Behavioral Science

The National Academy of Sciences recently celebrated its 150th birthday by, among other things, conferring membership on Ben Barres, MD, PhD. Additional NAS admittees from Stanford were sleep scientist Emmanuel Mignot, MD, PhD, and bioengineer Steve Quake, PhD.

A distinguished scientist by anybody’s yardstick, as well as the chair of Stanford’s ironically named neurobiology department, Barres is a leading light in the study of glial cells (collectively known as glia), the 90 percent of all the cells in the brain that aren’t nerve cells.

The term”glia” is derived from the Greek word for glue. Like Rodney Dangerfield, glial cells once got no respect. They were thought of, in fact, as not much more than “brain glue”: mere structural scaffolds for the organ’s much more revered nerve cells.

Barres’ research has proved that hypothesis incorrect, to say the least. (For details, click here.) Discoveries coming out of his lab include, to name one example, glial cells’ crucial role in determining exactly when and where nerve-cell connections in the brain are made, tweaked to strengthen or weaken them, or destroyed.

You don’t get much more respectable than that: Those connections pretty much define the thoughts we have, the emotions and sensations we experience and the actions we take.

The man who, as much as anyone, has brought a set of unsung cells a newly elevated status would like to see another group get more respect: the estimated 0.3 percent of Americans who are transgender.

“I’m the first transgender scientist to make into the National Academy of Science,” says Barres, who began life under another first name: Barbara.

“We don’t know if other members past or present are or were transgender,” demurs an NAS representative. And after all, how would they? What kind of statistics could be compiled by an organization that doesn’t ask or track the sexual orientations, much less the gender identities, of its membership? Who would have even considered asking such a question 20 or 30 years ago, much less running sex-chromosome tests on cheek swabs from prospective, current or posthumous members?

But it’s a pretty safe bet that if any previously admitted NAS member were openly transgender, we’d have heard about it. (Transgendered computer scientist Lynn Conway was admitted to the National Academy of Engineering in 1989.)

One is tempted to compare Barres to Jackie Robinson, who broke the Major League Baseball’s color barrier in 1947 - except that the latter had to put up with a whole lot more grief from his fellow major-league ballplayers than Barres is likely to encounter from his peers.

“We heartily congratulate Prof. Barres on his election,” says NAS spokesperson Bill Skane.

In science, if anywhere, diverse perspectives drive innovation. ”Don’t ever let anyone make you feel bad about being different,” Barres tells young scientists. “Your difference is your greatest advantage.”

Previously: Malfunctioning glia - brains cells that aren’t nerve cells - may contribute big time to ALS and other neurological disorders, Neuroinflammation, microglia, and brain health in the balance and Unsung brain-cell population implicated in variety of autism

Your brain and my brain are shaped slightly differently. But, it’s a good bet, in almost the identical spot within each of them sits a clump of perhaps 1 to 2 million nerve cells that gets much more excited at the sight of numerals (“5,” for example) than when we see their spelled-out equivalents (“five”), lookalike letters (“5″ versus “S”) or scrambled symbols composed of rearranged components of the numerals themselves.

Josef Parvizi, MD, PhD, director of Stanford’s Human Intracranial Cognitive Electrophysiology Program, and his colleagues identified this numeral-recognition module by recording electrical activity directly from the brain surfaces of epileptic volunteers. Their study describing these experiments was just published in The Journal of Neuroscience.

As I explained in my release about the work:

[A]s a first step toward possible surgery to relieve unremitting seizures that weren’t responding to therapeutic drugs, [the patients had] had a small section of their skulls removed and electrodes applied directly to the brain’s surface. The procedure, which doesn’t destroy any brain tissue or disrupt the brain’s function, had been undertaken so that the patients could be monitored for several days to help attending neurologists find the exact location of their seizures’ origination points. While these patients are bedridden in the hospital for as much as a week of such monitoring, they are fully conscious, in no pain and, frankly, a bit bored.

