Posts Tagged ‘neuroscience’

By Bradley J. Fikes

A diabetes drug developed by a San Diego biotech company from a venomous lizard’s saliva reduces Parkinson’s disease symptoms, according to a study published Thursday.

The placebo-controlled study of 62 patients found the drug, exenatide, provided statistically significant effectiveness in preserving motor control. It may actually slow down disease progression, although this has to be confirmed with more research.

For Parkinson’s patients, the trial represents stronger grounds to expect more effective treatments. For San Diego’s life science community, it represents another example of the benefits of original research and innovation.

The study was published in The Lancet by researchers led by Thomas Foltynie and Dilan Athauda, both of University College London in London, England. While the study wasn’t particularly large, with 62 patients, it was placebo-controlled, and is in line with a previous clinical study published in 2014.

Exenatide was found in Gila monster saliva by Dr. John Eng, an endocrinologist at Bronx Veterans Affairs Medical Center in New York. The venomous lizard, native to the Southwestern United States and northwestern Mexico, delivers excruciating pain with its bite.

San Diego’s Amylin Pharmaceuticals licensed the discovery in 1996. Further development yielded exenatide, sold under the brand name Byetta.

The drug became a hit, providing a major reason for Amylin’s 2012 purchase for $7 billion by Bristol-Myers Squibb. As for Amylin, the company was disbanded and no longer exists.

Exenatide/Byetta reduces insulin resistance in Type 2 diabetes, allowing for better control of blood glucose. There’s evidence that Parkinson’s disease is also related to problems with insulin signaling.

The new clinical study improves on the previous study because it is placebo-controlled, according to an accompanying commentary in The Lancet. But the study has limitations that prevent it from being considered definitive.

“Whether exenatide acts as a novel symptomatic agent or has neuroprotective effects on the underlying Parkinson’s disease pathology remains unclear, but Athauda and colleagues’ study opens up a new therapeutic avenue in treatment of Parkinson’s disease,” the commentary stated.

Christian Weyer, M.D., a former Amylin executive, said one of the most interesting parts of the study was exenatide’s potential for modifying the course of Parkinson’s disease. Weyer is now president of Chula Vista’s ProSciento, a clinical services provider.

Patients were measured on motor skills after getting 48 weeks of injections, either with exenatide or placebo. The treated group showed an advantage of 4 points on a 132-scale test, which was statistically significant.

Exenatide mimics the action of a hormone, and such drugs often show disease-modifying properties, said Weyer, who was Amylin’s Senior Vice President of Research and Development.

“It’s not conclusive that exenatide has the potential for disease-modification, but I was impressed by the fact that the endpoint of the test was in the off-medication period, so you actually assess whether there’s an effect even after the treatment had been stopped,” Weyer said.

Amylin had performed early preclinical research on exenatide for Parkinsons’ disease, Weyer said. The research was funded by a small grant from the Michael J. Fox Foundation.

In chronic diseases such as Type 2 diabetes and Parkinson’s, finding disease-modifying therapies is the “Holy Grail,” Weyer said.

“These are life-long diseases, and anything you can do to either delay or prevent the onset of the disease, or to slow its progression over a long period of time” has great benefit, Weyer said.

Insulin has many biological roles in the body, so it’s not surprising that an abnormal response to insulin could play a role in Parkinson’s disease as well as diabetes, Weyer said.


by Jerry Useem

If power were a prescription drug, it would come with a long list of known side effects. It can intoxicate. It can corrupt. It can even make Henry Kissinger believe that he’s sexually magnetic. But can it cause brain damage?

