Friday, September 14, 2012

More Studies Link Fluoride to Brain Damage

Newly discovered and translated published studies reveal fluoride is linked to lower IQ, even at levels added to US water supplies, reports the Fluoride Action Network (FAN). Further, fluoridation promoters misrepresented newly published Harvard fluoride/IQ research.

Thirty-four studies now link fluoride to reduced IQ in humans. Dozens of other studies correlate fluoride to impaired learning and memory, altered neurobehavioral function, fetal brain damage, and altered thyroid hormone levels. Full studies available at FAN's website
"Legislators who mandate fluoridation without carefully considering this research are doing a profound disservice to the health and welfare of their constituents," says attorney Michael Connett of FAN.

Harvard researchers recently concluded, after reviewing 27 fluoride/IQ studies, that fluoride's effect on children's developing brains should be a "high research priority" especially in the US which has never investigated brain/fluoride effects.

Fluoridation advocates, however, misinterpreted this research and mislead legislators in Phoenix, Portland, Wichita and elsewhere by stating the Harvard research isn't relevant to Americans. Advocates claimed the Harvard study found only a ½ point difference in IQ, and that the fluoride levels were much higher than Americans experience.

That's wrong. The Harvard team found that fluoride exposure was associated with a statistically significant reduction of 7 IQ points, not the ½ point claimed by advocate, Dr. Myron Allukian.  The Pew Children's Dental Campaign and other fluoridation advocates, including Allukian and Portland Mayor Sam Adams, have stated the Harvard study focused on fluoride levels of 11.5 mg/l.  Only one of the studies, however, was at 11.5 mg/l.

The majority of water studies examined by the Harvard team investigated fluoride levels which the US EPA says is safe – less than 4 mg/l.
  • One study, sponsored by UNICEF, found reduced IQ at just 0.88 mg/l – a level within the "optimal" fluoride range added to the drinking water of over 200 million Americans.
  • Seven found reduced IQs among children drinking water with fluoride levels between 2.1 and 4 mg/l — levels that 1.4 million Americans drink everyday.
  • Four found effects at levels between 1.8 and 2.0 mg/l — levels that over 200,000 Americans drink everyday.
EPA's conventional approach to risk assessment limits chemical exposure to levels ten times less than those known to cause adverse effects. With fluoride and IQ, the levels of fluoride in water and urine are — at most — just two or three times more than the amount experienced by tens of millions of American children
Children with iodine deficiencies are particularly harmed by fluoride. And iodine deficiency has increased significantly, now affecting up to 12% of the US population.

"The question legislators should be asking themselves is 'Do I wait until public health officials catch up with the scientific literature that now shows fluoride can cause serious neurological harm to children, or do I take my leadership role seriously and stop fluoridation immediately," says FAN Executive Director, Paul Connett, Ph.D. "I think the latter is the only ethical answer."

Read more here:

New links between ghrelin and brain cells involved in development of alcoholism

Researchers at The Scripps Research Institute have found new links between a protein that controls our urge to eat and brain cells involved in the development of alcoholism. The discovery points to new possibilities for designing drugs to treat alcoholism and other addictions.

The new study, published online ahead of print by the journal Neuropsychopharmacology, focuses on the peptide ghrelin, which is known to stimulate eating.

"This is the first study to characterize the effects of ghrelin on neurons in a brain region called the central nucleus of the amygdala," said team leader Scripps Research Institute Associate Professor Marisa Roberto, who was knighted last year by the Italian Republic for her work in the alcoholism field. "There is increasing evidence that the peptide systems regulating food consumption are also critical players in excessive alcohol consumption. These peptide systems have the potential to serve as targets for new therapies aimed at treating alcoholism."

Excessive alcohol use and alcoholism cause approximately 4 percent of deaths globally each year. In the United States, that translates to 79,000 deaths annually and $224 billion in healthcare and other economic costs, according to a 2011 report by the Centers for Disease Control and Prevention.

Key Brain Region
The brain region known as the central nucleus of the amygdala is thought to be a key region in the transition to alcohol dependence, that is, a biological change from experiencing a pleasant sensation upon the consumption of alcohol to the need to consume alcohol to relieve unpleasant, negative feelings due to the lack of its consumption. In animals addicted to alcohol, the central nucleus of the amygdala controls increased consumption.