Seven patients, in whom electrodes happened to be positioned near the area Parvizi’s team wanted to explore, gave the researchers permission to perform about an hour’s worth of tests. In the first, they watched a laptop screen on which appeared a rapid-fire random series of letters or numerals, scrambled versions of them, or foreign number symbols with which the experimental subjects were unfamiliar. In a second test, the experimental subjects viewed, again in thoroughly mixed-up sequence, numerals along with words for them as well as words that sounded the same (1″, “one”, “won”, “2″, “two”, “too”, etc.).

A region within a part of the brain called the inferior temporal gyrus showed activity in response to all kinds of squiggly lines, angles and curves. But within that area a small spot measuring about one-fifth of an inch across lit up preferentially in response to numerals compared with all the other stimuli.

The fact that this spot is embedded in a larger brain area generally responsive to lines, angles, and curves testifies to the human brain’s “plasticity:” its ability to tailor its form and function according to the dictates of experience.

“Humans aren’t born with the ability to recognize numbers,” says Parvizi. He thinks evolution may have generated, in the brains of our tree-dwelling primate ancestors, a brain region particularly adept at computing lines, angles and curves, facilitating snap decisions required for swinging quickly from one branch to the next.

Apparently, one particular spot within that larger tree-branch-interesection recognition area is easily diverted to the numeral-recognition activity constantly rewarded by parents and teachers during the numeracy boot camp called childhood.

Nobody can say those little monkeys don’t learn anything in kindergarten.

Previously: Metamorphosis: At the push of a button, a familiar face becomes a strange one and Why memory and math don’t mix: They require opposing states of the same brain circuitry
Photo by qthomasbower

Ever wonder - say, while sitting quietly in a concert hall or screaming your lungs out in a crowded ampitheater - whether the musical experience you’re having is anything like that of the person three seats up or three sheets to the wind on your right?

A partial answer is in: Our brains process music in pretty much the same way, providing it’s got the requisite combination of components (rhythm, melody, harmony, etc.), according to Stanford neuroscientist Vinod Menon, PhD. In a just-published study, Menon’s group monitored several healthy peoples’ brains while these subjects listened to the same piece of music. As the music played on, activity in a broadly distributed network of neuroanatomically connected brain areas waxed and waned very similarly for each listener. This synchrony among individual responses was absent when participants listened to “pseudomusic” stripped of either rhythmic or tonal characteristics.

The inter-subject synchronization extended to the brain’s movement-planning zone. Evolution, it seems, has designed us this way. As I wrote in my release about the study:

[O]ur brains respond naturally to musical stimulation by foreshadowing movements that typically accompany music listening: clapping, dancing, marching, singing or head-bobbing. The apparently similar activation patterns among normal individuals make it more likely our movements will be socially coordinated.

It’s easy to imagine the survival value of coordinated movement in response to auditory cues. Hunting, gathering, warmaking - all benefit from choreography. That would objectively explain how people who run, shout and pump their fists in synch might win the evolutionary race.

But about the subjective aspect of this synchronization, I’m not so sure.

Look. It’s important that our brains respond similarly to identical stimuli. But what about our minds? In the house of mirrors that is our consciousness, how can we know whether music sounds the same, or color looks the same, to different people?

This takes me back to long ago when, as a philosophy major at the University of Wisconsin, I flunked a course in epistemology. That’s the philosophy of what we know and how we know it, and what we think we know that, actually, we don’t. Turns out I didn’t know much.

One day, the professor - a tweedy, pipe-puffing Princeton man who paced the room in an elbow-patch-bedecked jacket - shouted to the motley assortment of assembled esistentialist ectomorphs: “I PROPOSE. THAT. WHEN I SAY: ‘BLUE!’ ALL OF YOU. SEE. EXACTLY. THE SAME. COLOR!!!”

He paused. “Refute. That. Hypothesis,” he snarled, taking a toke from his pugnacious pipe.

I didn’t raise my hand. It raised itself. He called on me. “I see the same color slightly differently with each eye,” I said, illustrating my claim with alternating winks of my left and right eye. Seemed like a slam-dunk to this Milwaukee boy. (It also happened to be true.)

He glared at me, cross-examined me fiendishly for five long minutes and, striding to the blackboard (I did tell you this was long ago), multiplied the number of minutes we had dueled by the dwindled number of my classmates and thundered: “You’ve wasted 45 student-minutes of class time!”