When various lawmakers lit into John Stumpf at a congressional hearing last fall, each seemed to find a fresh way to flay the now-former CEO of Wells Fargo for failing to stop some 5,000 employees from setting up phony accounts for customers. But it was Stumpf’s performance that stood out. Here was a man who had risen to the top of the world’s most valuable bank, yet he seemed utterly unable to read a room. Although he apologized, he didn’t appear chastened or remorseful. Nor did he seem defiant or smug or even insincere. He looked disoriented, like a jet-lagged space traveler just arrived from Planet Stumpf, where deference to him is a natural law and 5,000 a commendably small number. Even the most direct barbs—“You have got to be kidding me” (Sean Duffy of Wisconsin); “I can’t believe some of what I’m hearing here” (Gregory Meeks of New York)—failed to shake him awake.

What was going through Stumpf’s head? New research suggests that the better question may be: What wasn’t going through it?

The historian Henry Adams was being metaphorical, not medical, when he described power as “a sort of tumor that ends by killing the victim’s sympathies.” But that’s not far from where Dacher Keltner, a psychology professor at UC Berkeley, ended up after years of lab and field experiments. Subjects under the influence of power, he found in studies spanning two decades, acted as if they had suffered a traumatic brain injury—becoming more impulsive, less risk-aware, and, crucially, less adept at seeing things from other people’s point of view.

Sukhvinder Obhi, a neuroscientist at McMaster University, in Ontario, recently described something similar. Unlike Keltner, who studies behaviors, Obhi studies brains. And when he put the heads of the powerful and the not-so-powerful under a transcranial-magnetic-stimulation machine, he found that power, in fact, impairs a specific neural process, “mirroring,” that may be a cornerstone of empathy. Which gives a neurological basis to what Keltner has termed the “power paradox”: Once we have power, we lose some of the capacities we needed to gain it in the first place.

That loss in capacity has been demonstrated in various creative ways. A 2006 study asked participants to draw the letter E on their forehead for others to view—a task that requires seeing yourself from an observer’s vantage point. Those feeling powerful were three times more likely to draw the E the right way to themselves—and backwards to everyone else (which calls to mind George W. Bush, who memorably held up the American flag backwards at the 2008 Olympics). Other experiments have shown that powerful people do worse at identifying what someone in a picture is feeling, or guessing how a colleague might interpret a remark.

The fact that people tend to mimic the expressions and body language of their superiors can aggravate this problem: Subordinates provide few reliable cues to the powerful. But more important, Keltner says, is the fact that the powerful stop mimicking others. Laughing when others laugh or tensing when others tense does more than ingratiate. It helps trigger the same feelings those others are experiencing and provides a window into where they are coming from. Powerful people “stop simulating the experience of others,” Keltner says, which leads to what he calls an “empathy deficit.”

Mirroring is a subtler kind of mimicry that goes on entirely within our heads, and without our awareness. When we watch someone perform an action, the part of the brain we would use to do that same thing lights up in sympathetic response. It might be best understood as vicarious experience. It’s what Obhi and his team were trying to activate when they had their subjects watch a video of someone’s hand squeezing a rubber ball.

For nonpowerful participants, mirroring worked fine: The neural pathways they would use to squeeze the ball themselves fired strongly. But the powerful group’s? Less so.

Was the mirroring response broken? More like anesthetized. None of the participants possessed permanent power. They were college students who had been “primed” to feel potent by recounting an experience in which they had been in charge. The anesthetic would presumably wear off when the feeling did—their brains weren’t structurally damaged after an afternoon in the lab. But if the effect had been long-lasting—say, by dint of having Wall Street analysts whispering their greatness quarter after quarter, board members offering them extra helpings of pay, and Forbes praising them for “doing well while doing good”—they may have what in medicine is known as “functional” changes to the brain.

I wondered whether the powerful might simply stop trying to put themselves in others’ shoes, without losing the ability to do so. As it happened, Obhi ran a subsequent study that may help answer that question. This time, subjects were told what mirroring was and asked to make a conscious effort to increase or decrease their response. “Our results,” he and his co-author, Katherine Naish, wrote, “showed no difference.” Effort didn’t help.

This is a depressing finding. Knowledge is supposed to be power. But what good is knowing that power deprives you of knowledge?

