Posts tagged neuroscience
Articles and news from the latest research reports.
Brain May Never Fully Recover from Exposure to Paint, Glue, Degreasers
People who are exposed to paint, glue or degreaser fumes at work may experience memory and thinking problems in retirement, decades after their exposure, according to a study published in the May 13, 2014, print issue of Neurology®, the medical journal of the American Academy of Neurology.
“Our findings are particularly important because exposure to solvents is very common, even in industrialized countries like the United States.” said study author Erika L. Sabbath, ScD, of Harvard School of Public Health in Boston. “Solvents pose a real risk to the present and future cognitive health of workers, and as retirement ages go up, the length of time that people are exposed is going up, too.”
The study involved 2,143 retirees from the French national utility company. Researchers assessed the workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene, including the timing of last exposure and lifetime dosage. Benzene is used to make plastics, rubber, dye, detergents and other synthetic materials. Chlorinated solvents can be found in dry cleaning solutions, engine cleaners, paint removers and degreasers. Petroleum solvents are used in carpet glue, furniture polishes, paint, paint thinner and varnish. Of the participants, 26 percent were exposed to benzene, 33 percent to chlorinated solvents and 25 percent to petroleum solvents.
Participants took eight tests of their memory and thinking skills an average of 10 years after they had retired, when they were an average age of 66. A total of 59 percent of the participants had impairment on one to three of the eight tests; 23 percent had impairment on four or more tests; 18 percent had no impaired scores.
The average lifetime solvent exposure was determined based on historical company records, and the participants were categorized as having no exposure, moderate exposure if they had less than the average and high exposure if they had higher than the average. They were also divided by when the last exposure occurred, with those last exposed from 12 to 30 years prior to the testing considered as recent exposure and those last exposed 31 to 50 years prior considered as more distant exposure.
The research found that people with high, recent exposure to solvents were at greatest risk for memory and thinking deficits. For example, those with high, recent exposure to chlorinated solvents were 65 percent more likely to have impaired scores on tests of memory and visual attention and task switching than those who were not exposed to solvents. The results remained the same after accounting for factors such as education level, age, smoking and alcohol consumption.
“The people with high exposure within the last 12 to 30 years showed impairment in almost all areas of memory and thinking, including those not usually associated with solvent exposure,” Sabbath said. “But what was really striking was that we also saw some cognitive problems in those who had been highly exposed much longer ago, up to 50 years before testing. This suggests that time may not fully lessen the effect of solvent exposure on some memory and cognitive skills when lifetime exposure is high.”
Sabbath said the results may have implications for policies on workplace solvent exposure limits. “Of course, the first goal is protecting the cognitive health of individual workers. But protecting workers from exposure could also benefit organizations, payers, and society by reducing workers’ post-retirement health care costs and enabling them to work longer,” said Sabbath. “That said, retired workers who have had prolonged exposure to solvents during their career may benefit from regular cognitive screening to catch problems early, screening and treatment for heart problems that can affect cognitive health, or mentally stimulating activities like learning new skills.”
Alternative pathways let right and left communicate in early split brains
During the last century, many patients have undergone a variety of brain surgeries in an attempt to alleviate all sorts of psychiatric maladies, from hysteria and depression (mainly in women) to schizophrenia and epilepsy. Early on, doctors believed that psychiatric patients suffered from aberrant wiring among different brain areas and that cutting the connections between these areas would help patients regain normal brain circuits as well as their mental health. For instance, since the 1940s, several patients with intractable epilepsy have been treated with callosotomy, a surgical procedure that severs part or most of the corpus callosum. Curiously, some individuals are already born without the corpus callosum, a condition known as callosal dysgenesis (CD).
In 1968, the neurobiologist Roger Sperry confirmed that both callosotomized and CD patients have either absent or massively diminished connections between brain hemispheres. However, these two types of patients show a paradoxical difference concerning the transfer of information between the two sides of their brains. While typical callosotomized patients suffer from a disconnection syndrome in which there is minor or no communication between the left and right brain hemispheres, in CD patients, the two hemispheres are in fact able to communicate with each other.
