Posts tagged science
Articles and news from the latest research reports.
People in their 90s are getting smarter
Ninety-somethings seem to be getting smarter. Today’s oldest people are surviving longer, and thankfully appear to have sharper minds than the people reaching their 90s 10 years ago.
Kaare Christensen, head of the Danish Aging Research Center at the University of Southern Denmark in Odense, and colleagues found Danish people born in 1915 were about a third more likely to live to their 90s than those born in 1905, and were smarter too.
During research, which spanned 12 years and involved more than 5000 people, the team gave nonagenarians born in 1905 and 1915 a standard test called a “mini-mental state examination”, and cognitive tests designed to pick up age-related changes. Not only did those born in 1915 do better at both sets of tests, more of them also scored top marks in the mini-mental state exam.
It’s a landmark study, says Marcel Olde Rikkert, head of the Alzheimer’s centre at Radboud University Nijmegen Medical Centre in the Netherlands. It is scientifically rigorous, it invited all over 90-year-olds in Denmark to participate, and it also overturns our ingrained views of old age, he says.
Getting better all the time
"The outcome underlines that ageing is malleable," Olde Rikkert says, adding that cognitive function can actually be a lot better than people would assume until a very high age.
"It’s motivating that people, their lifestyles, and their environments can contribute a lot to the way they age," he says, though he cautions that not everything is in our own hands and help is still needed for those with dementia or those who do experience cognitive decline as they age.
Improved education played a part in the changes, says Christensen. But the study does not disentangle the individual effects of the numerous things that could be responsible for the improvements. “The 1915 cohort had a number of factors on their side – they experienced better living and working conditions, they had radio, TV and newspapers earlier in their lives than those born 10 years before,” he says.
Tellingly, there was no difference in the physical test results between the two groups. The authors say this “suggests changes in the intellectual environment rather than in the physical environment are the basis for the improvement”.
(Source: newscientist.com)
New insight into the human genome through the lens of evolution
By comparing the human genome to the genomes of 34 other mammals, Australian scientists have described an unexpectedly high proportion of functional elements conserved through evolution.
Less than 1.5% of the human genome is devoted to conventional genes, that is, encodes for proteins. The rest has been considered to be largely junk. However, while other studies have shown that around 5-8% of the genome is conserved at the level of DNA sequence, indicating that it is functional, the new study shows that in addition much more, possibly up to 30%, is also conserved at the level of RNA structure.
DNA is a biological blueprint that must be copied into another form before it can be actualised. Through a process known as ‘transcription’, DNA is copied into RNA, some of which ‘encodes’ the proteins that carry out the biological tasks within our cells. Most RNA molecules do not code for protein, but instead perform regulatory functions, such as determining the ways in which genes are expressed.
Like infinitesimally small Lego blocks, the nucleic acids that make up RNA connect to each other in very specific ways, which force RNA molecules to twist and loop into a variety of complicated 3D structures.
Dr Martin Smith and Professor John Mattick, from Sydney’s Garvan Institute of Medical Research, devised a method for predicting these complex RNA structures – more accurate than those used in the past – and applied it to the genomes of 35 different mammals, including bats, mice, pigs, cows, dolphins and humans. At the same time, they matched mutations found in the genomes with consistent RNA structures, inferring conserved function. Their findings are published in Nucleic Acids Research, now online.
“Genomes accumulate mutations over time, some of which don’t change the structure of associated RNAs. If the sequence changes during evolution, yet the RNA structure stays the same, then the principles of natural selection suggest that the structure is functional and is required for the organism,” explained Dr Martin Smith.
“Our hypothesis is that structures conserved in RNA are like a common template for regulating gene expression in mammals – and that this could even be extrapolated to vertebrates and less complex organisms.”
“We believe that RNA structures probably operate in a similar way to proteins, which are composed of structural domains that assemble together to give the protein a function.”
“We suspect that many RNA structures recruit specific molecules, such as proteins or other RNAs, helping these recruited elements to bond with each other. That’s the general hypothesis at the moment – that non-coding RNAs serve as scaffolds, tethering various complexes together, especially those that control genome organization and expression during development.”
