October 29, 2009
The crowd of scientists was thinner for Elizabeth Phelps’ special lecture, “Changing Fear,” on the final day of the Society for Neuroscience annual meeting. But her work was among the most interesting I heard presented, in part because she studies humans as well as other animals.
October 22, 2009
A prion is among the simplest of the things that cause disease, and yet it's one of the most terrifying. Consisting of a single misfolded protein, this "mad cow" disease culprit is less invasion factory and more vampire; it has the unusual ability to corrupt other proteins it encounters, causing them to misfold as well, beginning a deadly cascade. In rare cases, such misfolded proteins can form spontaneously in people, but whatever the cause the resulting disease is untreatable and fatal.
A debate has raged among scientists over whether prions play a role in normal cells or whether they are simply an unfortunate aberration. After all, proponents of the former theory argue, evolution would tend to weed out disease-causing proteins unless they served some purpose necessary for survival.
In the final of four presidential lectures delivered here at the Society for Neuroscience annual meeting in Chicago, Nobel laureate Eric Kandel made a compelling argument that prion-like proteins, at the least, contribute to the formation of long-term memories in the brain. "The functional aggregate state [of prion-like proteins] does not kill the cell and is not a dead protein," he said.
Kandel's spirited talk ranged far and wide, outlining dozens of experiments he and his colleagues undertook to understand the molecular basis of memory, or "how one remembers an event for the rest of your life, like your first love." Working on the sea slug Aplysia and in rats, the researchers found that long-term memory formation relies on a chemical cascade that results in formations of new connections between brain cells. The cascade is dependent on the manufacture of new proteins, and that only happens when certain genetic blueprints known as mRNAs receive a molecular "mark" allowing them to make fruitful contact with the protein-making machinery of the cell.
But how does this mark happen, and how does it happen in the right place? The key molecule, Kandel said, seems to be cytoplasmic poly(A) element binding protein, or CPEB, which has some similar components to the prions seen in disease. Kandel's team discovered that CPEB appears to have two forms--including a folded form that, like a prion, can transform the other version of CPEB to resemble it. By studying it in detail over the course of several years, the researchers began to develop a picture of how this might initiate the memory-formation cascade.
According to the theory, the more a neuron is stimulated in response to a sensory stimulus, the more CPEB that cell produces at that particular connection. Some of the protein spontaneously changes into the alternative, folded form, proceeding to convert other CPEB molecules. At low levels of protein, this doesn't do much, but at some critical concentration, CPEB takes over. And this allows mRNAs in the region to be marked, possibly by providing a "scaffold" for them. Of course, if this happens in an uncontrolled fashion, then it could "destroy the cell," Kandel said. Luckily, it seems another molecule affects the CPEB to keep the process in check.
Much remains unclear about this process--including whether it works the same way in humans--and a complete theory of memory remains a far-off dream. But Kandel's speech was a particularly fitting way to end SfN's lecture series, and not just because this was his first presidential lecture despite his illustrious career and his status as a founding member of the society. It also shows just how meticulously and complexly our bodies and brains are crafted--and how nonetheless, with enough hard work and clever insights, we can still unravel those mysteries.
October 21, 2009
Neuroscientists don't talk to each other enough, say the creators of the Whole Brain Catalog.
That may seem like an odd sentiment here at the annual Society for Neuroscience meeting, where more than 32,000 neuroscientists and their colleagues have converged in Chicago to update each other on recent findings and spark new ideas. But researchers at the University of California, San Diego, aren't concerned about the kinds of information that can be easily pasted into a PowerPoint presentation or a poster--they worry about massive sets of useful data languishing away in laboratory backrooms because brain scientists don't have good ways to deal with them.
"There's a lot of data out there that just sits on people's hard drives, because we don't have a place where people can really get to it right away," says Stephen Larson, who helped create the software tool as part of his Ph.D. thesis work. "The open-source neuroscience community has not been as strong as it could be. We wanted to energize that community."
Larson and his colleagues’ solution took root from an unlikely source: video games. Aiming to create an appealing graphical interface for their program, the team turned to Java Monkey Engine, a 3-D gaming engine. The result is a free, open-source brain visualization program that allows scientists to upload, share and comment on all manners of brain data. "[JME] been used for entertainment up until now," Larson says. "But we thought it could be very useful for science visualization."
