Posts tagged memory
Articles and news from the latest research reports.
Neuroscience to Benefit from Hybrid Supercomputer Memory
To handle large amounts of data from detailed brain models, IBM, EPFL, and ETH Zürich are collaborating on a new hybrid memory strategy for supercomputers. This will help the Blue Brain Project and the Human Brain Project achieve their goals.
Motivated by extraordinary requirements for neuroscience, IBM Research, EPFL, and ETH Zürich through the Swiss National Supercomputing Center CSCS, are exploring how to combine different types of memory – DRAM, which is standard for computer memory, and flash memory that is akin to USB sticks – for less expensive and optimal supercomputing performance.
The Blue Brain Project, for example, is building detailed models of the rodent brain based on vast amounts of information – incorporating experimental data and a large number of parameters – to describe each and every neuron and how they connect to each other. The building blocks of the simulation consist of realistic representations of individual neurons, including characteristics like shape, size, and electrical behavior.
Given the roughly 70 million neurons in the brain of a mouse, a huge amount of data needs to be accessed for the simulation to run efficiently.
“Data-intensive research has supercomputer requirements that go well beyond high computational power,” says EPFL professor Felix Schürmann of the Blue Brain Project in Lausanne. “Here, we investigate different types of memory and how it is used, which is crucial to build detailed models of the brain. But the applications for this technology are much broader.”
70 Million Neurons for the New IBM Blue Gene/Q
The Blue Brain Project has acquired a new IBM Blue Gene/Q supercomputer to be installed at CSCS in Lugano, Switzerland. This machine has four times the memory of the supercomputer used by the Blue Brain Project up to now, but this still may not be enough to model the mouse brain at the desired level of detail.
The challenge for scientists is to modify the supercomputer so that it can model not only more neurons—as many as the 70 million in the mouse brain—but with even more detail while using fewer resources. The researchers aspire to do just that by engineering different types of memory. The Blue Gene/Q comes equipped with 64 terabytes of DRAM memory. But this type of memory, which is ubiquitous in personal computers, loses data almost instantaneously when the power is turned off.
The scientists plan to boost the supercomputer’s capacity by combining DRAM with another type of memory that has made its way into everyday devices, from cameras to mobile phones: flash memory. Unlike DRAM, flash memory can retain information, even without power, and is much more affordable. The Blue Brain Project’s new supercomputer efficiently integrates 128 terabytes of flash memory with the 64 terabytes of DRAM memory.
“These technological advancements will not only help scientists model the brain, but they will also contribute to future evidence-based systems,” says IBM Research computational scientist Alessandro Curioni, who is based in Zurich.
To take full advantage of this novel mix of memory, IBM has been developing a scalable memory system architecture, while EPFL and ETH Zürich researchers are working on high-level software to optimize this hybrid memory for large-scale simulations and interactive supercomputing.
“The resulting machine may not necessarily be the fastest supercomputer in the world, but it will certainly open up new avenues for data-intensive science,” says ETH Zürich professor and CSCS director Thomas Schulthess. “The results of this collaboration will support scientific investigations across all types of data intensive applications including astronomy, geosciences and healthcare.”
Towards the Human Brain
The Blue Brain Project has recently become the core of an even more ambitious project, the European Flagship Human Brain Project, also coordinated by EPFL. The Human Brain Project faces the daunting task of providing the technical tools to integrate as much data as possible into detailed models of the human brain by 2023. Estimated at 90 billion neurons, the human brain compared to that of a mouse contains roughly a thousand times more neurons. The new strategy to use hybrid memory is an important step towards helping the Human Brain Project meet its 10-year goal.
As it goes with research and innovation, a scientific pursuit is pushing the boundaries of technology, leading to new and more powerful tools. The Blue Brain and Human Brain Projects have brought into perspective the need to deal with complex and unusual calculations, requiring supercomputer technology where speed is simply not enough.
(Source: actu.epfl.ch)
Video Gamers Really Do See More
Hours spent at the video gaming console not only train a player’s hands to work the buttons on the controller, they probably also train the brain to make better and faster use of visual input, according to Duke University researchers.