For instance, when an unseen object is held in the right hand and thus recognized by the left hemisphere, both callosotomized and CD individuals can easily name that object verbally, because it is the left hemisphere that most often dominates verbal language. However, when an object is held in the left hand and thus recognized by the right hemisphere, callosotomized patients fail to verbally name the object because the missing corpus callosum prevents the right hemisphere from communicating with the left hemisphere. Conversely, CD patients have no difficulties in naming an unseen object regardless of the hand holding it.
The observation that the corpus callosum is the main connector between brain hemispheres earned Roger Sperry the Nobel Prize in 1981, but his own paradoxical discovery that CD patients do not present the classical disconnection syndrome observed in callosotomized patients remained unexplained until now.
In an article entitled “Structural and functional brain rewiring clarifies preserved inter-hemisphere transfer in humans born without the corpus callosum” and published in the Proceedings of the National Academy of Sciences (PNAS), a group of scientists from Rio de Janeiro and Oxford puts an end to Sperry’s paradox.
Previous work had led to the hypothesis that a defect in callosal formation would cause the brains of CD patients to create alternative pathways early on in life, but little was known about these potential pathways. The group led by Fernanda Tovar-Moll and Roberto Lent at the D’Or Institute for Research and Education and the Institute of Biomedical Sciences in Rio de Janeiro, Brazil, tested the brains of patients with CD using state of the art functional neuroimaging methods. The researchers were able to identify, morphologically describe and establish the function of two alternative pathways that help compensate for the lack of the corpus callosum. These pathways enable the transfer of complex tactile information between hemispheres, an ability missing in surgically callosotomized patients. Furthermore, by comparing six CD patients with 12 normal individuals, the group was able to demonstrate that CD patients present tactile recognition abilities similar to those observed in controls, indicating a functional role for these newly discovered brain pathways.
The authors believe that the development of alternative pathways results from the brain’s ability for long-distance plasticity and occurs in the utero during embryo development, which indicates that connections formed in the human brain early in development can be greatly modified, and most likely by environmental or genetic factors.
These findings will change the way we perceive the mechanisms of brain plasticity and may pave the way for a better understanding of a number of human disorders resulting from abnormal neuronal connections during embryonic development.
Electrical stimulation of brain alters dreams
Nighttime dreams in which you show up at work naked, encounter an ax-wielding psychopath or experience other tribulations may become a thing of the past thanks to a discovery reported on Sunday.
Applying electrical current to the brain, according to a study published online in Nature Neuroscience, induces “lucid dreaming,” in which the dreamer is aware that he is dreaming and can often gain control of the ongoing plot.
The findings are the first to show that inducing brain waves of a specific frequency produces lucid dreaming.
Regulate brain boosting devices so everyone can have a go
Gamers around the world are snapping up a new device that promises to give them an edge on competitors by boosting their gaming focus. It is certainly easy to see the appeal of being able to improve your levels of attention at the push of a colourful, glowing button.
The foc.us device works by electrically stimulating the brain to increase the activity of neurons. More neuron activity, more focus, more winning – or so the manufacturers claim. It is just one product in a growing market of cognitive enhancement devices. All these devices affect the brain in some way, be it by improving your memory, attention, learning speed or another mental process.
Study of neurogenesis in mice may have solved mystery of childhood amnesia in humans
A team of researchers working at the University of Toronto in Canada may have found the answer to the question of why we humans tend to have little to no memory of the first few years of our lives. In their paper published in the journal Science, the team describes several experiments they ran on mice and other small mammals that revealed the impact of neurogenesis on memory and how what they learned might be applied to memory retention in people. Lucas Mongiat and Alegandro Schinder offer a review of memory studies and how the research by the team in Toronto fits in with what has already been learned in a Perspective piece in the same journal edition.
Experiencing letters as colours: new insights into synaesthesia
Scientists studying the bizarre phenomenon of synaesthesia – best described as a “union of the senses” whereby two or more of the five senses that are normally experienced separately are involuntarily and automatically joined together – have made a new breakthrough in their attempts to understand the condition.