It was right about then that I started thinking maybe I should switch to science.

So, what is “music,” really? Well, we don’t really know. But whatever it is, it makes us wanna shout, kick our heels up and shout, throw our hands up and shout, throw our heads back and shout.

Previously: New research tracks “math anxiety” in the brain, Why memory and math don’t mix: They require opposing states of the same circuitry and Can playing familiar music boost cognitive response among patients with brain damage?
Photo by gilmorec

I felt a little guilty about pushing my colleague John Sanford to confront his blood phobia as part of a story he was writing for Stanford Medicine magazine. I feel fine about it now, though. While writing it, John overcame the phobia! And the story turned out very well too. In fact, it was recently singled out by long-form journalism curator Longreads as a story worth reading.

Here’s how it starts:

I awoke close to midnight. It was the middle of August, in 1992, and the windows were open in the room of the Paris hostel where I was staying. The air was warm and still. My chest felt moist with — sweat? I touched the substance with an index finger and pressed it to my thumb. It felt tacky. Blood!

(That’s John in the photo, by the way. Yes, he’s holding a test tube of blood.)

Previously: New issue of Stanford Medicine magazine asks, What do we know about blood? and Programmed to fear spiders?
Photo by Erin Kunkel

Sparks flew at a symposium hosted by the Stanford Center for Health Research on Women & Sex Differences in Medicine, which I attended yesterday. One invited speaker -Louann Brizendine, MD, of the University of California at San Francisco - is the author of a couple of books titled The Male Brain and The Female Brain. Another invited speaker - neuroscientist Daphna Joel, PhD, who’d flown in from the University of Tel Aviv, in Israel - emphatically maintained that there is no such thing as a “male” brain or a “female” brain. “What we know,” she said bluntly, “is that males have brains and females have brains.”

Whatever the semantics of that debate, two things are pretty clear any way you slice it. First, male and female brains are mostly alike. Second, there are measurable and meaningful differences in what goes on inside male versus female brains. As another neuroscientist, UCLA’s Art Arnold, PhD, put it: “Every cell in a female’s brain expresses a set of genes that the cells in a male’s brain express at much lower levels, if at all.”

Adding heft to Arnold’s comment was a presentation by Nirao Shah, MD, PhD, of UCSF. The neuroanatomist showcased research in his lab that had pinpointed specific genes whose activity levels differed significantly in the brains of male and female mice. Many of these genes, he noted, have human analogs that have been implicated in alcoholism, autism, breast and prostate cancers, and more. By conducting rigorous experiments with mice in which one or another of such genes had been put out of commission, Shah and his colleagues were able to tease out the behavioral consequences of specific genes’ inactivation. For example, knocking out a particular gene in female mouse moms results in a massive dimunition in their willingness to defend their nests from intruders - a maternal mandate that normal female mice observe rigorously - yet has no other observable effect on their maternal or sexual behavior. Torpedoing a different gene radically reduces Minnie Mouse’s mating mood; but the Mickeys in which this gene has been trashed “are completely normal, as far as we can tell,” Shah said.

The upshot: Yes, there are significant differences in behavior (and therefore in brain action) and in gene activity in the brain cells of males and females. Those of male and female mice, that is. What about humans’?

Well, nobody was talking about knocking any genes out of people to see if the men indulge in fewer barroom brawls and the women start laughing off their babies’ cries of distress. But there are certainly some strong hints of medically significant differences: The ratio of men to women with autism run somewhere in the neighborhood of 8:1 or even 16:1. Depression is twice as common among women as among men - but only between menarche and menopause. Alzheimer’s disease abounds more in women, even after taking into consideration women’s greater longevity (itself a medically important difference), as does autoimmunity. On the other hand, Parkinson’s and schizophrenia preferentially affect men. There seems to be more at work here than the simple “absorption of gender stereotypes,” and it’s good to see hardcore biologists attacking the problem with all the scientific rigor at their disposal.

Let’s not call the whole thing off.

