Posts Tagged ‘brain’

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by Linda Rodriguez McRobbie

If you ask Jill Price to remember any day of her life, she can come up with an answer in a heartbeat. What was she doing on 29 August 1980? “It was a Friday, I went to Palm Springs with my friends, twins, Nina and Michelle, and their family for Labour Day weekend,” she says. “And before we went to Palm Springs, we went to get them bikini waxes. They were screaming through the whole thing.” Price was 14 years and eight months old.

What about the third time she drove a car? “The third time I drove a car was January 10 1981. Saturday. Teen Auto. That’s where we used to get our driving lessons from.” She was 15 years and two weeks old.

The first time she heard the Rick Springfield song Jessie’s Girl? “March 7 1981.” She was driving in a car with her mother, who was yelling at her. She was 16 years and two months old.

Price was born on 30 December 1965 in New York City. Her first clear memories start from around the age of 18 months. Back then, she lived with her parents in an apartment across the street from Roosevelt Hospital in Midtown Manhattan. She remembers the screaming ambulances and traffic, how she used to love climbing on the living room couch and staring out of the window down 9th Avenue.

When she was five years and three months old, her family – her father, a talent agent with William Morris who counted Ray Charles among his clients; her mother, a former variety show dancer, and her baby brother – moved to South Orange, New Jersey. They lived in a three-storey, red brick colonial house with a big backyard and huge trees, the kind of place people left the city for. Jill loved it.

When she was seven years old, her father was offered a job with Columbia Pictures Television in Los Angeles. He spent a year commuting back and forth from California to New Jersey, until he and her mother decided to move the family out there in the spring of 1974. By 1 July 1974, when Jill was eight and a half, they were living in a rented house in Los Angeles. That was the day, she says, her “brain snapped”.

She had always had a talent for remembering. She had also always dreaded change. Knowing that after they left New Jersey, nothing could ever be the same, Price tried to commit to memory the world she was being ripped away from. She made lists, took pictures, kept every artefact, every passed note and ticket stub. If this was a conscious effort to train her memory, it worked, perhaps better than she ever imagined.

Price was the first person ever to be diagnosed with what is now known as highly superior autobiographical memory, or HSAM, a condition she shares with around 60 other known people. She can remember most of the days of her life as clearly as the rest of us remember the recent past, with a mixture of broad strokes and sharp detail. Now 51, Price remembers the day of the week for every date since 1980; she remembers what she was doing, who she was with, where she was on each of these days. She can actively recall a memory of 20 years ago as easily as a memory of two days ago, but her memories are also triggered involuntarily.

It is, she says, like living with a split screen: on the left side is the present, on the right is a constantly rolling reel of memories, each one sparked by the appearance of present-day stimuli. With so many memories always at the ready, Price says, it can be maddening: virtually anything she sees or hears can be a potential trigger.

Before Price, HSAM was a completely unknown condition. So what about the day she sent an email to a Dr James McGaugh at University of California, Irvine? That was 8 June 2000, a Thursday. Price was 34 years and five months old.

Dr James McGaugh remembers that day too. At the time, he was director of UC Irvine’s Center for the Neurobiology of Learning and Memory, the research institute that he founded in 1983. In her email, Jill Price said that she had a problem with her memory. McGaugh responded almost immediately, explaining that he worked at a research institute and not a clinic, and that he’d be happy to direct her to somewhere she could find help.

Price’s reply was swift and unexpected. “Whenever I see a date flash on the television (or anywhere else for that matter), I automatically go back to that day and remember where I was, what I was doing, what day it fell on and on and on and on and on. It is non-stop, uncontrollable and totally exhausting … Most have called it a gift but I call it a burden. I run my entire life through my head every day and it drives me crazy!!!”

McGaugh was a little wary, but he was intrigued. He invited her to his office to talk.

On the morning of Saturday, 24 June 2000, Price woke up “so, so, so excited”. She watched Apple’s Way, an obscure, short-lived 1970s series being re-run on TV, and felt, for the first time in ages, relaxed. She asked her father whether she should take all of the diaries that she had been keeping since Monday, 24 August 1981. No, he said, don’t take them all – you’ll freak him out. She packed a bag with six years’ worth, stowed them in the boot of her car, and set off to meet McGaugh.

She drove the hour south from her home in Encino, California, where she lived with her parents, and met McGaugh outside the Qureshey Research Building on the UC Irvine campus. It was a cloudy day, unusual for southern California. As they walked up to his second-floor office, she was still excited.

For Christmas the previous year, McGaugh had received a massive coffee-table book called 20th Century Day by Day, featuring photographs and brief accounts of the biggest news stories of the past 100 years. To test Price’s memory, he and his assistant used the book to come up with questions that someone with amazing powers of recall might plausibly be able to answer, beginning around 1974, when Price said her ability to remember really started.

Sitting across from Price, McGaugh asked, “When did the Iranian hostage crisis begin?”

After a brief pause, she answered, “4 November 1979.”

“No, that’s not right,” he said. “It was 5 November.”

“It was 4 November,” she said.

He checked another source: Price was right; the book was wrong.

The rest of Price’s responses came just as quickly, confidently, and for the most part, correctly. What day did the Los Angeles police beat taxi driver Rodney King? Sunday, 3 March 1991. What happened on 16 August 1977? Elvis Presley died in his Graceland bathroom. It was a Tuesday. When did Bing Crosby die? Friday, 14 October 1977, on a golf course in Spain. Price heard it on the radio in the car while her mother drove her to soccer practice.

McGaugh had been studying memory and learning for decades and he had never seen or heard of anything like this. After they had eaten lunch, Price remembers saying goodbye to McGaugh as he stood on the curb outside the restaurant, “literally scratching his head”.

Driving back, Price felt a little deflated. “I came home and I was kind of annoyed, and my dad said, ‘What did you expect, you’d get an answer?’” she recalled. “And I’m like, ‘Yeah! And I thought I’d get a pill for it, too!’”

