Posts tagged neuroscience
Articles and news from the latest research reports.
Late-Life Depression Associated with Prevalent Mild Cognitive Impairment, Increased Risk of Dementia
Depression in a group of Medicare recipients ages 65 years and older appears to be associated with prevalent mild cognitive impairment and an increased risk of dementia, according to a report published Online First by Archives of Neurology, a JAMA Network publication.
Depressive symptoms occur in 3 percent to 63 percent of patients with mild cognitive impairment (MCI) and some studies have shown an increased dementia risk in individuals with a history of depression. The mechanisms behind the association between depression and cognitive decline have not been made clear and different mechanisms have been proposed, according to the study background.
Edo Richard, M.D., Ph.D., of the University of Amsterdam, the Netherlands, and colleagues evaluated the association of late-life depression with MCI and dementia in a group of 2,160 community-dwelling Medicare recipients.
“We found that depression was related to a higher risk of prevalent MCI and dementia, incident dementia, and progression from prevalent MCI to dementia, but not to incident MCI,” the authors note.
Baseline depression was associated with prevalent MCI (odds ratio [OR], 1.4) and dementia (OR, 2.2), while baseline depression was associated with an increased risk of incident dementia (hazard ratio [HR], 1.7) but not with incident MCI (HR, 0.9). Patients with MCI and coexisting depression at baseline also had a higher risk of progression to dementia (HR, 2.0), especially vascular dementia (HR, 4.3), but not Alzheimer disease (HR, 1.9), according to the study results.
“Our finding that depression was associated cross sectionally with both MCI and dementia and longitudinally only with dementia suggests that depression develops with the transition from normal cognition to dementia,” the authors conclude.
(Source: media.jamanetwork.com)
Definitive proof for receptor’s role in synapse development
Jackson Laboratory researchers led by Associate Professor Zhong-wei Zhang, Ph.D., have provided direct evidence that a specific neurotransmitter receptor is vital to the process of pruning synapses in the brains of newborn mammals.
Faulty pruning at this early developmental stage is implicated in autism-spectrum disorders and schizophrenia. The definitive evidence for N-methyl-D-aspartate receptor (NMDAR) in pruning has eluded researchers until now, but in research published in the Proceedings of the National Academy of Sciences, Zhang’s lab had serendipitous help in the form of a mouse model containing brain cells lacking NMDAR side-by-side with cells containing the receptor.
Soon after birth, mammals’ brains undergo significant development and change. Initially, large numbers of synapses form between neurons. Then, in response to stimuli, the synaptic connections are refined—some synapses are strengthened and others eliminated, or pruned.
In most synapses, glutamate serves as the neurotransmitter, and NMDAR, a major type of post-synaptic glutamate receptor, was previously known to play an important role in neural circuit development. Previous research has implicated the importance of NMDARs in pruning, but it remained unclear whether they played a direct or indirect role.
Zhang and colleagues focused on the thalamus, a brain region where synapse pruning and strengthening can be monitored and quantified with relative ease. They got unexpected help when they realized the mouse model they were using had thalamus cells lacking NMDARs right next to cells with normal NMDAR levels.
The researchers showed that the refinement process was disrupted in the absence of NMDARs. At the same time, neighboring neurons with the receptors proceeded through normal synaptic strengthening and pruning, clearly establishing the necessity of NMDARs in postsynaptic neurons for synaptic refinement.
"Whenever I give a talk or meet colleagues," Zhang says, "the first question that comes up is whether the NMDA receptor is important. It’s good that this is now settled definitively."
There has been extensive research into synaptic strengthening, and most of these studies indicate that the presence of NMDARs may support the recruitment of larger numbers of another kind of glutamate receptor to strengthen the synaptic connections. How NMDARs regulate the pruning process remains largely unknown, however.
Soma by the Flaming Lotus Girls translates the anatomy of neurons into metal, fire and light; magnifying the microscopic world to an epic scale. In Soma, an elegant axon arch connects an earthbound neuron with its partner floating overhead.
