Posts Tagged ‘memory’


S. Inami et al., “Environmental light is required for maintenance of long-term memory in Drosophila,” J Neurosci, 40:1427–39, 2020.

by Diana Kwon

As Earth rotates around its axis, the organisms that inhabit its surface are exposed to daily cycles of darkness and light. In animals, light has a powerful influence on sleep, hormone release, and metabolism. Work by Takaomi Sakai, a neuroscientist at Tokyo Metropolitan University, and his team suggests that light may also be crucial for forming and maintaining long-term memories.

The puzzle of how memories persist in the brain has long been of interest to Sakai. Researchers had previously demonstrated, in both rodents and flies, that the production of new proteins is necessary for maintaining long-term memories, but Sakai wondered how this process persisted over several days given cells’ molecular turnover. Maybe, he thought, an environmental stimulus, such as the light-dark cycles, periodically triggered protein production to enable memory formation and storage.

Sakai and his colleagues conducted a series of experiments to see how constant darkness would affect the ability of Drosophila melanogaster to form long-term memories. Male flies exposed to light after interacting with an unreceptive female showed reduced courtship behaviors toward new female mates several days later, indicating they had remembered the initial rejection. Flies kept in constant darkness, however, continued their attempts to copulate.

The team then probed the molecular mechanisms of these behaviors and discovered a pathway by which light activates cAMP response element-binding protein (CREB)—a transcription factor previously identified as important for forming long-term memories—within certain neurons found in the mushroom bodies, the memory center in fly brains.

“The fact that light is essential for long-term memory maintenance is fundamentally interesting,” says Seth Tomchick, a neuroscientist at the Scripps Research Institute in Florida who wasn’t involved in the study. However, he adds, “more work will be necessary” to fully characterize the molecular mechanisms underlying these effects.

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by Amy Schleunes

When Lilian Kloft stumbled across a 2015 study showing a connection between cannabis use and susceptibility to false memories, she found herself wondering about the legal implications of the results. The study had discovered that heavy users of cannabis were more likely than controls to form false memories—recollections of events that never occurred, for example, or warped memories of events that did—even when they were not at the moment “high.”

This kind of false remembering can pose difficulties for people gathering reliable testimony in the event of a crime, says Kloft, a PhD student in psychopharmacology and forensic psychology at Maastricht University in the Netherlands. Consequently, the growing acceptance of cannabis worldwide raises questions not only about how the drug affects memory, but also about how law enforcement officials should conduct interviews with suspects, victims, and witnesses who may be under the influence or regular users of the drug.

In order to further investigate the connection between cannabis and false memory formation, Kloft and collaborators recruited 64 volunteers for a series of experiments. Participants, who were occasional cannabis users, were given a vaporizer containing either cannabis or a hemp placebo and then told to inhale deeply and hold their breath for 10 seconds. After that, the researchers tested them in three different tasks designed to induce false memories.

In the first task, the team asked the volunteers to memorize lists of words, and then to pick out those words from test lists that also included dummy words. As expected, both the sober and the intoxicated participants falsely remembered some of the dummy words. But while the sober participants mostly falsely remembered words that were strongly associated with words on the original lists, the intoxicated participants also selected less-related and completely unrelated terms.

In the next two tasks, the researchers wanted to see if they could induce false memories by providing misinformation to the participants. Hoping to imbue these tests with more real-world relevance than a list of words, Kloft and colleagues designed two immersive virtual reality scenarios involving common crimes. In the first, the “eyewitness scenario,” participants observed a fight on a train platform, after which a virtual co-witness recounted the incident but with several errors, including falsely recalling a police dog that wasn’t part of the altercation. In the “perpetrator scenario,” participants entered a crowded bar and were instructed to commit a crime themselves—to steal a purse.

The researchers observed a range of effects associated with cannabis as the intoxicated subjects interacted in these virtual environments. Some participants laughed and talked to the virtual characters in the scenarios, Kloft reports, while others became paranoid and required assistance in stealing the purse. “One person even ran away so quickly that they ripped out the whole VR setup and it fell to the ground,” she says. When researchers interviewed the participants afterward using a combination of leading and non-leading questions, those who were intoxicated showed higher rates of false memory for both the eyewitness and perpetrator scenarios compared with controls.

To look for longer-term effects of cannabis, the experimenters called the subjects back a week later and tested them again on the word lists, this time with a few different dummy words thrown in. They also re-interviewed the subjects about the VR scenarios using a combination of old and new questions. As before, they found lower memory accuracy in the word-association test in those who had been intoxicated compared with sober participants. There were no statistically significant differences between the groups for the virtual reality scenarios, a result that Kloft says may indicate memory decay over time in all participants.