The sunniest possible spin, it seems, is that these changes are only sometimes harmful. Power, the research says, primes our brain to screen out peripheral information. In most situations, this provides a helpful efficiency boost. In social ones, it has the unfortunate side effect of making us more obtuse. Even that is not necessarily bad for the prospects of the powerful, or the groups they lead. As Susan Fiske, a Princeton psychology professor, has persuasively argued, power lessens the need for a nuanced read of people, since it gives us command of resources we once had to cajole from others. But of course, in a modern organization, the maintenance of that command relies on some level of organizational support. And the sheer number of examples of executive hubris that bristle from the headlines suggests that many leaders cross the line into counterproductive folly.

Less able to make out people’s individuating traits, they rely more heavily on stereotype. And the less they’re able to see, other research suggests, the more they rely on a personal “vision” for navigation. John Stumpf saw a Wells Fargo where every customer had eight separate accounts. (As he’d often noted to employees, eight rhymes with great.) “Cross-selling,” he told Congress, “is shorthand for deepening relationships.”

Is there nothing to be done?

No and yes. It’s difficult to stop power’s tendency to affect your brain. What’s easier—from time to time, at least—is to stop feeling powerful.

Insofar as it affects the way we think, power, Keltner reminded me, is not a post or a position but a mental state. Recount a time you did not feel powerful, his experiments suggest, and your brain can commune with reality.

Recalling an early experience of powerlessness seems to work for some people—and experiences that were searing enough may provide a sort of permanent protection. An incredible study published in The Journal of Finance last February found that CEOs who as children had lived through a natural disaster that produced significant fatalities were much less risk-seeking than CEOs who hadn’t. (The one problem, says Raghavendra Rau, a co-author of the study and a Cambridge University professor, is that CEOs who had lived through disasters without significant fatalities were more risk-seeking.)

But tornadoes, volcanoes, and tsunamis aren’t the only hubris-restraining forces out there. PepsiCo CEO and Chairman Indra Nooyi sometimes tells the story of the day she got the news of her appointment to the company’s board, in 2001. She arrived home percolating in her own sense of importance and vitality, when her mother asked whether, before she delivered her “great news,” she would go out and get some milk. Fuming, Nooyi went out and got it. “Leave that damn crown in the garage” was her mother’s advice when she returned.

The point of the story, really, is that Nooyi tells it. It serves as a useful reminder about ordinary obligation and the need to stay grounded. Nooyi’s mother, in the story, serves as a “toe holder,” a term once used by the political adviser Louis Howe to describe his relationship with the four-term President Franklin D. Roosevelt, whom Howe never stopped calling Franklin.

For Winston Churchill, the person who filled that role was his wife, Clementine, who had the courage to write, “My Darling Winston. I must confess that I have noticed a deterioration in your manner; & you are not as kind as you used to be.” Written on the day Hitler entered Paris, torn up, then sent anyway, the letter was not a complaint but an alert: Someone had confided to her, she wrote, that Churchill had been acting “so contemptuous” toward subordinates in meetings that “no ideas, good or bad, will be forthcoming”—with the attendant danger that “you won’t get the best results.”

Lord David Owen—a British neurologist turned parliamentarian who served as the foreign secretary before becoming a baron—recounts both Howe’s story and Clementine Churchill’s in his 2008 book, In Sickness and in Power, an inquiry into the various maladies that had affected the performance of British prime ministers and American presidents since 1900. While some suffered from strokes (Woodrow Wilson), substance abuse (Anthony Eden), or possibly bipolar disorder (Lyndon B. Johnson, Theodore Roosevelt), at least four others acquired a disorder that the medical literature doesn’t recognize but, Owen argues, should.

“Hubris syndrome,” as he and a co-author, Jonathan Davidson, defined it in a 2009 article published in Brain, “is a disorder of the possession of power, particularly power which has been associated with overwhelming success, held for a period of years and with minimal constraint on the leader.” Its 14 clinical features include: manifest contempt for others, loss of contact with reality, restless or reckless actions, and displays of incompetence. In May, the Royal Society of Medicine co-hosted a conference of the Daedalus Trust—an organization that Owen founded for the study and prevention of hubris.

