Dana Foundation Blog

How music rewires the brain

Evidence continues to grow that musical training may not only serve as a powerful tool for treating mental illnesses but may also rewire the brain to be more nimble at learning math and other subjects.

This ability to alter brain connections was the focus of a recent “Music and the Brain” lecture at the Library of Congress in Washington, D.C. Gottfried Schlaug, an associate professor of neurology at Beth Israel Deaconess Medical Center and Harvard Medical School, outlined three lines of neurological research into musical experience and explained why scientists are optimistic about its potential for education and rehabilitation.

“Music making engages quite a lot of real estate in the brain,” he said. “We wanted to know if everyone has the potential to become an accomplished musician, or if [musicians] start off with an atypical brain.”

In adults, for instance, he said, musicians with a long history of practice tend to have bigger corpus callosa—the bundles of fibers that connect the right and left halves of the brain—as well as enhanced motor and auditory processing areas than do non-musicians. Many of these changes were specific to the primary type of instrument used by a musician. But everyone seems able to benefit: Adult non-musicians who took a crash course in piano showed changes in their sequencing, musical and math abilities even after just two weeks.

Schlaug also outlined results from a four-year study of young children he is conducting with Ellen Winner, a psychology professor at Boston University. After 15 months, children who began practicing music showed, as expected, improvements in motor skills and melody and rhythm identification tasks. There were also suggestive, but not statistically significant, evidence that the children were beginning to excel in nonmusical tasks such as vocabulary and abstract reasoning. This type of extension into a nonrelated mental ability is known as “far transfer.”

We have covered many of these findings in the context of neuroeducation, a new field that seeks to use neuroscience findings to improve teaching practices. Schlaug and Winner, for instance, were featured speakers at the “Learning, Arts and the Brain” summit in May, where they presented their 15-month data.

Since then, however, data from 30 months into the child study has been collected; although it is still in the process of being analyzed, far transfer trends seem to be continuing, Schlaug said, increasing interest in music’s potential educational benefits. Since the May conference, Schlaug and his colleagues have also compiled videos demonstrating the extent and rate of improvement in musical ability in their study participants.

Schlaug also presented a video showing how extensive rhythm and singing therapy helped a four-year old boy with autism speak his very first words. “Music,” Schlaug said, “may provide alternative entry into broken brain systems that may not be linking up properly.” (The use of music for autism is just the tip of the iceberg; music is also being used as treatment for spinal cord injuries, stroke and other conditions. Look for more extensive coverage of these therapies in the coming weeks.)

Schlaug’s presentation was the final “Music and the Brain” lecture of 2009. The series, presented by the Library of Congress and the Dana Foundation, will resume on Jan. 21 with “Music, Memories, and the Brain,” in which Petr Janata of the University of California, Davis, will outlining brain imaging results from people who have experienced musical “trances.” As an early Christmas present, the LOC has released free podcasts of earlier lectures in the series.

-Aalok Mehta

Mind reading leads to mind writing

People with spinal cord injuries or disorders such as Lou Gehrig’s disease may one day benefit from the findings of a new study at the Mayo Clinic campus in Jacksonville, Fla. Researchers there were able to predict (with almost 100 percent accuracy) and post on a computer screen the letters that patients were thinking of.

Most prior studies of such brain-machine interfaces had used electroencephalography, which involves collecting data from electrodes placed on the scalp. But neurologist Jerry Shih, who led the new work, recognized he could get far better results with electrocorticography—the recording of information from electrodes implanted directly on the brain. He had this option because his patients suffered from epilepsy; their seizures were already being monitored with “on the brain” electrodes.

Study participants were presented a large grid of letters. Letters within the grid began flashing, and a computer recorded the patients’ brain activity as each new letter became highlighted; then the participants were asked to concentrate on specific letters within the grid. With this information, the computer calibrated itself to each person’s specific brain waves and could ultimately produce the letter a patient was focusing on.

Such a high accuracy rate has been achieved before, but this approach is potentially faster and more localized. “Our goal is to find a way to effectively and consistently use a patient’s brain waves to perform certain tasks,” Shih said in a statement released last Sunday. These tasks could include something like moving a prosthetic arm.

Although Shih noted this study was just a “baby step” towards reaching such a goal—especially as it involves brain surgery—he also said the progress was “very encouraging.”

