Posts tagged science
Articles and news from the latest research reports.
Nano Drug Crosses Blood-Brain Tumor Barrier, Targets Brain Tumor Cells and Blood Vessels
An experimental drug in early development for aggressive brain tumors can cross the blood-brain tumor barrier, kill tumor cells and block the growth of tumor blood vessels, according to a study led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
The laboratory and animal study also shows how the agent, called SapC-DOPS, targets tumor cells and blood vessels. The findings support further development of the drug as a novel treatment for brain tumors.
Glioblastoma multiforme is the most common and aggressive form of brain cancer, with a median survival of about 15 months. A major obstacle to improving treatment for the 3,470 cases of the disease expected in the United States this year is the blood-brain barrier, the name given to the tight fit of cells that make up the blood vessels in the brain. That barrier protects the brain from toxins in the blood but also keeps drugs in the bloodstream from reaching brain tumors.
“Few drugs have the capacity to cross the tumor blood-brain barrier and specifically target tumor cells,” says principal investigator Balveen Kaur, PhD, associate professor of neurological surgery and chief of the Dardinger Laboratory of Neurosciences at the OSUCCC – James. “Our preclinical study indicates that SapC-DOPS does both and inhibits the growth of new tumor blood vessels, suggesting that this agent could one day be an important treatment for glioblastoma and other solid tumors.”
The findings were published in a recent issue of the journal Molecular Therapy.
SapC-DOPS (saposin-C dioleoylphosphatidylserine), is a nanovesicle drug that has shown activity in glioblastoma, pancreatic cancer and other solid tumors in preclinical studies. The nanovesicles fuse with tumor cells, causing them to self-destruct by apoptosis.
Key findings of the study, which used two brain-tumor models, include:
- SapC-DOPS binds with exposed patches of the phospholipid phosphatidylserine (PtdSer) on the surface of tumor cells;
- Blocking PtdSer on cells inhibited tumor targeting;
- SapC-DOPS strongly inhibited brain-tumor blood-vessel growth in cell and animal models, probably because these cells also have high levels of exposed PtdSer.
- Hypoxic cells were sensitized to killing by SapC-DOPS.
“Based on our findings, we speculate that SapC-DOPS could have a synergistic effect when combined with chemotherapy or radiation therapy, both of which are known to increase the levels of exposed PtdSer on cancer cells,” Kaur says.
(Source: cancer.osu.edu)
Low doses of psychedelic drug erases conditioned fear in mice
Low doses of a psychedelic drug erased the conditioned fear response in mice, suggesting that the agent may be a treatment for post-traumatic stress disorder and related conditions, a new study by University of South Florida researchers found.
The unexpected finding was made by a USF team studying the effects of the compound psilocybin on the birth of new neurons in the brain and on learning and short-term memory formation. Their study appeared online June 2 in the journal Experimental Brain Research, in advance of print publication.
Psilocybin belongs to a class of compounds that stimulate select serotonin receptors in the brain. It occurs naturally in certain mushrooms that have been used for thousands of years by non-Western cultures in their religious ceremonies.
While past studies indicate psilocybin may alter perception and thinking and elevate mood, the psychoactive substance rarely causes hallucinations in the sense of seeing or hearing things that are not there, particularly in lower to moderate doses.
There has been recent renewed interest in medicine to explore the potential clinical benefit of psilocybin, MDMA and some other psychedelic drugs through carefully monitored, evidence-based research.
“Researchers want to find out if, at lower doses, these drugs could be safe and effective additions to psychotherapy for treatment-resistant psychiatric disorders or adjunct treatments for certain neurological conditions,” said Juan Sanchez-Ramos, MD, PhD, professor of neurology and Helen Ellis Endowed Chair for Parkinson’s Disease Research at the USF Health Morsani College of Medicine.
Dr. Sanchez-Ramos and his colleagues wondered about psilocybin’s role in the formation of short-term memories, since the agent binds to a serotonin receptor in the hippocampus, a region of the brain that gives rise to new neurons. Lead author for this study was neuroscientist Briony Catlow, a former PhD student in Dr. Sanchez-Ramos’ USF laboratory who has since joined the Lieber Institute for Brain Development, a translational neuroscience research center located in the Johns Hopkins Bioscience Park.
The USF researchers investigated how psilocybin affected the formation of memories in mice using a classical conditioning experiment. They expected that psilocybin might help the mice learn more quickly to associate a neutral stimulus with an unpleasant environmental cue.