I asked Owen, who admits to a healthy predisposition to hubris himself, whether anything helps keep him tethered to reality, something that other truly powerful figures might emulate. He shared a few strategies: thinking back on hubris-dispelling episodes from his past; watching documentaries about ordinary people; making a habit of reading constituents’ letters.

But I surmised that the greatest check on Owen’s hubris today might stem from his recent research endeavors. Businesses, he complained to me, had shown next to no appetite for research on hubris. Business schools were not much better. The undercurrent of frustration in his voice attested to a certain powerlessness. Whatever the salutary effect on Owen, it suggests that a malady seen too commonly in boardrooms and executive suites is unlikely to soon find a cure.

By Emily Underwood

Viewed under a microscope, your tongue is an alien landscape, studded by fringed and bumpy buds that sense five basic tastes: salty, sour, sweet, bitter, and umami. But mammalian taste buds may have an additional sixth sense—for water, a new study suggests. The finding could help explain how animals can tell water from other fluids, and it adds new fodder to a centuries-old debate: Does water have a taste of its own, or is it a mere vehicle for other flavors?

Ever since antiquity, philosophers have claimed that water has no flavor. Even Aristotle referred to it as “tasteless” around 330 B.C.E. But insects and amphibians have water-sensing nerve cells, and there is growing evidence of similar cells in mammals, says Patricia Di Lorenzo, a behavioral neuroscientist at the State University of New York in Binghamton. A few recent brain scan studies also suggest that a region of human cortex responds specifically to water, she says. Still, critics argue that any perceived flavor is just the after-effect of whatever we tasted earlier, such as the sweetness of water after we eat salty food.

“Almost nothing is known” about the molecular and cellular mechanism by which water is detected in the mouth and throat, and the neural pathway by which that signal is transmitted to the brain, says Zachary Knight, a neuroscientist at the University of California, San Francisco. In previous studies, Knight and other researchers have found distinct populations of neurons within a region of the brain called the hypothalamus that can trigger thirst and signal when an animal should start and stop drinking. But the brain must receive information about water from the mouth and tongue, because animals stop drinking long before signals from the gut or blood could tell the brain that the body has been replenished, he says.

In an attempt to settle the debate, Yuki Oka, a neuroscientist at the California Institute of Technology in Pasadena, and colleagues searched for water-sensing taste receptor cells (TRCs) in the mouse tongue. They used genetic knockout mice to look for the cells, silencing different types of TRCs, then flushing the rodents’ mouths with water to see which cells responded. “The most surprising part of the project” was that the well-known, acid-sensing, sour TRCs fired vigorously when exposed to water, Oka says. When given the option of drinking either water or a clear, tasteless, synthetic silicone oil, rodents lacking sour TRCs took longer to choose water, suggesting the cells help to distinguish water from other fluids.

Next, the team tested whether artificially activating the cells, using a technique called optogenetics, could drive the mice to drink water. They bred mice to express light-sensitive proteins in their acid-sensing TRCs, which make the cells fire in response to light from a laser. After training the mice to drink water from a spout, the team replaced the water with an optic fiber that shone blue light on their tongues. When the mice “drank” the blue light, they acted as though they were tasting water, Oka says. Some thirsty mice licked the light spout as many as 2000 times every 10 minutes, the team reports this week in Nature Neuroscience.

The rodents never learned that the light was just an illusion, but kept drinking long after mice drinking actual water would. That suggests that although signals from TRCs in the tongue can trigger drinking, they don’t play a role in telling the brain when to stop, Oka says.

More research is needed to precisely determine how the acid-sensing taste buds respond to water, and what the mice experience when they do, Oka says. But he suspects that when water washes out saliva—a salty, acidic mucus—it changes the pH within the cells, making them more likely to fire.