"Gamers see the world differently," said Greg Appelbaum, an assistant professor of psychiatry in the Duke School of Medicine. "They are able to extract more information from a visual scene."
It can be difficult to find non-gamers among college students these days, but from among a pool of subjects participating in a much larger study in Stephen Mitroff’s Visual Cognition Lab at Duke, the researchers found 125 participants who were either non-gamers or very intensive gamers.
Each participant was run though a visual sensory memory task that flashed a circular arrangement of eight letters for just one-tenth of a second. After a delay ranging from 13 milliseconds to 2.5 seconds, an arrow appeared, pointing to one spot on the circle where a letter had been. Participants were asked to identify which letter had been in that spot.
At every time interval, intensive players of action video games outperformed non-gamers in recalling the letter.
Earlier research by others has found that gamers are quicker at responding to visual stimuli and can track more items than non-gamers. When playing a game, especially one of the “first-person shooters,” a gamer makes “probabilistic inferences” about what he’s seeing — good guy or bad guy, moving left or moving right — as rapidly as he can.
Appelbaum said that with time and experience, the gamer apparently gets better at doing this. “They need less information to arrive at a probabilistic conclusion, and they do it faster.”
Both groups experienced a rapid decay in memory of what the letters had been, but the gamers outperformed the non-gamers at every time interval.
The visual system sifts information out from what the eyes are seeing, and data that isn’t used decays quite rapidly, Appelbaum said. Gamers discard the unused stuff just about as fast as everyone else, but they appear to be starting with more information to begin with.
The researchers examined three possible reasons for the gamers’ apparently superior ability to make probabilistic inferences. Either they see better, they retain visual memory longer or they’ve improved their decision-making.
Looking at these results, Applebaum said, it appears that prolonged memory retention isn’t the reason. But the other two factors might both be in play — it is possible that the gamers see more immediately, and they are better able make better correct decisions from the information they have available.
To get at this question, the researchers will need more data from brainwaves and MRI imagery to see where the brains of gamers have been trained to perform differently on visual tasks.
Scientists Map Process by Which Brain Cells Form Long-Term Memories
Scientists at the Gladstone Institutes have deciphered how a protein called Arc regulates the activity of neurons – providing much-needed clues into the brain’s ability to form long-lasting memories.
These findings, reported Sunday in Nature Neuroscience, also offer newfound understanding as to what goes on at the molecular level when this process becomes disrupted.
Led by Gladstone senior investigator Steve Finkbeiner, MD, PhD, this research delved deep into the inner workings of synapses. Synapses are the highly specialized junctions that process and transmit information between neurons. Most of the synapses our brain will ever have are formed during early brain development, but throughout our lifetimes these synapses can be made, broken and strengthened. Synapses that are more active become stronger, a process that is essential for forming new memories.
However, this process is also dangerous, as it can overstimulate the neurons and lead to epileptic seizures. It must therefore be kept in check.
Neuroscientists recently discovered one important mechanism that the brain uses to maintain this important balance: a process called “homeostatic scaling.” Homeostatic scaling allows individual neurons to strengthen the new synaptic connections they’ve made to form memories, while at the same time protecting the neurons from becoming overly excited. Exactly how the neurons pull this off has eluded researchers, but they suspected that the Arc protein played a key role.
“Scientists knew that Arc was involved in long-term memory, because mice lacking the Arc protein could learn new tasks, but failed to remember them the next day,” said Finkbeiner, who is also a professor of neurology and physiology at UC San Francisco, with which Gladstone is affiliated. “Because initial observations showed Arc accumulating at the synapses during learning, researchers thought that Arc’s presence at these synapses was driving the formation of long-lasting memories.”
But Finkbeiner and his team thought there was something else in play.
The Role of Arc in Homeostatic Scaling
In laboratory experiments, first in animal models and then in greater detail in the petri dish, the researchers tracked Arc’s movements. And what they found was surprising.
“When individual neurons are stimulated during learning, Arc begins to accumulate at the synapses – but what we discovered was that soon after, the majority of Arc gets shuttled into the nucleus,” said Erica Korb, PhD, the paper’s lead author who completed her graduate work at Gladstone and UCSF.