Previously: A call to advance research on women’s health issues
Photo by namuit

Trying to change the health behavior of U.S. adults - like encouraging more people to get a flu shot? The findings of a new Stanford psychology study, which shows that appealing to a person’s sense of independence, versus their desire to do something that could potentially benefit others, may prove helpful. Writer Brooke Donald explains more in an article.

Previously: Understanding the science and psychology of how habits work, Can movie passes and other perks encourage patients to make healthier choices? and Can behavioral changes in virtual spaces affect material world habits?

A new paper published this week in JAMA Psychiatry draws exciting conclusions at the intersection of two fields dear to me: pediatrics and personality science. The paper reports on the success of a personality-based program to reduce teen drinking. In a nutshell, an alcohol-prevention program tailored to teens with high-risk personality traits shows promise for preventing drinking among the young people who might be most prone to drink.

More on that in a minute, but first, a quick anecdote about why I care about personality research: Back when I was in graduate school, my roommate would sometimes do a web search for cheap, last-minute airline tickets, then jet off on almost no notice to some exotic locale. Once, when she neglected to tell her mom that she was going out of the country, I answered our phone to hear her very worried mother say “Erin, do you know where Gina is?” My reply: “Uh, Venezuela?”

If you asked Gina, then a psychology PhD student who was studying personality, about the motivation for these adventures, she sometimes jokingly replied in the jargon of her academic field, pointing out that she scores highly on “openness to new experiences,” one of the standard dimensions by which personality is assessed.

A brief program of cognitive behavioral therapy reduced high-risk teens’ total drinking by 29 percent and binge drinking by 43 percent

Now Gina and I are grown-ups with real jobs. I write about pediatrics at Stanford, while my old friend, known in her professional life as Angelina Sutin, PhD, is an assistant professor at Florida State University, where she is continuing her personality research. When I saw the new paper, I jumped at the chance to call Dr. Sutin, as I guess I’d better refer to her, to get her thoughts on this work that’s relevant to both of our professional lives.

The teen-drinking researchers, who are from Canada, the U.K. and Australia, screened young teens for four personality traits that could predispose them to high-risk behaviors, and then provided prevention programs targeted to the specific high-risk traits. Instead of simply being told, “Don’t drink,” high-risk teens received a brief program of cognitive behavioral therapy to help them recognize healthy and risky coping behaviors that could arise from emotional responses specific to their personalities. Substance abuse was mentioned as one of several risky coping behaviors, but was not the main focus of the program.

This approach reduced high-risk teens’ total drinking by 29 percent and binge drinking by 43 percent. Schools where high-risk students received the intervention also had less total drinking than control schools, suggesting that low-risk students drank less if they saw less drinking among their peers.

Continue Reading »

The National Institutes of Health’s Office of Behavioral and Social Sciences Research introduced a new blog today titled The Connector. More details from an NIH release:

The Connector will keep readers informed of the office’s activities, trainings, educational resources and funding opportunity announcements, as well as podcasts and videos of conversations with engaging behavioral and social sciences. These include:

• Dr. Andrea Gielen on “The Science of Injury Prevention Research”
• Dr. Charlene Quinn on the promise of mobile health technologies in managing diabetes
• Dr. Brian Wansink on “mindless eating,” why we eat more than we think

In addition, the blog include commentaries from Robert Kaplan, PhD, director of the Office of Behavioral and Social Sciences Research. Kaplan plans to explore a range of topics on the blog including mHealth, systems science, dissemination and implementation research and the NIH Toolbox. He also will discuss achieving better population health through improved dissemination of evidence-based interventions.

Previously: NIH deputy director discusses blogging and science policy

Here’s a heart-warming story about a 12-year-old boy making a difference in scientific research. Julian Levy, the son of University of British Columbia psychologist Alan Kingstone, PhD, proposed his father use the Monster Manual from the fantasy role-playing Dungeons and Dragons in a study on tracking gaze-copying behavior. The manual, which includes a diverse range of creatures, allowed Kingstone to overcome an important roadblock in his research.

This isn’t just an academic exercise … It might also help to explain why people with autism often fail to make eye contact with other people, and which parts of the brain are responsible.