To test the hypothesis, they played an auditory tone, followed by a silent pause before delivering a brief shock similar to static electricity. The mice eventually learned to link the tone with the shock and would freeze, a fear response, whenever they heard the sound.
Later in the study, the researchers played the sound without shocking the mice after each silent pause. They assessed how many times it took for the mice to resume their normal movements, without freezing in anticipation of the shock.
Regardless of the doses administered, neither psilocybin nor ketanserin, a serotonin inhibitor, made a difference in how quickly the mice learned the conditioned fear response. However, mice receiving low doses of psilocybin lost their fearful response to the sound associated with the unpleasant shock significantly more quickly than mice getting either ketanserin or saline (control group). In addition, only low doses of psilocybin tended to increase the growth of neurons in the hippocampus.
“Psilocybin enhanced forgetting of the unpleasant memory associated with the tone,” Dr. Sanchez-Ramos said. “The mice more quickly dissociated the shock from the stimulus that triggered the fear response and resumed their normal behavior.”
The result suggests that psilocybin or similar compounds may be useful in treating post-traumatic stress disorder or related conditions in which environmental cues trigger debilitating behavior like anxiety or addiction, Dr. Sanchez-Ramos said.
Information in brain cells’ electrical activity combines memory, environment, and state of mind
The information carried by the electrical activity of neurons is a mixture of stored memories, environmental circumstances, and current state of mind, scientists have found in a study of laboratory rats. The findings, which appear in the journal PLoS Biology, offer new insights into the neurobiological processes that give rise to knowledge and memory recall.
The study was conducted by Eduard Kelemen, a former graduate student and post-doctoral associate at the State University of New York (SUNY) Downstate Medical Center, and André Fenton, a professor at New York University’s Center for Neural Science and Downstate Medical Center. Kelemen is currently a postdoctoral fellow at University of Tuebingen in Germany.
The idea that recollection is not merely a replay of our stored experiences dates back to Plato. He believed that memory retrieval was, in fact, a much more intricate process—a view commonly accepted by today’s cognitive psychologists and couched in the theory of constructive recollection. The theory posits that during memory retrieval, information across different experiences may combine during recall to form a single experience. Such a process may explain the prevalence of false memories. For example, studies have shown that people mistakenly recalled seeing a school bus in a movie if the bus was mentioned after they watched the movie.
In addition, other scholarship has shown that a subject’s mindset can also influence the retrieved information. For example, looking at a house from the perspective of a homebuyer or a burglar leads to different recollections—potential purchasers may recall the house’s leaky roof while would-be burglars may remember where the jewelry is kept.
But while the psychological contours of retrieval are well-documented, very little is known about the neural activity that underlies this process.
With this in mind, Fenton and Kelemen centered their study on the neurophysiological processes rats employ as they solve problems that require memory retrieval. To do so, they employed techniques developed during the last two decades. These involve monitoring the electrical activity of neurons in the rats’ hippocampus—the part of the brain used to encode new memories and retrieve old ones. By spotting certain types of neuronal activity, researchers have historically been able to perform what amounts to a mind reading exercise to decode what the rat is thinking and even comprehend the specifics of the rats’ memory retrieval.
In their experiments, Fenton and Kelemen tested the viability of a concept, “cross-episode retrieval”— stimulating the brain activity in a given circumstance that was also activated in a previous, distinctive experience.
“Such cross-episode expression of past activity can create opportunities for generating novel associations and new information that was never directly experienced,” the authors wrote.
To test their hypotheses, rats were placed in a stable, circular arena, then in a rotating, circular arena of the same size, followed by a return to the stable arena. In the rotating arena condition, the surface turned slowly, making it necessary for the rat to think about its location either in terms of the rotating floor or in terms of the stationary room.
Overall, the results showed district neural activity between the stable and rotating conditions. However, during the rotating task, the researchers intermittently observed “cross-episode retrieval”—that is, at times, neurons expressed patterns of electrical activity under the rotating-arena condition that were similar to those activity patterns that were used in the stable-arena condition. Notably, cross-episode retrieval occurred more frequently when the angular position of the rotating arena was about to complete a full rotation and return to the same position as in the stable condition, demonstrating that retrieval is influenced by the environment.