UCSD's robust information infrastructure provided another key component to getting the program off the ground. To use the Whole Brain Catalog, scientists upload their data--which can easily exceed tens of gigabtyes--onto a dedicated server set up by the catalog team using seed money from the Wiatt Family Foundation. The visualization software then remaps the data against standard models of the brain and serves it up from UCSD computers in a manner similar to Google Maps.
The application's scope is anything but modest. It is designed to work at all levels, incorporating 2-D photos of large brain slices as easily as it can add individual molecules imaged in three dimensions using electron microscopy. And it's not just static data--it can use sequences of images to render detailed simulations of brain activity. One popular demonstration at the catalog's booth is an animation of new neuron growth in the dentate gyrus, based on data from a recent Neuron paper.
Researchers also have plenty of options for data already in the system. Uploaders can decide whether they want to keep the data private for the time being or make it open for everyone to see. A robust annotation program allows anyone to make comments on noteworthy items and ensures that the data is always tagged with the name of the person who uploaded the data. The database is searchable by keyword, and allows researchers directly overlay other people's data onto their own. Easy ways to pull up gene expression data from the Allen Brain Atlas and direct links to Neurolex, a Wikipedia-like database of brain science terms relevant to researchers, are included.
The developers seem to be on target. Interest in the Whole Brain Catalog, which debuted in a beta form here at the conference, has been pretty high. Despite the hubbub of the meeting, several scientists have been so impressed that they have already taken time out of their schedules to upload their data, Larson says.
"This is not going to be the solution to all our issues with data," he adds. "But making it very graphical, very visual, is going to open up and help us solve many problems in neuroscience."
October 20, 2009
Music training might serve as an effective deterrent of or treatment for dyslexia and other language learning disorders, suggests a new study that explores how years of musical experience can boost the brain's hearing abilities.
It's not terribly surprising that musicians are better at processing sounds than the rest of us. What was unexpected, though, was that only certain specific aspects of hearing are affected, said study leader Dana Strait, a Ph.D. student at Northwestern University, speaking at the Society for Neuroscience meeting in Chicago on Monday. And those areas, it turns out, are the same ones that seem to go awry to children who have difficulty learning to read and write.
In her experiment, Strait had 15 musicians and 15 non-musicians play a simple video game she had adapted to test various hearing skills. The groups were pretty similar when it came to very basic tasks, such as what range of sounds they could hear or whether they could detect simple musical tones. The veteran musicians, however, showed increased abilities to focus on sounds and enhanced memory of them afterwards, Strait said, as well as improvements on a few more complicated listening tasks. Furthermore, this was directly related to the amount of musical experience; the longer a musician had played, the better his or her scores.
"Those very aspects enhanced in musicians are impaired in people with learning disabilities," Strait added. For instance, children with dyslexia often have trouble teasing out important sounds from background noise and with distinguishing between certain very similar English consonants. This suggests that reading- and language-related cognitive abilities might be boosted in children with musical training, she said.
This isn't the first research to connect music training and possible educational benefits. Several prior studies have hinted that musical training might convey substantial lifelong learning benefits not just for language but also for thinking in general. Michael Posner, a professor of psychology at the University of Oregon, earlier this year outlined one way this could might happen: Since musical training requires intense time commitments, it may enhance attention, or the ability to focus on one task despite competing demands. And at least one survey has found a rough correlation between SAT scores and prior musical experience, Mark Tramo of Harvard Medical School said at the conference.
But that work, as well as many other studies in the field, do not answer the question of what comes first--better hearing, better attention abilities or an interest in music--Tramo said. Do people born with brains more adept at sound processing or focus naturally decide to become musicians, or did their training boost those abilities? Such questions are vital to figuring out whether music can be employed to combat dyslexia, but because the field is so young, the long, large surveys needed to get answers have not yet been conducted, Tramo said.
Strait echoed those concerns, emphasizing that much more work remains to be done before any recommendations could be made about treatment. She may have some of those answers soon, though; in an interview, she said that this particular study is just one element of a larger project looking at music and the brain. The full plan includes studying not just adults but also children to decipher how precisely the brain processes speech and music, how this changes when people learn to read or write, how learning an instrument might differ from that and what changes the brain shows during the development of musical skill. She even plans to investigate whether the instrument played makes a difference--say, a piano versus a violin versus a set of drums.
