Posts tagged neuroscience
Articles and news from the latest research reports.
Efficacy of Transcranial Magnetic Stimulation for Depression Confirmed in New Study
ScienceDaily (July 26, 2012) — In one of the first studies to look at transcranial magnetic stimulation (TMS) in real-world clinical practice settings, researchers at Butler Hospital, along with colleagues across the U.S., confirmed that TMS is an effective treatment for patients with depression who are unable to find symptom relief through antidepressant medications. The study findings are published online in the June 11, 2012 edition of Depression and Anxiety in the Wiley Online Library.
(Credit: Butler Hospital)
Previous analysis of the efficacy of TMS has been provided through more than 30 published trials, yielding generally consistent results supporting the use of TMS to treat depression when medications aren’t sufficient. “Those previous studies were key in laying the groundwork for the FDA to approve the first device for delivery of TMS as a treatment for depression in 2008,” said Linda Carpenter, MD, lead author of the report and chief of the Mood Disorders Program and the Neuromodulation Clinic at Butler Hospital. “Naturalistic studies like ours, which provide scrutiny of real-life patient outcomes when TMS therapy is given in actual clinical practice settings, are the next step in further understanding the effectiveness of TMS. They are also important for informing healthcare policy, particularly in an era when difficult decisions must be made about allocation of scarce resources.”
Carpenter explains that naturalistic studies differ from controlled clinical trials because they permit the inclusion of subjects with a wider range of symptomatology and comorbidity, whereas controlled clinical trials typically have more rigid criteria for inclusion. “As a multisite study collecting naturalistic outcomes from patients in clinics in various regions in the U.S., we were also able to capture effects that might arise from introducing a novel psychiatric treatment modality like TMS in non-research settings,” said Carpenter. In all, the study confirms how well TMS works in diverse settings where TMS is administered to a real-life population of patients with depression that have not found relief through many other available treatments.
The published report summarized data collected from 42 clinical TMS practice sites in the US, and included outcomes from 307 patients with Major Depressive Disorder (MDD) who had persistent symptoms despite the use of antidepressant medication. Change during TMS was assessed using both clinicians’ ratings of overall depression severity and scores on patient self-report depression scales, which require the patient to rate the severity of each symptom on the same standardized scale at the end of each 2-week period. Rates for “response” and “remission” to TMS were calculated based on the same cut-off scores and conventions used for other clinical trials of antidepressant treatments. Fifty-eight percent positive response rate to TMS and 37 percent remission rate were observed.
"The patient outcomes we found in this study demonstrated a response rate similar to controlled clinical trial populations," said Dr. Carpenter, explaining that this new data validates TMS efficacy in treating depression for those who have failed to benefit from antidepressant medications. "Continued research and confirmation of the effectiveness of TMS is important for understanding its place in everyday psychiatric care and to support advocacy for insurance coverage of the treatment." Thanks in part to the advocacy efforts of Dr. Carpenter, TMS was recently approved for coverage by Medicare in New England, and it is also now covered by BCBSRI. "Next steps for TMS research involve enhancing our understanding of how to maintain positive response to TMS over time after the course of therapy ends and learning how to customize the treatment for patients using newer technologies, so TMS can help even more patients."
Source: Science Daily
Do Ovaries Continue to Produce Eggs During Adulthood?
A compelling new genetic study tracing the origins of immature egg cells, or ‘oocytes’, from the embryonic period throughout adulthood adds new information to a growing controversy. The notion of a “biological clock” in women arises from the fact that oocytes progressively decline in number as females get older, along with a decades-old dogmatic view that oocytes cannot be renewed in mammals after birth.
After careful assessment of data from a recent study published in PLoS Genetics, scientists from Massachusetts General Hospital and the University of Edinburgh argue that the findings support formation of new eggs during adult life; a topic that has been historically controversial and has sparked considerable debate in recent years.
What Caffeine Really Does to Your Brain
What caffeine does do is one heck of an impersonation. In your brain, caffeine is the quintessential mimic of a neurochemical called adenosine. Adenosine is produced by neurons throughout the day as they fire, and as more of it is produced, the more your nervous system ratchets down.
Your nervous system monitors adenosine levels through receptors, particularly the A1 receptor that is found in your brain and throughout your body. As the chemical passes through the receptors, your adenosine tab increases until your nervous system pays it off by putting you to sleep.
