Scientists encode memories in a way that bypasses damaged brain tissue

Researchers at University of South Carolina (USC) and Wake Forest Baptist Medical Center have developed a brain prosthesis that is designed to help individuals suffering from memory loss.

The prosthesis, which includes a small array of electrodes implanted into the brain, has performed well in laboratory testing in animals and is currently being evaluated in human patients.

Designed originally at USC and tested at Wake Forest Baptist, the device builds on decades of research by Ted Berger and relies on a new algorithm created by Dong Song, both of the USC Viterbi School of Engineering. The development also builds on more than a decade of collaboration with Sam Deadwyler and Robert Hampson of the Department of Physiology & Pharmacology of Wake Forest Baptist who have collected the neural data used to construct the models and algorithms.

When your brain receives the sensory input, it creates a memory in the form of a complex electrical signal that travels through multiple regions of the hippocampus, the memory center of the brain. At each region, the signal is re-encoded until it reaches the final region as a wholly different signal that is sent off for long-term storage.

If there’s damage at any region that prevents this translation, then there is the possibility that long-term memory will not be formed. That’s why an individual with hippocampal damage (for example, due to Alzheimer’s disease) can recall events from a long time ago – things that were already translated into long-term memories before the brain damage occurred – but have difficulty forming new long-term memories.

Song and Berger found a way to accurately mimic how a memory is translated from short-term memory into long-term memory, using data obtained by Deadwyler and Hampson, first from animals, and then from humans. Their prosthesis is designed to bypass a damaged hippocampal section and provide the next region with the correctly translated memory.

That’s despite the fact that there is currently no way of “reading” a memory just by looking at its electrical signal.

“It’s like being able to translate from Spanish to French without being able to understand either language,” Berger said.

Their research was presented at the 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society in Milan on August 27, 2015.

The effectiveness of the model was tested by the USC and Wake Forest Baptist teams. With the permission of patients who had electrodes implanted in their hippocampi to treat chronic seizures, Hampson and Deadwyler read the electrical signals created during memory formation at two regions of the hippocampus, then sent that information to Song and Berger to construct the model. The team then fed those signals into the model and read how the signals generated from the first region of the hippocampus were translated into signals generated by the second region of the hippocampus.

In hundreds of trials conducted with nine patients, the algorithm accurately predicted how the signals would be translated with about 90 percent accuracy.

“Being able to predict neural signals with the USC model suggests that it can be used to design a device to support or replace the function of a damaged part of the brain,” Hampson said.
Next, the team will attempt to send the translated signal back into the brain of a patient with damage at one of the regions in order to try to bypass the damage and enable the formation of an accurate long-term memory.

http://medicalxpress.com/news/2015-09-scientists-bypass-brain-re-encoding-memories.html#nRlv

People with recurrent depression have significantly smaller hippocampus than healthy individuals

The brains of people with recurrent depression have a significantly smaller hippocampus – the part of the brain most associated with forming new memories – than healthy individuals, a new global study of nearly 9,000 people reveals.

Published in Molecular Psychiatry, the ENIGMA study is co-authored by University of Sydney scholars at the Brain and Mind Research Institute.

The research is the largest international study to compare brain volumes in people with and without major depression. It highlights the need to identify and treat depression effectively when it first occurs, particularly among teenagers and young adults.

Using magnetic resonance imaged (MRI) brain scans, and clinical data from 1,728 people with major depression and 7,199 healthy individuals, the study combined 15 datasets from Europe, the USA and Australia.

Major depression is a common condition affecting at least one in six people during their lifetime. It is a serious clinical mood disorder in which feelings of sadness, frustration, loss, or anger interfere with a person’s everyday life for weeks, months or years at a time.

The key finding that people with major depression have a smaller hippocampus confirms earlier clinical work conducted at the BMRI. In this study, the key finding was largely explained by subjects with recurrent depression.

People with recurrent depression represented 65 per cent of study subjects with major depression.

People with an early age of onset of major depression (before the age of 21 years) also had a smaller hippocampus than healthy individuals, consistent with the notion that many of these young people go on to have recurrent disorders.

However, people who had a first episode of major depression (34 per cent of study subjects with major depression) did not have a small hippocampus than healthy individuals, indicating that the changes are due to the adverse effects of depressive illness on the brain.

“These findings shed new light on brain structures and possible mechanisms responsible for depression,” says Associate Professor Jim Lagopoulos of the University of Sydney’s Brain and Mind Research Institute.

“Despite intensive research aimed at identifying brain structures linked to depression in recent decades, our understanding of what causes depression is still rudimentary.

“One reason for this has been the lack of sufficiently large studies, variability in the disease and treatments provided, and the complex interactions between clinical characteristics and brain structure.”