“We know that many RNA transcripts are associated with diseases and developmental conditions, and that they are differentially expressed in distinct cells.”
“Our structural predictions can serve as an annotative tool to help researchers understand the function of these RNA transcripts.”
“That is the first step – the next is to describe the structures in more detail, figure out exactly what they do in the cell, then work out how they relate to our normal development and to disease.”
(Source: garvan.org.au)
The brain is alive, will new MRI diffusion techniques let us see it move and shake?
Pioneering experiments back in 1982 by Tasaki and Iwasa at the NIH revealed that action potentials in neurons are more than just the electrical blips that physiologists readily amplify and record. These so-called “spikes” are in fact multi-modal signalling packages that include mechanical and thermal disturbances propagating down the axon at their own rates. Nobel Laureate Francis Crick published a paper that same year, in which he postulated potential mechanisms that would explain twitching in dendritic spines, adding to an emerging picture of a brain more vibrant and motile than had been previously imagined. More recently, researchers have developed diffusion-based MRI methods, like diffusion tensor imaging (DTI), to trace the trajectories of axons, and perhaps more intriguingly, determine their directional polarity. Working at the EPFL in Switzerland, Denis Le Bihan and his co-workers have been using diffusional MRI in slightly different way. They now appear to be able to directly measure neuronal activity from the subtle movements of membranes, the water within them, and in the extracellular space around them. Their work, just published in PNAS, provides a much needed conceptual shift away from currently established, but typically nebulous, ideas regarding neurovascular coupling of brain activity to blood flow.
Present-day imaging methods, like blood oxygen level-dependent (BOLD) MRI, are only indirectly and remotely related to the cortical activity they often claim to measure. In 2006, Le Bihan reported a water “phase transition” response that preceded the neurovascular response normally detected by functional MRI. He attributed the changes in water diffusion to previously established effects involving membrane expansion and cell swelling secondary to activity. At the biophysical level, interpreting action potentials as phase transitions is a little off the beaten path from traditional neurobiology, but it can be an informative approach when to trying to understand what might be going on when cells fire.
As biophysicist Gerald Pollack has previously pointed out, spikes may involve the propagation of the line of transition of water from the ordered phase, (as patterned by hydrophic interactions nucleated at the surfaces of membranes and proteins) to a disordered phase.
Traditionally, the so-called bound surface water only extends out a only a couple of molecules from the surface of nondiffusable features. That idea may need to be revisited in light of more recent understanding when attempting to account for the diffusion of water in axons. A decrease in water diffusion as measured by MRI may be in part explained by a decrease in extracellular space, and that has been suggested from experiments measuring intrinsic optical effects. The larger picture of water diffusion, however, is likely a bit more complicated than this.
In his new study, Le Bihan stimulated the forepaw of a rat and looked at responses in the somatosensory cortex. The key experiment was to infuse nitroprusside in attempt to inhibit neurovascular coupling. It is a tricky alteration because nitroprusside apparently has many diffuse effects. It can induce potent vasodilation, particularly on the vascular end (mainly the smaller venules), after it breaks down to produce nitric oxide. It is also a diamagnetic molecule, and each molecule releases five cyanide ions, which are presumably detoxified by the mitochondrial enzyme rhodanese. The experiments were done under isoflurane anesthesia, which also introduces a few uncertainties, particularly with regard to responses to different frequencies of forepaw stimulation.
If nitroprusside is indeed a realistic experimental proxy for neurovascular uncoupling, then the results of Le Bihan appear to show that the diffusion response is not of vascular origin, and that it is closely linked to neural activation. He found that the standard BOLD MRI responses were completely quenched under nitroprusside, whereas the diffusion MRI responses were only slightly suppressed. Local field potentials were also simultaneously measured and suggested at least, that the neuronal responses were also intact.
The work of Le Bihan indicates that diffusion-based MRI can be used to infer neural activity directly from the structural changes that affect the molecular displacements of water. The ability to use shape changes in neurons, astrocytes, or even spines, raises the question of whether these kinds of techniques might eventually be of use in creating larger scale, and more detailed, Brain Activity Maps (BAMs). I asked Konrad Kording, author on the recent theoretical paper which discussed the theoretical limits to MRI and other activity recording methods, whether methods that probe water movements might be applied to this end.