Epidemiology, literally the “study of what is upon people”, is concerned with the dynamics of health and disease in human populations. Research in epidemiology aims to identify the distribution, incidence, and etiology of human diseases to improve the understanding of the causes of diseases and to prevent their spread. Traditionally, epidemiology has been based on data collected by public health agencies through health personnel in hospitals, doctors’ offices, and out in the field. In recent years, however, novel data sources have emerged where data are frequently collected directly from individuals through the digital traces they leave as a consequence of modern communication and an increased use of electronic devices.
Controlling Monkey Brains and Behavior With Light
ScienceDaily (July 26, 2012) — Researchers reporting online on July 26 in Current Biology, a Cell Press publication, have for the first time shown that they can control the behavior of monkeys by using pulses of blue light to very specifically activate particular brain cells. The findings represent a key advance for optogenetics, a state-of-the-art method for making causal connections between brain activity and behavior. Based on the discovery, the researchers say that similar light-based mind control could likely also be made to work in humans for therapeutic ends.
(Credit: © Eric Isselée / Fotolia)
"We are the first to show that optogenetics can alter the behavior of monkeys," says Wim Vanduffel of Massachusetts General Hospital and KU Leuven Medical School. "This opens the door to use of optogenetics at a large scale in primate research and to start developing optogenetic-based therapies for humans."
In optogenetics, neurons are made to respond to light through the insertion of light-sensitive genes derived from particular microbial organisms. Earlier studies had primarily validated this method for use in invertebrates and rodents, with only a few studies showing that optogenetics can alter activity in monkey brains on a fine scale.
In the new study, the researchers focused on neurons that control particular eye movements. Using optogenetics together with functional magnetic resonance imaging (fMRI), they showed that they could use light to activate these neurons, generating brain activity and subtle changes in eye-movement behavior.
The researchers also found that optogenetic stimulation of their focal brain region produced changes in the activity of specific neural networks located at some distance from the primary site of light activation.
The findings not only pave the way for a much more detailed understanding of how different parts of the brain control behavior, but they may also have important clinical applications in treating Parkinson’s disease, addiction, depression, obsessive-compulsive disorder, and other neurological conditions.
"Several neurological disorders can be attributed to the malfunctioning of specific cell types in very specific brain regions," Vanduffel says. "As already suggested by one of the leading researchers in optogenetics, Karl Deisseroth from Stanford University, it is important to identify the underlying neuronal circuits and the precise nature of the aberrations that lead to the neurological disorders and potentially to manipulate those malfunctioning circuits with high precision to restore them. The beauty of optogenetics is that, unlike any other method, one can affect the activity of very specific cell types, leaving others untouched."
Source: Science Daily
Eye-Writing Technology: Writing in Cursive With Your Eyes Only
A new technology might allow people who have almost completely lost the ability to move their arms or legs to communicate freely, by using their eyes to write in cursive. The eye-writing technology tricks the neuromuscular machinery into doing something that is usually impossible: to voluntarily produce smooth eye movements in arbitrary directions.
The technology relies on changes in contrast to trick the eyes into the perception of motion. When viewing that changing visual display, people can learn to control their eye movements smoothly and at will, the new study shows. It doesn’t take very much practice either.
Piglets substitute for human babies in cognitive science maze test
A team from the Beckman Institute at the University of Illinois is using piglets instead of human babies to try and model the cognitive development of infants.
Human infants cannot be used as laboratory subjects. The idea to use piglets came when one of neuroscientist Rodney Johnson’s former students, who was working for an infant formula company, asked him about finding ways to monitor the differences in cognitive development between breast-fed and formula-fed children.
As a result he and his colleague Ryan Dilger became interested in using the neonatal piglet as a model for human brain development. The growth and development of the piglet brain is similar to that of the human brain — at birth the human brain is 25 percent of adult size. In the first two years of life, it reaches 85 to 90 percent of adult size. The piglet brain grows in a similar way in a shorter time.
They wanted to see whether they could develop tests to look at learning and memory development using these pigs. First of all they developed MRI techniques to quantify the size of the brain, taking measurements at regular intervals.
They then developed a test using a maze to assess piglets’ learning and memory. This turned out to be much more complicated than expected. Johnson said: “When we first started these studies, we used things like Skittles and apple slices as a reward because that’s what people using older pigs had done.”
However, the piglets were used to being fed on infant formula and so had no interest in solid food, nor were they motivated to perform tasks if the reward was the same as their regular food. The solution was to use Nesquik chocolate milk as a reward.