Cognitive neuropsychopharmacologist Manoj Doss, a postdoc at Johns Hopkins University who was not involved in the study, has used word association and other tasks in his own research to demonstrate that tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, increases false memories when participants attempt to retrieve information they’d previously learned. Doss says that the study by Kloft and collaborators is novel not only because it employs virtual reality, but because it shows that both the real-world scenarios and the word association task can induce false memories.

For the tests administered after one week, however, Doss notes that it’s difficult to determine if the researchers were observing actual false memories, because participants might remember both the accurate and the dummy information they encountered in the original experiment. In the follow-up test, “people might say yes to the things they’re not supposed to just because they saw them in that first test,” says Doss. He suggests that increasing the number of items tested, as well as separately analyzing the new and previously used word tests and interview questions, could reveal a higher incidence of false memories in the delayed test for the participants who took cannabis.

Giovanni Marsicano, a neuroscientist at the University of Bordeaux in France who did not participate in the research, says that the new results match up with findings he’s made in mice: animals that receive injections of THC are more likely than controls to associate unrelated stimuli—itself a sort of false memory. His work has also shown that a cannabinoid receptor known as CB1 that is highly abundant in the hippocampus and prefrontal cortex probably plays a key role in the formation of these incidental associations. One of this receptor’s main jobs is to decrease the release of neurotransmitters. Marsicano hypothesizes that when the CB1 receptor is activated, neural signaling is inhibited in such a way that the brain is less able to separate correct from incorrect information.

Roger Pertwee, a pharmacologist at the University of Aberdeen in the UK who was not involved in the research, says that the Dutch team’s results aren’t surprising given what’s known about how cannabinoids affect memory. Unlike endogenous cannabinoids, which tend to selectively activate some CB1 receptors and not others, compounds in cannabis activate all CB1 receptors at once; this indiscriminate activation may also somehow contribute to the formation of false memories, explains Pertwee, who works with GW Pharmaceuticals, a company that makes prescription medicines derived from cannabis.

In the future, Kloft says she’s interested in looking at how people regard the memories they form when high in order to find out whether they “trust” those memories. “Are they confident in them, and is there any strategy they pursue to correct for their probably impaired memory?”

Study coauthor Elizabeth Loftus, a cognitive psychologist and human memory expert at the University of California, Irvine, says that the team’s study should prompt people to think about best practices when it comes to intoxicated witnesses. “The law recognizes that there are vulnerable witnesses who need extra special care and attention when you’re interviewing them: young children, people with mental disabilities, sometimes the elderly are included in that category,” Loftus says. “Might not [people who are high] be another example of . . . vulnerable witnesses where you’ve got to be extra careful?”

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The 60 souls that signed on for Dr. Alain Brunet’s memory manipulation study were united by something they would rather not remember. The trauma of betrayal.

For some, it was infidelity and for others, a brutal, unanticipated abandonment. “It was like, ‘I’m leaving you. Goodbye,” the McGill University associate professor of psychiatry says.

In cold, clinical terms, his patients were suffering from an “adjustment disorder” due to the termination (not of their choosing) of a romantic relationship. The goal of Brunet and other researchers is to help people like this — the scorned, the betrayed, the traumatized — lose their total recall. To deliberately forget.

Over four to six sessions, volunteers read aloud from a typed script they had composed themselves — a first-person account of their breakup, with as many emotional details as possible — while under the influence of propranolol, a common and inexpensive blood pressure pill. The idea was to purposely reactivate the memory and bring the experience and the stinging emotions it aroused to life again. “How did you feel about that?” they were asked. How do you feel right now? And, most importantly: Has your memory changed since last week?

The investigators had hypothesized that four to six sessions of memory reactivation under propranolol would be sufficient to dramatically blunt the memories associated with their “attachment injury.” Decrease the strength of the memory, Brunet says, and you decrease the strength of the pain.

The study is now complete, and Brunet is hesitant to discuss the results, which have been submitted to a journal for peer review and publication. However, the participants “just couldn’t believe that we could do so much in such a small amount of time,” he confides.

“They were able to turn the page. That’s what they would tell us — ‘I feel like I’ve turned the page. I’m no longer obsessed by this person, or this relationship.’”