Kording observed that the spatial resolution of standard MRI is ultimately limited by the diffusion of water, but more importantly perhaps, the temporal resolution of all known MRI methods is nowhere near that required to create spike maps. None-the-less, detecting mechanical responses in the brain could provide many unique insights into function. For example, experiments using agents that dissolve the extracellular matrix, like the clot-busting drug TPA, result in more twitching, or vibration if you will, in dendritic spines. Other studies have shown that the greater the electrical drive on a spine, the less it tends to twitch or change size, particularly during periods of rapid development.
Similarly, sensory deprivations appear to increase these kinds of movements as neurons grow and reorganize connections. While these effects are far below that which could be detected by any large external method of MRI, new tools may permit us to access these newly-revealed activities. Diffusional MRI in particular, can be done with a little modification of the standard MRI procedure. For example, to determine directional diffusion parameters, or diffusion tensors, typically six gradients are used to measure three directional vectors. As these capabilities become more common, hopefully the results of Le Bihan can be further explored and verified.
Fighting Alzheimer’s disease with protein origami
The human protein prefoldin can reduce the neuronal toxicity of clumps of amyloid-β proteins that collect in the brains of Alzheimer’s patients
Alzheimer’s disease is a progressive degenerative brain disease most commonly characterized by memory deficits. Loss of memory function, in particular, is known to be caused by neuronal damage arising from the misfolding of protein fragments in the brain. Now, a group of researchers led by Mizuo Maeda of the RIKEN Bioengineering Laboratory, and including researchers from the Laboratory for Proteolytic Neuroscience at the RIKEN Brain Science Institute, has found that the human protein prefoldin can change the way these misfolded protein aggregates form and potentially reduce their toxic impact on the brains of Alzheimer’s patients.
The formation of insoluble fibril aggregates of the protein amyloid-β has been identified as a key mechanism responsible for memory loss in Alzheimer’s patients. These fibrils are toxic to neurons, and finding a means of preventing their formation represents a key strategy in the development of a therapy for the disease. Recent studies suggest methods that alter the mechanism of amyloid-β aggregates could offer a promising approach.
Prefoldin is a molecular chaperone involved in preventing the clumping of misfolded proteins and helping misfolded proteins return to their normal shape. The researchers found that amyloid-β molecules incubated with even just a small amount of human prefoldin underwent a change in aggregation behavior—they instead formed into small, soluble oligomer clumps. The observations suggest that human prefoldin interacts with amyloid-β molecules to alter their binding properties.
As in the brain, amyloid-β fibrils also kill neurons in cell culture. Using neurons from the brains of mice, the researchers showed that the amyloid-β oligomers formed in the presence of human prefoldin induced less neuron death than amyloid-β fibrils. Prefoldin expression actually increases in the brains of mice with high levels of amyloid-β, suggesting that the upregulation of prefoldin expression might be a response mechanism used by the brain to protect itself from the toxic effects of amyloid-β fibrils.
Many researchers currently believe that amyloid-β oligomers are themselves a toxin that induces neuronal dysfunction. The present results, however, suggest that certain types of oligomers may in fact be less toxic than other conformations of amyloid-β aggregates. Increasing the expression of human prefoldin in the brain may therefore increase the proportion of less toxic amyloid-β aggregates, presenting a potential means of fighting the disease.
“Our findings may also apply to various other neurological diseases caused by protein misfolding, such as prion disease, Huntington’s disease and Parkinson’s disease,” explains Tamotsu Zako from the research team.
Whole brain imaging of zebrafish reveals neuronal networks involved in retrieving long-term memories during decision making
In mammals, a neural pathway called the cortico-basal ganglia circuit is thought to play an important role in the choice of behaviors. However, where and how behavioral programs are written, stored and read out as a memory within this circuit remains unclear. A research team led by Hitoshi Okamoto and Tazu Aoki of the RIKEN Brain Science Institute has for the first time visualized in zebrafish the neuronal activity associated with the retrieval of long-term memories during decision making.