"Given the importance of the central nucleus of the amygdala in alcohol dependence, we wanted to test ghrelin's effects in this region," said Maureen Cruz, the first author of the study and former research associate in the Roberto laboratory, now an associate at Booz Allen Hamilton in Rockville, MD.

The peptide ghrelin is best known for stimulating eating through its action on a receptor known as GHSR1A in the hypothalamus region of the brain. But scientists had recently shown that gene defects in both ghrelin and the GHSR1A receptor were associated with severe cases of alcoholism in animal models. In addition, alcoholic patients have higher levels of the ghrelin peptide circulating in their blood compared to non-alcoholic patients. And, the higher the ghrelin levels, the higher the patients' reported cravings for alcohol.

New Evidence
In the new study, Roberto, Cruz, and colleagues at Scripps Research and the Oregon Health and Sciences University first demonstrated that GHSR1A is present on neurons in the central nucleus of the amygdala in the rat brain.

Using intracellular recording techniques, the team then measured how the strength of the GABAergic synapses (the area between neurons transmitting the inhibitory neurotransmitter GABA) changed when ghrelin was applied. They found that ghrelin caused increased GABAergic transmission in the central amygdala neurons. With further testing, the scientists determined that most likely this was due to increased release of the GABA neurotransmitter. Next, the researchers blocked the GHSR1A receptor with a chemical inhibitor and measured a decrease in GABA transmission. This revealed tonic, or continuous, ghrelin activity in these neurons.

In the final set of experiments, the researchers examined neurons from alcohol-addicted and control rats when both ghrelin and ethanol were added. First, the scientists added ghrelin followed by ethanol. This resulted in an even stronger increase in GABAergic responses in these neurons. However, when the scientists reversed the order, adding ethanol first and ghrelin second, ghrelin did not further increase GABAergic transmission. This suggests that ghrelin could be potentiating the effects of alcohol in the central nucleus of the amygdala, in effect, priming the system.

New Possibilities
"Our results point to both shared and different mechanisms involved in the effects of ghrelin and ethanol in the central nucleus of the amygdala," said Roberto. "Importantly, there is a tonic ghrelin signal that appears to interact with pathways activated by both acute and chronic ethanol exposure. Perhaps if we could find a way to block ghrelin's activity in this region, we could dampen or even turn off the cravings felt by alcoholics."
Roberto cautions, though, that current therapies for alcoholism only work in a subset of patients.

"Because alcohol affects a lot of systems in the brain, there won't be a single pill that will cure the multiple and complex aspects of this disease," she said. "That is why we are studying alcoholism from a variety of angles, to understand the different brain targets involved."

One aging brain cell can affect entire brain, study finds

Brain cells may undergo aging in much the same way as skin cells do — with one aging cell affecting many of its neighbors, a new study from England says.

Researchers found that aging mouse neurons produced several substances, including free radicals and other molecules that can promote inflammation and alter DNA, which can damage nearby cells.

It was known that skin cells produce such substances as they age, becoming "rotten apples" that can affect other cells near them, but it was thought that neurons would age in a completely different way, the researchers said. Skin cells, such as fibroblasts, which are involved in repairing wounds, maintain their ability to divide, whereas most neurons in adults can't divide.

"This study provides us with a new concept as to how damage can spread from the first affected area to the whole brain," said study researcher Thomas von Zglinicki, a professor of cellular gerontology at Newcastle University.

The finding may open up new ways to treat brain disorders such as dementia, motor neuron disease or age-related hearing loss, the researchers said. However, they noted that mouse research doesn't always hold up in studies of people.

"We will now need to find out whether the same mechanisms we detected in mouse brains are also associated with brain aging and cognitive loss in humans," von Zglinicki said.

If the finding does apply to humans, "we might have opened up a shortcut towards understanding brain aging," he said.

Social deprivation impairs brain functions

Social deprivation impairs brain functions
Social deprivation impairs brain functions
Research from Boston Children's Hospital has revealed, for the first time, how these functional impairments arise.

Social isolation during early life prevents the cells that make up the brain's white matter from maturing and producing the right amount of myelin, the fatty "insulation" on nerve fibers that helps them transmit long-distance messages within the brain, the study found.

