Painting Neural Circuitry With a Viral Brush

The "Molecules of the Mind" column appears monthly in the Psychiatric Times. Learn more about "Brain Rules" at www.brainrules.net.

We often describe neural connections in the brain as if they were a cellular version of Michelangelo’s famous painting “Hand of God Giving Life to Adam,” on the ceiling of the Sistine Chapel. Like the painting, the neural explanations usually invoke 2 outstretched limbs nearly touching each other—one presynaptic,one postsynaptic—that are separated by their 20-nanometer synaptic cleft.

Such descriptions hardly depict the neurological reality of the brain, of course. A better metaphor for 2 neurons might be 2 trees that have been uprooted and turned 90 degrees so their root systems face each other. Then, some Paul Bunyan–type character jams both ends together. Thousands of connections from 1 tree now face thousands of connections from the other. Multiply those 2 neurons by thousands while all their root systems are still jammed together with the same Bunyanesque enthusiasm and you can visualize an approximation of the real world of brain wiring. Not as elegant as 2 limbs—and not as simple either.

How can we understand the way all those myriad connections work together to produce the various neurological abilities of the brain? Given its complexity, the task is enormous. Since we are only in the initial stages, it will take a long time before we will be able to map structure to function.

Like any exploration in its initial stages, we first need a good map—a schematic that shows how each slender dendritic branch interacts with a specific nerve cell. From Nissl and Weigert stains to the canonical Golgi stain, we have traditionally used dye technology to help us visualize these interactions. However, there are severe limitations to most of these staining technologies that center around their inability to make visible all the connections that actual neurons possess. We need something with far greater resolution and, perhaps, with a bit more elegance.

The topic of this column and the next is a technology that promises to deliver just such circuit diagrams at a very high level of resolution. The technology involves the exploration of viruses, which in their native form cause some pretty tough diseases (eg, rabies, cancer). Thoughtful genetic engineering has transformed these viruses’ job description from fearful disease inducer to doughty cartographer cartographer. We are going to follow how this transformation has occurred.

Download the full column (PDF), which appears in the October issue of Psychiatric Times.

Blood Tests for Bipolar I Disorder

I experienced an interesting confluence of events the other day. My 11-year-old son has been finding out about the great power of online information. Although we limit his access to assistance with homework, he is already a digital whiz kid who knows where to find a great deal of information for writing tomes like Norse history reports. In my day, it would have taken an entire afternoon of digging through texts at a university library to obtain items he found in a few seconds.

The confluence came about because of what I was doing while sitting next to him. While he was busy downloading information about Vikings, I was reading an update on a story that I have been following for a few years: the attempt to create a simple, objective blood test that could properly identify mood disorders. That would be a truly handy gadget for mental health professionals to have in their diagnostic tool kits! Going through the literature, which relies heavily on gene expression data, it hit me how profoundly the judicious use of online databases has contributed to the scientific rigor of the research. The Internet was not only seminal to my son’s work but also to this blood test research.

In this column, I will discuss new progress on this Internet-boosted line of inquiry. I will begin with a few basics about differential gene expression and microarrays and will then move on to something that researchers are calling “convergent functional genomics.” As you shall see, the clever use of online databases both confirmed and extended the work done at the bench. As a result, it may very well be possible in the next few years to have a clinic-ready blood test that is capable of diagnosing unipolar and bipolar depression. There may even be a diagnostic test for schizophrenia.

Download the column (PDF), which appears in the September issue of Psychiatric Times.

Oxytocin and the Bottom Line

Trust can be a scary proposition. Among other characteristics, trusting someone involves the ability to measurably predict a behavior on the basis of nothing more than a memory, an impression, or a whim. For creatures like us, who spend a ridiculous amount of time with unpredictable strangers, brokering trust is an oddly important survival strategy.

Trusting behaviors have fascinated a broad swath of the behavioral research community, from social scientists and evolutionary theorists to cellular and molecular biologists. This community has, over the past few years, acquired insight from unlikely corners of academia, including, of all places, business schools. This column is all about an interesting collision between biologists, economists, and the human capacity to rely on the character or integrity of other people.

Those of you who are already familiar with the topic know I am about to discuss one of biology’s most ancient neurotransmitters: oxytocin. Its molecular mechanisms have become increasingly well characterized and have strong links to behaviors that involve the seemingly subjective experience of trust. Oxytocin has even been hypothesized to influence economic decisions. Can it?

To read the rest of the column, download the PDF (it's too long to post on the blog). "Oxytocin and the Bottom Line" was published in the August issue of Psychiatric Times. You can download all the 2008 "Molecules of the Mind" columns below or here.