Commenting on the clinical significance of the findings, Co-Director of the Brain and Mind Research Institute, Professor Ian Hickie says: “This large study confirms the need to treat first episodes of depression effectively, particularly in teenagers and young adults, to prevent the brain changes that accompany recurrent depression.

“This is another reason that we need to ensure that young people receive effective treatments for depression – a key goal of our Centre of Research Excellence in Optimising Early Interventions for Young People with Emerging Mood Disorder.

“This new finding of smaller hippocampal volume in people with major depression may offer some support to the neurotrophic hypothesis of depression,” adds Jim Lagopoulos.

“This hypothesis argues that a range of neurobiological processes such as elevated glucocorticoid levels in those with chronic depression may induce brain shrinkage.

“Clearly, there’s a need for longitudinal studies that can track changes in hippocampal volume among people with depression over time, to better clarify whether hippocampal abnormalities result from prolonged duration of chronic stress, or represent a vulnerability factor for depression, or both,” he said.
http://www.news-medical.net/news/20150630/People-with-recurrent-depression-have-significantly-smaller-hippocampus-than-healthy-individuals.aspx

New research shows that people with ‘O’ blood type have decreased risk of cognitive decline

A pioneering study conducted by leading researchers at the University of Sheffield has revealed blood types play a role in the development of the nervous system and may impact the risk of developing cognitive decline.

The research, carried out in collaboration with the IRCCS San Camillo Hospital Foundation in Venice, shows that people with an ‘O’ blood type have more grey matter in their brain, which helps to protect against diseases such as Alzheimer’s, than those with ‘A’, ‘B’ or ‘AB’ blood types.

Research fellow Matteo De Marco and Professor Annalena Venneri, from the University’s Department of Neuroscience, made the discovery after analysing the results of 189 Magnetic Resonance Imaging (MRI) scans from healthy volunteers.

The researchers calculated the volumes of grey matter within the brain and explored the differences between different blood types.

The results, published in the Brain Research Bulletin, show that individuals with an ‘O’ blood type have more grey matter in the posterior proportion of the cerebellum.

In comparison, those with ‘A’, ‘B’ or ‘AB’ blood types had smaller grey matter volumes in temporal and limbic regions of the brain, including the left hippocampus, which is one of the earliest part of the brain damaged by Alzheimer’s disease.

These findings indicate that smaller volumes of grey matter are associated with non-‘O’ blood types.

As we age a reduction of grey matter volumes is normally seen in the brain, but later in life this grey matter difference between blood types will intensify as a consequence of ageing.

“The findings seem to indicate that people who have an ‘O’ blood type are more protected against the diseases in which volumetric reduction is seen in temporal and mediotemporal regions of the brain like with Alzheimer’s disease for instance,” said Matteo DeMarco.

“However additional tests and further research are required as other biological mechanisms might be involved.”

Professor Annalena Venneri added: “What we know today is that a significant difference in volumes exists, and our findings confirm established clinical observations. In all likelihood the biology of blood types influences the development of the nervous system. We now have to understand how and why this occurs.”

More information: “‘O’ blood type is associated with larger grey-matter volumes in the cerebellum,” Brain Research Bulletin, Volume 116, July 2015, Pages 1-6, ISSN 0361-9230, dx.doi.org/10.1016/j.brainresbull.2015.05.005

Scientists Have Figured Out How to Recover Forgotten Memories Still Lurking in the Brain

memory

All might not be lost. Researchers recently announced a discovery that could have significant implications later down the road for helping people with severe amnesia or Alzheimer’s disease.

The research tackles a highly debated topic of whether memory loss due to damaged brain cells means that memories cannot be stored anymore or if just accessing that memory is inhibited in some way.

Scientists from MIT found in new research that the latter is most likely the case, demonstrating how lost memories could be recovered using technology known as optogenetics, which a news release about the study described as when “proteins are added to neurons to allow them to be activated with light.”

“The majority of researchers have favored the storage theory, but we have shown in this paper that this majority theory is probably wrong,” Susumu Tonegawa, a professor in MIT’s biology department and director of the RIKEN-MIT Center at the Picower Institute for Learning and Memory, said in a statement. “Amnesia is a problem of retrieval impairment.”

First, the scientists demonstrated how “memory engram cells” — brain cells that trigger a memory upon experiencing a related sight or smell, for example — could be strengthened in mice.

The researchers then gave the mice anisomycin, which blocked protein synthesis in neurons, after they had formed a new memory. In doing so, the researchers prevented the engram cells from strengthening.

A day later, the scientists tried to trigger the memory in mice, but couldn’t see any activation that would indicate the mice were remembering it.

“So even though the engram cells are there, without protein synthesis those cell synapses are not strengthened, and the memory is lost,” Tonegawa explained of this part of the research.