McGaugh is a big deal in memory research. His office at UC Irvine is situated across a courtyard from another building, McGaugh Hall, named in his honour. He has written more than 550 papers and books, many on his specialist subject of how we form long-term memories. In 2015 he received a Grawemeyer award, a significant recognition in the crowded field of psychology that comes with a $100,000 prize, for his contribution to understanding memory and emotion. The small plaque sits on a shelf on his desk. Thumbtacked to a bulletin board next to his computer monitor is a colour photograph of McGaugh – trim grey beard, square glasses, academic robes – standing behind President Barack Obama during UCI’s graduation ceremony in 2014. The funny thing about that picture, McGaugh told me when I visited him last autumn, is that the photographer was actually trying to get a picture of him, not the president, for an article in the Los Angeles Times about McGaugh’s 50th anniversary at the university. “This is the absolute truth, but no one will believe it!” he said, chuckling.

McGaugh, who is now 85 and closing in on retirement, first began studying memory in the 1950s. By the time Price contacted him, his research focused on showing that the more emotionally provocative an experience, the more likely the neurobiological systems involved in making memory will ensure that you remember it. When something even slightly stimulating happens, positive or negative, it causes the release of adrenal stress hormones, which in turn activate the amygdala. The amygdala then projects to other brain regions that the thing that has just happened is important and needs to be remembered. It is through this system, McGaugh explained, that the strength of our memories is controlled.

McGaugh had spent his professional career studying strongly formed memories, and Price seemed to have the strongest memories he had ever encountered. McGaugh’s earlier work had changed how we understand the mechanisms of memory, and his interest in Price was about more than just understanding her extraordinary abilities of recollection. He hoped that her unique condition could teach us something new about how we make and store memories. “The big pay-off on this,” he said, “is understanding how memory works.”

Still, he started from a position of scepticism. “In interrogating her, I started with the scientific assumption that she couldn’t do it,” he told me. And even though Price showed that she could, repeatedly, McGaugh was still unmoved. “Yeah, it got my attention, but I didn’t say, ‘Wow.’ We had to do a lot more. So we did a lot more.” (In Price’s recollection, however, her ability to remember “really freaked Dr McGaugh out.”)

After his first meeting with Price, McGaugh assembled a team to determine the depth and breadth of her memory. Elizabeth Parker, a neuropsychologist, mapped Price’s ability to learn and remember, and Larry Cahill, a neurobiologist, helped to analyse the results. Over the next five years, Price was given a battery of standardised memory, IQ and learning tests, as well as a series of specially devised ones. For example, they asked Price, who is Jewish, to write down the date of every Easter from 1980 to 2003 – she got only one wrong and in that case, she was off by only two days. Price was also able to say what she had done on those days. When the researchers asked her to do the same exercise again two years later, she not only corrected the date she had got wrong, but also gave the same answers for the personal details (a sample of those details: 17 April 1987 – “vomit up carrots”; 12 April 1998: “house smells like ham”).

Confirming whether or not autobiographical memories are accurate is usually a tricky job but, McGaugh said, “fortunately, she kept a diary”. Price had begun recording the details of her life in earnest on 24 August 1980, during a high-school romance she wanted to remember. She would make at least one, usually more, entry each day, comprising of short references to the most salient details of the day. Her journals were kept on calendars, on typing paper held together with binder clips, in notebooks, on index cards, even scrawled on the wallpaper in her childhood bedroom.

For Price, writing down her memories meant that they were “real”, part of a permanent historical record independent of herself. (When she dies, she told me, she wants her journals buried with her, or blown up in the desert.) They also functioned as a way to pin down the swirling mess in her head, to organise her thoughts. Price says she does not re-read her journals, and given the random dates the researchers threw at her, there is no reason to assume she could have prepared for their questions. The UCI researchers cross-referenced what she said she did with what was written in her diary; in some cases, they were also able to verify memories with her mother.

Over time, it became clear that Price’s autobiographical memory was potentially unprecedented. But when it came to remembering details that did not relate to her personally, Price proved no better than average. She recalled the date the Iran hostage crisis began because, as a self-described “news junkie”, she had made that detail part of her personal narrative of the day it happened. School, she says, was “torture” for her – she couldn’t remember facts and figures – but she’s unbelievably good at trivia about television of the 60s and 70s, her nostalgia years. Other details, if they didn’t relate to her or her interests, were forgotten: once, she was asked to close her eyes and recall what her two interviewers, who she’d spent several hours with that day, were wearing – she couldn’t. When asked to look at a bank of random numbers and memorise their order in a given period of time, she laughed and said it was impossible. Price’s memory is as selective as yours or mine, storing the things that she finds important – she is just a good deal better at retaining and retrieving those memories.

There was very little scientific literature about superior forms of memory, and none about a memory like Jill Price’s. Much of what did exist was about people who had the ability to memorise pi out to 22,514 decimal places or remember the order of a randomly shuffled deck of cards. The scientific consensus about these abilities was that they were the result of practice and acquired skill – strategy, rather than innate ability. Other people who are able to name the day of the week for any given date are also able to do it for dates outside of their lifetimes, and they tend to be autistic. Price can’t and is not. There was no one – as far as the UCI team could find – who had ever exhibited anything like Price’s automatic ability to recall her personal memories.

On 13 August 2003, three years after she first came to Irvine, McGaugh, Parker, and Cahill presented their initial findings on Jill Price’s memory to the UCI medical community in a large open forum. Price was invited to exhibit her memory, to show how she could “see” dates and memories in her head, and to explain how she conceives time: for her, each year is like a circle, with January in the 11 o’clock position, and the months progressing in an anti-clockwise motion. She was nervous about speaking in front of a large audience, especially of doctors – she has a phobia of doctors, she says – but it was the beginning of her seeing a “bigger picture” reason for her years of suffering: scientific progress.

Two years later, the UCI researchers asked Price to read a draft of the paper they had written about her before they submitted it. In it, they described Price as both the “warden and prisoner” of her memories. “I thought, God, if I didn’t know better, it sounds like this person has brain damage or something,” she said of “AJ”, the pseudonym they used for her. “I cried. I wept while I read it. Someone had finally heard me. Because I’ve spent my whole life screaming at the top of my lungs and nobody has heard anything.”

“A Case of Unusual Autobiographical Remembering” was published by the neuropsychology journal Neurocase in February 2006. “We made the mistake of calling it ‘hyperthymesia’” – from the Greek thymesis, remembering – “which was a terrible idea, because when you name it in that way, it sounds as if you know what it is,” McGaugh said. In truth, all they had, in Price, was a data point of one, a lot of description, and no clear understanding of the mechanisms behind her memory. What they were about to get, however, was more people like Jill Price.