Soma is an interactive sculptural installation depicting two communicating neurons made of stainless steel, copper, aluminum, bronze, resin, fire and light. Each of Soma’s two neurons has a spinning fire nucleus. The nuclei are counter spinning balls of flame with variable speed motors.
Fire and light flow like electrochemical signals between Soma’s two neurons. Spinning balls of fire form the neuron’s nuclei. Slender dendrites extend to the sky and reach down to the earth, emitting constant flame and color changing light.
Soma is 25 feet high and 50 feet long. It is roughly a rectangular shape that occupies approximately 5,000 square feet including the fuel depot. She uses up to 100 gallons of fuel per hour.
There are 35 Dendrites using approx. 21’ of stainless steel tubing each. 735 feet of stainless steel tubing was used for dendrites over all.
Two dodecahedrons constructed from 24 stainless steel pentagons comprise the cell bodies of Soma, and enclose the nuclei. Each pentagon used about 10’ of stainless steel tubing. A total 240 feet of stainless steel tubing was used for the dodecahedrons.
There are flame effects running down the axon which simulate signal neurotransmission. Participants control the “neurotransmission” by pushing buttons. A “Sparkle Poof” simulates release of neurotransmitters at the synapse. Each aerial dendrite and the axon burn with continuous flame effects.
It’s All About the Genes and the Brain Machines
(Image: U.S. Dept. of Energy Office of Science)
The amount of time and money needed to sequence genomes continued to fall this year, perhaps to no one’s surprise. But while the field seemed to be finally approaching the heralded $1,000 human genome, the implications of reaching that milestone are not clear. Without expert analysis, the result of sequencing a human genome is just a large file of letters. You still need to manipulate and understand what those letters mean. Different companies announced services to help, from initial processing and storage of data to interpretation of the genetic data into medical meaning.
As human genomics garnered more attention from the medical community, the technology attracted new business opportunities. In April, the company behind the most widely used DNA sequencer, Illumina, fought off a hostile bid from pharmaceutical giant Roche. Just seven months later, Illumina tried to take over Complete Genomics, a company with technology well suited to medical genomics but which has never achieved financial success. That offer followed what seemed to be an all-but-assured purchased of Complete Genomics by China’s BGI. Illumina and BGI continue to fight over Complete Genomics.
Still, the medical community is only at the cusp of its understanding of how genome sequences can be used to help patients. Two branches of medicine that seem to be at the forefront of bringing on board DNA technology are reproductive medicine and cancer. Early in the summer, scientists at the University of Washington in Seattle reported a technique for determining the genome sequence of a fetus by analyzing DNA in the mother’s blood and from the father. Illumina’s CEO Jay Flatley said that prenatal diagnostics will be a major focus for the company, which has been expanding its business from sequencer manufacturing to broad DNA analysis service. In September, Illumina purchased BlueGnome, a chromosome-focused diagnostic company whose technology can detect abnormal numbers of chromosomes in IVF embryos. DNA analysis could also help prior to conception, according to a start-up called GenePeeks. That company announced it would offer predictive genome analysis for sperm bank clients to help guide them away from risky donor matches.
Cancer patients and their doctors were also early adopters of medical genome science this year. Cancer is a disease of the genome: genetic mutations lead to abnormal cellular proliferation and behavior. Each person’s tumor and even different cells within a single tumor can have a unique profile of mutations, which makes finding the right drug to treat each patient difficult. Cambridge, Massachusetts-based Foundation Medicine offered a sequencing service that searches for mutations that can be addressed with drugs in a patient’s tumor. Another Cambridge company, H3 Biomedicine, is using public databases of tumor sequences to find new drug targets specific to certain patient populations.
Genetic medicines also got a boost with the first Western approval of gene therapy in November. Amsterdam-based Uniqure will begin selling its virus-mediated gene correction for a rare metabolic disorder sometime next year. The announcement could be good news for other companies trying to develop gene therapies as well as other groups developing molecular medicines, such as gene-silencing RNAi treatments that continue to move through clinical trials.