The notion that one of the ways animals detect water is by the removal of saliva “makes a lot of sense,” Knight says. But it is still only one of many likely routes for sensing water, including temperature and pressure, he adds.

The “well-designed, intriguing” study also speaks to a long-standing debate over the nature of taste, Di Lorenzo says. When you find a counterexample to the dominant view that there are only five basic taste groups, she says, “it tells you you need to go back to the drawing board.”


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.

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.”


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.


by Dr. Travis Bradberry

You may have heard that multitasking is bad for you, but new studies show that it kills your performance and may even damage your brain. Every time you multitask you aren’t just harming your performance in the moment; you may very well be damaging an area of your brain that’s critical to your future success at work.

Research conducted at Stanford University found that multitasking is less productive than doing a single thing at a time. The researchers found that people who are regularly bombarded with several streams of electronic information cannot pay attention, recall information, or switch from one job to another as well as those who complete one task at a time.

A Special Skill?

But what if some people have a special gift for multitasking? The Stanford researchers compared groups of people based on their tendency to multitask and their belief that it helps their performance. They found that heavy multitaskers—those who multitask a lot and feel that it boosts their performance—were actually worse at multitasking than those who like to do a single thing at a time. The frequent multitaskers performed worse because they had more trouble organizing their thoughts and filtering out irrelevant information, and they were slower at switching from one task to another.

Multitasking reduces your efficiency and performance because your brain can only focus on one thing at a time. When you try to do two things at once, your brain lacks the capacity to perform both tasks successfully.

Multitasking Lowers IQ

Research also shows that, in addition to slowing you down, multitasking lowers your IQ. A study at the University of London found that participants who multitasked during cognitive tasks experienced IQ score declines that were similar to what they’d expect if they had smoked marijuana or stayed up all night. IQ drops of 15 points for multitasking men lowered their scores to the average range of an 8-year-old child.

So the next time you’re writing your boss an email during a meeting, remember that your cognitive capacity is being diminished to the point that you might as well let an 8-year-old write it for you.

Brain Damage From Multitasking?

It was long believed that cognitive impairment from multitasking was temporary, but new research suggests otherwise. Researchers at the University of Sussex in the UK compared the amount of time people spend on multiple devices (such as texting while watching TV) to MRI scans of their brains. They found that high multitaskers had less brain density in the anterior cingulate cortex, a region responsible for empathy as well as cognitive and emotional control.

While more research is needed to determine if multitasking is physically damaging the brain (versus existing brain damage that predisposes people to multitask), it’s clear that multitasking has negative effects.

Neuroscientist Kep Kee Loh, the study’s lead author, explained the implications:

“I feel that it is important to create an awareness that the way we are interacting with the devices might be changing the way we think and these changes might be occurring at the level of brain structure.”

The EQ Connection

Nothing turns people off quite like fiddling with your phone or tablet during a conversation. Multitasking in meetings and other social settings indicates low Self- and Social Awareness, two emotional intelligence (EQ) skills that are critical to success at work. TalentSmart has tested more than a million people and found that 90% of top performers have high EQs. If multitasking does indeed damage the anterior cingulate cortex (a key brain region for EQ) as current research suggests, doing so will lower your EQ while it alienates your coworkers.

Bringing It All Together

If you’re prone to multitasking, this is not a habit you’ll want to indulge—it clearly slows you down and decreases the quality of your work. Even if it doesn’t cause brain damage, allowing yourself to multitask will fuel any existing difficulties you have with concentration, organization, and attention to detail.

St. Jude Children’s Research Hospital scientists have linked disruption of a brain circuit associated with schizophrenia to an age-related decline in levels of a single microRNA in one brain region

St. Jude Children’s Research Hospital scientists have identified a small RNA (microRNA) that may be essential to restoring normal function in a brain circuit associated with the “voices” and other hallucinations of schizophrenia. The microRNA provides a possible focus for antipsychotic drug development. The findings appear today in the journal Nature Medicine.