Price remembers 12 March 2006 as a very important day. “That was the last day that my life was my own,” she told me. The following morning, the first newspaper article about the discovery of “hyperthymesia” came out in the Orange County Register. By that afternoon, McGaugh’s assistant had already been contacted by five more media outlets who wanted to interview Price. A month later, the university was getting so many calls about Price that it asked her to hire a publicist to handle all the requests. (Price, who was still known to the public only as AJ, invented a publicist and fielded all the queries herself. “I had control over what was happening. For a year, nobody knew they were talking to me,” she says, “it was really quite hysterical.”)

Almost immediately, emails also began to trickle in to McGaugh’s office from people who believed that they or someone they knew had the same condition. One email even pointed out that the scientists at UC Irvine were not the first to find someone with a memory like this – an 1871 article in the Journal of Speculative Philosophy described the curious case of Daniel McCartney, then a 54-year-old blind man living in Ohio who could remember the day of the week, the weather, what he was doing, and where he was for any date back to 1 January 1827, when he was nine years and four months old.

http://www.jstor.org/stable/25665736?seq=1#page_scan_tab_contents

Dozens of people contacted McGaugh’s lab, where his assistant handled the first round of vetting, putting potential candidates through the same public events date test that McGaugh had initially given Price. The second person verified as having the condition was Brad Williams, a radio announcer in Wisconsin whose brother contacted McGaugh in 2007 after coming across an article about the UCI research. The third was Rick Baron, whose sister had read about “AJ” in online reports.

The fourth was Bob Petrella, a standup comic turned writer and TV producer for reality programmes such as The Deadliest Catch. Petrella had known since adolescence that his memory was different to other people’s, but he never thought it was all that unusual. “I just thought it was like being a redhead or being left-handed,” he told me when we met in Los Angeles in October.

Petrella sought out the UCI team after a friend suggested, on 19 June 2007, that he should learn the science behind his memory. He was referred to Elizabeth Parker, the neuropsychologist who had co-written the original paper on hyperthymesia. They met several times. After testing him, she confirmed that yes, Petrella had it, and sent him to McGaugh for further study. He met McGaugh and Cahill for the first time over lunch on 28 June 2008 (a “beautiful day”), where McGaugh quizzed him on dates just as he had done with Jill Price.

For the scientists, the research was exciting, but there was a concern as well, that it might all be a waste of time: given that such a tiny number of people with the condition had been identified, what could they definitively say about the condition? And what could this unique group reveal about memory? The only way to move forward was to continue testing the existing subjects and hope for more. By 2012, researchers had only identified six confirmed cases of what had been renamed highly superior autobiographical memory, or HSAM. (“Hyperthymesia”, McGaugh said, sounded “like a venereal disease”.) That’s when the news magazine programme 60 Minutes came calling.

In August 2010, 60 Minutes interviewed the “memory wizards” Bob Petrella, Brad Williams, Rick Baron, Louise Owen, and the actress Marilu Henner, best known for her role on the 1970s sitcom Taxi, for a segment entitled “Endless Memory”. (Price was not involved; by this time, she was no longer anonymous, having published a memoir in 2008, but she had begun to sour on media appearances, which she felt reduced her condition to a “sideshow”, and she has never met any of the other people with the condition.)

It was the first time that the HSAM subjects had met anyone like themselves and, watching the show today, the shock and delight in their mutual recognition is evident. When they first met on camera, there was a lot of hugging. Later, when quizzed on the date of a San Francisco earthquake, they give the answer almost in unison, some of them grinning. The programme aired on 19 December 2010 – a Sunday night – and was seen by nearly 19 million people.

After the programme was over, McGaugh said: “I turned on my computer and I had over 600 emails.” Most were from people who believed they or someone they knew had HSAM. McGaugh spent the week between Christmas and New Year’s Day responding to the emails. Graduate and undergraduate students were pressed into service to staff a phone bank, using the public events quiz to screen callers. Most were rejected, but a small group were invited to UCI for more testing. It is a measure of just how rare HSAM is that by 2011, even after millions of people had heard about it, researchers had identified only 22 people with the condition.

In May 2012, the journal Neurobiology of Learning and Memory published a follow-up study by UCI neuroscience graduate student Aurora LePort and neurobiologist Dr Craig Stark, then the director of the UCI Center for the Neurobiology of Learning and Memory. It was now nearly 12 years since Price first reached out to McGaugh, but researchers were only fractionally closer to finding the answer she was looking for.

In order to figure out how HSAM worked, researchers first needed to understand what it was and was not. LePort’s paper, the second to be published on the subject, established that Price and the 10 others in the study were not just high achievers on a spectrum of “good” to “bad” memory, they were in a separate, outlying class by themselves. The HSAM subjects turned out to be far better than people with average memories at recalling long-past autobiographical data; in memories that could be verified, they were correct 87% of the time. And the paper was able to offer some clues as to why they could do what they do.

For example, most of the HSAM subjects described mental systems that would seemingly improve retrieval, sorting memories chronologically or categorically (as in, every 15 April as far back as they could remember). This date-based structure seemed to help them organise their memories, as though they were tagging them for easy reference. Significantly, research shows that people with average memories are bad at temporally placing remembered events – we don’t have a sense of whether that thing happened two weeks ago or two months ago. (It is important to note here, as LePort, McGaugh, and Stark all did, that their research is limited by what they, as investigators, can verify as a real memory. Dates are the easiest and perhaps surest way to do that. “Everything we do is built around the ability to date. So are there people who have strong autobiographical memory who simply don’t bother to date them?” McGaugh said. “We’re missing them.”)

All of the HSAM subjects reported that they enjoyed replaying their memories in their minds, challenging themselves to remember days and events. When Jill Price is blow-drying her hair, she said, she flips through her memories of, say, every 4 October she can remember. “I’ll just do like the last 40 years in my head, the last 42 years in my head,” she said. “And then I’ll turn to an imaginary person in my head and say, ‘Now you do that. Go.’” When Bob Petrella is stuck in traffic, he scrolls through memories of that date, catalogues the best Saturdays in June he’s ever had, or tries to remember every day from 2002.