To show that cross-episode retrieval was influenced by current state of mind, Fenton and Kelemen took advantage of an earlier finding from their experiments: during the arena rotation, neural activity switches between signaling the rat’s location in the stationary room and the rat’s location on the rotating arena floor. Cross-episode retrieval was also more likely when neuronal activity represented the position of the rat in the stationary room than when it represented positions that rotate with the arena. This showed that retrieval is influenced by internal cognitive variables that are encoded by hippocampal discharge—i.e., a state of mind.
“These experiments demonstrate novel, key features of constructive human episodic memory in rat hippocampal discharge,” explained Fenton, “and suggest a neurobiological mechanism for how experiences of different events that are separate in time can nonetheless comingle and recombine in the mind to generate new information that can sometimes amount to valuable, creative insight and knowledge.”
(Source: nyu.edu)
Birds and humans have similar brain wiring
You may have more in common with a pigeon than you realise, according to new research.
It shows that humans and birds have brains that are wired in a similar way.
A researcher from Imperial College London and his colleagues have developed for the first time a map of a typical bird brain, showing how different regions are connected together to process information. By comparing it to brain diagrams for different mammals such as humans, the team discovered that areas important for high-level cognition such as long-term memory and problem solving are wired up to other regions of the brain in a similar way. This is despite the fact that both mammal and bird brains have been evolving down separate paths over hundreds of millions of years.
The team suggest that evolution has discovered a common blueprint for high-level cognition in brain development.
Birds have been shown in previous studies to possess a range of skills such as a capacity for complex social reasoning, an ability to problem solve and some have even demonstrated the capability to craft and use tools.
Professor Murray Shanahan, author of the study from the Department of Computing at Imperial College London, says:
“Birds have been evolving separately from mammals for around 300 million years, so it is hardly surprising that under a microscope the brain of a bird looks quite different from a mammal. Yet, birds have been shown to be remarkably intelligent in a similar way to mammals such as humans and monkeys. Our study demonstrates that by looking at brains that are least like our own, yet still capable of generating intelligent behaviour, we can determine the basic principles governing the way brains work.”
The team developed their map by analysing 34 studies of the anatomy of the pigeon brain, which is typical for a bird. They focussed on areas called ‘hub nodes’, which are regions of the brain that are major centres for processing information and are important for high level cognition.
In particular, they looked at the hippocampus, which is important for navigation and long-term memory in both birds and mammals. They found that these hub nodes had very dense connections to other parts of the brain in both kinds of animal, suggesting they function in a similar way.
They also compared the prefrontal cortex in mammals, which is important for complex thought such as decision making, with the nidopallium caudolaterale, which has a similar role in birds. They discovered that despite both hub nodes having evolved differently, the way they are wired up within the brain looks similar.
The long-term goal of the team is to use the information generated from the wiring diagram to build computer models that mimic the way that animal brains function, which would be used to control a robot.
The study was published this month in the Frontiers in Computational Neuroscience journal.
Potential neurological treatments often advance to clinical trials on shaky evidence
Clinical trials of drug treatments for neurological diseases such as Alzheimer’s and Parkinson’s often fail because the animal studies that preceded them were poorly designed or biased in their interpretation, according to a new study from an international team of researchers. More stringent requirements are needed to assess the significance of animal studies before testing the treatments in human patients, the researchers say.
The team — led by John Ioannidis, MD, DSc, a professor of medicine at the Stanford University School of Medicine and an expert in clinical trial design — assessed the results of more than 4,000 animal studies in 160 meta-analyses of potential treatments for neurological disorders from Alzheimer’s disease, Parkinson’s disease, stroke, spinal-cord injury and a form of multiple sclerosis. (A meta-analysis is a study that compiles and assesses information and conclusions from many independent experiments of a treatment, or intervention, for a particular condition.).
They determined that only eight of the 160 studies of potential treatments yielded the statistically significant, unbiased data necessary to support advancing the treatment to clinical trials. In contrast, 108 of the treatments were deemed at least somewhat effective at the time they were published.
Ioannidis and his collaborators at the University of Edinburgh in Scotland and the University of Ioannina School of Medicine in Greece say that animal studies of potential interventions can be made more efficient and reliable by increasing average sample size, being aware of statistical bias, publishing negative results and making all the results of all experiments on the effectiveness of a particular treatment — regardless of their outcome — freely accessible to scientists.