It also identifies a molecular pathway that is involved in these abnormalities, showing it is disrupted by social isolation and suggesting it could potentially be targeted with drugs. Finally, the research indicates that the timing of social deprivation is an important factor in causing impairment.

The researchers, led by Gabriel Corfas, PhD, and Manabu Makinodan, MD, PhD, both of the F.M. Kirby Neurobiology Center at Boston Children's Hospital, modeled social deprivation in mice by putting them in isolation for two weeks.

When isolation occurred during a "critical period," starting three weeks after birth, cells called oligodendrocytes failed to mature in the prefrontal cortex, a brain region important for cognitive function and social behavior. As a result, nerve fibers had thinner coatings of myelin, which is produced by oligodendrocytes, and the mice showed impairments in social interaction and working memory.

Studies of children raised in institutions where neglect was rampant, including another recent study from Boston Children's Hospital, have found changes in white matter in the prefrontal cortex, but the mechanism for the changes hasn't been clear. The new study adds to a growing body of evidence that so-called glial cells, including oligodendrocytes, do more than just support neurons, but rather participate actively in setting up the brain's circuitry as they receive input from the environment.

"In general, the thinking has been that experience shapes the brain by influencing neurons," explained Corfas, the study's team leader and senior investigator, who also holds an appointment in the Departments of Neurology and Otolaryngology at Boston Children's Hospital and Harvard Medical School.

"We are showing that glial cells are also influenced by experience, and that this is an essential step in establishing normal, mature neuronal circuits. Our findings provide a cellular and molecular context to understand the consequences of social isolation," he added.

Myelin is essential in boosting the speed and efficiency of communication between different areas of the brain, so the decreased myelination may explain the social and cognitive deficits in the mice. Corfas has previously shown that abnormal myelination alters dopaminergic signaling in the brain, which could provide an alternative explanation for the findings.

The new study also showed that effects of social isolation are timing-dependent. If mice were isolated during a specific period in their development, they failed to recover functioning even when they were put back in a social environment. Conversely, if mice were put in isolation after this so-called critical period, they remained normal.

Finally, Corfas and colleagues identified a molecular signaling pathway through which social isolation leads to abnormal myelination. The brains of socially isolated mice had less neuregulin-1 (NRG1), a protein essential to the development of the nervous system. Furthermore, when the team eliminated an NRG1 receptor known as ErbB3 from oligodendrocytes, the effect was the same as being in isolation—myelination and behavior were abnormal even when the mice were in a stimulating, social environment.

"These observations indicate that the mechanisms we found are necessary for the brain to 'benefit' from early social experience," said Corfas.

The Corfas lab is now investigating drugs that might stimulate myelin growth by targeting NRG1, ErbB3 or related pathways.

A number of neuropsychiatric disorders such as schizophrenia and mood disorders have been linked to pathologic changes in white matter and myelination, and to disturbances in the NRG1-ErbB signaling pathway, Corfas notes. Thus, the findings of this study may offer a new approach to these disorders.

Brain Implant Improves Thinking in Monkeys, First Such Demonstration in Primates

Scientists have designed a brain implant that sharpened decision making and restored lost mental capacity in monkeys, providing the first demonstration in primates of the sort of brain prosthesis that could eventually help people with damage from dementia, strokes or other brain injuries.
The device, though years away from commercial development, gives researchers a model for how to support and enhance fairly advanced mental skills in the frontal cortex of the brain, the seat of thinking and planning.
The new report appeared Thursday in The Journal of Neural Engineering.