Brunet insists he isn’t interested in deleting or scrubbing painful memories out entirely. The idea of memory erasure, of finding the cellular imprint of a specific, discreet memory in the brain, of isolating and inactivating the brain cells behind that memory, unnerves him. ‘It’s not going to come from my lab,” he says, although others are certainly working on it. Memories are part of who we are, what forms our identity, what makes us authentic, “and as long as only one choice exists right now, and it’s toning down a memory, we feel on very solid and comfortable ground,” ethically speaking, Brunet says.

“However, if one day you had two options — I can tone down your memory, or I can remove it altogether, from your head, from your mind — what would you choose?”

The choice might soon be yours.

“If you could erase the memory of the worst day of your life, would you,” Elizabeth Phelps and Stefan Hofmann write in the journal, Nature. “How about your memory of a person who has caused you pain?”

What was once purely science fiction is moving ever closer to clinical reality. Researchers are working on techniques and drugs that might enable us to edit our memories or at least seriously dull their impact — to make the intolerable bearable — by, say, swallowing a pill to block the synaptic changes needed for a memory to solidify. A pill that could be taken hours, even months or years after the event.

Much of the work is based on the theory of memory reconsolidation – the belief that the mere conscious act of recalling or conjuring a memory makes it vulnerable to tinkering or meddling. When a memory is evoked, a reconsolidation window opens for a brief period of time (two to five hours, according to Brunet), during which time the memory returns to a state of “lability.” It becomes pliable, like Play-Doh. It also becomes susceptible to modification, before “reconsolidating” or re-storage. The thought is that propranolol interferes with proteins in the brain needed to lock down the memory again.

A similar line of thinking holds that a memory isn’t an exact impression of the original event, an Iphone video of the past, says Boston University neuroscientist Steve Ramirez. Rather it’s more like Plato’s wax tablet. Press a signet ring into the wax and it leaves an imprint, but the wax can melt when we recall the memory, form again and then melt all over again. “Memory is dynamic,” Ramirez says. It isn’t static. Memories can also be updated with new information when they’re recalled, like hitting “save as” every time you go into a Word file.

But the idea that memories can be edited, softened or dialled down, is more than a little discomfiting to some, and not just for what it means for eyewitness testimony. “We’re not reliable narrators when it comes to some details, and sometimes even entire scenarios,” Ramirez says. More profoundly, without good and bad memories it’s hard to imagine how we would know how to behave, says Dr. Judy Illes, professor of neurology and Canada Research Chair in neuroethics at the University of British Columbia.

Learning doesn’t occur without memory. How do we learn from a bad relationship, if we can’t remember it? “And so now, if we pre-select what memories stick and don’t stick, it almost starts to be like the eugenics of memory,” Illes says. “We ought to think carefully about that.”

She has absolutely no qualms about using memory manipulation for people suffering desperately from post-traumatic stress disorder, people whose burden of suffering from horrifying experiences exceeds any moral argument against using it.

“To me, a PTSD that is profound and debilitating is like a disease of any other and, to the extent that we can have an intervention that treats it, we should vigorously pursue it.”

Even the heartbroken recruited for Brunet’s study were experiencing symptoms congruent with PTSD. We’re geared to form attachments, he says, and not so much to detach.

But memory manipulation has a slippery slope. Would it bleed into not-so-disabling disorders? If someone misbehaves at a cocktail party and would really sooner forget what happened, is that an appropriate use? Isn’t it good to be embarrassed by your past behaviour, to keep you from doing it again? What about war fighters, asks Illes. “If we had a drug that can mitigate a bad memory, could we possibly use it in advance of an act to actually prevent a memory from forming, and therefore enable people to fight less fearfully, and more fiercely, because there’s no consolidation of the acts of crime, or acts of war?”

The pull of moral responsibility — “one’s future ‘oughtness’” — is grounded in our life story, writes bioethicist Dr. Peter DePergola in the Journal of Cognition and Neuroethics. Using blood pressure pills or some other intervention like, say, transcranial direct current stimulation, to deaden or blast away memories of trauma “ultimately undermines one’s ability to seek, identify and act on the good,” DePergola argues.

And how do you manipulate a bad memory, without risking happy, shiny, positive ones? What does a memory even look like in the brain? Can we visualize it? Can we see what happens when positive and negative memories form? And where would all the bad memories go? Saved in glass bottles in the Ministry of Magic?

We can’t go into the brain and erase memories in an Eternal-Sunshine-of-the-Spotless-Mind kind of way, Ramirez says, at least not yet. We can’t touch or poke a memory. However, scientists are starting to get unprecedented glimpses into the physical structure of memory in the brain. The goal is to identify the brain cells a particular memory gloms onto, and artificially manipulate those cells.