"Some researchers have postulated that animals may not be good models for human diseases," said Ioannidis. "I don’t agree. I think animal studies can be useful and perfectly fine. The problem is more likely to be related to the selective availability of information about the studies conducted on animals." Although the researchers focused here on neurological disorders, they believe it is likely that similar bias exists in animal studies of other types of disorders.
Ioannidis, who directs the Stanford Prevention Research Center, is the senior author of the research, published online in PLoS Biology on July 16. Lecturer Konstantinos Tsilidis, PhD, and postgraduate fellow Orestis Panagiotou, MD, of the University of Ioannina share lead authorship of the study. Panagiotou is currently a researcher at the National Cancer Institute’s Division of Cancer Epidemiology and Genetics.
Ioannidis is known for his efforts to strengthen the way that research is planned, carried out and reported. He was called “one of the world’s foremost experts on the credibility of medical research” in a profile published in The Atlantic magazine in 2010. He outlined some of the problems he observed in a 2005 essay in PLoS-Medicine titled, “Why most published research findings are false.” The essay is one of the most-downloaded articles in the history of the Public Library of Science, according to the journal’s media relations office.
For the new study, Ioannidis and his colleagues evaluated results in a database of the thousands of animal studies compiled over the years through the CAMARADES initiative (Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies), led by professor Malcolm MacLeod, PhD, from the University of Edinburgh, who is also a co-author of the study.
The team compared the number of experiments in the meta-analyses that would have been expected to yield positive results (based on their predicted statistical power) with the actual number of experiments with published positive results. The difference was striking: 919 expected versus the 1,719 that were published, implying that either negative results were not published, or that the results of the experiments were interpreted too optimistically.
"We saw that it was very common for these interventions to have published evidence that they would work," said Ioannidis. "It was extremely common to have results that suggest they would be effective in humans."
Furthermore, nearly half (46 percent) of the 160 meta-analyses showed evidence of small-study effects — a term used to describe the fact that a small study using fewer numbers of animals is more likely to find the intervention more effective than a larger study with many animals.
Ioannidis speculated that a reluctance to publish negative findings (that is, those that conclude that a particular intervention did not work any better than the control treatment) and a perhaps unconscious desire on the part of researchers to find a promising treatment has colored the field of neurological research. Obscuring access to studies that conclude a particular treatment is ineffective, while also publishing positive results that are likely to be statistically flawed, tilts the perception toward the potential effectiveness of an intervention and encourages unwarranted human clinical trials.
"There are no standard rules that guide a decision to move from animal studies into human clinical trials," said Ioannidis, who also holds C.F. Rehnborg Professorship at Stanford. "Sometimes interventions are tested in humans with very little evidence that they may be effective. Of the 160 analyses we studied, only eight had what we would call strong evidence of potential effectiveness with no hint of bias in the preliminary animal studies. And of these eight, only two have given positive results in humans."
Ioannidis believes the development of consortiums of groups of researchers studying a particular intervention, coupled with the free sharing of all data about its effectiveness, or lack thereof, is a good first step in reducing bias in animal studies.
"Under the current conditions, only a tiny proportion of interventions that have published some promising results in animals have shown to be at all effective in humans. For example, while dozens of treatments on ischemic or hemorrhagic stroke seem to work in the animal literature, almost none of them have worked in humans," said Ioannidis. "It is hard to believe we could not improve upon that translation record. If we raise the bar for moving into human trials, centralize researchers’ efforts and make all results available, it will be much easier for researchers to know whether they have a potential winner, and it would increase the efficiency of human clinical trials enormously."
(Source: med.stanford.edu)
Distinctive brain blood flow patterns associated with sexual dysfunction
Premenopausal women who aren’t interested in sex and are unhappy about this reality have distinctive blood flow patterns in their brains in response to explicit videos compared to women with normal sexual function, researchers report.
A study of 16 women – six with normal sexual function and 10 with clear symptoms of dysfunction – showed distinct differences in activation of brain regions involved in making and retrieving memories, and determining how attentive they are to their response to sexual stimuli, researchers report in the journal Fertility and Sterility.
Up to 20 percent of women may have this form of sexual dysfunction, called hypoactive sexual desire disorder, for which there are no proven therapies, said Dr. Michael P. Diamond, Chairman of the Department of Obstetrics and Gynecology at the Medical College of Georgia at Georgia Regents University.