Tests took place in a plus-sign-shaped maze with one arm blocked off to leave a T shape. Piglets were trained to locate the milk reward using visual cues from outside the maze. When they learned how to do this and the reward location was moved, and the pigs were retested to assess learning and working memory.
Having established that the tests can be used to measure cognitive abilities, the team will examine how nutrient deficiencies (such as iron) and infections (such as pneumonia) affect the human brain during this time of early brain growth.
Johnson said: “There is a lot of interest in the concept of programming, the notion that things that occur early in life set that individual up for problems that occur many years later. Because the pig brain grows so much like a human brain, we thought this could be a very attractive model.”
In order to measure changes in the brain they look at neuroinflammation, neuron growth and changes, as well as biochemical in the brain.
The team hopes to receive funding to look at maternal viral infections, where pregnant pigs will be infected with diseases to see how it affects the brain development of their offspring.
Connectomics: Mapping the Neural Network Governing Male Roundworm Mating
In a study published today online in Science, researchers at Albert Einstein College of Medicine of Yeshiva University have determined the complete wiring diagram for the part of the nervous system controlling mating in the male roundworm Caenorhabditis elegans, an animal model intensively studied by scientists worldwide.
The study represents a major contribution to the new field of connectomics – the effort to map the myriad neural connections in a brain, brain region or nervous system to find the specific nerve connections responsible for particular behaviors. A long-term goal of connectomics is to map the human “connectome” – all the nerve connections within the human brain.
Because C. elegans is such a tiny animal – adults are one millimeter long and consist of just 959 cells – its simple nervous system totaling 302 neurons make it one of the best animal models for understanding the millions-of-times-more-complex human brain.
The Einstein scientists solved the structure of the male worm’s neural mating circuits by developing software that they used to analyze serial electron micrographs that other scientists had taken of the region. They found that male mating requires 144 neurons – nearly half the worm’s total number – and their paper describes the connections between those 144 neurons and 64 muscles involving some 8,000 synapses. A synapse is the junction at which one neuron (nerve cell) passes an electrical or chemical signal to another neuron.
"Establishing the complete structure of the synaptic network governing mating behavior in the male roundworm has been highly revealing," said Scott Emmons, Ph.D., senior author of the paper and professor in the department of genetics and in the Dominick P. Purpura Department of Neuroscience at Einstein. "We can see that the structure of this network has spatial characteristics that help explain how it exerts neural control over the multi-step decision-making process involved in mating."
In addition to determining how the neurons and muscles are connected, Dr. Emmons and his colleagues for the first time accurately measured the weights of those connections, i.e., an estimate of the strength with which one neuron or muscle communicates with another.
Chemical Makes Blind Mice See; Compound Holds Promise for Treating Humans
ScienceDaily (July 25, 2012) — A team of University of California, Berkeley, scientists in collaboration with researchers at the University of Munich and University of Washington, in Seattle, has discovered a chemical that temporarily restores some vision to blind mice, and is working on an improved compound that may someday allow people with degenerative blindness to see again.
Mice with a genetic disease that causes blindness regained some sight after injection with a chemical “photoswitch.” The eye of the untreated mouse on the left shows no response to light, while the pupil of the mouse on the right, which was injected with the chemical, contracts in light. (Credit: Image courtesy of University of California - Berkeley)
The approach could eventually help those with retinitis pigmentosa, a genetic disease that is the most common inherited form of blindness, as well as age-related macular degeneration, the most common cause of acquired blindness in the developed world. In both diseases, the light sensitive cells in the retina — the rods and cones — die, leaving the eye without functional photoreceptors.
The chemical, called AAQ, acts by making the remaining, normally “blind” cells in the retina sensitive to light, said lead researcher Richard Kramer, UC Berkeley professor of molecular and cell biology. AAQ is a photoswitch that binds to protein ion channels on the surface of retinal cells. When switched on by light, AAQ alters the flow of ions through the channels and activates these neurons much the way rods and cones are activated by light.
"This is similar to the way local anesthetics work: they embed themselves in ion channels and stick around for a long time, so that you stay numb for a long time," Kramer said. "Our molecule is different in that it’s light sensitive, so you can turn it on and off and turn on or off neural activity."
Because the chemical eventually wears off, it may offer a safer alternative to other experimental approaches for restoring sight, such as gene or stem cell therapies, which permanently change the retina. It is also less invasive than implanting light-sensitive electronic chips in the eye.