The challenge is that human memories aren’t localized to one specific location in the brain. There’s no spot X you can point to, and say, Aha! There it is. Rather, they’re scattered throughout the organ. The sights and sounds and smells and emotions of a memory are going to recruit different corners of the brain that are involved in processing the sights and sounds and smells and emotions, Ramirez says.

“Right now, there are a lot of memories that are asleep in your brain. If I asked you, ‘what did you do last night?’, that memory just woke up. How did that happen? You just did that effortlessly in, like, 500 milliseconds. And yet we don’t know how that process works.”

However, we know that it does happen, and scientists have some pretty good indications of what happens physiologically when we recall a memory, and what it means for that memory to become awake again.

American-Canadian neurosurgeon Wilder Penfield was one of the first to hint at where to look. When Penfield stimulated cells in the hippocampus of people who were undergoing surgery for epilepsy in the 1940s with mild jolts of electricity, specific episodic memories — memories of actual experiences — suddenly popped into their minds. “It was like, ‘I have no idea why, but I’m randomly remembering my 16th birthday and I was walking my cat,’’” Ramirez said on a National Geographic podcast earlier this year.

In experiments that helped open the floodgates, Ramirez and other scientists at MIT reported that they could identify — in mice — the cells that make up part of an engram, the coding for a specific memory, and reactive those same cells using a technology called optogenetics.

Briefly, here’s what they did: Viruses were inserted into the brain cells of genetically modified mice that made the cells glow green in response to light. Next, the researchers isolated cells in the hippocampus of a mouse as the rodents were forming a specific memory — in this case, the memory of receiving a mild electric foot shock while exploring a box.

A day later, the mouse was placed in a different box — different smells, different floor, meaning there should be no reason for them to be fearful. But when those memory cells were activated with a laser, the mouse froze in fear.

More recently, in a paper published earlier this year, Ramirez and co-author Briana Chen mapped out which cells in the hippocampus were being activated when male mice made new memories of positive (meeting a female mouse) and negative (those mild electric foot zaps again) experiences. They were able to trigger the memories again later, using laser light to activate the memory cells. When memory cells in the bottom part of the hippocampus were stimulated, it seemed to dial up the negative memories. But stimulating memory cells in the top part of the hippocampus seemed to dial them down.

The goal, says Ramirez, is to artificially activate positive memories to overwrite the bad ones — in a sense, using the brain as a drug. “In depression, there is a bias toward negative thinking,” Ramirez says. We’ve been using drugs like Xanax and Prozac for decades, but we haven’t really advanced all that much since the 1970s, Ramirez says. “Maybe we need to tackle these kinds of disorders from all angles.”

Ten years ago, Sheena Josselyn’s lab was the first to offer fairly convincing evidence that we can erase a specific fear memory in mice, without erasing every one of the rodent’s fears. The University of Toronto neuroscientist used a toxin to destroy a handful of neurons housing the memory “It wasn’t like a huge legion. If you take out the entire brain, the mouse doesn’t remember a darn thing.”

That’s obviously not technically, or ethically ideal in humans. No one is talking about ablating neurons in people, or injecting viruses into human brain cells to make them glow green. “But it does tell us that in order to manipulate a memory in people we don’t have to give an entire, systemic thing,” Josselyn says. Rather, we could go in and just hit the target neurons using some kind of smart bomb.

Mice aren’t humans, and efforts to translate the results from animal experiments to healthy humans have been mixed, Phelps and Hoffman note in their Nature article. Still, whether it’s beta-blockers like propranolol, or ecstasy or ketamine or other drugs being tested that might block the synthesis of proteins required to lock down a memory after it’s been retrieved, Ramirez and others believe we could tackle the emotional “oomph,” the psychological sting, of a traumatic memory, while leaving the autobiographic experience — the actual, conscious recollection of the event — intact. No, you may not be able to erase the memory of the “venomous, evil snake that is my ex,” as one Redditor asked Ramirez. There isn’t a memory anti-venom. With memory manipulation, people would still remember the breakup, and the person, but the toxic, gut-twisting emotions associated with it would melt, like ice cream in the sun. And, just as doctors shouldn’t hand out anti-depressants to the entire population of Boston, Ramirez says memory manipulation should be reserved for those suffering crippling anxiety, depression or other symptoms.