“A closer look revealed three regions within the Arc protein itself that direct its movements: one exports Arc from the nucleus, a second transports it into the nucleus, and a third keeps it there,” she said. “The presence of this complex and tightly regulated system is strong evidence that this process is biologically important.”
In fact, the team’s experiments revealed that Arc acted as a master regulator of the entire homeostatic scaling process. During memory formation, certain genes must be switched on and off at very specific times in order to generate proteins that help neurons lay down new memories. From inside the nucleus, the authors found that it was Arc that directed this process required for homeostatic scaling to occur. This strengthened the synaptic connections without overstimulating them – thus translating learning into long-term memories.
Implications for a Variety of Neurological Diseases
“This discovery is important not only because it solves a long-standing mystery on the role of Arc in long-term memory formation, but also gives new insight into the homeostatic scaling process itself – disruptions in which have already been implicated in a whole host of neurological diseases,” said Finkbeiner. “For example, scientists recently discovered that Arc is depleted in the hippocampus, the brain’s memory center, in Alzheimer’s disease patients. It’s possible that disruptions to the homeostatic scaling process may contribute to the learning and memory deficits seen in Alzheimer’s.”
Dysfunctions in Arc production and transport may also be a vital player in autism. For example, the genetic disorder Fragile X syndrome – a common cause of both mental retardation and autism, directly affects the production of Arc in neurons.
“In the future,” added Dr. Korb, “we hope further research into Arc’s role in human health and disease can provide even deeper insight into these and other disorders, and also lay the groundwork for new therapeutic strategies to fight them.”
(Image: Wikimedia)
Weird: Nuclear Bomb Tests Reveal Adults Grow New Brain Cells
Aboveground nuclear bomb testing in the 1950s and 1960s inadvertently gave modern scientists a way to prove the adult brain regularly creates new neurons, research reveals.
Researchers used to believe that the brain changed little once it finished maturing. That view is now considered out of date, as studies have revealed how changeable — or plastic — the adult brain can be.
Much of this plasticity is related to the brain’s organization; brain cells can alter their connections and communications with other brain cells. What has been less clear is whether, and to what extent, the human brain grows brand-new neurons in adulthood.
"There was a lot in the literature showing there was neurogenesis in rodents and every animal studied," said study researcher Kirsty Spalding, a biologist at the Karolinska Institute in Sweden, "But there was very little evidence of whether this happens in humans."
Tantalizing clues
Scientists had reason to believe it does. In adult mice, the hippocampus, a structure deep in the brain involved in memory and navigation, turns over cells all the time. Some of the biological markers linked to this turnover are seen in the human hippocampus. But the only direct evidence of new brain cells forming in the region came from a 1998 study in which researchers looked at the brains of five people who had been injected with a compounded called BrdU that cells take up into their DNA. (The compound was once used in experimental cancer studies, but is not used anymore for safety reasons.)
The BrdU study revealed that neurons in the hippocampuses of the participants contained the compound in their DNA, indicating these brain cells had formed after the injections. The oldest person in the study was 72, suggesting new neuron creation, known as neurogenesis, continues well into old age.
The 1998 study was the only direct evidence of such neurogenesis in the human hippocampus, however. Spalding and her colleagues wanted to change that. Ten years ago, they began a project to track the age of neurons in the human brain using an unusual tool: spare molecules left over from Cold War-era nuclear bomb tests.
Learning to love the bomb
Between 1945 and 1962, the United States conducted hundreds of aboveground nuclear bomb tests. These tests largely stopped with the Limited Test Ban Treaty of 1963, but their effects remained in the atmosphere. The neutrons sent flying by the bombs reacted with nitrogen in the atmosphere, creating a spike in carbon 14, an isotope (or variation) of carbon.
This carbon 14, in turn, did what carbon in the atmosphere does. It combined with oxygen to form carbon dioxide, and was then taken in by plants, which use carbon dioxide in photosynthesis. Humans ate some of these plants, along with some of the animals that also ate these plants, and the carbon 14 inside ended up in their bodies.