V.S. Ramachandran and Elizabeth Seckel from the University of San Diego studied four synaesthetes who experience colour when seeing printed letters of the alphabet. Their aim was to determine at what point during sensory processing these ‘colours’ appeared.
To do this, the researchers asked their synaesthetes – as well as a control group – to complete three children’s picture puzzles in which words were printed backwards or were not immediately visible.
When the results were processed, Ramachandran and Seckel discovered that the synaesthetes were able to complete the puzzles three times faster than the control subjects, and with fewer errors. The synaesthetes also revealed that they saw the obscured letters in the puzzles in the same colour as they would the ‘normal’ letters. This process effectively clued them in to what the letters were, and allowed them to read the distorted words much more quickly than the controls could.
Although it was just a small study, Ramachandran and Seckel’s work, published in the current issue of Neurocase, ‘strongly supports the interpretation that the synthetic colours are evoked preconsciously early in sensory processing’. The four synaesthetes had an advantage in completing the puzzles because the ‘extra’ information they received when looking at the letters was then sent up to ‘higher levels of sensory processing, providing additional insight for reading the distorted and backwards text’: a fascinating and important insight into a condition those of us who see letters as just letters find simply baffling.
From the Phenomenology to the Mechanisms of Consciousness: Integrated Information Theory 3.0
This paper presents Integrated Information Theory (IIT) of consciousness 3.0, which incorporates several advances over previous formulations. IIT starts from phenomenological axioms: information says that each experience is specific – it is what it is by how it differs from alternative experiences; integration says that it is unified – irreducible to non-interdependent components; exclusion says that it has unique borders and a particular spatio-temporal grain. These axioms are formalized into postulates that prescribe how physical mechanisms, such as neurons or logic gates, must be configured to generate experience (phenomenology). The postulates are used to define intrinsic information as “differences that make a difference” within a system, and integrated information as information specified by a whole that cannot be reduced to that specified by its parts. By applying the postulates both at the level of individual mechanisms and at the level of systems of mechanisms, IIT arrives at an identity: an experience is a maximally irreducible conceptual structure (MICS, a constellation of concepts in qualia space), and the set of elements that generates it constitutes a complex. According to IIT, a MICS specifies the quality of an experience and integrated information ΦMax its quantity. From the theory follow several results, including: a system of mechanisms may condense into a major complex and non-overlapping minor complexes; the concepts that specify the quality of an experience are always about the complex itself and relate only indirectly to the external environment; anatomical connectivity influences complexes and associated MICS; a complex can generate a MICS even if its elements are inactive; simple systems can be minimally conscious; complicated systems can be unconscious; there can be true “zombies” – unconscious feed-forward systems that are functionally equivalent to conscious complexes.
Discovery links rare, childhood neurodegenerative diseases to common problem in DNA repair
St. Jude Children’s Research Hospital scientists studying two rare, inherited childhood neurodegenerative disorders have identified a new, possibly common source of DNA damage that may play a role in other neurodegenerative diseases, cancer and aging. The findings appear in the current issue of the scientific journal Nature Neuroscience.
Researchers showed for the first time that an enzyme required for normal DNA functioning causes DNA damage in the developing brain. DNA is the molecule found in nearly every cell that carries the instructions needed to assemble and sustain life.
The enzyme is topoisomerase 1 (Top1). Normally, Top1 works by temporarily attaching to and forming a short-lived molecule called a Top1 cleavage complex (Top1cc). Top1ccs cause reversible breaks in one strand of the double-stranded DNA molecule. That prompts DNA to partially unwind, allowing cells to access the DNA molecule in preparation for cell division or to begin production of the proteins that do the work of cells.
Different factors, including the free radicals that are a byproduct of oxygen metabolism, result in Top1ccs becoming trapped on DNA and accumulating in cells. This study, however, is the first to link the buildup to disease. The results also broaden scientific understanding of the mechanisms that maintain brain health.