The researchers also noted that most of the HSAM subjects exhibited obsessive behaviours. Rick Baron used to keep every banknote in alphabetical order by the name of city of the Federal Reserve Bank from which it was issued. Price has a storage space jammed with neatly organised collection of personal artefacts that she couldn’t let go of – dolls and toys, dozens of Beanie Babies, tapes of songs she recorded off the radio. Bob Petrella used to clean his groceries with an antibacterial wipe when he got home from the grocery store. “There was a nice positive correlation there, showing that the better their memory, the more OCD they were,” LePort said, adding that it makes sense: if subjects are exhibiting obsessive behaviours generally, then they might also be obsessively recalling their memories, rehearsing and therefore retrenching them, making them stronger. Every time they access that memory, it is easier because they have done it before – repetition is one of the surest ways to memorise information.

There were also neuro-physical differences between HSAM subjects and people with average memories. Examination of their brain scans showed that HSAM subjects exhibited structural differences in areas of the brain associated with autobiographical memory creation: increases in the parahippocampal gyrus, for example – an area that some studies show is engaged during the recollection of emotional memories – and increases in the uncinate fascicle, the bridge between the frontal and temporal cortices that transmits information and is involved in episodic memory retention.

But none of these findings fully explains what enables people with HSAM to remember so much. After all, correlation is not causation. Whether their mental organisational systems helped the HSAM subjects to retain memories or whether they needed to develop elaborate systems because they could retain all those memories is unclear. Plenty of people rehearse their memories and don’t have HSAM, and plenty of people with OCD don’t have incredible recall of their autobiographical memories.

Even the structural differences in the brain, though significant, do not provide a satisfying explanation for why and how HSAM works. How we use our brain can change it physically – for example, a 2011 study of London taxi drivers found that the exercise of navigating the city’s dense streets led to an increase in grey matter volume in the mid-posterior hippocampus and an accompanying decrease in volume of the anterior hippocampus. Whether the differences in the HSAM brain is the cause of their memory or, as in the London taxi drivers, the result of it, or a combination of both, remains unclear. “Pulling that apart, in science, isn’t going to be easy. Especially when your population is so rare,” said Stark.

For both Price and Petrella, there is a specific point in their lives that they feel triggered their ability to remember things with extraordinary clarity. For Petrella, it was when he was seven years old and playing a deliriously fun game in his backyard with a childhood friend. The next day, Petrella invited his friend over to play it again, but they only played for a few minutes before getting bored. Petrella realised then that nothing ever stays the same and that it was important that he remember things before they changed. For Price, it was her family’s traumatic move to the west coast. In each case, Price and Petrella say they already had strong memories before this decisive moment, but after it, their ability to remember was transformed.

When I asked McGaugh what he thought of these backstory narratives, he was cautious. “How much of what they say is their own attempt at explanation for what exists as opposed to what really happened?” he asked. But Craig Stark is interested in those stories. He suggested that someone who feels anxiety about losing memories, the way Price and Petrella did, might be compelled to retain them, and therefore might think about them a lot.

Despite their amazing recall, however, there is one way that HSAM subjects are just like everyone else – they are just as prone to memory “distortions”, the editing, assumptions, conflation of time, and other discrepancies that are part and parcel of making memories.

In a study published in 2013, Dr Lawrence Patihis, a memory researcher at the University of Southern Mississippi working with scientists at UCI, asked 20 HSAM subjects and 38 people with standard memories to participate in a series of tests designed to assess their susceptibility to false memories. HSAM subjects were equally likely as the control group to claim words that had not appeared on a list had appeared, they showed a higher overall propensity to form false memories of a photographic slideshow, and they were equally likely to mistakenly report that they had seen non-existent video footage of the United 93 plane crash on 9/11.

The findings suggest that no one, not even a “memory wizard”, is immune to the reconstructive mechanisms that enable memory distortions. When people with average memory recall an experience, it is formed not only by what they think happened and how they felt at the time, but by what they know and feel now. “We’re pulling together everything in the present to come up with an approximation of the past, and that’s the same with HSAM people,” Patihis said. The findings were not popular with some of the HSAM subjects because, as Stark, a co-author on the paper, pointed out, having accurate memories is central to their identities.

But the findings square with two other important ideas. First, the initial process of encoding memories – that is, when the brain makes an experience into a memory, translating elements of that experience into a network of neurons and synaptic connections – seems no different for people with HSAM than for the rest of us.

In a study published in 2016, LePort and the other researchers tested the quality and quantity of autobiographical memories of HSAM and control groups at one week, one month, one year, and 10 years. At one week, both groups were the same in terms of the quality and quantity of information they recalled. After that first week, however, the controls’ powers of recall dropped off significantly, while HSAM people continued to be able to remember seemingly into perpetuity, with a much shallower forgetting curve. The evidence suggests that HSAM subjects form memories in much the same way as those of us with normal memories: like us, they make stronger memories of emotionally arousing experiences, and like us, they are prone to the same distortions in reconstruction.

The second idea is that however good they are at mentally representing and organising their memories, HSAM people don’t seem to be pulling up that information via a novel retrieval system. “It’s the same mechanism, it’s just better,” Stark, whose lab is now running most of the HSAM research, explained. This also implies that the thing HSAM people are doing differently to the rest of us happens somewhere in between the encoding of a memory and its retrieval – in the space where consolidation into a long-term memory takes place.

Testing that hypothesis is fairly straightforward: get HSAMs and controls into a functional MRI and ask them both to recall memories from about a week earlier, the time frame that both groups are performing at about the same level. “Are we thinking about it and reliving it in a different way?” said Stark. But that research is not happening – in part because of a lack of funding. HSAM is fascinating, but funding science for science’s sake is not popular in the US right now. Grant-giving institutions want to know what studying HSAM can do for us.

In 1953, 27-year-old Henry Molaison of Hartford, Connecticut, underwent a desperate surgery to cure his severe epilepsy. Drilling several holes in his head, surgeons performed a “bilateral medial temporal lobe resection”, essentially sucking away part of his hippocampus and much of his amygdala. The surgery worked – Molaison suffered fewer seizures – but it also left him unable to form new memories. His memories from before the surgery were intact, and he was able to learn new motor skills, but he was never able to recognise the researcher who worked with him for decades, whom he saw almost every day.

Molaison, who was known in medical journals as “HM” for the rest of his life, profoundly changed our scientific understanding of memory by showing that we don’t have a single, unified “memory system”. Instead, McGaugh explained, “We have different memory systems in the brain that handle different kinds of information for different periods of time.”