Although still untested in patients, another genetic manipulation is proving to be a powerful tool for neuroscientists. With optogenetics, scientists can manipulate neuron activity with flashes of light, and this year a group demonstrated for the first time that primate behavior could be controlled with the technique. Lab animal studies this year suggest optogenetics might one day help patients with blindness caused by retinal degeneration.
The melding of mind and machine was also big this year. Scientists in Winston-Salem, North Carolina, demonstrated that a brain implant could replace some cognitive function in primates, which could one day help people with brain damage. On the flip side, two research groups published the first accounts of quadriplegic people using brain implants to control robotic limbs. The implants recorded the participants’ intentions to move, which were translated by a computer into instructions for a robotic arm. The idea is that one day people with severe paralysis or amputations could use such neural prosthetics at home to help with the tasks of daily life.
Brain electronics were also implanted into Alzheimer’s patients this year in an attempt to slow a disease that has so far evaded pharmaceutical treatment. The urgency for treatment is growing, but the community still doesn’t know what sets into motion the cascade of molecular events that robs people of their memory and thinking skills. With better diagnostic tools and the discovery that there are warnings decades before symptoms, scientists are turning to treating patients with a genetic predisposition for the disease before they start having symptoms. Perhaps this will be the key to treatments in future years.
(Source: technologyreview.com)
Are Babies Born Good?
Arber Tasimi is a 23-year-old researcher at Yale University’s Infant Cognition Center, where he studies the moral inclinations of babies—how the littlest children understand right and wrong, before language and culture exert their deep influence.“What are we at our core, before anything, before everything?” he asks. His experiments draw on the work of Jean Piaget, Noam Chomsky, his own undergraduate thesis at the University of Pennsylvania and what happened to him in New Haven, Connecticut, one Friday night last February.
It was about 9:45 p.m., and Tasimi and a friend were strolling home from dinner at Buffalo Wild Wings. Just a few hundred feet from his apartment building, he passed a group of young men in jeans and hoodies. Tasimi barely noticed them, until one landed a punch to the back of his head.
There was no time to run. The teenagers, ignoring his friend, wordlessly surrounded Tasimi, who had crumpled to the brick sidewalk. “It was seven guys versus one aspiring PhD,” he remembers. “I started counting punches, one, two, three, four, five, six, seven. Somewhere along the way, a knife came out.” The blade slashed through his winter coat, just missing his skin.
At last the attackers ran, leaving Tasimi prone and weeping on the sidewalk, his left arm broken. Police later said he was likely the random victim of a gang initiation.
After surgeons inserted a metal rod in his arm, Tasimi moved back home with his parents in Waterbury, Connecticut, about 35 minutes from New Haven, and became a creature much like the babies whose social lives he studies. He couldn’t shower on his own. His mom washed him and tied his shoes. His sister cut his meat.
Spring came. One beautiful afternoon, the temperature soared into the 70s and Tasimi, whose purple and yellow bruises were still healing, worked up the courage to stroll outside by himself for the first time. He went for a walk on a nearby jogging trail. He tried not to notice the two teenagers who seemed to be following him. “Stop catastrophizing,” he told himself again and again, up until the moment the boys demanded his headphones.
The mugging wasn’t violent but it broke his spirit. Now the whole world seemed menacing. When he at last resumed his morality studies at the Infant Cognition Center, he parked his car on the street, feeding the meter every few hours rather than risking a shadowy parking garage.
“I’ve never been this low in life,” he told me when we first met at the baby lab a few weeks after the second crime. “You can’t help wonder: Are we a failed species?”
At times, he said, “only my research gives me hope.”