When a cell divides, it uses this carbon 14, integrating it into the DNA of the new cells that are forming. Carbon 14 decays over time at a known rate, so scientists can pinpoint from that decay exactly when the new cells were born.
Over the past decade, Spalding and her colleagues have used the technique in a variety of cells, including fat cells, refining it along the way until it became sensitive enough to measure tiny amounts of carbon 14 in small hippocampus samples. The researchers collected samples, with family permission, from autopsies in Sweden.
They found the tantalizing 1998 evidence was correct: Human hippocampuses do grow new neurons. In fact, about a third of the brain region is subject to cell turnover, with about 700 new neurons being formed each day in each hippocampus (humans have two, a mirror-image set on either side of the brain). Hippocampus neurons die each day, too, keeping the overall number more or less in balance, with some slow loss of cells with aging, Spalding said.
This turnover occurs at a ridge in the hippocampus known as the dentate gyrus, a spot known to contribute to the formation of new memories. Researchers aren’t sure what the function of this constant renewal is, but it could relate to allowing the brain to cope with novel situations, Spalding told LiveScience.
"Neurogenesis gives a particular kind of plasticity to the brain, a cognitive flexibility," she said.
Spalding and her colleagues had used the same techniques in other regions of the brain, including the cortex, the cerebellum and the olfactory bulb, and found no evidence of newborn neurons being integrated into those areas. The researchers now plan to study whether there are any links between neurogenesis and psychiatric conditions such as depression.
The new findings are detailed in the journal Cell.
Manipulating Memory in the Hippocampus
Protein modification may help control Alzheimer’s and epilepsy, TAU researchers find
In the brain, cell-to-cell communication is dependent on neurotransmitters, chemicals that aid the transfer of information between neurons. Several proteins have the ability to modify the production of these chemicals by either increasing or decreasing their amount, or promoting or preventing their secretion. One example is tomosyn, which hinders the secretion of neurotransmitters in abnormal amounts.
Dr. Boaz Barak of Tel Aviv University’s Sagol School of Neuroscience, in collaboration with Prof. Uri Ashery, used a method for modifying the levels of this protein in the mouse hippocampus — the region of the brain associated with learning and memory. It had a significant impact on the brain’s activity: Over-production of the protein led to a sharp decline in the ability to learn and memorize information, the researchers reported in the journal NeuroMolecular Medicine.
"This study demonstrates that it is possible to manipulate various processes and neural circuits in the brain," says Dr. Barak, a finding which may aid in the development of therapeutic procedures for epilepsy and neurodegenerative diseases such as Alzheimer’s. Slowing the transmission rate of information when the brain is overactive during epileptic seizures could have a beneficial effect, and readjusting the levels of tomosyn in an Alzheimer’s patient may help increase cognition and combat memory loss.
A maze of memory loss
The researchers teamed up with a laboratory at the National Institutes of Health (NIH) in Baltimore to create a virus which produces the tomosyn protein. In the lab, the virus was injected into the hippocampus region in mice. Then, in order to test the consequences, they performed a series of behavioral tests designed to measure functions like memory, cognitive ability, and motor skills.
In one experiment, called the Morris Water Maze, mice had to learn to navigate to, and remember, the location of a hidden platform placed inside a pool with opaque water. During the first five days of testing, researchers found that the test group with an over-production of tomosyn had a significant problem in learning and memorizing the location of the platform, compared to a control group that received a placebo injection. And when the platform was removed from the maze, the test group spent less time swimming around the area where the platform once was, indicating that they had no memory of its existence. In comparison, the control group of mice searched for the missing platform in its previous location for two or even three days after its removal, notes Dr. Barak.
These findings were further verified by measuring electrical activity in the brains of both the test group and the control group. In the test group, researchers found decreased levels of transmissions between neurons in the hippocampus, a physiological finding that may explain the results of the behavioral tests.
