Until quite recently, anatomists desiring a peek inside the human brain had to content themselves with dissecting dead tissue or, when the rare opportunity arose, examining people who had traumatic skull injuries. Only in the past few decades has it been possible to glimpse, in real time, the working brain in action. First came computerized tomography or CT scans, which use a series of X-rays to create a three-dimensional picture. Next, positron emission tomography, or PET scanning, revealed blood flow and metabolism by tracing the path of an injected radioactive chemical. Magnetic resonance imaging (MRI), now gaining the edge in brain research, produces detailed views of both anatomy and brain activity by agitating the body's hydrogen atoms using magnetic fields. Result: a sudden wealth of clues about everything from the mechanisms behind mental illnesses to what happens when a memory is triggered or a skill is learned.
[Learn about more new developments in Secrets of Your Brain.]
"The details, shapes, and patterns in the brain are exquisite on aesthetic grounds alone. But then you realize this is the machinery of thought," marvels Carl Schoonover, a doctoral candidate in neuroscience at Columbia University who was so inspired by the imagery now possible that he created a coffee-table book, Portraits of the Mind, to give it center stage.
For all that these technologies promise to reveal, equally remarkable is the boost they already give physicians in practice. Victims of severe concussions are imaged quickly to pinpoint internal bleeding. Stroke patients are scanned to gauge whether clot-busting drugs will be effective. And surgeons can locate and map their way around territories vital to language, vision, and motor skills before plunging in the knife. Imaging is especially important for doctors working with the brain, says Joseph A. Helpern, professor and vice chairman for research in radiology at the Medical University of South Carolina in Charleston. "You don't want to have to cut into it to find out what's going on."
Even the lowly microscope, used to study tissue sliced out of an animal brain or a human brain after autopsy, has been making significant new contributions. The problem with microscopes that use light (remember your high school's equipment?) is that numerous structures, including many all-important synapses where neurons communicate, are smaller than a light wave and thus invisible. But treating the samples with dyes that can be switched on or off by pulses of light allows scientists to view ever-tinier structures. And microscopes relying on much smaller electron waves to magnify and illuminate brain tissue are powerful enough now to reveal even the minuscule spines, thought to store memory, that protrude from the tentacle-like dendrites of a single neuron.
One cutting-edge microscope can even view those spines in a living animal. New York University School of Medicine scientists recently used this "two-photon" microscope, which employs infrared light and fluorescent dyes, to probe the brains of mice before and after challenging them by, for example, changing something in their cages or speeding up their walkway. During the course of several weeks, the microscope revealed a correlation between these experiences and the creation of new spines. "We're documenting how daily sensory experiences leave minute but permanent marks in the brain," says study coauthor Guang Yang, assistant professor of anesthesiology.
It's the study of the living human brain, however, that has seen the most exhilarating leaps. In some cases, older technologies are offering up new secrets; PET scans, for instance, capture neurons reacting when a person is under stress, and electrodes inserted into the brain reveal which neurons fire when a person thinks certain thoughts. But many of the latest findings hail from two advances in magnetic resonance imaging, "functional" and "diffusion" MRIs.
Back in the early 1990s, scientists realized that MRI magnets could be used to get images of where blood and nutrients rush when an area of the brain becomes engaged—when, say, a person is instructed to think a certain thought. These functional MRIs can then be compared to pictures taken minutes earlier. "I refer to functional MRI as a 'mindoscope,' because it allows us to connect the intangibles of conscious experience with the structure and function in the brain," says Joy Hirsch, who directs the Functional MRI Research Laboratory at Columbia University Medical Center in New York and helped curate "Brain: The Inside Story," an exhibit running through August 2011 at the city's American Museum of Natural History. While fMRIs are imperfect instruments, not least because blood takes a while to respond whereas neurons fire in a flash, the fact that subjects don't need to be cut into or injected with radioactive substances has made them the tool of choice for many researchers.
Diffusion MRI, meanwhile, relies on the understanding that water moving around inside a structure can reveal the structure's shape. For example, monitoring the water inside axons—those long, slender projections that carry nerve impulses but are too tiny to be detected with normal MRI—reveals each axon's position. Similarly, water leaking in unexpected places likely indicates defects in the axon's myelin coating, thought to be a factor with multiple sclerosis and other conditions. An even more advanced technique developed by Helpern and researcher Jens Jensen at New York University School of Medicine, diffusional kurtosis imaging, uses mathematical formulas to yield more detailed information about the diffusing water. In preliminary findings not yet published, DKI scans correctly identified people with mild cognitive impairment, a condition that increases the odds of later Alzheimer's. "We're looking for changes in the brain tissue microarchitecture before the brain shows evidence of shrinkage, akin to an engineer seeking out fissures inside a building's wall well before the wall begins to collapse," Helpern says. One day this may produce the holy grail of brain research, a way to identify and help people at risk for further impairment before the damage is done. Among brain researchers' other areas of exploration:
How emotion affects decision-making. Philosophers have long been stymied by the conflicting responses people give when faced with two seemingly similar moral dilemmas. Told that a runaway train is heading for five people on the track, most people find it acceptable to throw a switch and divert the train toward a single man in harm's way, yet they rebel at the idea of pushing the man off a footbridge onto the track to save the same five people. Using fMRI to image brain areas involved in decision-making, Joshua Greene, assistant professor of psychology at Harvard, has begun untangling the mystery. The prospect of actively shoving a man to his death seems to trigger an emotion-related part of the prefrontal cortex, the "ventromedial" section, while pondering the more neutral action of throwing a switch lights up areas involved with rational thought in the "dorsolateral" section nearby. Once the emotional system is engaged, choices become less reasoned. Subsequent studies of people with ventromedial damage have found that, as would be expected, they don't have the same difficulty pushing the man off the bridge.
