of smell perception and the biology of anxiety as the brain rewires itself under stressful circumstances and reinforces negative sensations and feelings.
"After anxiety induction, neutral smells become clearly negative," explains Li, who conducted the study with UW-Madison colleagues Elizabeth Krusemark and Lucas Novak, and Darren Gitelman of Northwestern University’s Feinberg School of Medicine. "People experiencing an increase in anxiety show a decrease in the perceived pleasantness of odors. It becomes more negative as anxiety increases."
Using behavioral techniques and functional magnetic resonance imaging (fMRI), Li’s group looked at the brains of a dozen human subjects with induced anxiety as they processed known neutral odors.
Functional MRI is a technology that enables clinicians and researchers to observe the working brain in action. Before entering the MRI where screens cycle through a series of disturbing pictures and text, subjects were exposed to and rated a panel of neutral smells.
In the course of the experiment, the Wisconsin team observed that two distinct and typically independent circuits of the brain — one dedicated to olfactory processing, the other to emotion — become intimately intertwined under conditions of anxiety. Subsequent to anxiety induction and the imaging process, subjects were asked again to rate the panel of neutral smells, most assigning negative responses to smells they previously rated as neutral.
"In typical odor processing, it is usually just the olfactory system that gets activated," says Li. "But when a person becomes anxious, the emotional system becomes part of the olfactory processing stream."
Although those two systems of the brain are right next to each other, under normal circumstances there is limited crosstalk between the two. However, under conditions of induced anxiety, the Wisconsin team observed the emergence of a unified network cutting across the two systems.
The results may have clinical implications in the sense that it begins to uncover the biological mechanisms at play during periods of anxiety. “We encounter anxiety and as a result we experience the world more negatively. The environment smells bad in the context of anxiety. It can become a vicious cycle, making one more susceptible to a clinical state of anxiety as the effects accumulate. It can potentially lead to a higher level of emotional disturbances with rising ambient sensory stress.”
Alzheimer’s progression tracked prior to dementia
For years, scientists have attempted to understand how Alzheimer’s disease harms the brain before memory loss and dementia are clinically detectable. Most researchers think this preclinical stage, which can last a decade or more before symptoms appear, is the critical phase when the disease might be controlled or stopped, possibly preventing the failure of memory and thinking abilities in the first place.
Important progress in this effort is reported in October in Lancet Neurology. Scientists at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University School of Medicine in St. Louis, working in collaboration with investigators at the University of Maastricht in the Netherlands, helped to validate a proposed new system for identifying and classifying individuals with preclinical Alzheimer’s disease.
Their findings indicate that preclinical Alzheimer’s disease can be detected during a person’s life, is common in cognitively normal elderly people and is associated with future mental decline and mortality. According to the scientists, this suggests that preclinical Alzheimer’s disease could be an important target for therapeutic intervention.
A panel of Alzheimer’s experts, convened by the National Institute on Aging in association with the Alzheimer’s Association, proposed the classification system two years ago. It is based on earlier efforts to define and track biomarker changes during preclinical disease.
According to the Washington University researchers, the new findings offer reason for encouragement, showing, for example, that the system can help predict which cognitively normal individuals will develop symptoms of Alzheimer’s and how rapidly their brain function will decline. But they also highlight additional questions that must be answered before the classification system can be adapted for use in clinical care.
“For new treatments, knowing where individuals are on the path to Alzheimer’s dementia will help us improve the design and assessment of clinical trials,” said senior author Anne Fagan, PhD, research professor of neurology. “There are many steps left before we can apply this system in the clinic, including standardizing how we gather and assess data in individuals, and determining which of our indicators of preclinical disease are the most accurate. But the research data are compelling and very encouraging.”
The classification system divides preclinical Alzheimer’s into three stages:
- Stage 1: Levels of amyloid beta, a protein fragment produced by the brain, begin to fall in the spinal fluid. This indicates that the substance is beginning to form plaques in the brain.
- Stage 2: Levels of tau protein start to rise in the spinal fluid, indicating that brain cells are beginning to die. Amyloid beta levels are still abnormal and may continue to fall.
- Stage 3: In the presence of abnormal amyloid and tau biomarker levels, subtle cognitive changes can be detected by neuropsychological testing. By themselves, these changes cannot establish a clinical diagnosis of dementia.