The field of coma and consciousness has produced some eye-opening stories in the past few years, most remarkably the case of Terry Wallis, a severely brain-damaged patient who regained the ability to talk. The new findings in this area have led to new ethical questions. Among them: Could doctors be erring in some cases, diagnosing as vegetative patients who are actually minimally conscious—and whose prognosis thus is better? Can people in vegetative or minimally conscious states feel pain, and should they be treated with painkillers?
Steven Laureys of the University of Liege addressed these questions on Monday during the David Kopf Lecture on Neuroethics at the Society for Neuroscience annual meeting. His lecture was called “Eyes Wide Open, Brain Wide Shut? (Un)consciousness in the vegetative state.”
Regarding diagnosis, Laureys cited a study in which 45 of 103 “post-comatose” patients were clinically diagnosed as vegetative. However, diagnosis using the Coma Recovery Scale showed that only 27 of those patients actually belonged in the “vegetative” category, a misdiagnosis of a vegetative state in 40 percent of these cases. Laureys said clinicians should take the time to carefully assess clinical signs of consciousness and not stop their search for signs of it prematurely.
Insight from brain imaging was a recurring theme in Laureys’ lecture. After noting that different levels of consciousness correspond with levels of overall brain activity, Laureys described how functional magnetic resonance imaging (fMRI) can measure activity in a brain at rest—thus providing a gauge by which to test activity in patients in various comatose states and help with diagnosis.
Imaging also can shed light on a patient’s prognosis. “New technologies, especially MRI … will really revolutionize [how] we can predict recovery,” Laureys said. He cited a study in which two of seven patients in a vegetative state showed “high-level” cortical activation. Three months later, only those two had recovered other signs of consciousness.
Clinicians might also adjust treatment based on imaging findings, Laureys said. For example, imaging studies suggest that patients in a vegetative state do not sense pain. But minimally conscious patients show greater brain activity in response to pain, including in an area important in the emotional perception of pain.
“In our view, this should lead to the systematic use of pain-killers and analgesia in patients in a minimally conscious state,” he said.
Laureys concluded by addressing ethical challenges directly, including the need for an overall ethical framework for how physicians deal with impaired consciousness following injury. Such a framework could take into account the quality of life of people living with locked-in syndrome (which is higher than we might expect, surveys indicate) and, as has arisen in Europe, end-of-life decisions such as organ donation from a patient with limited consciousness who sought physician-assisted death.
October 19, 2009
While the recent deluge of stimulus money to fund science research is very welcome, the chief of the National Institutes of Health said on Monday, the devil is in the details—will the support continue?
“Science is not a 100-yard dash—it’s a marathon,” said Francis Collins during an address at Neuroscience 2009, the Society for Neuroscience's annual meeting in Chicago. Collins is the first sitting NIH chief director to speak at the annual meeting; his talk attracted several thousand of the more than 30,000 neuroscientists and others who have converged on McCormick Place this week.
There could not be a more important time to reinforce the importance of science than now, as the president and Congress begin the difficult debate over the next fiscal budget, Collins argued. Most experiments started now won’t be completed in the two years covered by the stimulus grants, he pointed out. They “are down payments on results in the future,” and “to take away the fuel midstream would not lead to good outcomes” for the research or the researchers, he said. “Science doesn’t resonate very well with feast-or-famine circumstances."
In the past year, the agency received around 20,000 applications for stimulus challenge grant funding; it had expected several thousand. “We weren’t able to fund but a percentage,” Collins said, “but were inspired by the outpouring of creativity.”
Continued funding in 2011 and after will be its own challenge given the economic downturn, however, and the agency could again find itself in the all-then-nothing cycle it suffered this past decade. Funding doubled between 1998 and 2003 and then was flat for the next five years, letting inflation carve “a deep loss” in money available for grants, he said.
After just receiving $10 billion in stimulus funding for the 2008-2009 budget, funding more 12,000 research projects, “I do think there’s some risk” that the cycle will repeat, Collins said. He urged scientists and science advocates to “make the case that science research really is important to the nation’s health, its economy and to the rest of the world’s health.”