-Andrew Kahn

Naked mole rats reveal rugged brains

They can barely see, are impervious to pain, have almost no hair, and spend the bulk of their lives eking out a hardscrabble underground existence. Yet naked mole rats may hold the key to developing better treatments for strokes and drowning, scientists have discovered.

Research in the Dec. 9 issue of NeuroReport outlines the amazing hardiness of the bucktoothed rodents’ brains, which can withstand extreme oxygen deprivation for more than a half-hour, far longer than other mammals. In humans, for example, lack of oxygen begins to cause permanent brain damage within minutes.

This unique property is part of suite of adaptations that help mole rats survive in their harsh environment—in cramped networks of tunnels dug beneath the East African soil. In such tight quarters, the air’s oxygen gets used up quickly and concentrations of carbon dioxide skyrocket. Brain researchers have already found that naked mole rats lack a key chemical, substance P, needed to transmit pain signals, for instance, which is believed to allow them to ignore acidic buildup in their tissues that would to us feel excruciating.

The new study found that, in many ways, naked mole rat neurons resemble the brain cells of fetuses; because the womb is a low-oxygen environment, such immature brain cells show much greater resistance to oxygen deprivation than those seen in adults. Finding out how naked mole rats retain this youthful ruggedness could help doctors stave off the neuron death that often follows heart attacks, traumatic accidents, or medical emergencies, the study authors say.

—Aalok Mehta

Consciousness experts assess Houben case

Editor’s Note: On Nov. 23, scientists reported that a man thought for 23 years to be in a vegetative state actually was conscious. Videos showed him supposedly communicating by tapping out messages with the aid of a caregiver, a claim that sparked controversy. We asked Nicholas Schiff and Joseph Fins, who have studied consciousness following brain injury extensively, to comment on the case and on research into minimal consciousness.

We are grateful to the Dana Foundation for the opportunity to discuss the case of Rom Houben, the Belgian man whose diagnosis of being in a vegetative state for 23 years was recently overturned upon further assessment. This request presents several challenges. Since we are outsiders without firsthand knowledge of the patient and the details of the assessments that have taken place, it is difficult to make specific comments. Instead, we will limit our response to general points about diagnostic confusion and questions about Houben’s functional status associated with online video footage, which, in our view, will need further clarification.

Two points have proved newsworthy. First, the patient carried a vegetative state diagnosis for more than two decades. This was proved to be erroneous when he was reassessed three years ago using a formal behavioral rating scale—the Coma Recovery Scale-Revised—that makes clearer distinctions between a vegetative state and minimally conscious states. Second, there are claims, as yet unproved, that the patient’s level of cognitive function is normal. This later claim, if true, coupled with a lack of motor ability, would—by definition—confer upon him the diagnosis of locked-in state (LIS). The LIS diagnosis has been controversial in the media because it has been linked to video clips in which Houben is assisted or facilitated by an aide. In the context of our experience with LIS patients, the information transfer rate ("bit-rate," or rate at which he is able to communicate) seen in the video appears surprisingly fast. Moreover, the patient’s eye opening or gaze direction is hard to gauge in connection to the activity of his hands.

That small signs can distinguish vegetative and minimally conscious states is well-known, and a patient in either state can survive for decades under a misdiagnosis. There are multiple reports of this in the literature, and we are familiar personally with cases in which patients lingered falsely under the diagnosis of a vegetative state when they were indeed conscious and in the minimally conscious state. This aspect of the case is consistent with past experience and appears credible: Houben was first identified as part of a study on the prevalence of misdiagnosis in this population using the Coma Recovery Scale-Revised. This appears consistent with other case reports; little, if anything, needs to be added to his story to believe this.

H.M. brain dissection live online

The brain of Henry Molaison, the most famous amnesic and perhaps the most-studied neurological patient in history, will go under the knife starting Wednesday morning. Mr. Molaison, who died in February, donated his brain to science; as part of the Brain Observatory Project, his contribution will help thousands of researchers worldwide.

Brain Project scientists plan to Webcast the slicing and preservation of brain matter on thousands of slides; extra-high-resolution digital images of the slides will eventually be posted on the open-access site. The operation is scheduled to start Wednesday mid-morning and may take up to 30 hours. Part of this project is supported by a grant from the Dana Foundation.