Understanding HSAM, he says, may lead to a similar revelation about the nature of memory. “That’s what is of interest,” he told me. “It’s not that HSAM is interesting, it’s that memory is interesting.”

Price and Petrella said that they hoped that studying their memories could aid research that would find a cure for the thing that surveys in Britain and America show people are most terrified of: dementia. Price, with characteristic directness, said: “I expect them to find a cure for Alzheimer’s. I told Dr McGaugh, ‘This is now your turn, go. Do what you got to do … No pressure, but just find a cure for Alzheimer’s.’”

In all likelihood, studying HSAM will not lead directly to a cure for Alzheimer’s or dementia. It is still unclear whether HSAM will turn out to be a fascinating curiosity, or a key that unlocks the deepest mysteries about how memory works. At the very least, Dr Dorthe Berntsen, founder of Aarhus University’s Center on Autobiographical Memory Research, told me, it shows the extraordinary potential of autobiographical memory. “Could I, as a non-HSAM person, have memory from each day in my life stored, but I just can’t get to it? Is that a retrieval problem or is it a storage and retention problem? Potentially, it can be very important, because it asks these new questions, it shows that we may have to revise how we have thought about our ability to remember the past.”

Every memory researcher I have ever spoken to describes our memories as the things that define us; they are us. There is a reason that people are more afraid of dementia than cancer. When someone you love dies, you fear the day you will forget how they laughed or the sound of their voice, because you will. It hurts to think of all the wonderful, thrilling, important, terrible, devastating things we’ve forgotten. But people with HSAM do remember. Besides the scientific questions HSAM raises, then, there is a different kind of question: would you want a memory like that, if you could have it?

“We call it forgetting but on the other hand, simple storage of information is stupid, it’s just data hoarding. What’s the point? You need to extract something useful from it, then we call it knowledge or wisdom,” Stark told me. “Memory is not about looking backwards, that is not why we have it. It’s there so that your past experiences will make you more adaptive in the here and now and in the future.” But when LePort asked her HSAM subjects in the 2012 study whether they considered their hoard of memories a burden, most said they did not.

Jill Price is not representative of everyone with HSAM, but she is the first data point in this small population. And Price wrote to McGaugh on Thursday 8 June, 2000, because she had a problem. “Everyone has those forks in the road, ‘If I had just done this and gone here, and nah nah nah,’ everyone has those,” she told me. “Except everyone doesn’t remember every single one of them.” Her memory is a map of regrets, other lives she could have lived. “I do this a lot: what would be, what would have been, or what would be today,” she said.

Price is now a freelance script supervisor for film and TV. She lives in an immaculate apartment in Encino, California with her parents, with whom she has lived for much of her adult life. She has a habit of looking off to the right, to the side of the split screen where her memories are, when we talk. She is cynical but not quite bitter – her life, all the details that she can remember so clearly, seems to have made her tired, although that may be the fact that she doesn’t sleep well and hasn’t really ever. She cuts quickly to the point and doesn’t hide her emotions, but she also has an easy, though often wry, laugh.

McGaugh likes to say – and it is written on a board in the lobby of the Center for the Neurobiology of Learning and Memory – that memory is our bridge to the future. But for Price, it doesn’t feel like that. “I’m paralysed, because I’m afraid I’m going to fuck up another whole decade,” she said. She has felt this way since 30 March, 2005, the day her husband, Jim, died at the age of 42. Price bears the weight of remembering their wedding on Saturday, 1 March 2003, in the house she had lived in for most of her life in Los Angeles, just before her parents sold it, as heavily as she remembers seeing Jim’s empty, wide-open eyes after he suffered a major stroke, had fallen into a coma and been put on life support on Friday, 25 March 2005.

But for all the terrible things that people with HSAM can never forget, there are also wonderful memories. When Petrella turned 50, he put together the Book of Bob, a catalogue of the most memorable days he has ever had, one for each calendar day of the year. “It’s totally uninhibited, it talks about sex, drugs, and rock’n’roll,” he said. “I didn’t hold back.” And when he recalls 15 April 1967, he gets a kind of glow and a grin – that was the day that 16-year-old Petrella sat on the rooftop of the local newspaper, where he wrote sports pieces and obituaries, and listened to a battle of the bands contest going on in the street below. He felt like the “king of the town”, he says. “I just felt so good. I just felt so good about my life. That was my second-best April. But a time like that, just sticks in my mind.”

When I first spoke to McGaugh, he told me that the real question at the heart of HSAM wasn’t why his subjects remember, but why we forget. “The overall summary of all of this is that they’re bad forgetters,” he said. And forgetting is what humans do; often what we need to do. The title character in Jorge Luis Borges’s story Funes the Memorious, who acquires a perfect memory as the result of an accident, can no longer sleep because he is kept awake by the thousand mundane memories that whined like mosquitoes in his ears. The “peculiar mixture of forgetting with our remembering,” wrote William James, one of the founders of modern psychology, “is the very keel on which our mental ship is built.” “If we remembered everything,” he continued, “we should on most occasions be as ill off as if we remembered nothing.”

https://www.theguardian.com/science/2017/feb/08/total-recall-the-people-who-never-forget?CMP=oth_b-aplnews_d-1

Wendy was barely 20 years old when she received a devastating diagnosis: juvenile amyotrophic lateral sclerosis (ALS), an aggressive neurodegenerative disorder that destroys motor neurons in the brain and the spinal cord.

Within half a year, Wendy was completely paralyzed. At 21 years old, she had to be artificially ventilated and fed through a tube placed into her stomach. Even more horrifyingly, as paralysis gradually swept through her body, Wendy realized that she was rapidly being robbed of ways to reach out to the world.

Initially, Wendy was able to communicate to her loved ones by moving her eyes. But as the disease progressed, even voluntary eye twitches were taken from her. In 2015, a mere three years after her diagnosis, Wendy completely lost the ability to communicate—she was utterly, irreversibly trapped inside her own mind.

Complete locked-in syndrome is the stuff of nightmares. Patients in this state remain fully conscious and cognitively sharp, but are unable to move or signal to the outside world that they’re mentally present. The consequences can be dire: when doctors mistake locked-in patients for comatose and decide to pull the plug, there’s nothing the patients can do to intervene.