Researchers hope that a clearer understanding of physiological differences in these women will provide novel therapy targets as well as a method to objectively assess therapies, said Diamond, the study’s senior author.
"There are site-specific alterations in blood flow in the brains of individuals with hypoactive sexual disorders versus those with normal sexual function," Diamond said. "This tells me there is a physiologic means of assessing hypoactive sexual desire and that as we move forward with therapeutics, whether it’s counseling or medications, we can look to see whether changes occur in those regions."
Viagra, developed in the 1990s as way to increase the heart rate of sick babies, was approved by the Food and Drug Administration in 1998 to also treat male impotence, a major cause of sexual dysfunction. While several more options for men have been developed since, no FDA-approved options are available for women experiencing hypoactive sexual desire, Diamond said. He notes that a possible critical flaw in developing and evaluating therapies for women may be the inability to objectively measure results, other than with a woman’s self-reporting of its impact on sexual activity.
Years ago, Diamond, a reproductive endocrinologist, became frustrated by the inability to help these women. In fact, many women did not bother discussing the issue with their physicians, possibly because it’s an awkward problem with no clear solutions, he said.
While still at Wayne State University, he and his colleagues began looking for objective measures of a woman’s sexual response, identifying sexually explicit film clips, then using functional magnetic resonance imaging, which measures real-time brain activation in response to a stimulus, to look at responses.
Their latest study links acquired hypoactive sexual desire disorder to a distinct pattern of blood flow in the brain, with significant activation of cortical structures involved in attention and reflection about emotion and mental state. Researchers noted that paying more attention to response to sexual stimuli already is implicated in sexual dysfunction. They also note activation of the anterior cingulate gyrus, an area involved in a broad range of emotions including homeostasis, pain, depression, and apathy. Another key area was the amygdala, which has a central role in processing emotion, learning, and memory.
Women with normal sexual function showed significantly greater activation of areas such as the right thalamus - a sort of relay station for handling sensory and motor input – that also plays a role in sexual arousal. They also experienced activation of the parahippocampal gyrus, involved in making and recalling memories. Interestingly, this area has been found to be more significantly activated in women with surgical menopause receiving hormone therapy.
Diamond notes that the official diagnosis of the sexual disorder requires distress regarding persistent disinterest in sex. Study participants were heterosexual, in stable relationships and had previously viewed sexually explicit images. Those with sexual dysfunction had a mean age of 37 versus 29 in the control group. Part of assessing blood flow patterns included also measuring baseline responses to neutral videos.
Next steps include taking these measurements in a larger number of women and beginning to use brain blood flow patterns to assess therapies, Diamond said.
(Source: eurekalert.org)
Inner Speech Speaks Volumes About the Brain
Whether you’re reading the paper or thinking through your schedule for the day, chances are that you’re hearing yourself speak even if you’re not saying words out loud. This internal speech — the monologue you “hear” inside your head — is a ubiquitous but largely unexamined phenomenon. A new study looks at a possible brain mechanism that could explain how we hear this inner voice in the absence of actual sound.
In two experiments, researcher Mark Scott of the University of British Columbia found evidence that a brain signal called corollary discharge — asignal that helps us distinguish the sensory experiences we produce ourselves from those produced by external stimuli — plays an important role in our experiences of internal speech.
The findings from the two experiments are published in Psychological Science, a journal of the Association for Psychological Science.
Corollary discharge is a kind of predictive signal generated by the brain that helps to explain, for example, why other people can tickle us but we can’t tickle ourselves. The signal predicts our own movements and effectively cancels out the tickle sensation.
And the same mechanism plays a role in how our auditory system processes speech. When we speak, an internal copy of the sound of our voice is generated in parallel with the external sound we hear.
“We spend a lot of time speaking and that can swamp our auditory system, making it difficult for us to hear other sounds when we are speaking,” Scott explains. “By attenuating the impact our own voice has on our hearing — using the ‘corollary discharge’ prediction — our hearing can remain sensitive to other sounds.”
Scott speculated that the internal copy of our voice produced by corollary discharge can be generated even when there isn’t any external sound, meaning that the sound we hear when we talk inside our heads is actually the internal prediction of the sound of our own voice.
If corollary discharge does in fact underlie our experiences of inner speech, he hypothesized, then the sensory information coming from the outside world should be cancelled out by the internal copy produced by our brains if the two sets of information match, just like when we try to tickle ourselves.