On Monday, the San Diego Union-Tribune published a nice explanatory story on Mr. Molaison and the work of the Brain Project, which is based at the University of California, San Diego. I also wrote a short piece (with an audio link) about him for Dana's 2008 annual report.

 

—Nicky Penttila

Advice from the “doctor’s doctor”

When a loved one or a friend has been diagnosed with a brain disorder, we want to learn more about what’s going on, and often the first place checked for that information is the Web. But that’s not the necessarily the best reference; in our new book, Treating the Brain: What the Best Doctors Know, you’ll get direct access to Walter G. Bradley, the “doctor’s doctor.”

In the book, Bradley outlines in clear and accessible language the diagnosis, prognosis and treatment options for all of the most common neurological disorders. His expertise in these areas is well-known; not only does he have more than 40 years of experience, but he is also the current and founding editor of the leading neurology reference for medical practitioners and students, Neurology in Clinical Practice.

Recently, Bradley was a guest speaker at the Miami Book Fair International, one of the country’s leading literary events. In this engaging discussion, seen in the videos below, Bradley offers advice to patients and their loved ones coping with neurological disease and offers new information on conditions such as stroke, epilepsy, memory and Alzheimer’s.

Part One:

Part Two:

-Leticia Barnes

Financial wisdom as we age

“The Peak Age of Financial Reason,” an article appearing today on smartmoney.com, addresses a topic we covered in Cerebrum earlier this year: the idea that our financial decision-making can suffer as we age. In Cerebrum, Natalie Denburg and Lyndsay Harshman outline research that links decision-making deficits to abnormalities in the prefrontal cortex. The authors suggest that such problems often occur in the elderly but that they should be considered neither a part of normal aging nor a sign of Alzheimer’s or other dementia.

The Smart Money article takes a behavioral economics perspective and focuses on a not-yet-published paper by Harvard economist David Laibson and colleagues (including two Federal Reserve employees), who suggest that our ability to make good financial decisions is all downhill after age 53 because of the deterioration of our bodies and brains.

I’m not sure I buy the specificity of this “peak” age, but some of the economists’ guidance for how older people can avoid making mistakes goes hand-in-hand with Denburg and Harshman’s suggestions. For example, the Cerebrum authors note that people may not be aware that their decision-making abilities have diminished. Addressing that possibility, Laibson suggests planning ahead, such as by giving someone—a spouse or grown child, ideally—power of attorney in case of incapacitation. Both articles also suggest that legal protections could help manage the problem.

In my introduction to the Cerebrum article, I wrote about two incidents of poor financial decision-making, related by people close to me, that occurred days apart. I hope that these articles raise awareness and encourage people to prepare well. The fewer such stories we hear, the better.

--Dan Gordon

Alzheimer’s gene therapy trial takes another step

Those who take care of someone with Alzheimer’s or follow developments in the field are well aware that there are no good treatments for the disease. The handful of drugs that have been approved for use in patients—such as donepezil, sold under the name Aricept—only manage symptoms; they do not reverse or even slow the loss of nerve cells that ultimately leads to death.

Now scientists are testing a treatment that does show promise for arresting the progression of Alzheimer’s. Twelve sites around the country are recruiting patients for a Phase II trial of CERE-110, a gene therapy treatment. In this approach, doctors perform surgery to implant a virus into the brain; the virus then inserts new genetic material into nerve cells that stimulates them to overproduce nerve growth factor (NGF). This protein promotes nerve growth survival; increased levels of NGF have reversed nerve cell degeneration in monkeys and rats.

Phase I trials, conducted over the past five years, have shown that the gene therapy is safe for people and does not cause side effects such as cancer or immune reactions, which had occurred in prior gene therapy trials. Because Phase I trials test primarily for safety, however, information on how well or if the treatment works is pretty sparse. The Phase II trial will test the effectiveness of the therapy in a total of 50 people with mild to moderate Alzheimer’s, with half receiving the treatment and the other half serving as controls by getting “sham” surgeries. If the trial were successful, the latter group would be eligible to receive the full treatment.

Directly tackling the underlying causes of Alzheimer’s has proven extremely difficult. Last year, for instance, a highly touted and 1,700-subject Phase III trial of flurizan, a drug that targets the amyloid protein clumps that form in Alzheimer’s, failed to show a significant benefit. Bapineuzumab, an experimental vaccine against amyloid proteins, showed positive effects only in a select group of patients in a recent Phase II trial.