Betrayal and abandonment themselves are “no small stuff,” adds Brunet. “This is the material Greek tragedies are made of.” People can become hyper vigilant, he says. They have intrusive thoughts. Everything around them reminds them of the former relationship. “It affects negatively your world views, your self esteem and the trust you can place in other people,” Brunet says.

However, a memory buster is challenging, Illes, of UBC says, because it interferes with our experience as humans.

Our brains are hardwired to remember emotionally charged events. “Do you remember where you were on 9/11? Do you remember five supermarkets ago?” Illes asks.

Our memories are so closely interrelated and interconnected, she adds, that you can’t just pull one brick out without the integrity of the entire wall being affected.

“Go back to your dating question,” Illes says as a thought experiment. “We have a bad relationship. Unless two people are on an isolated island and don’t interact with other humans, your bad relationship has other people in there. And, so, how do you remove all the memories associated with all the complexities that we have on a daily basis?”

Memories give us a sense of consciousness, she says, of who we are and what we know to be right and wrong and moral and immoral.

A prescient 2003 report from the U.S. President’s Council on Bioethics asked whether the then-emerging field of memory-alteration would mean abandoning our own truthful identities.

“Armed with new powers to ease the suffering of bad memories, we might come to see all psychic pain as unnecessary and in the process come to pursue a happiness that is less than human,” the authors wrote, “an unmindful happiness, unchanged by time and events, unmoved by life’s vicissitudes.”

Steve Ramirez was running in the Boston marathon in 2013 when two crude pressure cooker bombs detonated 12 seconds apart near the finish line, killing three and injuring several hundred more. The sights, the sounds, the smells — “they helped carve a very deep corner into my personality,” he says.

“It exposed a darker aspect of humanity, but I wouldn’t really find any personal gain in not knowing that corner, either.”

If you could erase the worst memory of your life, would you? Scientists are working on a pill for that

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

by ABBY OLENA

Animals learn by imitating behaviors, such as when a baby mimics her mother’s speaking voice or a young male zebra finch copies the mating song of an older male tutor, often his father. In a study published today in Science, researchers identified the neural circuit that a finch uses to learn the duration of the syllables of a song and then manipulated this pathway with optogenetics to create a false memory that juvenile birds used to develop their courtship song.

“In order to learn from observation, you have to create a memory of someone doing something right and then use this sensory information to guide your motor system to learn to perform the behavior. We really don’t know where and how these memories are formed,” says Dina Lipkind, a biologist at York College who did not participate in the study. The authors “addressed the first step of the process, which is how you form the memory that will later guide [you] towards performing this behavior.”

“Our original goals were actually much more modest,” says Todd Roberts, a neuroscientist at UT Southwestern Medical Center. Initially, Wenchan Zhao, a graduate student in his lab, set out to test whether or not disrupting neural activity while a young finch interacted with a tutor could block the bird’s ability to form a memory of the interchange. She used light to manipulate cells genetically engineered to be sensitive to illumination in a brain circuit previously implicated in song learning in juvenile birds.

Zhao turned the cells on by shining a light into the birds’ brains while they spent time with their tutors and, as a control experiment, when the birds were alone. Then she noticed that the songs that the so-called control birds developed were unusual—different from the songs of birds that had never met a tutor but also unlike the songs of those that interacted with an older bird.

Once Zhao and her colleagues picked up on the unusual songs, they decided to “test whether or not the activity in this circuit would be sufficient to implant memories,” says Roberts.

The researchers stimulated birds’ neural circuits with sessions of 50- or 300-millisecond optogenetic pulses over five days during the time at which they would typically be interacting with a tutor but without an adult male bird present. When these finches grew up, they sang adult courtship songs that corresponded to the duration of light they’d received. Those that got the short pulses sang songs with sounds that lasted about 50 milliseconds, while the ones that received the extended pulses held their notes longer. Some song features—including pitch and how noisy harmonic syllables were in the song—didn’t seem to be affected by optogenetic manipulation. Another measure, entropy, which approximates the amount of information carried in the communication, was not distinguishable in the songs of normally tutored birds and those that received 50-millisecond optogenetic pulses, but was higher in the songs of birds who’d received tutoring than in the songs of either isolated birds or those that received the 300-millisecond light pulses.

While the manipulation of the circuit affected the duration of the sounds in the finches’ songs, other elements of singing behavior—including the timeline of vocal development, how frequently the birds practiced, and in what social contexts they eventually used the songs—were similar to juveniles who’d learned from an adult bird.