Correcting neuronal processes
In the future, Dr. Barak believes that the ability to modify proteins directly in the brain will allow for more control over brain activities and the correction of neurodegenerative processes, such as providing stricter regulation in neuronal activity for epileptic patients or stimulating neurotransmitters to help with learning and memory loss in Alzheimer’s patients. Indeed, a separate study conducted by the researchers demonstrates that mouse models for Alzheimer’s disease do have an over-production of tomosyn in the hippocampus region, so countering the production of this protein could have a beneficial effect.
Now Dr. Barak and Prof. Ashery are working towards a method for artificially decreasing levels of the protein, which they believe will have the opposite effect on the cognitive ability of the mice. “We hypothesize that with an under-production in tomosyn, the mice will show a marked improvement in their performance in behavioral testing,” he says.
(Source: aftau.org)
Healthy lifestyle choices mean fewer memory complaints
Research has shown that healthy behaviors are associated with a lower risk of Alzheimer’s disease and dementia, but less is known about the potential link between positive lifestyle choices and milder memory complaints, especially those that occur earlier in life and could be the first indicators of later problems.
To examine the impact of these lifestyle choices on memory throughout adult life, UCLA researchers and the Gallup organization collaborated on a nationwide poll of more than 18,500 individuals between the ages of 18 and 99. Respondents were surveyed about both their memory and their health behaviors, including whether they smoked, how much they exercised and how healthy their diet was.
As the researchers expected, healthy eating, not smoking and exercising regularly were related to better self-perceived memory abilities for most adult groups. Reports of memory problems also increased with age. However, there were a few surprises.
Older adults (age 60–99) were more likely to report engaging in healthy behaviors than middle-aged (40–59) and younger adults (18–39), a finding that runs counter to the stereotype that aging is a time of dependence and decline. In addition, a higher-than-expected percentage of younger adults complained about their memory.
"These findings reinforce the importance of educating young and middle-aged individuals to take greater responsibility for their health — including memory — by practicing positive lifestyle behaviors earlier in life," said the study’s first author, Dr. Gary Small, director of the UCLA Longevity Center and a professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA who holds the Parlow–Solomon Chair on Aging.
Published in the June issue of International Psychogeriatrics, the study may also provide a baseline for the future study of memory complaints in a wide range of adult age groups.
For the survey, Gallup pollsters conducted land-line and cell phone interviews with 18,552 adults in the U.S. The inclusion of cell phone–only households and Spanish-language interviews helped capture a representative 90 percent of the U.S. population, the researchers said.
"We found that the more healthy lifestyle behaviors were practiced, the less likely one was to complain about memory issues," said senior author Fernando Torres-Gil, a professor at UCLA’s Luskin School of Public Affairs and associate director of the UCLA Longevity Center.
In particular, the study found that respondents across all age groups who engaged in just one healthy behavior were 21 percent less likely to report memory problems than those who didn’t engage in any healthy behaviors. Those with two positive behaviors were 45 percent less likely to report problems, those with three were 75 percent less likely, and those with more than three were 111 percent less likely.
Interestingly, the poll found that healthy behaviors were more common among older adults than the other two age groups. Seventy percent of older adults engaged in at least one healthy behavior, compared with 61 percent of middle-aged individuals and 58 percent of younger respondents.
In addition, only 12 percent of older adults smoked, compared with 25 percent of young adults and 24 percent of middle-aged adults, and a higher percentage of older adults reported eating healthy the day before being interviewed (80 percent) and eating five or more daily servings of fruits and vegetables during the previous week (64 percent).
According to the researchers, older adults may participate in more healthy behaviors because they feel the consequences of unhealthy living and take the advice of their doctors to adopt healthier lifestyles. Or there simply could be fewer older adults with bad habits, since they may not live as long.
While 26 percent of older adults and 22 percent of middle-aged respondents reported memory issues, it was surprising to find that 14 percent of the younger group complained about their memory too, the researchers said.
"Memory issues were to be expected in the middle-aged and older groups, but not in younger people," Small said. "A better understanding and recognition of mild memory symptoms earlier in life may have the potential to help all ages."