Investigators made the connection between DNA damage and accumulation of Top1cc while studying DNA repair problems in the rare neurodegenerative disorders ataxia telangiectasia (A-T) and spinocerebellar ataxia with axonal neuropathy 1(SCAN1). The diseases both involve progressive difficulty with walking and other movement. This study showed that A-T and SCAN1 also share the buildup of Top1ccs as a common mechanism of DNA damage. A-T is associated with a range of other health problems, including an increased risk of leukemia, lymphoma and other cancers.
“We are now working to understand how this newly recognized source of DNA damage might contribute to tumor development or the age-related DNA damage in the brain that is associated with neurodegenerative disorders like Alzheimer’s disease,”said co-corresponding author Peter McKinnon, Ph.D., a member of the St. Jude Department of Genetics. The co-corresponding author is Sachin Katyal, Ph.D., of the University of Manitoba Department of Pharmacology and Therapeutics and formerly of St. Jude.
A-T and SCAN1 are caused by mutations in different enzymes involved in DNA repair. Mutations in the ATM protein lead to A-T. Alterations in the Tdp1 protein cause SCAN1.
Working in nerve cells growing in the laboratory and in the nervous system of specially bred mice, researchers showed for the first time that ATM and Tdp1 work cooperatively to repair breaks in DNA. Scientists also demonstrated how the proteins accomplish the task.
The results revealed a new role for ATM in repairing single-strand DNA breaks. Until this study, ATM was linked to double-strand DNA repair. ATM was also known to work exclusively as a protein kinase. Kinases are enzymes that use chemicals called phosphate groups to regulate other proteins.
Scientists reported that when Top1ccs are trapped ATM functions as a protein kinase and alert cells to the DNA damage. But researchers found ATM also serves a more direct role by marking the trapped Top1ccs for degradation by the protein complex cells use to get rid of damaged or unnecessary proteins. ATM accomplishes that task by promoting the addition of certain proteins called ubiquitin and SUMO to the Top1cc surface.
Tdp1 then completes the DNA-repair process by severing the chemical bonds that tether Top1 to DNA.
Mice lacking either Atm or Tdp1 survived with apparently normal neurological function. But compared to normal mice, the animals missing either protein had elevated levels of Top1cc. Those levels rose sharply during periods of rapid brain development and in response to radiation, oxidation and other factors known to cause breaks in DNA.
When researchers knocked out both Atm and Tdp1, Top1cc accumulation rose substantially as did a form of programmed cell death called apoptosis. Investigators reported that apoptosis was concentrated in the developing brain and few mice survived to birth. McKinnon said the results add to evidence that the brain is particularly sensitive to DNA damage.
Researchers then used the anti-cancer drug topotecan to link elevated levels of Top1cc to the cell death and other problems seen in mice lacking Atm and Tdp1. Topotecan works by trapping Top1ccs in tumor cells, resulting in the DNA damage that triggers apoptosis. Investigators showed that the impact of Top1cc accumulation was strikingly similar whether the cause was topotecan or the loss of Atm and Tdp1.
(Source: stjude.org)
Autism-related protein shown to play vital role in addiction
In a paper published in the latest issue of the neuroscience journal Neuron, McLean Hospital investigators report that a gene essential for normal brain development, and previously linked to Autism Spectrum Disorders, also plays a critical role in addiction-related behaviors.
"In our lab, we investigate the brain mechanisms behind drug addiction – a common and devastating disease with limited treatment options," explained Christopher Cowan, PhD, director of the Integrated Neurobiology Laboratory at McLean and an associate professor of Psychiatry at Harvard Medical School. "Chronic exposure to drugs of abuse causes changes in the brain that could underlie the transition from casual drug use to addiction. By discovering the brain molecules that control the development of drug addiction, we hope to identify new treatment approaches."
The Cowan lab team, led by Laura Smith, PhD, an instructor of Psychiatry at Harvard Medical School, used animal models to show that the fragile X mental retardation protein, or FMRP, plays a critical role in the development of addiction-related behaviors. FMRP is also the protein that is missing in Fragile X Syndrome, the leading single-gene cause of autism and intellectual disability. Consistent with its important role in brain function, the team found that cocaine utilizes FMRP to facilitate brain changes involved in addiction-related behaviors.