The researchers then determined that when the birds received light stimulation at the same time as they interacted with a singing tutor, their adult songs were more like those of birds that had only received light stimulation, indicating that optogenetic stimulation can supplant tutoring.

When the team lesioned the circuit before young birds met their tutors, they didn’t make attempts to imitate the adult courtship songs. But if the juveniles were given a chance to interact with a tutor before the circuit was damaged, they had no problem learning the song. This finding points to an essential role for the pathway in forming the initial memory of the timing of vocalizations, but not in storing it long-term so that it can be referenced to guide song formation.

“What we were able to implant was information about the duration of syllables that the birds want to attempt to learn how to sing,” Roberts tells The Scientist. But there are many more characteristics birds have to attend to when they’re learning a song, including pitch and how to put the syllables in the correct order, he says. The next steps are to identify the circuits that are carrying other types of information and to investigate the mechanisms for encoding these memories and where in the brain they’re stored.

Sarah London, a neuroscientist at the University of Chicago who did not participate in the study, agrees that the strategies used here could serve as a template to tease apart where other characteristics of learned song come from. But more generally, this work in songbirds connects to the bigger picture of our understanding of learning and memory, she says.

Song learning “is a complicated behavior that requires multiple brain areas coordinating their functions over long stretches of development. The brain is changing anyway, and then on top of that the behavior’s changing in the brain,” she explains. Studying the development of songs in zebra finches can give insight into “how maturing neural circuits are influenced by the environment,” both the brain’s internal environment and the external, social environment, she adds. “This is a really unique opportunity, not just for song, not just for language, but for learning in a little larger context—of kids trying to understand and adopt behavioral patterns appropriate to their time and place.”

W. Zhao et al., “Inception of memories that guide vocal learning in the songbird,” Science, doi:10.1126/science.aaw4226, 2019.

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In a pilot study of 14 older adults with mild cognitive problems suggestive of early Alzheimer’s disease, Johns Hopkins Medicine researchers report that a high-fat, low-carbohydrate diet may improve brain function and memory.

Although the researchers say that finding participants willing to undertake restrictive diets for the three-month study—or partners willing to help them stick to those diets—was challenging, those who adhered to a modified Atkins diet (very low carbohydrates and extra fat) had small but measurable improvements on standardized tests of memory compared with those on a low-fat diet.

The short-term results, published in the April issue of the Journal of Alzheimer’s Disease, are far from proof that the modified Atkins diet has the potential to stave off progression from mild cognitive impairment to Alzheimer’s disease or other dementias. However, they are promising enough, the researchers say, to warrant larger, longer-term studies of dietary impact on brain function.

“Our early findings suggest that perhaps we don’t need to cut carbs as strictly as we initially tried. We may eventually see the same beneficial effects by adding a ketone supplement that would make the diet easier to follow,” says Jason Brandt, Ph.D., professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine. “Most of all, if we can confirm these preliminary findings, using dietary changes to mitigate cognitive loss in early-stage dementia would be a real game-changer. It’s something that 400-plus experimental drugs haven’t been able to do in clinical trials.”

Brandt explains that, typically, the brain uses the sugar glucose—a product of carbohydrate breakdown—as a primary fuel. However, research has shown that in the early stage of Alzheimer’s disease the brain isn’t able to efficiently use glucose as an energy source. Some experts, he says, even refer to Alzheimer’s as “type 3 diabetes.”

Using brain scans that show energy use, researchers have also found that ketones—chemicals formed during the breakdown of dietary fat—can be used as an alternative energy source in the brains of healthy people and those with mild cognitive impairment. For example, when a person is on a ketogenic diet, consisting of lots of fat and very few sugars and starches, the brain and body use ketones as an energy source instead of carbs.

For the current study, the researchers wanted to see if people with mild cognitive impairment, often an indicator of developing Alzheimer’s disease, would benefit from a diet that forced the brain to use ketones instead of carbohydrates for fuel.

After 2 1/2 years of recruitment efforts, the researchers were able to enroll 27 people in the 12-week diet study. There were a few dropouts, and so far, 14 participants have completed the study. The participants were an average age of 71. Half were women, and all but one were white.

To enroll, each participant required a study partner (typically a spouse) who was responsible for ensuring that the participant followed one of two diets for the full 12 weeks. Nine participants followed a modified Atkins diet meant to restrict carbs to 20 grams per day or less, with no restriction on calories. The typical American consumes between 200 and 300 grams of carbs a day. The other five participants followed a National Institute of Aging diet, similar to the Mediterranean diet, that doesn’t restrict carbohydrates, but favors fruits, vegetables, low- or fat-free dairy, whole grains and lean proteins such as seafood or chicken.