Small said that, generally, memory issues in younger people may be different from those that plague older generations. Stress may play more of a role. He also noted that the ubiquity of technology — including the Internet, texting and wireless devices that can result in constant multi-tasking, especially with younger people — may impact attention span, making it harder to focus and remember.
Small noted that further study and polling may help tease out such memory-complaint differences. Either way, he said, the survey reinforces the importance, for all ages, of adopting a healthy lifestyle to help limit and forestall age-related cognitive decline and neurodegeneration.
The Gallup poll used in the study took place between December 2011 and January 2012 and was part of the Gallup–Healthways Well-Being Index, which includes health- and lifestyle-related polling questions. The five questions asked were: (1) Do you smoke? (2) Did you eat healthy all day yesterday? (3) In the last seven days, on how many days did you have five or more servings of vegetables and fruits? (4) In the last seven days, on how many days did you exercise for 30 minutes or more? (5) Do you have any problems with your memory?
(Source: newsroom.ucla.edu)
New neuron formation could increase capacity for new learning, at the expense of old memories
Cause of infantile amnesia revealed
New research presented today shows that formation of new neurons in the hippocampus - a brain region known for its importance in learning and remembering - could cause forgetting of old memories by causing a reorganization of existing brain circuits. Drs. Paul Frankland and Sheena Josselyn, both from the Hospital for Sick Children in Toronto, argue this reorganization could have the positive effect of clearing old memories, reducing interference and thereby increasing capacity for new learning. These results were presented at the 2013 Canadian Neuroscience Meeting, the annual meeting of the Canadian Association for Neuroscience - Association Canadienne des Neurosciences (CAN-ACN).
Researchers have long known of the phenomenon of infantile amnesia: This refers to the absence of long-term memory of events occurring within the first 2-3 years of life, and little long-term memories for events occurring until about 7 years of age. Studies have shown that though young children can remember events in the short term, these memories do not persist. This new study by Frankland and Josselyn shows that this amnesia is associated with high levels of new neuron production - a process called neurogenesis - in the hippocampus, and that more permanent memory formation is associated with a reduction in neurogenesis.
Dr. Frankland and Dr. Josselyn’s approach was to look at retention of memories in young mice in which they suppressed the usual high levels of neurogenesis in the hippocampus (thereby replicating the circuit stability normally observed in adult mice), but also in older mice in which they stimulated increased neurogenesis (thereby replicating the conditions normally seen in younger mice). Dr. Frankland was able to show a causal relationship between a reduction in neurogenesis and increased remembering, and the converse, decreased remembering when neurogenesis increased.
Dr. Frankland concludes: ” Why infantile amnesia exists has long been a mystery. We think our new studies begin to explain why we have no memories from our earliest years.”
Deep brain stimulation: a fix when the drugs don’t work
Neurological disorders can have a devastating impact on the lives of sufferers and their families.
Symptoms of these disorders differ extensively – from motor dysfunction in Parkinson’s disease, memory loss in Alzheimer’s disease to inescapable cravings in drug addiction.
Drug treatments are often ineffective in these disorders. But what if there was a way to simply switch off a devastating tremor, or boost a fading memory?
Recent advances using Deep Brain Stimulation (DBS) in selective brain regions have provided therapeutic benefits and have allowed those affected by these neurological disorders freedom from their symptoms, in absence of an existing cure.
A pacemaker for the brain
Artificial cardiac pacemakers are typically associated with controlling and resynchronising heartbeats by electrical stimulation of the heart muscle.
In a similar manner, DBS sends electrical impulses to specific parts of the brain that control discrete functions. This stimulation evokes control over the neural activity within these regions.
Prior to switching on the electrical stimulation, electrodes are surgically implanted within precise brain regions to control a specific function.
The neurosurgery is conducted under local anaesthetic to maintain consciousness in the patient. This ensures that the electrode does not damage critical brain regions.
The brain itself has no pain receptors so does not require anaesthetic.
Following recovery from surgery the electrodes are activated and the current calibrated by a neurologist to determine the optimal stimulation parameters.
The patient can then control whether the electrodes are on or off by a remote battery-powered device.