It will be several years before the results of this trial are reported, but scientists and patients have a good reason for optimism, as this has been a breakthrough year for gene therapy. Recently researchers restored color vision in two color-blind monkeys using gene therapy. Earlier this month, scientists also announced that they had halted the progression of a devastating brain disease, X-linked adrenoleukodystrophy, in two young boys.

-Aalok Mehta

BrainWeb offers Internet insights

As editor of BrainWeb for the past four years, I frequently evaluate health-related Web sites looking for things to add to the compilation of links to sites about brain diseases and disorders. Once I pick possible sites, they then go to our advisory committee, Bernice Grafstein, Ph.D., and Murray Grossman, M.D., Ph.D., for final review and approval. This vetting process helps ensure the quality of the material that BrainWeb recommends to its users.

Finding accurate health information online can be difficult—the sheer volume of information available makes it hard to know what can be trusted. Here are some things I keep in mind when assessing Web sites:

1. Where is this information coming from? It’s important to notice who sponsors the site: an organization, a pharmaceutical company, a government agency or an individual. The site’s affiliation can color the information presented.
2. Are there a large number of advertisements or requests for donations? If so, I would be less likely to trust the site. A site from a pharmaceutical company, for instance, functions as one large advertisement, even if it appears to be something else at first glance.
3. Is there a scientific advisory committee listed somewhere on the site? This committee indicates that experts have looked over the information and approved the content.
4. When was the site last updated? Health information changes very quickly, and Web sites should be revised accordingly.

And forget Google—there are better places to begin searching for health information. BrainWeb, of course, is one place to go. The National Institutes of Health is another. The search bar on the homepage will connect you information from all of its institutes and centers, in addition to the National Library of Medicine and the fabulous Medline Plus.

-Johanna Goldberg

The DSM debate

In the Nov. 9 New York Times, there is an interesting column by autism expert Simon Baron-Cohen about the Diagnostic and Statistical Manual of Mental Disorders (DSM), including a discussion by its editors about whether to remove Asperger syndrome from the forthcoming fifth edition.

Baron-Cohen touches on some of the same points made in Cerebrum’s recent look at the DSM update. The complementary articles, one by DSM editors, the other by psychiatrist Paul R. McHugh, suggest how the revision might bring more certainty to diagnoses and why looking at disorders’ causes—not just their symptoms, as is the case now—is important.

The DSM update is scheduled for publication in 2012, and many important discussions about it lie ahead. Stay tuned.

-Dan Gordon

To dream, perchance to prepare

I was 17 and a month from leaving for college when a friend told her sister and me about her impending divorce from Anderson. But this friend was also 17, about to be a senior in high school and most certainly not married. She was having a conversation in her sleep.

This episode, hilarious at the time, came to mind when I read the Nov. 9 New York Times article “A Dream Interpretation: Tuneups for the Brain.” It recounts a new hypothesis for why we dream by Harvard psychiatrist and sleep researcher J. Allan Hobson: that the brain is preparing itself for conscious awareness.

According to Hobson’s hypothesis, dreaming is a “parallel state of consciousness that is continually running but normally suppressed during waking.” (New York University neurologist and physiologist Rodolfo Llinás goes further, contending that dreaming represents consciousness itself—and that when we’re awake, our senses “correct” the underlying procession of dreams.)

Hobson, who has written about consciousness and dreaming in Cerebrum, presented his theory in a recent paper in Nature Reviews Neuroscience. The hypothesis stems in part from advances in studying REM sleep, the article notes. Evidence indicates that this dream-laden sleep stage helps neurons wire up, particularly in areas of the brain related to vision. Other research suggests that in lucid dreaming, in which people observe their own dreams, brain-wave activity reflects elements of both REM sleep and waking awareness.

As for the dream my friend was relaying? It would seem to be among the approximately 80 percent of dreams that comprise people and places the dreamer has never encountered—before or since, in my friend’s case.

Anderson, you can rest easy.

-Dan Gordon

Genes and criminals: Italian court makes controversial ruling

“Don’t blame me—it was my genes’ fault.” Could this be the plea of future criminals? In Italy, the case of a man who confessed to murder in 2007 may set a precedent.