The team first developed a clever technique to selectively label the neurons representing what is known as a memory engram – in other words, the brain cells involved in forming a specific memory. They did this by genetically engineering mice so they had extra genes in all their neurons. As a result, when neurons fire as a memory is formed, they produce red proteins visible under a microscope, allowing the researchers to tell which cells were part of the engram. They also inserted a gene that made the neurons fire when illuminated by blue light.

After the researchers induced amnesia, they used optogenetic tools on the mice and witnessed the animals experiencing full recollection.

“If you test memory recall with natural recall triggers in an anisomycin-treated animal, it will be amnesiac, you cannot induce memory recall. But if you go directly to the putative engram-bearing cells and activate them with light, you can restore the memory,” Tonegawa said.

With this discovery, the researchers wrote in the study published this week in the journal Science that they believe a “specific pattern of connectivity of engram cells may be crucial for memory information storage and that strengthened synapses in these cells critically contribute to the memory retrieval process.”

James Bisby, a neuroscientist at University College London, told New Scientist that it’s “not surprising that they could trigger the memories, but it is a cool way to do it.”

http://www.newscientist.com/article/dn27618-lost-memories-recovered-in-mice-with-a-flash-of-light.html

Thanks to Steven Weihing for bringing this to the It’s Interesting community.

Scientists achieve implantation of memory into the brains of mice while they sleep

Sleeping minds: prepare to be hacked. For the first time, conscious memories have been implanted into the minds of mice while they sleep. The same technique could one day be used to alter memories in people who have undergone traumatic events.

When we sleep, our brain replays the day’s activities. The pattern of brain activity exhibited by mice when they explore a new area during the day, for example, will reappear, speeded up, while the animal sleeps. This is thought to be the brain practising an activity – an essential part of learning. People who miss out on sleep do not learn as well as those who get a good night’s rest, and when the replay process is disrupted in mice, so too is their ability to remember what they learned the previous day.

Karim Benchenane and his colleagues at the Industrial Physics and Chemistry Higher Educational Institution in Paris, France, hijacked this process to create new memories in sleeping mice. The team targeted the rodents’ place cells – neurons that fire in response to being in or thinking about a specific place. These cells are thought to help us form internal maps, and their discoverers won a Nobel prize last year.

Benchenane’s team used electrodes to monitor the activity of mice’s place cells as the animals explored an enclosed arena, and in each mouse they identified a cell that fired only in a certain arena location. Later, when the mice were sleeping, the researchers monitored the animals’ brain activity as they replayed the day’s experiences. A computer recognised when the specific place cell fired; each time it did, a separate electrode would stimulate brain areas associated with reward.

When the mice awoke, they made a beeline for the location represented by the place cell that had been linked to a rewarding feeling in their sleep. A brand new memory – linking a place with reward – had been formed.

It is the first time a conscious memory has been created in animals during sleep. In recent years, researchers have been able to form subconscious associations in sleeping minds – smokers keen to quit can learn to associate cigarettes with the smells of rotten eggs and fish in their sleep, for example.

Previous work suggested that if this kind of subconscious learning had occurred in Benchenane’s mice, they would have explored the arena in a random manner, perhaps stopping at the reward-associated location. But these mice headed straight for the location, suggesting a conscious memory. “The mouse develops a goal-directed behaviour to go towards the place,” says Benchenane. “It proves that it’s not an automatic behaviour. What we create is an association between a particular place and a reward that can be consciously accessed by the mouse.”

“The mouse is remembering enough abstract information to think ‘I want to go to a certain place’, and go there when it wakes up,” says neuroscientist Neil Burgess at University College London. “It’s a bigger breakthrough [than previous studies] because it really does show what the man in the street would call a memory – the ability to bring to mind abstract knowledge which can guide behaviour in a directed way.”

Benchenane doesn’t think the technique can be used to implant many other types of memories, such as skills – at least for the time being. Spatial memories are easier to modify because they are among the best understood.

His team’s findings also provide some of the strongest evidence for the way in which place cells work. It is almost impossible to test whether place cells function as an internal map while animals are awake, says Benchenane, because these animals also use external cues, such as landmarks, to navigate. By specifically targeting place cells while the mouse is asleep, the team were able to directly test theories that specific cells represent specific places.

“Even when those place cells fire in sleep, they still convey spatial information,” says Benchenane. “That provides evidence that when you’ve got activation of place cells during the consolidation of memories in sleep, you’ve got consolidation of the spatial information.”

Benchenane hopes that his technique could be developed to help alter people’s memories, perhaps of traumatic events (see “Now it’s our turn”, below).

Loren Frank at the University of California, San Francisco, agrees. “I think this is a really important step towards helping people with memory impairments or depression,” he says. “It is surprising to me how many neurological and psychiatric illnesses have something to do with memory, including schizophrenia and obsessive compulsive disorder.”

“In principle, you could selectively change brain processing during sleep to soften memories or change their emotional content,” he adds.