And this is precisely what the data showed. The impact of an external sound was significantly reduced when participants said a syllable in their heads that matched the external sound. Their performance was not significantly affected, however, when the syllable they said in their head didn’t match the one they heard.
These findings provide evidence that internal speech makes use of a system that is primarily involved in processing external speech, and may help shed light on certain pathological conditions.
“This work is important because this theory of internal speech is closely related to theories of the auditory hallucinations associated with schizophrenia,” Scott concludes.
New mode of cellular communication discovered in the brain
Glial cells send ‘care packages’ including protective proteins and genetic information to nerve cells
Researchers at Johannes Gutenberg University Mainz (JGU) have discovered a new form of communication between different cell types in the brain. Nerve cells interact with neighboring glial cells, which results in a transfer of protein and genetic information. Nerve cells are thus protected against stressful growth conditions. The study undertaken by the Mainz-based cell biologists shows how reciprocal communication between the different cell types contributes to neuronal integrity. Their results have been recently published in the journal PLOS Biology.
Brain function is determined by the communication between electrically excitable neurons and the surrounding glial cells, which perform many tasks in the brain. Oligodendrocytes are a type of glial cell and these form an insulating myelin sheath around the axons of neurons. In addition to providing this protective insulation, oligodendrocytes also help sustain neurons in other ways that are not yet fully understood. If this support becomes unavailable, axons can die off. This is what happens in many forms of myelin disorders, such as multiple sclerosis, and it results in a permanent loss of neuron impulse transmission.
Like other types of cell, oligodendrocytes also secrete small vesicles. In addition to lipids and proteins, these membrane-enclosed transport packages also contain ribonucleic acids, in other words, genetic information. In their study, Carsten Frühbeis, Dominik Fröhlich, and Wen Ping Kuo of the Institute of Molecular Cell Biology at Johannes Gutenberg University Mainz found that oligodendrocytes release nano-vesicles known as ‘exosomes’ in response to neuronal signals. These exosomes are taken up by the neurons and their cargo can then be used for neuronal metabolism. “This works on a kind of ‘delivery on call’ principle,” explained Dr. Eva-Maria Krämer-Albers, who is leading the current study. “We believe that what are being delivered are ‘care packages’ that are sent by the oligodendrocytes to neurons.”
While studying cell cultures, the research group discovered that the release of exosomes is triggered by the neurotransmitter glutamate. By means of labeling them with reporter enzymes, the researchers were able to elegantly demonstrate that the small vesicles are absorbed into the interior of the neurons. “The entire package of substances, including the genetic information, is apparently utilized by the neurons,” said Krämer-Albers. If neurons are subjected to stress, cells that have been aided with ‘care packages’ subsequently recover. “This maintenance contributes to the protection of the neurons and probably also leads to de novo synthesis of proteins,” stated Carsten Frühbeis and Dominik Fröhlich. Among the substances that are present in the exosomes and are channeled to the neurons are, for instance, protective proteins such as heat shock proteins, glycolytic enzymes, and enzymes which counter oxidative stress.
The study has demonstrated that exosomes from oligodendrocytes participate in a previously unknown form of bidirectional cell communication that could play a significant role in the long-term preservation of nerve fibers. “An interaction like this, in which an entire package of substances including genetic information is exchanged between cells of the nervous system, has not previously been observed”, stated Krämer-Albers, summarizing the results. “Exosomes are thus similar to viruses in certain respects, with the major difference that they do not inflict damage on the target cells but are instead beneficial.” In the future, the researchers hope to develop exosomes as possible ‘cure’ packages that could be used in the treatment of nerve disorders.
Scientists identify neural origins of hot flashes in menopausal women
A new study from neuroscientists at the Wayne State University School of Medicine provides the first novel insights into the neural origins of hot flashes in menopausal women in years. The study may inform and eventually lead to new treatments for those who experience the sudden but temporary episodes of body warmth, flushing and sweating.
The paper, “Temporal Sequencing of Brain Activations During Naturally Occurring Thermoregulatory Events,” by Robert Freedman, Ph.D., professor of psychiatry and behavioral neurosciences, founder of the Behavioral Medicine Laboratory and a member at the C.S. Mott Center for Human Growth and Development, and his collaborator, Vaibhav Diwadkar, Ph.D., associate professor of psychiatry and behavioral neurosciences, appears in the June issue of Cerebral Cortex, an Oxford University Press journal.