It’s not that unusual that an Italian court gave Abdelmalek Bayout three years less than it otherwise would have because his lawyer argued Bayout was mentally ill at the time of the crime. What is unprecedented, though, is that at an appeal hearing in September the judge removed an additional year from the defendant’s sentence based on genetic tests. The judge believed Bayout’s genes made him “particularly aggressive in stressful situations,” basing his decision on the tests that revealed Bayout to have low levels of MAOA, a trait which has been linked to criminal behavior.

It was the first time in a European court that behavioral genetics has affected a sentence. In the United States, this type of defense has been used more than 200 times in the past five years and in rare cases has influenced sentencing.

“There’s increasing evidence that some genes together with a particular environmental insult may predispose people to certain behavior,” Pietro Pietrini, a molecular neuroscientist at Italy’s University of Pisa and one of the researchers investigating Bayout’s genetic makeup, said in a Nature news article.

Many people argue that this is true for anyone. It’s certainly a worthwhile question: Isn’t anyone who commits murder at least a little bit mentally ill? While this particular criminal’s sentence was reduced, others have argued that courts could rule the other way—if the person’s genes are “bad,” perhaps the sentencing should be stricter.

Many researchers contacted by Nature also questioned the court’s decisions. Giuseppe Novelli, a forensic scientist and geneticist, said that tests for single genes are “useless.” The judge may not have considered some additional relevant factors when analyzing the results, according to geneticist Terrie Moffitt.

It’s an interesting debate and likely one with too many factors to be settled any time soon.

—Andrew Kahn

When senses combine

Synesthesia is a phenomenon in which people’s senses seem to be crossed. Some people with the condition can feel tastes or see sounds; others taste voices (think of the opposite of anesthesia, literally “no senses”). Neurologist Richard Cytowic has studied such people for more than three decades, starting with a man in the rare latter category.

“Some people are born with two or more senses hooked together,” Cytowic told an audience of around 120 people at the Library of Congress on Oct. 30. For example, for the first synesthete he studied, some flavors “were more than a mouthful.”

Synesthesia experts estimate that one in 23 people has some form of this involuntary sense-mixing. Some scientists working with infants theorize that all babies are born synesthetic but lose the trait at around three months, when their sense networks start to firm up.

In 1979, when he was a young researcher, Cytowic said, no one had heard of synesthesia, and if they had they thought it wasn’t real. But he was hooked—“it interested me to explain a subjective experience that seems impossible to prove.”

He and others eventually did prove it, through well-designed experiments and a mass of data from people who started calling and writing to describe their experiences. Now “a new generation in 15 countries” studies the trait, from its individualistic expression in behavior to its possible molecular and genetic components.

“Five groups around the world are working on analyzing for the synesthesia gene,” he said. Researchers currently think the trait is genetic (“hyperconnectivity between disparate brain systems”) but requires early exposure to over-learned groupings. For example, many synesthetes see colors or shapes related to such sequences as days of the week, calendars and other common number forms, including music. (Are you synesthetic? Take a computer-based test at http://www.synesthete.org/.)

Cytowic played two short films to help illustrate the ability. The first paired Chopin’s Valse Brillante with a moving pattern of dashes of color changing in time with the music. The second, a short film by Terri Timely seen below, cleverly captures the idea of living with many forms of synesthesia, Cytowic said. One difference, though, is that instead of the discrete objects such as cats seen in the video, synesthetes are more likely to see general shapes or colors.

Crossing sense pathways can run in families and seems to be more common in artistically creative people, Cytowic said. Examples include writers Douglas Coupland and Vladimir Nabokov (and his family); artists David Hockney and Wassily Kandinsky; musicians Olivier Messiaen, Itzak Perlman and Billy Joel; and performer Marilyn Monroe. Stevie Wonder also has a form of sound-color synesthesia. “Synesthesia is very common in blind people because you don’t need your eyes to see—you see with your brain,” Cytowic said.

Their experiences are not always positive, though. One audience member described herself as a mild sound-taste synesthete and her son a stronger one. One year at school, she said, her son found that his new teacher’s voice “brought a bad taste to his mouth” to such an extent that she had to arrange to move him to a new classroom, “and it was ridiculously difficult. Nobody believed it” when he kept saying “her voice makes me sick.”

Sometimes it’s a synesthete’s friends and family who need to close their eyes. Cytowic told of a taste-color synesthete who had to wait until his wife was out of town to eat a favorite, “very blue,” dish: baked chicken Alaska drenched in orange juice and topped with ice cream.