Turning off tremors
Perhaps the most documented success of DBS is in the control of tremors and motor coordination in Parkinson’s disease.
This is caused by the degeneration of neurons in an area of the brain called the substantia nigra. These neurons secrete the neurotransmitter dopamine.
Deterioration of these neurons reduces the amount of dopamine available to be released in a brain area involved in movement, the basal ganglia.
Drug therapy for Parkinson’s disease involves the use of levodopa (L-DOPA), a form of dopamine that can cross the blood brain barrier and then be synthesised into dopamine.
The administration of L-DOPA temporarily reduces the motor symptoms by increasing dopamine concentrations in the brain. However, side effects of this treatment include nausea and disordered movement.
DBS has been shown to provide relief from the motoric symptoms of Parkinson’s disease and essential tremors.
For the treatment of Parkinson’s disease electrodes are implanted into regions of the basal ganglia – the subthalamic nucleus or globus pallidus, to restore control of movement.
These are regions innervated by the deteriorating substantia nigra, therefore the DBS boosts stimulation to these areas.
Patients can then switch on the electrodes, stimulating these brain regions to enhance control of movement and diminish tremors.
Restoring fading memories
Recently, DBS has been used to diminish memory deficits associated with Alzheimer’s disease, a progressive and terminal form of dementia.
The pathologies associated with Alzheimer’s disease involve the formation of amyloid plaques and neurofibrillary tangles within the brain leading to dysfunction and death of neurons.
Brain regions primarily affected include the temporal lobes, containing important memory structures including the hippocampus.
Recent clinical trials with DBS involve the implantation of electrodes within the fornix – a structure connecting the left and right hippocampi together.
By stimulating neural activity within the hippocampi via the fornix, memory deficits associated with Alzheimer’s disease can be improved, enhancing the daily functioning of patients and slowing the progression of cognitive decline.
Deactivating addiction
Another use of DBS is in the treatment of substance abuse and drug addiction. Substance-related addictions constitute the most frequently occurring psychiatric disease category and patients are prone to relapse following rehabilitative treatment.
Persistent drug use leads to long term changes in the brain’s reward system.
Understanding of the reward systems affected in addiction has created a range of treatment options that directly target dysregulated brain circuits in order to normalise functionality.
One of the key reward regions in the brain is the nucleus accumbens and this has been used as a DBS target to control addiction.
Translational animal research has indicated that stimulation of the nucleus accumbens decreases drug seeking in models of addiction. Clinical studies have shown improved abstinence in both heroin addicts and alcoholics.
Studies have extended the use of DBS to potentially restore control of maladaptive eating behaviours such as compulsive binge eating.
In a recent study, binge eating of a high fat food in mice was decreased by DBS of the nucleus accumbens. This is the first study demonstrating that DBS can control maladaptive eating behaviours and may be a potential therapeutic tool in obesity.
Despite its therapeutic use for more than a decade, the neural mechanism of DBS is still not yet fully understood.
The remedial effect is proposed to involve modulation of the dopamine system – and this seems particularly relevant in the context of Parkinson’s disease and addiction.
DBS potentially has effects on the functional activity of other interconnected brain systems. While it can provide therapeutic relief from symptoms of neurological diseases, it does not treat the underlying pathology.
But it provides both effective and rapid intervention from the effects of debilitating illnesses, restoring activity in deteriorating brain regions and aids understanding of the brain circuits involved in these disorders.
Brain rewires itself after damage or injury
When the brain’s primary “learning center” is damaged, complex new neural circuits arise to compensate for the lost function, say life scientists from UCLA and Australia who have pinpointed the regions of the brain involved in creating those alternate pathways — often far from the damaged site.
The research, conducted by UCLA’s Michael Fanselow and Moriel Zelikowsky in collaboration with Bryce Vissel, a group leader of the neuroscience research program at Sydney’s Garvan Institute of Medical Research, appears this week in the early online edition of the journal Proceedings of the National Academy of Sciences.
The researchers found that parts of the prefrontal cortex take over when the hippocampus, the brain’s key center of learning and memory formation, is disabled. Their breakthrough discovery, the first demonstration of such neural-circuit plasticity, could potentially help scientists develop new treatments for Alzheimer’s disease, stroke and other conditions involving damage to the brain.