The researchers applied these criteria to research participants studied from 1998 through 2011 at the Knight Alzheimer Disease Research Center. The center annually collects extensive cognitive, biomarker and other health data on normal and cognitively impaired volunteers for use in Alzheimer’s studies.
The scientists analyzed information on 311 individuals age 65 or older who were cognitively normal when first evaluated. Each participant was evaluated annually at the center at least twice; the participant in this study with the most data had been followed for 15 years.
At the initial testing, 41 percent of the participants had no indicators of Alzheimer’s disease (stage 0); 15 percent were in stage 1 of preclinical disease; 12 percent were in stage 2; and 4 percent were in stage 3. The remaining participants were classified as having cognitive impairments caused by conditions other than Alzheimer’s (23 percent) or did not meet any of the proposed criteria (5 percent).
“A total of 31 percent of our participants had preclinical disease,” said Fagan. “This percentage matches findings from autopsy studies of the brains of older individuals, which have shown that about 30 percent of people who were cognitively normal had preclinical Alzheimer’s pathology in their brain.”
Scientists believe the rate of cognitive decline increases as people move through the stages of preclinical Alzheimer’s. The new data support this idea. Five years after their initial evaluation, 11 percent of the stage 1 group, 26 percent of the stage 2 group, and 52 percent of the stage 3 group had been diagnosed with symptomatic Alzheimer’s.
Individuals with preclinical Alzheimer’s disease were six times more likely to die over the next decade than older adults without preclinical Alzheimer’s disease, but researchers don’t know why.
“Risk factors for Alzheimer’s disease might also be associated with other life-threatening illnesses,” Fagan said. “It’s also possible that the presence of Alzheimer’s hampers the diagnosis and treatment of other conditions or contributes to health problems elsewhere in the body. We don’t have enough data yet to say, but it’s an issue we’re continuing to investigate.”
(Source: news.wustl.edu)
Researchers Identify Risk-Factors for Addictive Video-Game Use among Adults
New research from the University of Missouri indicates escapism, social interaction and rewards fuel problematic video-game use among “very casual” to “hardcore” adult gamers. Understanding individual motives that contribute to unhealthy game play could help counselors identify and treat individuals addicted to video games.
“The biggest risk factor for pathological video game use seems to be playing games to escape from daily life,” said Joe Hilgard, a doctoral candidate in the Department of Psychological Sciences in the MU College of Arts and Science. “Individuals who play games to get away from their lives or to pretend to be other people seem to be those most at-risk for becoming part of a vicious cycle. These gamers avoid their problems by playing games, which in turn interferes with their lives because they’re so busy playing games.”
Problematic video game use is more than just excessive use of video games; it also includes a variety of unhealthy behaviors, such as lying to others about how much time is spent playing games and missing work or other obligations to play games.
“People who play games to socialize with other players seem to have more problems as well,” Hilgard said. “It could be that games are imposing a sort of social obligation on these individuals so that they have to set aside time to play with other players. For example, in games like World of Warcraft, most players join teams or guilds. If some teammates want to play for four hours on a Saturday night, the other players feel obligated to play or else they may be cut from the team. Those play obligations can mess with individuals’ real-life obligations.”
Problematic video game use isn’t all that different from other types of addictive behavior, such as alcohol or drug abuse, which can be spurred by poor coping strategies, Hilgard said.
“Gamers who are really into getting to the next level or collecting all of the in-game items seem to have unhealthier video-game use,” Hilgard said. “When people talk about games being ‘so addictive,’ usually they’re referring to games like Farmville or Diablo that give players rewards, such as better equipment or stronger characters, as they play. People who are especially motivated by these rewards can find it hard to stop playing.”
Understanding individuals’ motives for playing video games can inform researchers, game developers and consumers about why certain games attract certain individuals, Hilgard said.
“Researchers have suspected that Massively Multiplayer Online Role-Playing Games (MMORPGs) are the most addictive genre of video games,” Hilgard said. “Our study provides some evidence that supports that claim. The games provide opportunities for players to advance levels, to join teams and to play with others. In addition, the games provide enormous fantasy worlds that gamers can disappear into for hours at a time and forget about their problems. MMORPGs may be triple threats for encouraging pathological game use because they present all three risk factors to gamers.”