Oxytocin and the Bottom Line (August 2008)

Of Stress and Alcoholism, Of Mice and Men (July 2008)

The Biology of Recognition Memory (June 2008)

Why Emotional Memories Are Unforgettable (May 2008)

Schizophrenia, DISC1, and Animal Models (April 2008)

Neurobiology of PTSD—Part 3 (March 2008)

Neurobiology of PTSD—Part 2 (February 2008)

Neurobiology of PTSD—Part 1 (January 2008)

Repeat to Remember, Remember to Repeat

It takes years to consolidate a memory. Not minutes, hours, or days but years. What you learn in first grade is not completely formed until your sophomore year in high school.

Watch John Medina explain how long-term memory works. View on YouTube.


BRAIN RULE RUNDOWN
Rule #5: Repeat to remember

• The human brain can only hold about seven pieces of information for less than 30 seconds! Which means, your brain can only handle a 7-digit phone number. If you want to extend the 30 seconds to a few minutes or even an hour or two, you will need to consistently re-expose yourself to the information. Memories are so volatile that you have to repeat to remember.
• Improve your memory by elaborately encoding it during its initial moments. Many of us have trouble remembering names. If at a party you need help remembering Mary, it helps to repeat internally more information about her. “Mary is wearing a blue dress and my favorite color is blue.” It may seem counterintuitive at first but study after study shows it improves your memory.
• Brain Rules in the classroom. In partnership with the University of Washington and Seattle Pacific University, Medina tested this Brain Rule in real classrooms of 3rd graders. They were asked to repeat their multiplication tables in the afternoons. The classrooms in the study did significantly better than the classrooms that did not have the repetition. If brain scientists get together with teachers and do research, we may be able to eliminate need for homework since learning would take place at school, instead of the home.

More Resources
->Short-term memory tutorial (Brain Rule #5)
->Short-term memory references (PDF)
->Long-term memory tutorial (Brain Rule #6)
->Long-term memory references (PDF)

Hang Up and Drive

View the 2-minute "Hang Up and Drive" video on YouTube. Driving while talking on a cell phone is like driving drunk.

Brain Rules for PowerPoint & Keynote presenters

Garr Reynolds, author of "Presenation Zen," has a great post on his blog discussing the book: Brain Rules for PowerPoint & Keynote presenters.

Here's what Garr says about the book:

"Brain Rules is one of the most informative, engaging, and useful books of our time. Required reading for every educator and every business person. My favorite book of 2008!"

View Upload your own

Above: here's a slide presentation Garr created based on some of the ideas in Brain Rules.

Brain Rules Webinar - Tuesday, June 3 at 2pm EDT/11am PDT

Join John Medina for a live Brain Rules Webinar covering Exercise, Stress, and Multitasking. The free Webinar is hosted by Alvaro Fernandez, the co-founder of SharpBrains.

Date and time: Tuesday, June 3 at 2pm EDT/11am PDT
Register: Here

SharpBrains Blog Post
Brain Rules

Harvard Business Review Interview - "The Science of Thinking Smarter"

The May issue of Harvard Business Review features an interview with John Medina, author of "Brain Rules." The article is called The Science of Thinking Smarter (click to read the full article on the HBR site). Below is the executive summary.



Neuroscience can show managers ways to improve productivity.
A Conversation with brain expert John J. Medina by Diane Coutu

Advances in neurobiology have demonstrated that the brain is so sensitive to external experiences that it can be rewired through exposure to cultural influences. Experiments have shown that in some people, parts of the brain light up only when they are presented with an image of Bill Clinton. In others, it’s Jennifer Aniston. Or Halle Berry. What other stimuli could rewire the brain? Is there a Boeing brain? A Goldman Sachs brain?

No one really knows yet, says Medina, a developmental molecular biologist, who has spent much of his career exploring the mysteries of neuroscience with laypeople. As tempting as it is to try to translate the growing advances to the workplace, he warns, it’s just too early to tell how the revolution in neurobiology is going to affect the way executives run their organizations. “If we understood how the brain knew how to pick up a glass of water and drink it, that would represent a major achievement,” he says.

Still, neuroscientists are learning much that can be put to practical use. For instance, exercise is good for the brain, and long-term stress is harmful, inevitably hurting productivity in the workplace. Stressed people don’t do math very well, they don’t process language very efficiently, and their ability to remember—in both the short and long terms—declines. In fact, the brain wasn’t built to remember with anything like analytic precision and shouldn’t be counted on to do so. True memory is a very rare thing on this planet, Medina says. That’s because the brain isn’t really interested in reality; it’s interested in survival.

What’s more, and contrary to what many twentieth-century educators believed, the brain can keep learning at any age. “We are lifelong learners,” Medina says. “That’s very good news indeed.”
Read the full interview in Harvard Business Review

Authors@Google, Freakonomics Blog, and More

Last week John spoke at Google about exercise and stress. You can watch the talk on YouTube or below.


John wrote a short essay for the Freakonomics Blog on the New York Times Web site. He addressed the question: How Much Progress Have Psychology and Psychiatry Really Made?