Now, thanks to a new system developed by an international team of European researchers, Wendy and others like her may finally have a rudimentary link to the outside world. The system, a portable brain-machine interface, translates brain activity into simple yes or no answers to questions with around 70 percent accuracy.

That may not seem like enough, but the system represents the first sliver of hope that we may one day be able to reopen reliable communication channels with these patients.

Four people were tested in the study, with some locked-in for as long as seven years. In just 10 days, the patients were able to reliably use the system to finally tell their loved ones not to worry—they’re generally happy.

The results, though imperfect, came as “enormous relief” to their families, says study leader Dr. Niels Birbaumer at the University of Tübingen. The study was published this week in the journal PLOS Biology.

Breaking Through

Robbed of words and other routes of contact, locked-in patients have always turned to technology for communication.

Perhaps the most famous example is physicist Stephen Hawking, who became partially locked-in due to ALS. Hawking’s workaround is a speech synthesizer that he operates by twitching his cheek muscles. Jean-Dominique Bauby, an editor of the French fashion magazine Elle who became locked-in after a massive stroke, wrote an entire memoir by blinking his left eye to select letters from the alphabet.

Recently, the rapid development of brain-machine interfaces has given paralyzed patients increasing access to the world—not just the physical one, but also the digital universe.

These devices read brain waves directly through electrodes implanted into the patient’s brain, decode the pattern of activity, and correlate it to a command—say, move a computer cursor left or right on a screen. The technology is so reliable that paralyzed patients can even use an off-the-shelf tablet to Google things, using only the power of their minds.

But all of the above workarounds require one critical factor: the patient has to have control of at least one muscle—often, this is a cheek or an eyelid. People like Wendy who are completely locked-in are unable to control similar brain-machine interfaces. This is especially perplexing since these systems don’t require voluntary muscle movements, because they read directly from the mind.

The unexpected failure of brain-machine interfaces for completely locked-in patients has been a major stumbling block for the field. Although speculative, Birbaumer believes that it may be because over time, the brain becomes less efficient at transforming thoughts into actions.

“Anything you want, everything you wish does not occur. So what the brain learns is that intention has no sense anymore,” he says.


First Contact

In the new study, Birbaumer overhauled common brain-machine interface designs to get the brain back on board.

First off was how the system reads brain waves. Generally, this is done through EEG, which measures certain electrical activity patterns of the brain. Unfortunately, the usual solution was a no-go.

“We worked for more than 10 years with neuroelectric activity [EEG] without getting into contact with these completely paralyzed people,” says Birbaumer.

It may be because the electrodes have to be implanted to produce a more accurate readout, explains Birbaumer to Singularity Hub. But surgery comes with additional risks and expenses to the patients. In a somewhat desperate bid, the team turned their focus to a technique called functional near-infrared spectroscopy (fNIRS).

Like fMRI, fNIRS measures brain activity by measuring changes in blood flow through a specific brain region—generally speaking, more blood flow equals more activation. Unlike fMRI, which requires the patient to lie still in a gigantic magnet, fNIRS uses infrared light to measure blood flow. The light source is embedded into a swimming cap-like device that’s tightly worn around the patient’s head.

To train the system, the team started with facts about the world and personal questions that the patients can easily answer. Over the course of 10 days, the patients were repeatedly asked to respond yes or no to questions like “Paris is the capital of Germany” or “Your husband’s name is Joachim.” Throughout the entire training period, the researchers carefully monitored the patients’ alertness and concentration using EEG, to ensure that they were actually participating in the task at hand.

The answers were then used to train an algorithm that matched the responses to their respective brain activation patterns. Eventually, the algorithm was able to tell yes or no based on these patterns alone, at about 70 percent accuracy for a single trial.

“After 10 years [of trying], I felt relieved,” says Birbaumer. If the study can be replicated in more patients, we may finally have a way to restore useful communication with these patients, he added in a press release.

“The authors established communication with complete locked-in patients, which is rare and has not been demonstrated systematically before,” says Dr. Wolfgang Einhäuser-Treyer to Singularity Hub. Einhäuser-Treyer is a professor at Bielefeld University in Germany who had previously worked on measuring pupil response as a means of communication with locked-in patients and was not involved in this current study.

Generally Happy

With more training, the algorithm is expected to improve even further.

For now, researchers can average out mistakes by repeatedly asking a patient the same question multiple times. And even at an “acceptable” 70 percent accuracy rate, the system has already allowed locked-in patients to speak their minds—and somewhat endearingly, just like in real life, the answer may be rather unexpected.

One of the patients, a 61-year-old man, was asked whether his daughter should marry her boyfriend. The father said no a striking nine out of ten times—but the daughter went ahead anyway, much to her father’s consternation, which he was able to express with the help of his new brain-machine interface.

Perhaps the most heart-warming result from the study is that the patients were generally happy and content with their lives.

We were originally surprised, says Birbaumer. But on further thought, it made sense. These four patients had accepted ventilation to support their lives despite their condition.

“In a sense, they had already chosen to live,” says Birbaumer. “If we could make this technique widely clinically available, it could have a huge impact on the day-to-day lives of people with completely locked-in syndrome.”

For his next steps, the team hopes to extend the system beyond simple yes or no binary questions. Instead, they want to give patients access to the entire alphabet, thus allowing them to spell out words using their brain waves—something that’s already been done in partially locked-in patients but never before been possible for those completely locked-in.

“To me, this is a very impressive and important study,” says Einhäuser-Treyer. The downsides are mostly economical.

“The equipment is rather expensive and not easy to use. So the challenge for the field will be to develop this technology into an affordable ‘product’ that caretakers [sic], families or physicians can simply use without trained staff or extensive training,” he says. “In the interest of the patients and their families, we can hope that someone takes this challenge.”

https://singularityhub.com/2017/02/12/families-finally-hear-from-completely-paralyzed-patients-via-new-mind-reading-device/?utm_source=Singularity+Hub+Newsletter&utm_campaign=978304f198-Hub_Daily_Newsletter&utm_medium=email&utm_term=0_f0cf60cdae-978304f198-58158129

Two simple mind-body practices improved cognition and helped reverse perceived memory loss in older adults with subjective cognitive decline, in a pilot study published in the Journal of Alzheimer’s Disease.

Researchers randomly assigned 60 older adults with subjective cognitive decline—a strong predictor of Alzheimer’s disease—to a program of either beginner meditation (Kirtan Kriya) or music listening over 6 months. For the first 3 months, participants were directed to practice their intervention 12 minutes daily. For the remaining 3 months, participants were told to engage in their intervention at their discretion.