The participants and their partners were also asked to keep food diaries. Prior to starting the diets, those assigned to the modified Atkins diet were consuming about 158 grams of carbs per day. By week six of the diet, they had cut back to an average of 38.5 grams of carbs per day and continued dropping at nine weeks, but still short of the 20-gram target, before rising to an average of 53 grams of carbs by week 12. Participants on the National Institute of Aging diet continued to eat well over 100 grams of carbs per day.

Each participant also gave urine samples at the start of the dietary regimens and every three weeks up to the end of the study, which were used to track ketone levels. More than half of the participants on the modified Atkins diet had at least some ketones in their urine by six weeks into the diet until the end; as expected, none of the participants on the National Institute of Aging control diet had any detectable ketones.

Participants completed the Montreal Cognitive Assessment, the Mini-Mental State Examination and the Clinical Dementia Rating Scale at the start of the study. They were tested with a brief collection of neuropsychological memory tests before starting their diets and at six weeks and 12 weeks on the diet. At the six-week mark, the researchers found a significant improvement on memory tests, which coincided with the highest levels of ketones and lowest carb intakes.

When comparing the results of tests of delayed recall—the ability to recollect something they were told or shown a few minutes earlier—those who stuck to the modified Atkins diet improved by a couple of points on average (about 15% of the total score), whereas those who didn’t follow the diet on average dropped a couple of points.

The researchers say the biggest hurdle for researchers was finding people willing to make drastic changes to their eating habits and partners willing to enforce the diets. The increase in carbohydrate intake later in the study period, they said, suggests that the diet becomes unpalatable over long periods.

“Many people would rather take a pill that causes them all kinds of nasty side effects than change their diet,” says Brandt. “Older people often say that eating the foods they love is one of the few pleasures they still enjoy in life, and they aren’t willing to give that up.”

But, because Brandt’s team observed promising results even in those lax with the diet, they believe that a milder version of the high-fat/low-carb diet, perhaps in conjunction with ketone supplement drinks, is worth further study. As this study also depended on caregivers/partners to do most of the work preparing and implementing the diet, the group also wants to see if participants with less severe mild cognitive impairment can make their own dietary choices and be more apt to stick to a ketogenic diet.

A standardized modified Atkins diet was created and tested at Johns Hopkins Medicine in 2002, initially to treat some seizure disorders. It’s still used very successfully for this purpose.

According to the Alzheimer’s Association, about 5.8 million Americans have Alzheimer’s disease, and by 2050 the number is projected to increase to 14 million people.

Jason Brandt et al. Preliminary Report on the Feasibility and Efficacy of the Modified Atkins Diet for Treatment of Mild Cognitive Impairment and Early Alzheimer’s Disease, Journal of Alzheimer’s Disease (2019). DOI: 10.3233/JAD-180995

https://medicalxpress.com/news/2019-06-low-carb-keto-diet-atkins-style-modestly.html

by PETER DOCKRILL

When bad things happen, we don’t want to remember. We try to block, resist, ignore – but we should perhaps be doing the opposite, researchers say.

A new study led by scientists in Texas suggests the act of intentionally forgetting is linked to increased cerebral engagement with the unwanted information in question. In other words, to forget something, you actually need to focus on it.

“A moderate level of brain activity is critical to this forgetting mechanism,” explains psychologist Tracy Wang from the University of Texas at Austin.

“Too strong, and it will strengthen the memory; too weak, and you won’t modify it.”

Trying to actively forget unwanted memories doesn’t just help prevent your brain from getting overloaded.

It also lets people move on from painful experiences and emotions they’d rather not recall, which is part of the reason it’s an area of active interest to neuroscientists.

“We may want to discard memories that trigger maladaptive responses, such as traumatic memories, so that we can respond to new experiences in more adaptive ways,” says one of the researchers, Jarrod Lewis-Peacock.

“Decades of research has shown that we have the ability to voluntarily forget something, but how our brains do that is still being questioned.”

Much prior research on intentional forgetting has focussed on brain activity in the prefrontal cortex, and the brain’s memory centre, the hippocampus.

In the new study, the researchers monitored a different part of the brain called the ventral temporal cortex, which helps us process and categorise visual stimuli.

In an experiment with 24 healthy young adults, the participants were shown pictures of scenes and people’s faces, and were instructed to either remember or forget each image.