The work was done in a mouse model of a human disorder that is one of the genetic causes of schizophrenia. Building on previous St. Jude research, the results offer important new details about the molecular mechanism that disrupts the flow of information along a neural circuit connecting two brain regions involved in processing auditory information. The findings also provide clues about why psychotic symptoms of schizophrenia are often delayed until late adolescence or early adulthood.

“In 2014, we identified the specific circuit in the brain that is targeted by antipsychotic drugs. However, the existing antipsychotics also cause devastating side effects,” said corresponding author Stanislav Zakharenko, M.D., Ph.D., a member of the St. Jude Department of Developmental Neurobiology. “In this study, we identified the microRNA that is a key player in disruption of that circuit and showed that depletion of the microRNA was necessary and sufficient to inhibit normal functioning of the circuit in the mouse models.

“We also found evidence suggesting that the microRNA, named miR-338-3p, could be targeted for development of a new class of antipsychotic drugs with fewer side effects.”

There are more than 2,000 microRNAs whose function is to silence expression of particular genes and regulate the supply of the corresponding proteins. Working in a mouse model of 22q11 deletion syndrome, researchers identified miR-338-3p as the microRNA that regulates production of the protein D2 dopamine receptor (Drd2), which is the prime target of antipsychotics.

Individuals with the deletion syndrome are at risk for behavior problems as children. Between 23 and 43 percent develop schizophrenia, a severe chronic disorder that affects thinking, memory and behavior. Researchers at St. Jude are studying schizophrenia and other brain disorders to improve understanding of how normal brains develop, which provides insights into the origins of diseases like cancer.

The scientists reported that Drd2 increased in the brain’s auditory thalamus when levels of the microRNA declined. Previous research from Zakharenko’s laboratory linked elevated levels of Drd2 in the auditory thalamus to brain-circuit disruptions in the mutant mice. Investigators also reported that the protein was elevated in the same brain region of individuals with schizophrenia, but not healthy adults.

Individuals with the deletion syndrome are missing part of chromosome 22, which leaves them with one rather than the normal two copies of more than 25 genes. The missing genes included Dgcr8, which facilitates production of microRNAs.

Working in mice, researchers have now linked the 22q11 deletion syndrome and deletion of a single Dgcr8 gene to age-related declines in miR-338-3p in the auditory thalamus. The decline was associated with an increase in Drd2 and reduced signaling in the circuit that links the thalamus and auditory cortex, a brain region implicated in auditory hallucination. Levels of miR-338-3p were lower in the thalamus of individuals with schizophrenia compared to individuals of the same age and sex without the diagnosis.

The miR-338-3p depletion did not disrupt other brain circuits in the mutant mice, and the findings offer a possible explanation. Researchers found that miR-338-3p levels were higher in the thalamus than in other brain regions. In addition, miR-338-3p was one of the most abundant microRNAs present in the thalamus.

Replenishing levels of the microRNA in the auditory thalamus of mutant mice reduced Drd2 protein and restored the circuit to normal functioning. That suggests that the microRNA could be the basis for a new class of antipsychotic drugs that act in a more targeted manner with fewer side effects. Antipsychotic drugs, which target Drd2, also restored circuit function.

The findings provide insight into the age-related delay in the onset of schizophrenia symptoms. Researchers noted that microRNA levels declined with age in all mice, but that mutant mice began with lower levels of miR-338-3p. “A minimum level of the microRNA may be necessary to prevent excessive production of the Drd2 that disrupts the circuit,” Zakharenko said. “While miR-338-3p levels decline as normal mice age, levels may remain above the threshold necessary to prevent overexpression of the protein. In contrast, the deletion syndrome may leave mice at risk for dropping below that threshold.”

The study’s first authors are Sungkun Chun, Fei Du and Joby Westmoreland, all formerly of St. Jude. The other authors are Seung Baek Han, Yong-Dong Wang, Donnie Eddins, Ildar Bayazitov, Prakash Devaraju, Jing Yu, Marcia Mellado Lagarde and Kara Anderson, all of St. Jude.