“Synesthetes have taught us that cross-talk is the rule, not the exception,” Cytowik said. “Minds that work differently are not that different at all, and we can learn from them.”

With David Eagleman, Cytowik co-authored Wednesday Is Indigo Blue: Discovering the Brain of Synesthesia, which was recently reviewed in Cerebrum. His lecture is part of the “Music and the Brain” series, presented by the Library of Congress and the Dana Foundation. The next event, on music and trance states, is tonight; a lecture on dangerous music takes place Friday, Nov. 6.

—Nicky Penttila

Refunds on the way for Baby Einstein videos

On Saturday, Tamar Lewin of the New York Times reported that the Walt Disney Company is now offering refunds for its popular but controversial Baby Einstein videos.

According to the article, Baby Einstein was founded in 1997; Disney acquired the company in 2001 and expanded it to offer a full line of DVDs, books, toys, flash cards and apparel aimed at infants and toddlers. It’s estimated that Baby Einstein now controls 90 percent of the baby media market, selling $200 million worth of products annually.

The move comes after a heated battle over the marketing claims Disney has used to sell the line. Lewin, for instance, quotes Susan Linn, the director of Campaign for a Commercial-Free Childhood, which has been pushing Disney and other baby media companies to acknowledge that the videos are not, indeed, educational. “The unusual video refunds appear to be a tacit admission that they did not increase infant intellect,” Lewin writes.

Perhaps this will serve as a death knell to the marketing hype that began when the so-called “Mozart effect” was first reported in a 1993 letter published in the journal Nature. The paper claimed that college students exposed to classical music had better spatial reasoning skills, which are important to success in math and science. Scientists, however, have not reliably replicated the phenomenon. And there is little hard evidence for the effectiveness of any of the products available commercially.

The lack of science-based data, however, is being rectified by scientists doing more quantifiable studies in arts training. In the “Learning, Arts, and the Brain” report, the Dana Foundation’s Arts and Cognition Consortium reported on some of the initial studies looking at the connections between media, education and the brain. Since then researchers have gained a more sophisticated understanding of how young minds develop and learn, including new findings reported this May at a summit in Baltimore. Acknowledging that much more research needs to be done, neuroscientists also recently outlined plans to grow and unify work in the field.

In the meantime, for lack of a better alternative, many parents have gone with their intuition and concluded that the best teaching “device” for brain development is low-tech. Parental involvement with one’s child, whether in the form of conversation, games and book reading, may provide the best stimulation for growing brains and minds.

Neuroscientists and pediatricians back this idea up. Lewin notes that the American Academy of Pediatrics recommends no TV time at all for children under age 2. In the Ten Guideposts for Parents chapter in Dana Press book A Good Start in Life, Norbert Herschkowitz and Elinore Chapman Herschkowitz make a similar suggestion.

—Rosemary Shields

Have no fear—not after this research

    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.

   Phelps’ main point was that the fear response can change, sometimes for the better. “Something that is fearful today may be rewarding tomorrow,” she said in her introduction.

   Humans, like other animals, can be conditioned to associate a tone with a mild shock. We will then display a fear response when we hear the tone. In the brain, it’s the amygdala that is responsible for the physical expression (such as sweating, increased blood pressure or a quickening pulse) of a learned fear response.

   Humans can also learn a fear via instruction—simply from being told that there may be a shock, for example—or via observation, such as by watching someone else receive a shock after hearing a tone. Understanding this, researchers can develop models of fear learning in complex, uniquely human social environments, Phelps said.

   These models will help explain what Phelps called a critical question regarding human fears: how to diminish or extinguish them. For example,exposure therapy, which includes learning that a previously fear-inducing stimulus is safe, is a successful model, she said.

   In animal models of what’s called fear extinction, the response in the amygdala decreases because it is inhibited by another region, the ventromedial prefrontal cortex, which Phelps said is necessary for keeping the fear from returning later. One interesting facet of this area of research is that humans were able to decrease their own fear response by thinking of something calming when shown a fear-related stimulus, with corresponding variations in brain activity.

   Phelps and her colleagues are now studying how to erase a fear memory altogether, perhaps by disrupting the reconsolidation of such a memory. Their theory is that when we retrieve a memory, it may be “fragile,” offering an opportunity to influence or change it. Studies in humans have offered evidence that extinction training during reconsolidation can prevent the reinstatement of fear.