In just the past decade, scientists have developed brain implants that improve vision or allow disabled people to use their thoughts to control prosthetic limbs or move computer cursors. The new paper, led by researchers at Wake Forest Baptist Medical Center and the University of Southern California, describes a device that improves brain function internally, by fine-tuning communication among neurons.
Previous studies have shown that a neural implant can do this for memory in rodents, but the new report extends that work significantly, experts said — into brains that are much closer to those of humans.
In the study, researchers at Wake Forest trained five rhesus monkeys to play a picture-matching game. The monkeys saw an image on a large screen — of a toy, a person, a mountain range — and tried to select the same image from a larger group of images that appeared on the same screen a little while later. The monkeys got a treat for every correct answer.
After two years of practice, the animals developed some mastery, getting about 75 percent of the easier matches correct and 40 percent of the harder ones, markedly better than chance guessing.
The monkeys were implanted with a tiny probe with two sensors; it was threaded through the forehead and into two neighboring layers of the cerebral cortex, the thin outer covering of the brain.
The two layers, called L-2/3 and L-5, are known to communicate with each other during decision making of the sort that the monkeys were doing when playing the matching game.
The device recorded the crackle of firing neurons during the animals’ choices and transmitted it to a computer. Researchers at U.S.C., led by Theodore Berger, analyzed this neural signal, and determined its pattern when the monkeys made correct choices.
To test the device, the team relayed this “correct” signal into the monkeys’ brains when they were in the middle of choosing a possible picture match, and it improved their performance by about 10 percent.
The researchers then impaired the monkeys’ performance deliberately, by dosing them with cocaine. Their scores promptly fell by 20 percent.
“But when you turn on the stimulator, they don’t make those errors; in fact, they do a little better than normal,” said Robert E. Hampson of Wake Forest, a study author.
His co-authors were Sam A. Deadwyler, Ioan Opris and Lucas Santos, all of Wake Forest; Dr. Berger, Vasilis Marmarelis and Dong Song of U.S.C.; and Greg A. Gerhardt of the University of Kentucky.
The technology used in the study could easily be contained on an implantable chip, Dr. Deadwyler said, and it is possible to envision a system that could help people with brain damage.
“The whole idea is that the device would generate an output pattern that bypasses the damaged area, providing an alternative connection” in the brain, he said.
Many hurdles remain. Decision making, like memory, is a multifaceted process that involves many neural circuits, depending on the decision being made.
A device focused on just one circuit is likely to be very limited. But not long ago, even a simple neural prosthesis would have seemed like science fiction.

Studies: Alzheimer Drug May Stabilize Brain Plaque

(AP) - An experimental drug that failed to stop mental decline in Alzheimer's patients also signaled potential benefit that suggests it might help if given earlier, fuller results of two major studies show.

Some patients on the drug had stable levels of brain plaque and less evidence of nerve damage compared to others who were given a dummy treatment, researchers reported Tuesday.

The drug is called bapineuzumab, made by Pfizer Inc. and Johnson & Johnson. The new results suggest it might work if given sooner, before so much damage and memory loss have occurred that it might not be possible to reverse, experts say.

"We're very disappointed that we were not able to come up with a treatment to provide to our dementia patients in the near term," said Dr. Reisa Sperling, director of the Alzheimer's center at Brigham and Women's Hospital in Boston and leader of one of the studies.

But brain imaging and spinal fluid tests are "very encouraging" and suggest the drug was "doing something to the biology of the disease."

"We've got a path forward" now to test it in people with mild mental impairment or those who show plaque on brain imaging but have not yet developed symptoms of dementia, Sperling said. Of people with mild cognitive impairment, about 15 to 20 percent a year will develop Alzheimer's disease.

About 35 million people worldwide have dementia, and Alzheimer's is the most common type. In the U.S., about 5 million have Alzheimer's. Current medicines such as Aricept and Namenda just temporarily ease symptoms. There is no known cure.

This year researchers had been hopeful of major progress in treating the disease, but study after study has proved disappointing, including results reported earlier on bapineuzumab. The drug failed to slow mental decline or improve activities of daily living for patients with mild to moderate Alzheimer's in two studies in the United States and Canada.

Bapineuzumab is designed to attach to and help clear amyloid, the stuff that makes up the sticky plaque that clogs patients' brains, harming nerve cells and impairing memory and thought. Doctors don't know whether amyloid is a cause or just a symptom of Alzheimer's, but many companies are testing drugs to try to remove it.

Sperling's study involved people with a gene that raises the risk of developing the disease. Dr. Stephen Salloway, a neurologist at Brown Medical School in Providence, R.I., led the other study of people without the gene. Both researchers have consulted for the companies that make the drug and presented results Tuesday at a neurology conference in Stockholm.