How Neuroscientists Observe Brains Watching Movies
Unless you have been deaf and blind to the world over the past decade, you know that functional magnetic resonance brain imaging (fMRI) can look inside the skull of volunteers lying still inside the claustrophobic, coffinlike confines of a loud, banging magnetic scanner. The technique relies on a fortuitous property of the blood supply to reveal regional activity. Active synapses and neurons consume power and therefore need more oxygen, which is delivered by the hemoglobin molecules inside the circulating red blood cells. When these molecules give off their oxygen to the surrounding tissue, they not only change color—from arterial red to venous blue—but also turn slightly magnetic.
(Image: Todd Davidson/Stock Illustration Source)
Activity in neural tissue causes an increase in the volume and flow of fresh blood. This change in the blood supply, called the hemodynamic signal, is tracked by sending radio waves into the skull and carefully listening to their return echoes. FMRI does not directly measure synaptic and neuronal activity, which occurs over the course of milliseconds; instead it uses a relatively sluggish proxy—changes in the blood supply—that rises and falls in seconds. The spatial resolution of fMRI is currently limited to a volume element (voxel) the size of a pea, encompassing about one million nerve cells.
Neuroscientists routinely exploit fMRI to infer what volunteers are seeing, imagining or intending to do. It is really a primitive form of mind reading. Now a team has taken that reading to a new, startling level.
A number of groups have deduced the identity of pictures viewed by volunteers while lying in the magnet scanner from the slew of maplike representations found in primary, secondary and higher-order visual cortical regions underneath the bump on the back of the head.
Jack L. Gallant of the University of California, Berkeley, is the acknowledged master of these techniques, which proceed in two stages. First, a volunteer looks at a couple of thousand images while lying in a magnet. The response of a few hundred voxels in the visual cortex to each image is carefully registered. These data are then used to train an algorithm to predict the magnitude of the fMRI response for each voxel. Second, this procedure is inverted. That is, for a given magnitude of hemodynamic response, a probabilistic technique called Bayesian decoding infers the most likely image that gave rise to the observed response in that particular volunteer (human brains differ substantially, so it is difficult to use one brain to predict the responses of another).
The best of these techniques exploit preexisting, or prior, knowledge about pictures that could have been seen before. The number of mathematically possible images is vast, but the types of actual scenes that are encountered in a world populated by people, animals, trees, buildings and other objects encompass a tiny fraction of all possible images. Appropriately enough, the images that we usually encounter are called natural images. Using a database of six million natural images, Gallant’s group showed in 2009 how brain responses of volunteers to photographs they had not previously encountered could be reconstructed.
(Source: scientificamerican.com)
The Role of Medial Prefrontal Cortex in Memory and Decision Making
Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation.
Alzheimer’s Muddles Memory of How Things Work
Which is bigger, a key or an ant? That question might be easy for you to answer quickly, but it could be a little more confusing for a person with Alzheimer’s.
The most obvious trait of the mind-ruining disease is memory loss, with patients forgetting once-familiar people, places and experiences. New research shows how this mental deterioration extends to semantic memory, which has more to do with remembering facts and concepts and underlies a basic understanding of how things works.
For their study, researchers recruited 70 cognitively healthy people, 27 patients with Alzheimer’s 25 patients with mild cognitive impairment (MCI), often considered a precursor to dementia. All were tested on their ability to make size judgments about two pictures shown to them — the premise being that the bigger the difference in size between two objects, the faster a person would be able to answer the question.
"If you ask someone what is bigger, a key or an ant, they would be slower in their response than if you asked them what is bigger, a key or a house," researcher Terry Goldberg, of the Hofstra North Shore-LIJ School of Medicine, said in a statement.
This held true in the experiments, but the MCI and Alzheimer’s patients had much more trouble when asked to respond to a task with small size differences.
The experiment was then tweaked so that the participants were shown pictures of a small ant and a big house or a big ant and a small house. The MCI and Alzheimer’s patients did not have a problem making judgments about the small ant and big house, but had trouble with the more incongruent set. They were confused about which object was actually larger when shown a big ant and a small house, and were more likely to answer incorrectly or take longer to arrive at a response, the researchers said.
Goldberg said the findings indicate “that something is slowing down the patient and it is not episodic memory but semantic memory.”