"It's good that we have strong emotional reaction to committing an act of violence. But where that violence would actually save lives, this automatic response may not be the best," Greene says. Reworking the footbridge scenario to remove some of the emotion—say, by creating a trapdoor activated by the press of a button—appears to quiet that part of the brain and make the act more tolerable. This is no esoteric exercise: Understanding this response could help people overcome their gut-level opposition to such emotionally charged practices as physician-assisted suicide or organ donation, Greene says.
Differences in the ADHD brain. "We know that during the teenage years the brain undergoes significant structural development and becomes much more architecturally complex," says Helpern. Using DKI to scan the prefrontal cortex of a dozen teens with attention deficit hyperactivity disorder and an equal number without, Helpern's team has just revealed strikingly different developmental progress. In the prefrontal cortex, both the white matter (where the myelin-sheathed axons aiding cell communication are located) and gray matter (home of the neuron cell bodies) developed less extensively in kids with ADHD. A difference in white matter has previously been a suspect in the decision-making challenge that is a hallmark of ADHD, but Helpern thinks this finding, published in the January issue of the Journal of Magnetic Resonance Imaging, is one of the first objective measures showing that the microstructure of the gray matter is different, too. The payoff of understanding the ADHD brain should eventually be more effective therapies.
[Surviving ADHD at Work and School]
The limits of willpower. Every dieter knows that keeping the weight off is often harder than losing it. By performing fMRI scans on six obese individuals as they viewed photographs of food, both before and after they lost 10 percent of their body weight, Columbia University researchers have illuminated at least part of the reason. When the participants were shown the pictures after they'd lost the weight, sections of the brainstem involved in processing rewards were much more active than they had been in the pre-diet scans, presumably making that chocolate cake tougher to resist than in the past. Then the subjects got a shot of the appetite-dampening hormone leptin, which unhelpfully becomes less plentiful after dieting. Sure enough, with the artificial help the reward center returned to its pre-dieting calm, when logically it would be easier to push the cake away. "We're realizing that if you want to study obesity, you've got to look in the brain," says Hirsch, coauthor of the study. "It's clear there's so much more than willpower going on in a dieter struggling with overeating."
Gender's relationship to mood. Why do depression and anxiety disorders strike women more frequently than men? Two preliminary studies suggest key brain differences. When scientists at Children's Hospital of Philadelphia stressed both male and female rats by forcing them to swim, then examined slices of their brains using an electron microscope, they found the males had an ingenious stress-reduction response: They tucked some receptors for a stress-inducing hormone inside their brain cells. Female rats, by contrast, kept all the receptors exposed on the surface. In addition, the hormone bound more tightly to the receptors in the female brains. "The females were more sensitive to the stress neural hormone, and they didn't adapt as readily," says researcher Rita Valentino, director of stress neurobiology at the hospital. Similarly, when PET scans were performed on 46 men and women at the Karolinska Institutet in Stockholm, Sweden, the women turned out to have significantly more binding sites in certain parts of their brains for a chemical believed to be associated with depression.
The neuron-thought connection. Epilepsy patients sometimes need to have electrodes implanted inside their brains to reveal the sites of their seizures. An international team of scientists has taken advantage of this access to better understand the biology of memory. In a highly publicized 2005 study of volunteers with the electrodes, the team found that a specific neuron became activated when a patient viewed photographs of a well-known celebrity but not when he or she looked at photos of other stars or similar-looking women. Thanks to the discovery of what's been called the "Jennifer Aniston cell," scientists have realized that neurons are much more specialized than was previously believed, says coauthor Christof Koch, professor of biology and engineering at California Institute of Technology. The knowledge may one day lead to ways to identify and repair damaged neurons that impair certain memories.
How the mind focuses. Ever wonder how you can concentrate on a book in a noisy, crowded bus? Joy Hirsch's team has discovered the mechanisms that the brain apparently uses to stay focused in distracting situations. While monitoring the temporal lobe via fMRI, the researchers asked people to categorize, by profession, photographs of familiar actors or politicians as they flashed before them. In some cases, the labels on the pictures conflicted with the images; a photo of an actor might be marked with a politician's name. To help the brain focus on the images, extra blood rushed to the area believed to process faces. When the subjects were instructed to ignore the photos and instead categorize the profession based on the written name, the extra energy went to the "reading" center. Understanding how these processes "are engaged to either enhance or regulate behavior opens new doors for possibilities for treating many disorders of decision-making, including, perhaps, addictions," Hirsch says.
[Want to Be Happier? Keep Your Focus]
Integration of the whole network. Crowds simultaneously logging onto a single website can slow or crash the system. Neurologists believe the same sort of jam-up happens when something affects a part of the brain, be it a migraine or a devastating tumor. To better understand how the brain's wiring is interconnected, an international consortium of researchers is now creating a comprehensive diagram of the entire circuitry: the major highways leading to the smaller roads, down to each individual driveway or single neuron, says Olaf Sporns, professor of psychological and brain sciences at Indiana University. Using diffusion MRI on a handful of people, Sporns's team has already begun getting a sense of the routes within the cerebral cortex. The goal of this Human Connectome Project is to gather the wisdom that will come from imaging some 1,200 brains.
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