With its current funding, Collins said, NIH is supporting its bedrock, basic science research, but he also is looking to take advantage of five “areas of opportunity”:
Collins also separately met with groups of postdoctoral students, with reporters and with the board of the neuroscience society. “We are listening,” he said, urging people to e-mail NIH-LISTENS@nih.gov with questions, critiques and suggestions. “We are at a very exciting time scientifically,” he said, and “neuroscience is one of the areas of greatest excitement in science.
“Clearly, our community, after five years of flat budgets, came back to life with this opportunity provided by the recovery act, and put forth some bold and brilliant new ideas.”
October 18, 2009
It was only appropriate that one of the first events of this year's Society for Neuroscience meeting in Chicago focused on neuroscience education and outreach efforts, particularly those of Brain Awareness Week (BAW). SfN president Tom Carew chose education as the defining theme of his tenure as leader, and BAW is the most prominent annual event promoting the brain sciences to the general public around the globe.
More than 200 students, teachers and scientists packed a session room at McCormick Place to hear from Carew and Nick Spitzer of the University of California, San Diego, on how SfN is helping to promote educational activities and how those efforts might change in the future. "Brain awareness has not only expanded but continues to grow," said Spitzer, citing a record number of groups, 33, who presented posters of their outreach work at the session. Part of that growth, he added, is the wealth of material--much of it in now in convenient digital formats--available from SfN and other groups like the Dana Alliance for Brain Initiatives, which co-sponsored the event.
Carew described his experience speaking at a teacher's conference, which showed him that teachers are hungry for detailed knowledge of the brain. "They were so thrilled not only that I was talking science to them but that I was not talking down to them" by simplifying the material, he said. Teachers can be powerful allies in brain outreach activities by acting as "second messengers," he said. "If you get them involved, then after that the whole school comes on board, and then the school board comes on board."
Last week, SfN released a report from a June summit on neuroeducation, a fledgling field that combines neuroscience, psychology and education research to create better teaching methods. The field faces many challenges, as the different disciplines work in vastly different ways and use different vocabularies, Carew said, but the experts at the summit have outlined definite steps to take to advance the field. He's particularly optimistic about the field's prospects because of SfN's membership, which recently passed 40,000, about one-third are graduate students or postdocs. While many of them will pursue traditional academic careers, other career options are increasing, he said, including neuroeducation.
Also featured at the event were several special attendees, who had received travel stipends to the meeting in reward for their outreach efforts or accomplishments. Two undergraduate students--Allison Batties of Lycoming College and Michael Miller of Binghamton University--received SfN/Faculty for Undergraduate Neuroscience awards for their education efforts. In an interview after the event, Batties, who organized a series of hands-on activities for middle schoolers called "Brains Are Us," said her first SfN meeting has been an amazing experience so far. "There's a lot to look at--I'm excited to wander around," she said. "Since I attend a small liberal arts college, without this award, there's no way I could have gotten funding to come here."
Michael Reed, head coach of the science olympiad team at Grand Haven High School in Michigan, echoed her sentiments. SfN paid the way for him and two of his students, Kent Brummel and Blake Shultz, to attend the conference as a reward for teens' first-place win in the health sciences category of the national competition. "The focus on education seems appropriate," Reed added. "There is an awful lot of information available for people to learn about the brain. The key is to try to get people to think about it. It's information people need to know about, to be better students or teachers."
The audience member whom magician Apollo Robbins invited up to the stage appeared to harbor second thoughts—and with good reason. Robbins, “the Gentleman Thief,” specializes in pickpocketing, sleight-of-hand and con games.
Sure enough, despite the audience member’s heightened awareness, Robbins lifted the man’s watch from his wrist (and put it on his own) and swiped his cell phone.
Robbins and fellow magician Eric Mead were the guests of honor at the fifth “Dialogues Between Neuroscience and Society” lecture, one of the first events at this year’s Society for Neuroscience (SfN) meeting in Chicago.
“There’s no better way to find out how our brains work … and by extension how our minds work, than to find out how we can be deceived and how we can be made to believe the impossible,” SfN President Tom Carew said in introducing the pair.