Cowan, whose work tends to focus on identifying novel genes related to conditions such as autism and drug addiction, explained that FMRP controls the remodeling and strength of connections in the brain during normal development. Their current findings reveal that FMRP plays a critical role in the changes in brain connections that occur following repeated cocaine exposure.
"We know that experiences are able to modify the brain in important ways. Some of these brain changes help us, by allowing us to learn and remember. Other changes are harmful, such as those that occur in individuals struggling with drug abuse," noted Cowan and Smith. "While FMRP allows individuals to learn and remember things in their environment properly, it also controls how the brain responds to cocaine and ends up strengthening drug behaviors. By better understanding FMRP’s role in this process, we may someday be able to suggest effective therapeutic options to prevent or reverse these changes."
(Source: eurekalert.org)
Tracking the Source of “Selective Attention” Problems in Brain-Injured Vets
An estimated 15-20 percent of U.S. troops returning from Iraq and Afghanistan suffer from some form of traumatic brain injury (TBI) sustained during their deployment, with most injuries caused by blast waves from exploded military ordnance. The obvious cognitive symptoms of minor TBI — including learning and memory problems — can dissipate within just a few days. But blast-exposed veterans may continue to have problems performing simple auditory tasks that require them to focus attention on one sound source and ignore others, an ability known as “selective auditory attention.”
According to a new study by a team of Boston University (BU) neuroscientists, such apparent “hearing” problems actually may be caused by diffuse injury to the brain’s prefrontal lobe — work that will be described at the 167th meeting of the Acoustical Society of America, to be held May 5-9, 2014 in Providence, Rhode Island.
"This kind of injury can make it impossible to converse in everyday social settings, and thus is a truly devastating problem that can contribute to social isolation and depression," explains computational neuroscientist Scott Bressler, a graduate student in BU’s Auditory Neuroscience Laboratory, led by biomedical engineering professor Barbara Shinn-Cunningham.
For the study, Bressler, Shinn-Cunningham and their colleagues — in collaboration with traumatic brain injury and post-traumatic stress disorder expert Yelena Bogdanova of VA Healthcare Boston — presented a selective auditory attention task to 10 vets with mild TBI and to 17 control subjects without brain injuries. Notably, on average, veterans had hearing within a normal range.
In the task, three different melody streams, each comprised of two notes, were simultaneously presented to the subjects from three different perceived directions (this variation in directionality was achieved by differing the timing of the signals that reached the left and right ears). The subjects were then asked to identify the “shape” of the melodies (i.e., “going up,” “going down,” or “zig-zagging”) while their brain activity was measured by electrodes on the scalp.
"Whenever a new sound begins, the auditory cortex responds, encoding the sound onset," Bressler explains. "Attentional focus, however, changes the strength of this response: when a listener is attending to a particular sound source, the neural activity in response to that sound is greater." This change of the neural response occurs because the brain’s "executive control" regions, located in the brain’s prefrontal cortex, send signals to the auditory sensory regions of the brain, modulating their response.
The researchers found that blast-exposed veterans with TBI performed worse on the task — that is, they had difficulty controlling auditory attention — “and in all of the TBI veterans who performed well enough for us to measure their neural activity, 6 out of our 10 initial subjects, the brain response showed weak or no attention-related modulation of auditory responses,” Bressler says.
"Our hope is that some of our findings can be used to develop methods to assess and quantify TBI, identifying specific factors that contribute to difficulties communicating in everyday settings," he says. "By identifying these factors on an individual basis, we may be able to define rehabilitation approaches and coping strategies tailored to the individual."
Some TBI patients also go on to develop chronic traumatic encephalopathy (CTE) — a debilitating progressive degenerative disease with symptoms that include dementia, memory loss and depression — which can now only be definitively diagnosed after death. “With any luck,” Bressler adds, “neurobehavioral research like ours may help identify patients at risk of developing CTE long before their symptoms manifest.”
(Source: newswise.com)