During the experiment, each of the participants had their brain activity monitored by functional magnetic resonance imaging (fMRI) machines.

When the researchers examined activity in the ventral temporal cortex, they found that the act of forgetting effectively uses more brain power than remembering.

“Pictures followed by a forget instruction elicited higher levels of processing in [the] ventral temporal cortex compared to those followed by a remember instruction,” the authors write in their paper.

“This boost in processing led to more forgetting, particularly for items that showed moderate (vs. weak or strong) activation.”

Of course, forgetting specific images on demand in a contrived laboratory experiment is very different to moving on from painful or traumatic memories of events experienced in the real world.

But the mechanisms at work could be the same, researchers say, and figuring out how to activate them could be a huge benefit to people around the world who need to forget things, but don’t know how.

Especially since this finding in particular challenges our natural intuition to suppress things; instead, we should involve more rather than less attention to unwanted information, in order to forget it.

“Importantly, it’s the intention to forget that increases the activation of the memory,” Wang says.

“When this activation hits the ‘moderate level’ sweet spot, that’s when it leads to later forgetting of that experience.”

The findings are reported in JNeurosci.

https://www.sciencealert.com/to-forget-something-you-need-to-think-about-it-neuroscientists-reveal

what-is-your-first-memory-and-did-it-ever-really-happen-309444

By Dr. Lucy Justice

I can remember being a baby. I recall being in a vast room inside a doctor’s surgery. I was passed to a nurse and then placed in cold metal scales to be weighed. I was always aware that this memory was unusual because it was from so early in my life, but I thought that perhaps I just had a really good memory, or that perhaps other people could remember being so young, too.

What is the earliest event that you can remember? How old do you think you are in this memory? How do you experience the memory? Is it vivid or vague? Positive or negative? Are you re-experiencing the memory as it originally happened, through your own eyes, or are you watching yourself “acting” in the memory?

In our recent study, we asked more than 6,000 people of all ages to do the same, to tell us what their first autobiographical memory was, how old they were when the event happened, to rate how emotional and vivid it was and to report what perspective the memory was “seen” from. We found that on average people reported their first memory occurring during the first half of the third year of their lives (3.24 years to be precise). This matches well with other studies that have investigated the age of early memories.

What does this mean for my memory of being a baby then? Perhaps I do just have a really good memory and can remember those early months of life. Indeed, in our study, we found that around 40% of participants reported remembering events from the age of two or below – and 14% of people recalled memories from age one and below. However, psychological research suggests that memories occurring below the age of three are highly unusual – and indeed, highly improbable.

The origin of memory

Researchers who have investigated memory development suggest that the neurological processes needed to form autobiographical memories are not fully developed until between the ages of three and four years. Other research has suggested that memories are linked to language development. Language allows children to share and discuss the past with others, enabling memories to be organised in a personal autobiography.

So how can I remember being a baby? And why did 2,487 people from our study remember events that they dated from the age of two years and younger?

One explanation is that people simply gave incorrect estimates of their age in the memory. After all, unless confirmatory evidence is present, guesswork is all we have when it comes to dating memories from across our lives, including the very earliest.

But if incorrect dating explained the presence of these memories, we would expect that they would be about similar events to those memories from ages three and above. But this was not the case – we found that very early reported memories were of events and objects from infancy (pram, cot, learning to walk) whereas older memories were of things typical of childhood (toys, school, holidays). This finding meant that these two groups of memories were qualitatively different and ruled out the misdating explanation.

If research tells us that these very early memories are highly unlikely, and we have ruled out a misdating explanation, then why do people, including me, have them?

Pure fiction?

We concluded that these memories are likely to be fictional – that is, that they never in fact occurred. Perhaps, rather than recalling an experienced event, we recall imagery derived from photographs, home movies, shared family stories or events and activities that frequently happen in infancy. These facts are then, we suggest, linked with some fragmentary visual imagery and are combined together to form the basis of these fictitious early memories. Over time, this combination of imagery and fact begins to be experienced as a memory.

Although 40% of participants in our study retrieved these fictitious memories, they are not altogether surprising. Contemporary theories of memory highlight the constructive nature of memory; memories are not “records” of events, but rather psychological representations of the self in the past.

In other words, all of our memories contain some degree of fiction – indeed, this is the sign of a healthy memory system in action. But perhaps, for reasons not yet known, we have a psychological need to fictionalise memories from times of our lives that we are unable to remember. For now, these “stories” remain a mystery.

https://theconversation.com/what-is-your-first-memory-and-did-it-ever-really-happen-95953