Journal reference: Nature Neuroscience, doi:10.1038/nn.3970

http://www.newscientist.com/article/dn27115-new-memories-implanted-in-mice-while-they-sleep.html#.VP_L9uOVquD

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

New research suggests that memories may not be stored by synaptic connections between nerve cells

New research suggests that memories may not be stored by synaptic connections between neurons in the brain, but rather synapses may allow the expression of memories that are stored elsewhere in the neuron.

The revolutionary study by academics at the University of California has suggested for the first time that memories are not stored in synapses as previously thought. It is synapses, the connections between brain cells, that are destroyed by Alzheimer’s.

The breakthrough, reported in the highly regarded online journal eLife, could mean that it becomes possible to restore lost memories.

“Long-term memory is not stored at the synapse,” said David Glanzman, the study’s co-author and professor of integrative biology and physiology and of neurobiology at UCLA. “That’s a radical idea, but that’s where the evidence leads. The nervous system appears to be able to regenerate lost synaptic connections. If you can restore the synaptic connections, the memory will come back. It won’t be easy, but I believe it’s possible.”

Professor Glanzman’s team studied the marine snail Aplysia to understand the animal’s learning and memory functions. Glanzman was particularly interested in the Aplysia’s defensive reactions and the sensory and motor neurons responsible for its withdrawal response.

“If you train an animal on a task, inhibit its ability to produce proteins immediately after training, and then test it 24 hours later, the animal doesn’t remember the training,” said Prof. Glanzman. “However, if you train an animal, wait 24 hours, and then inject a protein synthesis inhibitor in its brain, the animal shows perfectly good memory 24 hours later. In other words, once memories are formed, if you temporarily disrupt protein synthesis, it doesn’t affect long-term memory. That’s true in the Aplysia and in human’s brains.”

As part of the test, the snails were given a number of electric shocks, which in themselves would not usually produce long-term memories. The team found that the memories they thought had been completely erased earlier in the experiment had returned, suggesting that synaptic connections that had previously been lost were apparently restored.

“That suggests that the memory is not in the synapses but somewhere else,” said Glanzman. “We think it’s in the nucleus of the neurons. We haven’t proved that, though.”

He added that the research could be a major breakthrough for Alzheimer’s sufferers as even though the disease destroys synapses in the brain, memories might not necessarily destroyed.

“As long as the neurons are still alive, the memory will still be there, which means you may be able to recover some of the lost memories in the early stages of Alzheimer’s,” said Prof Glanzman.

http://www.telegraph.co.uk/news/science/11307411/Cure-for-memory-loss-could-be-on-the-horizon.html

New research may help explain why curiosity promotes better memory

Everyone knows it’s easier to learn about a topic you’re curious about. Now, a new study reveals what’s going on in the brain during that process, revealing that such curiosity may give a person a memory boost.

When participants in the study were feeling curious, they were better at remembering information even about unrelated topics, and brain scans showed activity in areas linked to reward and memory.

The results, detailed October 2 in the journal Neuron, hint at ways to improve learning and memory in both healthy people and those with neurological disorders, the researchers said.

“Curiosity may put the brain in a state that allows it to learn and retain any kind of information, like a vortex that sucks in what you are motivated to learn, and also everything around it,” Matthias Gruber, a memory researcher at the University of California, Davis, said in a statement. “These findings suggest ways to enhance learning in the classroom and other settings.”

Gruber and his colleagues put people in a magnetic resonance imaging (MRI) scanner and showed them a series of trivia questions, asking them to rate their curiosity about the answers to those questions. Later, the participants were shown selected trivia questions, then a picture of a neutral face during a 14-second delay, followed by the answer. Afterward, the participants were given a surprise memory test of the faces, and then a memory test of the trivia answers.

Not surprisingly, the study researchers found that people remembered more information about the trivia when they were curious about the trivia answers. But unexpectedly, when the participants were curious, they were also better at remembering the faces, an entirely unrelated task. Participants who were curious were also more likley than others to remember both the trivia information and unrelated faces a day later, the researchers found.

The brain scans showed that, compared with when their curiosity wasn’t piqued, when people were curious, they showed more activation of brain circuits in the nucleus accumbens, an area involved in reward. These same circuits, mediated by the neurochemical messenger dopamine, are involved in forms of external motivation, such as food, sex or drug addiction.

Finally, being curious while learning seemed to produce a spike of activity in the hippocampus, an area involved in forming new memories, and strengthened the link between memory and reward brain circuits.

The study’s findings not only highlight the importance of curiosity for learning in healthy people, but could also give insight into neurological conditions. For example, as people age, their dopamine circuits tend to deteriorate, so understanding how curiosity affects these circuits could help scientists develop treatments for patients with memory disorders, the researchers said.

http://www.livescience.com/48121-curiosity-boosts-memory-learning.html