“The idea of understanding brain responses during thermoregulatory events has spawned many studies where thermal stimuli were applied to the skin. But hot flashes are unique because they are internally generated, so studying them presents unique challenges,” said Freedman, the study’s principal investigator. “Our participants had to lie in the MRI scanner while being heated between two body-size heating pads for up to two hours while we waited for the onset of a hot flash. They were heroic in this regard and the study could not have been conducted without their incredible level of cooperation.”
“Menopause and hot flashes are a significant women’s health issue of widespread general interest,” Diwadkar added. “However, understanding of the neural origins of hot flashes has remained poor. The question has rarely been assessed with in vivo functional neuroimaging. In part, this paucity of studies reflects the technical limitations of objectively identifying hot flashes while symptomatic women are being scanned with MRI. Nothing like this has been published because this is a very difficult study to do.”
During the course of a single year, 20 healthy, symptomatic postmenopausal women ages 47 to 58 who reported six or more hot flashes a day were scanned at the School of Medicine’s Vaitkevicius Imaging Center, located in Detroit’s Harper University Hospital.
The researchers collected skin conductance levels to identify the onset of flashes while the women were being scanned. Skin conductance is an electrical measure of sweating. The women were connected to a simple circuit passing a very small current across their chests, Diwadkar said. Changes in levels allowed researchers to identify a hot flash onset and analyze the concurrently acquired fMRI data to investigate the neural precedents and correlates of the event.
The researchers focused on regions like the brain stem because its sub regions, such as the medullary and dorsal raphe, are implicated in thermal regulation, while forebrain regions, such as the insula, have been implicated in the personal perception of how someone feels. They showed that activity in some brain areas, such as the brain stem, begins to rise before the actual onset of the hot flash.
“Frankly, evidence of fMRI-measured rise in the activity of the brain stem even before women experience a hot flash is a stunning result. When this finding is considered along with the fact that activity in the insula only rises after the experience of the hot flash, we gain some insight on the complexity of brain mechanisms that mediate basic regulatory functions,” Diwadkar said.
These results point to the plausible origins of hot flashes in specific brain regions. The researchers believe it is the first such demonstration in academic literature.
They are now evaluating the network-based interactions between the brain regions by using more complex modeling of the fMRI data. “We think that our study highlights the value of using well-designed fMRI paradigms and analyses in understanding clinically relevant questions,” Diwadkar said.
The researchers also are exploring possibilities for integrating imaging with treatment to examine whether specific pharmacotherapies for menopause might alter regional brain responses.
(Source: media.wayne.edu)
Computer smart as a 4-year-old
Artificial and natural knowledge researchers at the University of Illinois at Chicago have IQ-tested one of the best available artificial intelligence systems to see how intelligent it really is.
Turns out–it’s about as smart as the average 4-year-old, they will report July 17 at the U.S. Artificial Intelligence Conference in Bellevue, Wash.
The UIC team put ConceptNet 4, an artificial intelligence system developed at M.I.T., through the verbal portions of the Weschsler Preschool and Primary Scale of Intelligence Test, a standard IQ assessment for young children.
They found ConceptNet 4 has the average IQ of a young child. But unlike most children, the machine’s scores were very uneven across different portions of the test.
“If a child had scores that varied this much, it might be a symptom that something was wrong,” said Robert Sloan, professor and head of computer science at UIC, and lead author on the study.
Sloan said ConceptNet 4 did very well on a test of vocabulary and on a test of its ability to recognize similarities.
“But ConceptNet 4 did dramatically worse than average on comprehension—the ‘why’ questions,” he said.
One of the hardest problems in building an artificial intelligence, Sloan said, is devising a computer program that can make sound and prudent judgment based on a simple perception of the situation or facts–the dictionary definition of commonsense.
Commonsense has eluded AI engineers because it requires both a very large collection of facts and what Sloan calls implicit facts–things so obvious that we don’t know we know them. A computer may know the temperature at which water freezes, but we know that ice is cold.
“All of us know a huge number of things,” said Sloan. “As babies, we crawled around and yanked on things and learned that things fall. We yanked on other things and learned that dogs and cats don’t appreciate having their tails pulled.” Life is a rich learning environment.
“We’re still very far from programs with commonsense–AI that can answer comprehension questions with the skill of a child of 8,” said Sloan. He and his colleagues hope the study will help to focus attention on the “hard spots” in AI research.