The team will continue to study these patients over time to see if these semantic problems get worse as the disease advances.
Neural Pointillism: Lighting Up the Brain in Psychedelic Relief
During the last decade, researchers have labored intensively to find new methods to photograph the complex networks of nerve cells that make up the brain and spinal cord, an attempt to overcome the severe limitations of earlier imaging technologies. The emerging science of connectomics, intended to map such connections, will be made possible by deploying these techniques.
In 2007, Jeff Lichtman, Joshua Sanes and colleagues at Harvard University came up with one of the most notable examples of the new brain-cell imaging methods. Brainbow lights up neurons in about 100 different hues, enabling a precise tracking of neural circuitry and synapses, the gaps between brain cells.
Scientists engineer a mouse or another model animal with a gene that randomly causes each neuron to express differing amounts of a red, green or blue fluorescent protein, producing a palette of varying pastel-like colors. Slices of tissue are photographed and recombined to produce detailed imagery of the brain’s structural topography. (The original discovery of what is called green fluorescent protein by Martin Chalfie, Osamu Shinomura and Roger Y. Tsien, from which these new multi-colored fluorescent proteins are derived, was awarded the 2008 Nobel Prize in Chemistry.)
Virtual Reality and Robotics in Neurosurgery—Promise and Challenges
Robotic technologies have the potential to help neurosurgeons perform precise, technically demanding operations, together with virtual reality environments to help them navigate through the brain, according to a special supplement to Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.
"Virtual Reality (VR) and robotics are two rapidly expanding fields with growing application within neurosurgery," according to an introductory article by Garnette Sutherland, MD. The 22 reviews, commentaries, and original studies in the special supplement provide an up-to-the-minute overview of "the benefits and ongoing challenges related to the latest incarnations of these technologies."
Robotics and VR in Neurosurgery—What’s Here and What’s Next
Virtual reality and robotic technologies present exciting opportunities for training, planning, and actual performance of neurosurgical procedures. Robotic tools under development or already in use can provide mechanical assistance, such as steadying the surgeon’s hand or “scaling” hand movements. “Current robots work in tandem with human operators to combine the advantages of human thinking with the capabilities of robots to provide data, to optimize localization on a moving subject, to operate in difficult positions, or to perform without muscle fatigue,” writes Dr. Sutherland.
Virtual reality technologies play an important role, providing “spatial orientation” between robotic instruments and the surgeon. Virtual reality environments “recreate the surgical space” in which the surgeon works, providing 3-D visual images as well as haptic (sense of touch) feedback. The ability to plan, rehearse, and “play back” operations in the brain could be particularly valuable for training neurosurgery residents—especially since recent work hour changes have limited opportunities for operating room experience.
The special supplement to Neurosurgery presents authoritative updates by experts working in the field of surgical robotics and VR technology, drawn from a wide range of disciplines. Topics include robotic technologies already in use, such as the “neuroArm” image-guided neurosurgical robot; reviews of progress in areas such as 3-D neurosurgical planning and virtual endoscopy; and new thinking on the best approaches to development, evaluation, and clinical uses of VR and robotic technologies.
But numerous and daunting technical challenges remain to be met before robotic and VR technologies become widely used in clinical neurosurgery. For example, VR environments require extremely fast processing times to provide the surgeon with continuously updated sensory information—equal to or faster than the brain’s ability to perceive it.
Economic challenges include the high costs of developing and implementing VR and robotic technologies, especially in terms of showing that the costs are justified by benefits to the patient. Continued progress in miniaturization will play an important role both in overcoming the technical challenges and in making the technology cost-effective.
The editors of Neurosurgery hope their supplement will stimulate interest and further progress in the development and practical implementation of VR and robotic technologies for neurosurgery. Dr. Sutherland adds, “Collaboration between the fields of medicine, engineering, science, and technology will allow innovations in these fields to converge in new products that will benefit patients with neurosurgical disease.”
(Image courtesy: Imperial College London)