The team performed experiments on genetically engineered zebrafish expressing a fluorescent protein that changes its intensity when it binds to calcium ions in neurons and thereby acts as an indicator of neuronal activity. “Neurons in the fish cortical region form a neural circuit similar to the mammalian cortico-basal ganglia circuit,” says Okamoto.
The fish were trained on an avoidance task by placing individual fish into a two-compartment tank and shining a red light for several seconds into the compartment containing the fish. If the fish did not move into the other compartment in response to the light, it was ‘punished’ with a mild electric shock. After several repetitions, the fish learned to avoid the shock by switching compartments as soon as the light came on.
The researchers then examined the neuronal activity of the fish under the microscope in response to exposure to red light. One day after the learning task, the fish showed specific activity in a discrete region of the telencephalon, which corresponds to the cerebral cortex in mammals, when presented with the red light. However, just 30 minutes after the learning task no activity was observed in this part of the brain. The results suggest that this telencephalonic area encodes the long-term memory for the learned avoidance behavior. Confirming this, removing this part of the telencephalon abolished the long-term memory but did not affect learning or short-term storage of the memory.
In humans, the ability to choose the correct behavioral programs in response to environmental changes is indispensable for everyday life, and the ability to do so is thought to be impaired in various psychiatric conditions such as depression and schizophrenia.
“Combining the neural imaging technique with genetics, we will be able to investigate how neurons in the cortico-basal ganglia circuit choose the most suitable behavior in any given situation,” says Okamoto. “Our findings open the way to investigate and understand how these symptoms appear in human psychiatric disorders.”
Choline intake improves memory and attention-holding capacity
An experimental study in rats has shown that consuming choline, a vitamin B group nutrient found in foodstuffs like eggs and chicken or beef liver, soy and wheat germ, helps improve long-term memory and attention-holding capacity. The study, conducted by scientists at the University of Granada (Spain) Simón Bolívar University, (Venezuela) and the University of York (United Kingdom), has revealed that choline is directly involved in attention and memory processes and helps modulate them.
Researchers studied the effects of dietary supplements of choline in rats in two experiments aimed at analysing the influence of vitamin B intake on memory and attention processes during gestation and in adult specimens.
In the first experiment, scientists administered choline to rats during the third term of gestation in order to determine the effect of prenatal choline on the memory processes of their offspring. Three groups of pregnant rats were fed choline-rich, standard or choline-deficient diets. When their offspring had reached adult age, a sample of 30 was selected: 10 were female offspring of dams fed a choline-supplement, 10 had followed a choline-deficient diet and the other 10, a standard diet, acting as a control group.
Long-term memory
This sample of adult offspring underwent an experiment to measure their memory retention: 24 hours after being shown an object all the offspring (whether in the choline-supplement group or not) remembered it and it was familiar to them However, after 48 hours, the rats of dams fed a prenatal choline-rich diet recognized the object better than those in the standard diet group, while the choline-deficient group could not recognize it. Thus, the scientists concluded that prenatal choline intake improves long-term memory in the resulting offspring once they reach adulthood.
In the second experiment, the researchers measured changes in attention that occurred in adult rats fed a choline supplement for 12 weeks, versus those with no choline intake. They found that the rats which had ingested choline maintained better attention that the others when presented with a familiar stimulus. The control group, fed a standard diet, showed the normal learning delay when this familiar stimulus acquired a new meaning. However, the choline-rich intake rats showed a fall in attention to the familiar stimulus, rapidly learning its new meaning.
The study has been undertaken by University of Granada Department of Experimental Psychology researchers Isabel De Brugada-Sauras and Hayarelis Moreno-Gudiño (also on the research staff of Simón Bolívar University together with Diamela Carias); Milagros Gallo-Torre, researcher in the University of Granada Department of Psychobiology and Director of the “Federico Olóriz” University Research Institute for Neuroscience; and Geoffrey Hall, of the Department of Psychology of the University of York. Their study has recently given rise to publications in Nutritional Neuroscience and Behavioural Brain Research.