Kingstone was investigating two potential explanations for gaze-copying behavior: we are naturally drawn to people’s eyes and will look in the direction others are looking or we focus broadly on faces and the eyes happen to be in the middle. The problem was he couldn’t test the theories since all humans have eyes in the middle of their faces. But then Levy suggested using monsters inspired by Dungeons and Dragons and two years later the father-s0n team published their findings in the Royal Society’s Biology Letters. As reported in a recent post on Discover’s Not Exactly Rocket Science blog:

Levy asked 22 volunteers to stare at the corner of a screen, press a key to bring up one of 36 monster images, and let their eyes roam free. All the while, he tracked their eye movements with a camera.

The recordings showed that when volunteers looked at drawings of humans or humanoids (monsters with more or less human shapes), their eyes moved to the centre of the screen, and then straight up. If the volunteers saw monsters with displaced eyes, they stared at the centre, and then off in various directions. The volunteers looked at eyes early and frequently, whether they were on the creatures’ faces or not.

This isn’t just an academic exercise, says Kingstone. “If people are just targeting the centre of the head, like they target the centre of most objects, and getting the eyes for free, that’s one thing. But if they are actually seeking out eyes that’s another thing altogether,” he says. It means that different parts of the brain are involved when we glean social information from our peers. It might also help to explain why people with autism often fail to make eye contact with other people, and which parts of the brain are responsible.

Previously: Researcher shows how preschoolers are, quite literally, little scientists, No, really, the kid *should* see this, Stanford’s RISE program gives high-schoolers a scientific boost and A proposal to combat “science alienation”

Can you compute your taxes while simultaneously remembering what you had for lunch yesterday? Neither can I. But doing two things at once isn’t always hard - in fact, it can be as easy as listening to music while driving, or talking while washing the dishes.

Today, though, Stanford neuroscientist Josef Parvizi, MD, PhD, and his colleagues have shown in a study that recalling your own experiences and performing externally oriented tasks such as arithmetical reasoning are mutually exclusive. That’s because the same brain circuitry that must be activated for the former to proceed must be actively suppressed during the latter activity. As I describe in a release:

The researchers showed that groups of nerve cells in a structure called the posterior medial cortex, or PMC, are strongly activated during a recall task such as trying to remember whether you had coffee yesterday, but just as strongly suppressed when you’re engaged in solving a math problem.

The PMC sits roughly where the brain’s two hemispheres meet, making it one tough place to visit, technically speaking. Yet neuroscientists would love to learn much more about the PMC, because it’s known to be a key player in introspective activities such as remembering past experiences, imagining the future, and just plain daydreaming.

So Parvizi and his team turned to epileptics for assistance. These patients, whose seizures were unresponsive to drug therapy, had already had small sections of their skulls removed and plastic packets containing electrodes placed at the surface of their exposed brains. Their brain activity was then monitored for close to a week, so when seizures inevitably came, their exact point of origination could be identified. Then, surgeons could excise a tiny piece of tissue at that spot, breaking the positive-feedback loop of electrical-wave amplification that is a seizure.

Five to seven days of lying in a hospital bed leaves these people, shall we say, bored out of their skulls, yet perfectly conscious.

Finding eight patients whose electrodes were situated close to the PMC region (the brain’s hemispheres are spaced far enough apart to shoehorn in an electrode-containing packet without causing any damage or pain), Parvizi’s team got their permission to do a study requiring no further medical manipulation and only modest mental effort. The volunteers were given laptops on which appeared batteries of true/false statements about memory (“I had coffee this morning”) or math (“67 + 6 = 75″) and recorded activity in the PMC.

The result: All the brain circuits flagged by the electrodes as highly active during the recall exercise were not merely passively silent, but actively suppressed, during arithmetical calculation. “It’s essentially impossible to do both at once,” says Parvizi.

And another important point about the work, pointed out to me by Parvizi: Epileptics are the unsung heroes of brain research. Much of what we know about how our cerebral operating systems is the result of these patients’ willingness to put their brains in the service of scientific research - literally.

Previously: Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s, Brain imaging, and the “image-management” cells that make it possible and A one-minute mind-reading machine? Brain-scan results distinguish mental states
Photo by dierk schaefer