Here are links to other news and sites for Brain Rules readers:

- Seattle Times feature article - "12 rules to boost your brain power"
- Watch John's interview on Northwest Afternoon (KOMO-ABC)
- iTunes - download the exercise chapter from the audio book
- YouTube - watch dozens of videos from the Brain Rules DVD
- Web tutorials for all 12 brain rules.


John Medina testing the Sleep Pod at the Googleplex.

Introduction to Brain Rules

Go ahead and multiply the number 8,388,628 x 2 in your head. Can you do it in a few seconds? There is a young man who can double that number 24 times in the space of a few seconds. He gets it right every time. There is a boy who can tell you the exact time of day at any moment, even in his sleep. There is a girl who can correctly determine the exact dimensions of an object 20 feet away. There is a child who at age 6 drew such lifelike and powerful pictures, she got her own show at a gallery on Madison Avenue. Yet none of these children could be taught to tie their shoes. Indeed, none of them have an IQ greater than 50.

The brain is an amazing thing. Your brain may not be nearly so odd, but it is no less extraordinary. Easily the most sophisticated information-transfer system on Earth, your brain is fully capable of taking little black squiggles from a piece of bleached wood and deriving meaning from them. To accomplish this miracle, your brain sends jolts of electricity crackling through hundreds of miles of wires composed of brain cells so small that thousands of them could fit into the period at the end of this sentence. You accomplish all of this in less time than it takes you to blink. Indeed, you have just done it. What's equally incredible, given our intimate association with it, is this: Most of us have no idea how our brain works.

This has strange consequences. We try to talk on our cell phones and drive at the same time, even though it is literally impossible for our brains to multitask when it comes to paying attention. We have created high-stress office environments, even though a stressed brain is significantly less productive. Our schools are designed so that most real learning has to occur at home. This would be funny, if it weren't so harmful.

Blame it on the fact that brain scientists rarely have a conversation with teachers and business professionals, education majors and accountants, superintendents and CEOs. Unless you have the Journal of Neuroscience sitting on your coffee table, you're out of the loop. My book is meant to get you into the loop.

12 brain rules
My goal is to introduce you to 12 things we know about how the brain works. I call these Brain Rules. For each rule, I present the science and then offer ideas for investigating how the rule might apply to our daily lives, especially at work and school. The brain is complex, and I am taking only slivers of information from each subject—non-comprehensive but accessible.

A sampling of the ideas you'll encounter:

-For starters, we are not used to sitting at a desk for eight hours a day. From an evolutionary perspective, our brains developed while working out, walking as many as 12 miles a day. The brain still craves the experience, especially in sedentary populations like our own. That's why exercise boosts brain power (Brain Rule #1) in such populations. Exercisers outperform couch potatoes in long-term memory, reasoning, attention, problem-solving tasks, and more. I am convinced that integrating exercise into our eight hours at work or school would only be normal.

- As you no doubt have noticed if you've ever sat through a typical PowerPoint presentation, people don't pay attention to boring things (Brain Rule #4). You've got seconds to grab someone's attention, and only 10 minutes to keep it. At 9 minutes and 59 seconds, something must be done quickly—something emotional and relevant. Also, the brain needs a break. That's why I use stories in this book to make many of my points.

- Ever feel tired around 3 o'clock in the afternoon? That's because your brain really wants to take a nap. You might be more productive if you did: In one study, a 26-minute nap improved NASA pilots' performance by 34 percent. Even so, the brain isn't resting while it sleeps. It is surprisingly active. And whether you get enough rest affects your mental agility the next day. Sleep well, think well (Brain Rule #7).

- We'll meet a man who can read two pages at the same time, one with each eye, and remember everything in the pages forever. Most of us do more forgetting than remembering, of course, and that's why we must repeat to remember (Brain Rule #5). When you understand the brain's rules for memory, you'll see why I want to destroy the notion of homework.

- We'll find out why the terrible twos only look like active rebellion but are actually a child's powerful urge to explore. Babies may not have a lot of knowledge about the world, but they know a whole lot about how to get it. We are all natural explorers (Brain Rule #12), and this never leaves us, despite the artificial environments we've built for ourselves.

Back to the jungle
What we know about the brain comes from biologists who study brain tissues, experimental psychologists who study behavior, and cognitive neuroscientists who study how the first relates to the second. Evolutionary biologists have gotten into the act as well. Though we know precious little about how the brain works, our evolutionary history tells us this: The brain appears to be designed to solve problems related to surviving in an unstable outdoor environment, and to do so in nearly constant motion. I call this the brain's performance envelope. If you wanted to create an education environment that was directly opposed to what the brain was good at doing, you probably would design something like a classroom. If you wanted to create a business environment that was directly opposed to what the brain was good at doing, you probably would design something like a cubicle. And if you wanted to change things, you might have to tear down both and start over.

In many ways, starting over is what the book is all about.