"The advantage of this approach is that it is a simple chemical, which means that you can change the dosage, you can use it in combination with other therapies, or you can discontinue the therapy if you don’t like the results. As improved chemicals become available, you could offer them to patients. You can’t do that when you surgically implant a chip or after you genetically modify somebody," Kramer said.
"This is a major advance in the field of vision restoration," said co-author Dr. Russell Van Gelder, an ophthalmologist and chair of the Department of Ophthalmology at the University of Washington, Seattle.
Kramer, Van Gelder, chemist Dirk Trauner and their colleagues at UC Berkeley, the University of Washington, Seattle, and the University of Munich will publish their findings on July 26, in the journal Neuron.
The blind mice in the experiment had genetic mutations that made their rods and cones die within months of birth and inactivated other photopigments in the eye. After injecting very small amounts of AAQ into the eyes of the blind mice, Kramer and his colleagues confirmed that they had restored light sensitivity because the mice’s pupils contracted in bright light, and the mice showed light avoidance, a typical rodent behavior impossible without the animals being able to see some light. Kramer is hoping to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.
"The photoswitch approach offers real hope to patients with retinal degeneration," Van Gelder said. "We still need to show that these compounds are safe and will work in people the way they work in mice, but these results demonstrate that this class of compound restores light sensitivity to retinas blind from genetic disease."
From optogenetics to implanted chips
The current technologies being evaluated for restoring sight to people whose rods and cones have died include injection of stem cells to regenerate the rods and cones; “optogenetics,” that is, gene therapy to insert a photoreceptor gene into blind neurons to make them sensitive to light; and installation of electronic prosthetic devices, such as a small light-sensitive retinal chip with electrodes that stimulate blind neurons. Several dozen people already have retinal implants and have had rudimentary, low vision restored, Kramer said.
Eight years ago, Kramer, Trauner, a former UC Berkeley chemist now at the University of Munich, and their colleagues developed an optogenetic technique to chemically alter potassium ion channels in blind neurons so that a photoswitch could latch on. Potassium channels normally open to turn a cell off, but with the attached photoswitch, they were opened when hit by ultraviolet light and closed when hit by green light, thereby activating and deactivating the neurons.
Subsequently, Trauner synthesized AAQ (acrylamide-azobenzene-quaternary ammonium), a photoswitch that attaches to potassium channels without the need to genetically modify the channel. Tests of this compound are reported in the current Neuron paper.
New versions of AAQ now being tested are better, Kramer said. They activate neurons for days rather than hours using blue-green light of moderate intensity, and these photoswitches naturally deactivate in darkness, so that a second color of light is not needed to switch them off.
"This is what we are really excited about," he said.
Source: Science Daily
Gene Therapy Holds Promise for Reversing Congenital Hearing Loss
ScienceDaily (July 25, 2012) — A new gene therapy approach can reverse hearing loss caused by a genetic defect in a mouse model of congenital deafness, according to a preclinical study published by Cell Press in the July 26 issue of the journal Neuron. The findings present a promising therapeutic avenue for potentially treating individuals who are born deaf.
(Credit: © Vasiliy Koval / Fotolia)
"This is the first time that an inherited, genetic hearing loss has been successfully treated in laboratory mice, and as such represents an important milestone for treating genetic deafness in humans," says senior study author Lawrence Lustig of the University of California, San Francisco.
Hearing loss is one of the most common human sensory deficits, and it results from damage to hair cells in the inner ear. About half of the cases of congenital hearing loss are caused by genetic defects. However, the current treatment options — hearing amplification devices and cochlear implants — do not restore hearing to normal levels. Correcting the underlying genetic defects has the potential to fully restore hearing, but previous attempts to reverse hearing loss caused by genetic mutations have not been successful.
Addressing this challenge in the new study, Lustig and his team used mice with hereditary deafness caused by a mutation in a gene coding for a protein called vesicular glutamate transporter-3 (VGLUT3). This protein is crucial for inner hair cells to send signals that enable hearing. Two weeks after the researchers delivered the VGLUT3 gene into the inner ear through an injection, hearing was restored in all of the mice. This improvement lasted between seven weeks and one and a half years when adult mice were treated, and at least nine months when newborn mice received the treatment.
The therapy did not damage the inner ear, and it even corrected some structural defects in the inner hair cells. Because the specific gene delivery method used is safe and effective in animals, the findings hold promise for future human studies. “For years, scientists have been hinting at the possibility of gene therapy as a potential cure for deafness,” Lustig says. “In this study, we now provide a very real and big step towards that goal.”
Source: Science Daily