“Consistent with previous research, we did not find a perfect relationship between total time spent playing games and addictive video game behaviors,” said study co-author Christopher Engelhardt, a postdoctoral research fellow in the Department of Health Psychology in the MU School of Health Professions and the MU Thompson Center for Autism and Neurodevelopmental Disorders. “Additionally, other variables, such as the proportion of free time spent playing video games, seem to better predict game addiction above and beyond the total amount of time spent playing video games.”
The open-access journal, Frontiers in Psychology, published the article, “Individual differences in motives, preferences, and pathology in video games: the gaming attitudes, motives, and experiences scales (GAMES),” earlier in September.
Breakthrough Offers First Direct Measurement of Spinal Cord Myelin in Multiple Sclerosis
Real-time Imaging Technique Provides Essential Molecular Picture of Protective Nerve Sheath
Researchers have made an exciting breakthrough – developing a first-of-its-kind imaging tool to examine myelin damage in multiple sclerosis (MS). An extremely difficult disease to diagnose, the tool will help physicians diagnose patients earlier, monitor the disease’s progression, and evaluate therapy efficacy.
Case Western Reserve University School of Medicine scientists have developed a novel molecular probe detectable by positron emission tomography (PET) imaging. The new molecular marker, MeDAS, offers the first non-invasive visualization of myelin integrity of the entire spinal cord at the same time, as published today in an article in the Annals of Neurology.
“While MS originates in the immune system, the damage occurs to the myelin structure of the central nervous system. Our discovery brings new hope to clinicians who may be able to make an accurate diagnosis and prognosis in as little as a few hours compared to months or even years,” said Yanming Wang, PhD, senior author of study and associate professor of radiology at Case Western Reserve University School of Medicine. “Because of its shape and size, it is particularly difficult to directly detect myelin damage in the spinal cord; this is the first time we have been able to image its function at the molecular level.”
As the most common acquired autoimmune disease currently affecting more than two million people worldwide, MS is characterized by destruction of myelin, the membrane that protects nerves. Once damaged, it inhibits the nerves’ ability to transmit electrical impulses, causing cognitive impairment and mobility dysfunction. So far, there is no cure for MS, therapies are only available that modify the symptoms.
In addition to its role in monitoring the effects of myelin-repair drugs currently under development, the new imaging tool offers a real-time quantitative clinical diagnosis of MS. A long lag exists between the onset of disease, physical symptoms in the patient and diagnosis via behavioral testing and magnetic resonance imaging (MRI). The lesions, or plaques, as detected by a MRI in the brain and spinal cord are not myelin specific and thus poorly associated with a patient’s disease severity or progression. There is an urgent need to find a new imaging marker that correlates with a patient’s pathology.
“This discovery has open the door to develop new drugs that can truly restore nerve function, not just modify the symptoms,” said Robert Miller, PhD, co-author on the study, vice president for research for Case Western Reserve and the Allen C. Holmes Professor of Neurological Diseases at the School of Medicine. “A cure for MS requires both repairing myelin and a tool to measure the mechanism.”
For the past 20 years, Miller’s lab has been working tirelessly to create new myelin-repair therapies that would restore nerve function. Successful translation of new drugs from animal studies to human clinical trials is contingent upon researchers’ ability to measure and evaluate the effectiveness of a therapy.
Created by Wang’s laboratory, the MeDAS molecular probe works like a homing device. Injected into the body intravenously, it is programmed to seek out and bind only to myelin in the central nervous system, i.e., the brain, spinal cord and optic nerves. A positron-emitting radioisotope label on the molecule allows a PET scanner to detect the targets and quantify their intensity and location. The data can then be reconstructed into an image as shown in the article: http://onlinelibrary.wiley.com/doi/10.1002/ana.23965/abstract.
“This is an indispensable tool to help find a new way to treat MS down the road” said Chunying Wu, PhD, first author of the study and instructor of radiology at Case Western Reserve. “It can also be used as a platform technology to unlock the mysteries of other myelin related diseases such as spinal cord injury.”
(Source: casemed.case.edu)