The brain processes complex stimuli more cumulatively than we thought
A new study reveals that the representation of complex features in the brain may begin earlier—and play out in a more cumulative manner—than previously thought.
The finding represents a new view of how the brain creates internal representations of the visual world. “We are excited to see if this novel view will dominate the wider consensus” said senior author Dr. Miyashita, who is also Professor of Physiology at the University of Tokyo’s School of Medicine, “and also about the potential impact of our new computational principle on a wide range of views on human cognitive abilities.”
The brain recalls the patterns and objects we observe by developing distinct neuronal representations that go along with them (this is the same way it recalls memories). Scientists have long hypothesized that these neuronal representations emerge in a hierarchical process limited to the same cortical region in which the representations are first processed.
Because the brain perceives and recognizes the external world through these internal images, any new information about the process by which this takes place has the power to inform our understanding of related functions, including knowledge acquisition and memory.
However, studies attempting to uncover the functional hierarchy involved in the cortical process of visual stimuli have tried to characterize this hierarchy by analyzing the activity of single nerve cells, which are not necessarily correlated with neurons nearby, thus leaving these analyses lacking.
In a new study appearing in the 12 July issue of the journal Science, lead author Toshiyuki Hirabayashi and colleagues focus not on single neurons but instead on the relationship between neuron pairs, testing the possibility that the representation of an object in a single brain region emerges in a hierarchically lower brain area.
"I became interested in this work," said Dr. Hirabayashi, "because I was impressed by the elaborate neuronal circuitry in the early visual system, which is well-studied, and I wanted to explore the circuitry underlying higher-order visual processing, which is not yet fully understood."
Hirabayashi and colleagues analyzed nerve cell pairs in cortical areas TE and 36, the latter of which is hierarchically higher, in two adult macaques. After these animals looked at six sets of paired stimuli for several months to learn to associate related objects (a process that can lead to pair-coding neurons in the brain), the researchers recorded neuron responses in areas TE and 36 of both animals as they again performed this task.
The neurons exhibited pair association, but not where the researchers would have thought. “The most surprising result,” said senior author Dr. Yasushi Miyashita “was that the neuronal circuit that generated pair-association was found only in area TE, not in area 36.” Indeed, based on previous studies, which indicated that the number of pair-coding neurons in area TE is much smaller, the researchers would have expected the opposite.
During their study, Miyashita and other team members observed that in region TE of the macaque cortex, unit 1 neurons (or source neurons) provided input to unit 2 neurons (or target neurons), which—unlike unit 1 neurons—responded to both members of a stimulus pair.
"The representations generated in area TE did not reflect a mere random fluctuation of response patterns," explained Dr. Miyashita, "but rather, they emerged as a result of circuit processing inherent to that area of the brain."
In area 36, meanwhile, members of neuron pairs behaved differently; on average, unit 1 as well as unit 2 neurons responded to both members of a stimulus pair. Neurons in area 36 received input from area TE, but only from its unit 2 neurons.
Taken together, these findings lead the authors to hypothesize the existence of a hierarchical relationship between regions TE and 36, in which paired associations first established in the former region are propagated to the latter one. Here, area 36 represents the next level of a so-called feed forward hierarchy.
The work by Hirabayashi and colleagues suggests that the detailed representations of objects commonly observed in the brain are attained not by buildup of representations in a single area, but by emergence of these representations in a hierarchically prior area and their subsequent transfer to the brain region that follows. There, they become sufficiently prevalent for the brain to register. The work also reveals that the brain activity involved in recreating visual stimuli emerges in a hierarchically lower brain area than previously thought.
Moving forward, the Japanese research team has plans to expand upon this research, thus continuing to contribute to studies worldwide that aim to give scientists the best possible tools with which to obtain a dynamic picture of the brain. As a next step, the team hopes to further elucidate interactions between the various cortical microcircuits that operate in memory encoding. Dr. Miyashita has conjectured that these microcircuits are manipulated by a global brain network. Using the results of this latest study, he and colleagues are poised to further evaluate this assumption.