At 3 months, both the meditation and music listening groups showed marked and significant improvements in subjective memory function and objective cognitive performance, researchers found. What’s more, the substantial gains were maintained or improved at 6 months.

Brain Games Linked to Delayed Cognitive Decline in Elderly

“Findings of this preliminary randomized controlled trial suggest practice of meditation or music listening can significantly enhance both subjective memory function and objective cognitive performance in adults with subjective cognitive decline,” researchers concluded, “and may offer promise for improving outcomes in this population.”

Researchers had previously found that both interventions also improved sleep, mood, stress, well-being, and quality of life—with gains particularly pronounced in participants who practiced meditation. In that study, too, improvements were maintained or improved 3 months after baseline.

—Jolynn Tumolo

References

Innes KE, Selfe TK, Khalsa DS, Kandati S. Meditation and music improve memory and cognitive function in adults with subjective cognitive decline: a pilot randomized controlled trial. Journal of Alzheimer’s Disease. 2017;56:899-916.

Meditation and music may help reverse early memory loss in adults at risk for Alzheimer’s disease [press release]. Lansdale, PA: IOS Press; January 23, 2017.

Older people with a slow walking pace are at increased risk of cognitive decline and dementia, according to a new meta-analysis.

“In light of its characteristics of safety, cost-effectiveness, and ease to test and interpret, walking pace may be an effective indicator of the development of cognitive decline and dementia in older people,” Dr. Minghui Quan of Shanghai University of Sport in China and colleagues write in their report, published online December 6 in the Journal of Gerontology: Medical Sciences.

Past research has linked walking pace to cognitive dysfunction, but the size of the association and whether there is a dose-response relationship has not been studied systematically, the researchers state. To investigate, they reviewed 17 prospective studies of walking pace. Seven looked at cognitive decline, seven at dementia, and three studies included both outcomes.

The 10 studies of cognitive decline included nearly 10,000 participants, while the 10 studies with dementia as an outcome included more than 14,000. The slowest walkers had an 89% higher risk of cognitive decline (95% confidence interval, 1.54 – 2.31), but there was no linear relationship between walking pace and cognitive decline risk.

Dementia risk was 66% higher in individuals with the slowest walking pace versus those with the fastest pace (95% CI, 1.43 – 1.92). Three studies included data on dose-response relationship, and found a relative risk of cognitive decline of 1.13 for each decimeter/second drop in walking pace (95% CI, 1.08 – 1.18).

Walking pace may be an indicator of cognitive function for many reasons, Dr. Quan and colleagues note. For example, walking pace is associated with muscle strength, and muscle loss has been tied to inflammation, oxidative stress and other factors related to cognitive function.

Walking is not an automatic activity, they add, but “requires a seamless coordination of several neurologic systems including motor, sensory, and cerebellar activities.” Slow walking pace could also contribute to physical inactivity, they add, which in turn is associated with cognitive decline and dementia.

“Since a randomized clinical trial on walking pace and cognitive function may not be feasible due to practical considerations, future well-designed, large-scale, prospective cohort studies are needed to determine the age-, sex-, and population-specified cutoff values for walking pace, in order to enhance the effectiveness and efficiency of this early indicator of cognitive decline and dementia,” Dr. Quan and colleagues conclude.

Regular use of nicotine may normalize brain activity impairments linked with schizophrenia, according to a study using a mouse model, published online in Nature Medicine. The finding may explain why up to 90% of people with schizophrenia smoke—most of them heavily.

“Basically the nicotine is compensating for a genetically determined impairment,” said researcher Jerry Stitzel, PhD, of the University of Colorado Boulder. “No one has ever shown that before.”

Dr. Stitzel is part of an international research team that investigated whether a variant in the CHRNA5 gene, which is believed to increase schizophrenia risk, is associated with a reduction of neural firing in the brain’s prefrontal cortex, or hypofrontality. Researchers also examined whether nicotine could interrupt the effect.

In mice with the CHRNA5 gene variant, brain images confirmed hypofrontality, researchers reported. Behavioral tests further revealed that the mice shared key characteristics of people with schizophrenia, such as an inability to suppress a startle response and aversion to social interaction. The findings, they explained, suggest the CHRNA5 gene variant plays a role in schizophrenia by causing hypofrontality.

Nicotine, however, seemed to reverse hypofrontality. When researchers gave the mice daily nicotine, their sluggish brain activity improved within 2 days. Within a week, it was normal.

Researchers believe the nicotine corrected the impaired brain activity by acting on nicotinic receptors in regions important for healthy cognitive function.

Noting that hypofrontality is also linked with addiction, attention deficit hyperactivity disorder, bipolar disorder, and other psychiatric conditions, researchers believe the discovery could lead to new nonaddictive, nicotine-based medications.

“This defines a completely novel strategy for medication development,” said lead author Uwe Maskos, PhD, of Institut Pasteur, Paris, France.

—Jolynn Tumolo

References:

Koukouli F, Rooy M, Tziotis D, et al. Nicotine reverses hypofrontality in animal models of addiction and schizophrenia. Nature Medicine. 2017 January 23;[Epub ahead of print].

Nicotine normalizes brain deficits key to schizophrenia [press release]. Boulder, CO: University of Colorado Boulder; January 23, 2017.

synaesthesia

A surprising number of people experience a form of sensory cross wiring in which light flashes and visual movements are ‘heard’, research finds.

One in five people is affected by a synaesthesia-like phenomenon in which visual movements or flashes of light are “heard” as faint sounds, according to scientists.

The findings suggest that far more people than initially thought experience some form of sensory cross-wiring – which could explain the appeal of flashing musical baby toys and strobed lighting at raves.

Elliot Freeman, a cognitive neuroscientist at City University and the study’s lead author, said: “A lot of us go around having senses that we do not even recognise.”

More florid forms of synaesthesia, in which disparate sensory experiences are blended, are found in only about 2–4% of the population. To a synaesthete, the number seven might appear red, or the name Wesley might “taste” like boiled cabbage, for instance.

The latest work – only the second published on the phenomenon – suggests that many more of us experience a less intrusive version of the condition in which visual movements or flashes are accompanied by an internal soundtrack of hums, buzzes or swooshes. Since movements are very frequently accompanied by sounds in everyday life, the effect is likely to be barely discernible.