For the study, Fanselow and Zelikowsky conducted laboratory experiments with rats showing that the rodents were able to learn new tasks even after damage to the hippocampus. While the rats needed more training than they would have normally, they nonetheless learned from their experiences — a surprising finding.
"I expect that the brain probably has to be trained through experience," said Fanselow, a professor of psychology and member of the UCLA Brain Research Institute, who was the study’s senior author. "In this case, we gave animals a problem to solve."
After discovering the rats could, in fact, learn to solve problems, Zelikowsky, a graduate student in Fanselow’s laboratory, traveled to Australia, where she worked with Vissel to analyze the anatomy of the changes that had taken place in the rats’ brains. Their analysis identified significant functional changes in two specific regions of the prefrontal cortex.
"Interestingly, previous studies had shown that these prefrontal cortex regions also light up in the brains of Alzheimer’s patients, suggesting that similar compensatory circuits develop in people," Vissel said. "While it’s probable that the brains of Alzheimer’s sufferers are already compensating for damage, this discovery has significant potential for extending that compensation and improving the lives of many."
The hippocampus, a seahorse-shaped structure where memories are formed in the brain, plays critical roles in processing, storing and recalling information. The hippocampus is highly susceptible to damage through stroke or lack of oxygen and is critically inolved in Alzheimer’s disease, Fanselow said.
"Until now, we’ve been trying to figure out how to stimulate repair within the hippocampus," he said. "Now we can see other structures stepping in and whole new brain circuits coming into being."
Zelikowsky said she found it interesting that sub-regions in the prefrontal cortex compensated in different ways, with one sub-region — the infralimbic cortex — silencing its activity and another sub-region — the prelimbic cortex — increasing its activity.
"If we’re going to harness this kind of plasticity to help stroke victims or people with Alzheimer’s," she said, "we first have to understand exactly how to differentially enhance and silence function, either behaviorally or pharmacologically. It’s clearly important not to enhance all areas. The brain works by silencing and activating different populations of neurons. To form memories, you have to filter out what’s important and what’s not."
Complex behavior always involves multiple parts of the brain communicating with one another, with one region’s message affecting how another region will respond, Fanselow noted. These molecular changes produce our memories, feelings and actions.
"The brain is heavily interconnected — you can get from any neuron in the brain to any other neuron via about six synaptic connections," he said. "So there are many alternate pathways the brain can use, but it normally doesn’t use them unless it’s forced to. Once we understand how the brain makes these decisions, then we’re in a position to encourage pathways to take over when they need to, especially in the case of brain damage.
"Behavior creates molecular changes in the brain; if we know the molecular changes we want to bring about, then we can try to facilitate those changes to occur through behavior and drug therapy," he added. I think that’s the best alternative we have. Future treatments are not going to be all behavioral or all pharmacological, but a combination of both."
I first met Henry Molaison more than half a century ago, during the spring of my third year in graduate school. I have tried to resurrect the details of my interactions with him that week, but human memory does not allow such excursions. The explicit minutiae of unique episodes fade as time passes, making it impossible for us to vividly re-experience the details of events in the distant past. What I do know is that I was very excited to have the opportunity to study such a rare case as Henry, and I had spent months preparing. Looking back at the results of all the tests he did that week, it was clear even then that the consequences of the operation carried out on him in 1957 – an experimental procedure to cure his epilepsy – had been catastrophic. Henry was left in a permanent state of amnesia, unable to retain any new information.
At the time of Henry’s operation, little was known about how memory processes worked. The extensive damage to the inner part of the temporal lobes on both sides of Henry’s brain made him a vital case study for memory researchers then and now. As the years passed, his fame grew and eventually spread to countries outside North America – and all that time Henry was stuck in the same moment. From time to time, I would tell him how important and well known he was, and he would smile sheepishly, as the praise was already slipping out of his consciousness. In his lifetime he was known as HM; only after his death, in 2008, was his identity revealed to the world.