"It will also be important to weave the neuronal circuit mechanisms into a unified framework," said Dr. Hirabayashi," and to examine the effects of learning on these circuit organizations."
Equipped with their new view of cortical processing, the team also hopes to trace the causal chain of memory retrieval across different areas of the cortex. “I am excited by the recent development of genetic tools that will allow us to do this,” said Dr. Miyashita. A better understanding of object representations from one area of the brain to the next will shed even greater light on elusive aspects of this hierarchical organ.
(Source: eurekalert.org)
Daydreaming simulated by computer model
Scientists have created a virtual model of the brain that daydreams like humans do.
Researchers created the computer model based on the dynamics of brain cells and the many connections those cells make with their neighbors and with cells in other brain regions. They hope the model will help them understand why certain portions of the brain work together when a person daydreams or is mentally idle. This, in turn, may one day help doctors better diagnose and treat brain injuries.
“We can give our model lesions like those we see in stroke or brain cancer, disabling groups of virtual cells to see how brain function is affected,” said senior author Maurizio Corbetta, MD, the Norman J. Stupp Professor of Neurology at Washington University School of Medicine in St. Louis. “We can also test ways to push the patterns of activity back to normal.”
The study is now available online in The Journal of Neuroscience.
The model was developed and tested by scientists at Washington University School of Medicine in St. Louis, Universitat Pompeu Fabra in Barcelona, Spain, and several other European universities including ETH Zurich, Switzerland; University of Oxford, United Kingdom; Institute of Advanced Biomedical Technologies, Chieti, Italy; and University of Lausanne, Switzerland.
Scientists first recognized in the late 1990s and early 2000s that the brain stays busy even when it’s not engaged in mental tasks. Researchers have identified several “resting state” brain networks, which are groups of different brain regions that have activity levels that rise and fall in sync when the brain is at rest. They have also linked disruptions in networks associated with brain injury and disease to cognitive problems in memory, attention, movement and speech.
The new model was developed to help scientists learn how the brain’s anatomical structure contributes to the creation and maintenance of resting state networks. The researchers began with a process for simulating small groups of neurons, including factors that decrease or increase the likelihood that a group of cells will send a signal.
“In a way, we treated small regions of the brain like cognitive units: not as individual cells but as groups of cells,” said Gustavo Deco, PhD, professor and head of the Computational Neuroscience Group in Barcelona. “The activity of these cognitive units sends out excitatory signals to the other units through anatomical connections. This makes the connected units more or less likely to synchronize their signals.”
Based on data from brain scans, researchers assembled 66 cognitive units in each hemisphere, and interconnected them in anatomical patterns similar to the connections present in the brain.
Scientists set up the model so that the individual units went through the signaling process at random low frequencies that had previously been observed in brain cells in culture and in recordings of resting brain activity.
Next, researchers let the model run, slowly changing the coupling, or the strength of the connections between units. At a specific coupling value, the interconnections between units sending impulses soon began to create coordinated patterns of activity.
“Even though we started the cognitive units with random low activity levels, the connections allowed the units to synchronize,” Deco said. “The spatial pattern of synchronization that we eventually observed approximates very well—about 70 percent—to the patterns we see in scans of resting human brains.”
Using the model to simulate 20 minutes of human brain activity took a cluster of powerful computers 26 hours. But researchers were able to simplify the mathematics to make it possible to run the model on a typical computer.
“This simpler whole brain model allows us to test a number of different hypotheses on how the structural connections generate dynamics of brain function at rest and during tasks, and how brain damage affects brain dynamics and cognitive function,” Corbetta said.
Extroverts have more sensitive brain-reward system
Extroverts may be more outgoing and cheerful in part because of their brain chemistry, reports a study by Cornell neuroscientists.
People’s brains respond differently to rewards, say the neuroscientists. Some people’s brains release more of the neurotransmitter dopamine, which ultimately gives them more reasons to be excited and engaged with the world, says Richard Depue, professor of human development in the College of Human Ecology, who co-authored the study with graduate student Yu Fu.