Mead led off with a memory trick, asking an audience member to memorize shapes on a card. He then had her close her eyes and visualize a scene that included only four of the five shapes she had seen. Sure enough, she remembered only those four shapes afterward.
Memory is central to the magician’s craft, Mead said after the trick. “It’s important after the show that people remember certain things and forget certain things,” he said. If an audience member describes a show a week later, he wants them to have forgotten certain revealing details. His methods include distractions that prevent a memory from being encoded in the first place or implanting a benign false memory, such as getting a participant to agree that things happened in a subtly different way than they actually occurred.
Robbins, who has established a counter-theft organization that draws on knowledge from both law enforcement officials and former criminals, cited three tools he uses to deceive: proximity, movement and manipulating another person’s internal dialogue.
The use of personal space can begin to divide a subject’s attention, Robbins noted. Entering someone’s personal space head-on can be uncomfortable, but less so if eye contact breaks or if one person moves to the side of the other.
Certain movements, meanwhile, draw the eye—smooth motion in particular. Moving a coin in this way distracted Robbins’ audience member and helped the magician in his thievery. Robbins also got the man thinking about the coin and where Robbins would make it appear next; in second-guessing what Robbins was doing with the coin, the man stopped paying attention to his watch and cell phone.
“We’re your guides, and our job is to misguide you,” Robbins said. “Albert Einstein said, ‘Reality is an illusion, albeit a very good one.’ If somebody can control where you put your attention, then perhaps they can manipulate your reality.”
After the presentations, the magicians discussed the parallels between magic and brain science with Carew and Susana Martinez-Conde of the Barrow Neurological Institute in Arizona, who has studied the neuroscience of magic. In response to a question from the audience, Martinez-Conde noted that susceptibility to being fooled might help diagnose neurological problems.
A disease “might have something to do with the way a subject perceives magic,” she said. Carew added that magic might have therapeutic potential, too, as a means of working with attention.
The ability to use principles of magic to gain insight about the brain, it seems, is no illusion.
For a peek into the life and past of famed neuroscientist Eric Kandel, check out the new documentary "In Search of Memory" (which also happens to be the name of his well-regarded memoir). Here in Chicago, it’s playing through the week of Neuroscience 2009, the Society for Neuroscience's annual meeting, at the Facets Cinémathèque in Lincoln Park.
If you click over to Facets’ page or the main film page (which is partly in German), you can see the first two minutes of the film. It starts as it goes on; director and producer Petra Seeger shows Kandel primarily via his interactions, with family, with her and other interviewers, with colleagues in and outside the lab, with complete strangers and with politicians in Vienna, the city his family had to escape after the Nazis came to power.
Because there is no straight narration and people sometimes aren’t introduced by name, the story can feel fragmented. This impressionistic method works in its own way, though, switching quickly from a family trip to Vienna to research work on why some memories are stronger to a lecture Kandel gives at a synagogue on why he turned from studying human brains to marine mollusks. In its non-linear way, the film travels a pretty straight history of his life.
Kandel has worked to tease out exactly how we remember, including discovering that we have short-term and long-term memories and that they differ in significant ways, findings that led to a Nobel prize. Seeger emphasizes parallels in his life, from his describing leaving Vienna in panic to his return in glory more than 60 years later. Re-enactments of the strong memories he had in Vienna add additional visual parallels, and his interactions with family and lab colleagues now are contrasted with his interactions in his undergraduate days at Harvard.
She also gives Kandel space to describe himself, trademark laugh, a few tears and all. His Jewish faith is a strong current in his life, including “Never forget,” the motto reminding us to remember the Holocaust. “I’ve been investigating the biological basis of that motto,” how memory works in the brain, all his life, he says.
I enjoyed the glimpses of work in the lab--seeing sea creatures in the tank and then under the microscope, translating descriptions on a posterboard, seeing a neuron alight with nerve growth factor. But though the science sections are a good refresher course, they move so fast (and in fragments) that people new to the field will get only the biggest brushstrokes. Even so, we do get a fascinating glimpse into the world of memory and scientific life, given by one of its most successful—and most down-to-earth—practitioners. Do try to see it if you’re in Chicago this week (through Oct. 22), or keep an eye out for it to come near you.