When tested under laboratory conditions, the “hearing motion” effect appeared to enhance a person’s ability to interpret fine visual movements, but also interfered with the ability to hear real sounds when visual and audio signals were mis-matched.

“These internal sounds seem to be perceptually real enough to interfere with the detection of externally-generated sounds,” said Freeman. “The finding that this ‘hearing-motion’ phenomenon seems to be much more prevalent compared to other synaesthesias might occur due to the strength of the natural connection between sound and vision.”

In the study, published in the journal Consciousness and Cognition, 40 participants were presented with pairs of either visual or auditory Morse-code like patterns, and had to decide whether each pair contained the same or different sequences. Participants were then asked whether they were aware of hearing faint sounds accompanying the flashes.

Of the 40 participants, 22% reported hearing sounds accompanying the visual flashes in the ‘Morse-code’ task – and also tended to do better on this task.

“My data suggests there are two kinds of people,” said Freeman. “Those who generate sounds deliberately and those who get the internal sounds without trying.”

In a second task, participants had to detect faint sounds, similar to those given in audiology tests, presented with or without irrelevant visual flashes.

Those who scored better on the Morse-code task also appeared to find irrelevant light flashes more of a distraction to listening tasks, suggesting that the visual stimuli was effectively acting as an internal background noise.

In a separate study, the team tested for the phenomenon in trained musicians and found that it was much more common in the group. It is not clear if this is due to a natural disposition to link sounds and visual cues or whether thousands of hours of training might have strengthened the neural circuitry behind the effect.

https://www.theguardian.com/science/2017/jan/17/listen-with-your-eyes-one-in-five-of-us-may-hear-flashes-of-light-synaesthesia

Grid cell from the entorhinal cortex (EC) of the mouse brain, firing repeatedly and uniformly in a grid-like pattern. When a mouse moves through its environment, grid cells are activated, with each cell representing a specific location. This creates a triangular coordinate system that allows for spatial navigation. The accumulation of tau protein in the brain of a mouse model of Alzheimer’s disease was shown to disrupt the function of grid cells, causing problems with navigation. The findings explain why Alzheimer’s patients tend to wander and get lost. Source: Lab of Karen Duff, PhD, Columbia University Medical Center

Columbia University Medical Center (CUMC) researchers have discovered that the spatial disorientation that leads to wandering in many Alzheimer’s disease patients is caused by the accumulation of tau protein in navigational nerve cells in the brain. The findings, in mice, could lead to early diagnostic tests for Alzheimer’s and highlight novel targets for treating this common and troubling symptom.

The study was published online today in the journal Neuron.

An estimated three out of five people with Alzheimer’s disease wander and get lost, usually beginning in the early stages of the disease, leaving them vulnerable to injury. Researchers suspect that these problems originate in an area of the brain known as the entorhinal cortex (EC). The EC plays a key role in memory and navigation and is among the first brain structures affected by the buildup of neurofibrillary tangles that are largely composed of tau, a hallmark of Alzheimer’s disease. “Until now, no one has been able to show how tau pathology might lead to navigational difficulties,” said co-study leader Karen E. Duff, PhD, professor of pathology & cell biology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at Columbia.

Dr. Duff and her colleagues focused their investigations on excitatory grid cells, a type of nerve cell in the EC that fires in response to movement through space, creating a grid-like internal map of a person’s environment. The researchers made electrophysiological recordings of the grid cells of older mice—including mice engineered to express tau in the EC (EC-tau mice) and normal controls—as they navigated different environments. Spatial cognitive tasks revealed that the EC-tau mice performed significantly worse compared to the controls, suggesting that tau alters grid cell function and contributes to spatial learning and memory deficits, according to co-study leader Abid Hussaini, PhD, assistant professor of neurobiology (in pathology & cell biology and the Taub Institute).

Detailed histopathological analysis of the mouse brains revealed that only the excitatory cells, but not the inhibitory cells, were killed or compromised by pathological tau, which probably resulted in the grid cells firing less. “It appears that tau pathology spared the inhibitory cells, disturbing the balance between excitatory and inhibitory cells and misaligning the animals’ grid fields,” said co-first author Hongjun Fu, PhD, associate research scientist in the Taub Institute, who led the immunohistological and behavior studies.

“This study clearly shows that tau pathology, beginning in the entorhinal cortex, can lead to deficits in grid cell firing and underlies the deterioration of spatial cognition that we see in human Alzheimer’s disease,” said Eric Kandel, MD, Nobel laureate, University Professor, and Kavli Professor of Brain Science at Columbia. “This is a classic advance in our understanding of the early stages of Alzheimer’s disease.”

“This study is the first to show a link between grid cells and Alzheimer’s disease,” said Edvard E. Moser, Nobel laureate and head of the Kavli Institute for Systems Neuroscience at Norwegian University of Science and Technology. “These findings will be crucial for future attempts to understand the development of early Alzheimer’s disease symptoms, including the tendency to wander and get lost.”

The findings raise the possibility that spatial disorientation could be treated by correcting this imbalance through transcranial stimulation, deep-brain stimulation, or light-based therapy.

“We have a lot to learn about grid cells and how they are affected by Alzheimer’s disease,” said Gustavo A. Rodriguez, PhD, a postdoctoral research scientist in the Taub Institute and a co-author of the paper. “We don’t yet know what percentage of healthy grid cells are needed for proper navigation or whether this system is rescuable once it has been compromised.”

“In the meantime,” said Dr. Duff, “our findings suggest that it may be possible to develop navigation-based cognitive tests for diagnosing Alzheimer’s disease in its initial stages. And if we can diagnose the disease early, we can start to give therapeutics earlier, when they may have a greater impact.”

The study is titled, “Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction and Spatial Memory Deficits Reminiscent of Early Alzheimer’s Disease.” The other contributors are Mathieu Herman, Sheina Emrani, Eden Nahmani, Geoffrey Barrett, Helen Y. Figueroa, and Eliana Goldberg.

The study was supported by grants from National Institutes of Health (R01NS074874 and R01AG050425) and the Alzheimer’s Association (2015-NIRG-341570).

http://newsroom.cumc.columbia.edu/blog/2017/01/19/in-alzheimers-excess-tau-protein-damages-brains-gps/