Their study, published in Frontiers in Human Neuroscience in June, sheds new light on how differences in the way the brain responds to reward translate into extraverted behavior, the authors say.
“Rewards like food, sex and social interactions as well as more abstract goals such as money or getting a degree trigger the release of dopamine in the brain, producing positive emotions and feelings of desire that motivate us to work toward obtaining those goals. In extroverts, this dopamine response to rewards is more robust so they experience more frequent activation of strong positive emotions,” Depue says.
“Dopamine also facilitates memory for circumstances that are associated with the reward. Our findings suggest this plays a significant role in sustaining extroverted behavior,” Depue adds. “The extroverts in our study showed greater association of context with reward than introverts, which means that over time, extroverts will acquire a more extensive network of reward-context memories that activate their brain’s reward system.”
Over a week, the researchers engaged 70 young adult males – a mix of introverts and extroverts according to a standard personality test – in a set of laboratory tasks that included viewing brief video clips of several aspects of the lab environment. On the first four days, some participants received a low dose of the stimulant methylphenidate (MP), also known as Ritalin, which triggers the release of dopamine in the brain; the others received either a placebo or MP in a different lab location. The team tested how strongly participants associated contextual cues in the lab (presented in video clips) with reward (the dopamine rush induced by MP) by assessing changes in their working memory, motor speed at a finger-tapping task and positive emotions (all known to be influenced by dopamine).
Participants who had unconsciously associated contextual cues in the lab with the reward were expected to have greater dopamine release/reward system activation on day 4 compared with day 1 when shown the same video clips. This so-called “associative conditioning” response is exactly what the team found in the extroverts. The extroverts strongly associated the lab context with reward feelings, whereas the introverts showed little to no evidence of associative conditioning.
“At a broader level, the study begins to illuminate how individual differences in brain functioning interact with environmental influences to create behavioral variation. This knowledge may someday help us to understand how such interactions create more extreme forms of emotional behavior, such as personality disorders,” says Depue.
Study Finds Factors That May Cause Fluctuations in Deep Brain Stimulation Levels Over Time
Deep brain stimulation therapy blocks or modulates electrical signals in the brain to improve symptoms in patients suffering from movement disorders such as Parkinson’s disease, essential tremor and dystonia, but a new study suggests that several factors may cause electrical current to vary over time.
Led by Michele Tagliati, MD, director of Cedars-Sinai Medical Center’s Movement Disorders Program, the study identified variables that affect impedance – resistance in circuits that affect intensity and wavelength of electrical current. Doctors who specialize in programming DBS devices fine-tune voltage, frequency and other parameters for each patient; deviations from these settings may have the potential to alter patient outcomes.
“Deep brain stimulation devices are currently designed to deliver constant, steady voltage, and we believe consistency and reliability are critical in providing therapeutic stimulation. But we found that we cannot take impedance stability for granted over the long term,” said Tagliati, the senior author of a journal article that reveals the study’s findings.
“Doctors with experience in DBS management can easily make adjustments to compensate for these fluctuations, and future devices may do so automatically,” he added. “Although our study was not designed to link changes in impedance and voltage with clinical outcomes, we believe it is important for patients to have regular, ongoing clinic visits to be sure they receive a steady level of stimulation to prevent the emergence of side effects or the re-emergence of symptoms.”
Findings of the study – one of the largest of its kind and possibly the first to follow patients for up to five years – were published online ahead of print in Brain Stimulation. Researchers collected 2,851 impedance measurements in 94 patients over a period of six months to five years, evaluating fluctuations in individual patients and in individual electrodes. They looked at a variety of factors, including how long a patient had undergone treatment, the position of the implanted electrode, the side of the brain where the electrode was implanted, and even placement and function of contact positions along electrodes.
Medications usually are the first line of treatment for movement disorders, but if drugs fail to provide adequate relief or side effects are excessive, neurologists and neurosurgeons may supplement them with deep brain stimulation. Electrical leads are implanted in the brain, and an electrical pulse generator is placed near the collarbone. The device is then programmed with a remote, hand-held controller.
(Source: newswise.com)