   Still, “there are many things we don’t know at this point,” Phelps said. Among the more intriguing questions are whether such extinction training might affect not just conditioned fear but complex emotional memories, and, if so, whether such approaches might help treat anxiety disorders.

   Much more research lies ahead. Look for fascinating insights about emotion and memory along the way.

—Dan Gordon

Grief: a musical case study

   Grief and depression are distinctly different human experiences, but even experienced psychologists and brain scientists sometimes have trouble teasing the two apart.

   Those slivers of contrast were the central theme of “Music and Grief,” a panel discussion held on Tuesday at the Library of Congress in Washington, D.C. The event kicked off the second season of the “Music and the Brain”lecture series (an earlier program on the mystery of Beethoven’s deafness had to be rescheduled for next year).

   In keeping with the series’ mission to delve into how brain science gives us insight into the mysteries and benefits of music, the three speakers recounted their personal and professional experiences with music, grief and depression. Live illustrations were provided by the Julliard School graduate string quartet in residence.

   Kay Redfield Jamison, a psychiatry professor at Johns Hopkins University and co-director of its Mood Disorders Center, outlined the rawness of her grief following the 2002 death of her husband, Richard Wyatt, then chief of neuropsychiatry at the National Institute of Mental Health. Jamison, who was previously written at length about her struggles with bipolar disorder, read from her new memoir, “Nothing Was the Same,” about how her grief was at times overwhelming, even causing her to give away her entire music collection because of unpleasant associations. But, she said, she didn’t suffer from a single day of depression, which she had greatly feared given her history. Unlike grief, in which the comfort and company of others is powerfully helpful, “the capacity for solace does not exist in depression,” she added.

   Her colleague J. Raymond DePaulo, chairman of Johns Hopkins’s psychiatry department, expounded on some of her comments based on his experiences treating more than 15,000 patients. Grief generally begins with a period of numbness that is followed by a bout of “profound sadness” that has ups and downs and varies in length from weeks up to years, he said. People slowly re-engage with normal life, though memories of the lost loved one can bubble up suddenly and unexpectedly for decades afterward.

   In contrast, while extreme grief can cause depression, only a fraction of depressed people consider themselves sad. Rather, the dominant feeling in depression is one of hopelessness or emptiness, which erodes people’s self-confidence, causes them to pull away from friends and damages their ability to function in daily life. “We must distinguish these conditions, but it can be extremely difficult, and we must be prudent,” DePaulo said. “We don’t want to medicalize a universal human condition [grief], and at the same time we want to give them solace.”

   In between those presentations came an interesting case study: the extreme reaction of musical virtuoso Felix Mendelssohn to the death of his beloved sister Fanny. Ara Guzelimian, provost and dean of the Juilliard School, described how Mendelssohn—then at the height of his prowess and celebrity—largely withdrew from the world, writing only a few pieces of music before his death less than six months later. But his prolific correspondence emphasizes the depths of his feelings, as does his last major composition, String Quartet No. 6 in F minor, Guzelimian said. Characterized by an unrelenting bleakness and harshly conflicting notes, this is “an extraordinary extreme piece of music” with a “music vocabulary utterly uncharacteristic of Mendelssohn,” he said before the Julliard musicians played its first movement. “Every restraint comes off the music.”

   Responding to audience questions, the presenters emphasized that music has shown, at least anecdotally, therapeutic benefits both for grief and depression. Pieces like String Quartet No. 6, for instance, can help listeners purge or come to terms with their negative emotions, Guzelimian said, and the Julliard performers remarked about the emotional exhaustion they feel after playing the entire piece. Guzelimian gave a personal example of how music can serve different roles at different times: A particular piece that he had found comforting when undergoing a major surgery, contemplating his own possible death, was unbearable to him shortly after the death of a close friend.

   The Dana Foundation funds the Music and the Brain series. Jamison and DePaulo are members of the Dana Alliance for Brain Initiatives.

—Aalok Mehta

A memory for prions

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.

--Aalok Mehta

For neuroscientists, a new way to share

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."
--Aalok Mehta

In dyslexia, a brain out of tune?

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.

--Aalok Mehta

The neuroethics of consciousness

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.

--Dan Gordon