Brain imaging on a subset of patients in Sperling's study found 9 percent less amyloid in those on bapineuzumab compared to those on a dummy treatment. The drug group had stable levels while the others developed more plaque. Spinal fluid tests on some participants also showed the drug group had less of another substance called p-tau that is released when nerve cells are damaged.

There were potential safety concerns, including six deaths from various forms of cancer among those on bapineuzumab and none in the placebo group. But a wider review of all studies of the drug found that cancer was not more common among users.

"That's not raising any red flags," said an independent expert, Dr. Maria Carrillo, a senior scientist at the Alzheimer's Association. She said the biological changes suggest the drug is helping, so if it's used sooner, "we can perhaps affect cognition."

Salloway's study produced less evidence of benefit. Too few participants had brain imaging to make definitive conclusions about amyloid, and there was just a trend toward less of the nerve-damage substance in the group receiving the higher of two doses tested.

The hopeful signs on biomarkers are "the silver lining" in studies that failed to show the drug was helping patients, said Dr. Eric Yuen, head of clinical development for J&J's Janssen Alzheimer Immunotherapy unit.

Bapineuzumab is given as periodic intravenous infusions, and the companies have said they are stopping development of that form but continuing to test a version that can be given as a shot.

More results on this drug and a similar one - Eli Lilly & Co.'s solanezumab - will be presented at a conference in Boston next month. Lilly recently announced that combined results of two large studies of solanezumab suggested some benefit on cognition.

Global health group seeks to save brains' as well as lives

As many as 200 million children across the world fail to reach their full potential because their early brain development is held back by poverty, disease and malnutrition

Announcing backing for several projects aimed at "saving brains" as well as lives in poorer countries, health experts said global health and development efforts should focus not only on keeping children alive, but on improving their first 1,000 days.

The projects include plans to encourage so-called "kangaroo mother care", where low-weight newborns are held skin to skin rather than put into incubators, and ways of combating maternal depression to boost interaction between mothers and babies.

"There's a huge waste of brain power. It's like taking 200 million brains around the world and throwing them into 200 million waste bins," said Peter Singer, chief executive of Grand Challenges Canada (GCC), a non-profit group that funds health and development innovation in developing countries.

"Wasting brain power is a great way to make sure poor countries remain poor - that's why reversing it is so important."

Singer's group, funded by the Canadian government, is putting 11.8 million Canadian dollars ($12 million) into 11 projects in developing countries from Thailand to Pakistan to Bangladesh to Colombia aimed at helping children flourish and pull themselves and their countries out of poverty.

"Imagine harnessing all that potential," Singer said in a telephone interview. "It's critical because brain development equals child development equals development of countries."

In Bangladesh, expectant mothers and babies who were given vitamin A supplements to reduce infant deaths will be tracked to see the impact on cognitive development in older children. Experts think vitamin A may be key to brain and central nervous system development and function.

A separate project in Colombia will assess whether skin-to-skin "kangaroo mother care", which provides nutrition, warmth and bonding for newborns, may be better than incubator care for babies' brain development.

With malaria infecting up to 300 million children in high-risk countries each year, another project will look at whether using a suppository form of the anti-malarial drug artesunate during the sometimes hours-long trip to get a child to hospital may minimize any brain injury caused when the disease attacks the brain and central nervous system.

"These ideas are proven in the short term, but is important to understand how these innovations can impact children as they become adults, to see the real potential for improving lives," said Karlee Silver, GCC's expert on women's and children's health.

Neuroscience mapping brain connections

Discoveries could yield an understanding of and treatments for disorders such as autism, schizophrenia, depression and Parkinson's disease.

Brain scan

A brain scan of white matter fibers, color-coded by direction. 

Inside the human skull lies a 3-pound mystery. The brain — a command center composed of tens of billions of branching neurons — controls who we are, what we do and how we feel.

"It's the most amazing information structure anybody has ever been able to imagine," says Dr. Walter Koroshetz, deputy director of the National Institute of Neurological Disorders and Stroke in Bethesda, Md.
For centuries, the brain's inner workings remained largely unexplored. But all that is changing. With the help of new tools, researchers are delving deeper into this complex organ than ever before. We're in a brainy age of discovery that could change our understanding of how the brain works and why, in some cases, it fails to do its job.

Scientists already have an intimate knowledge of brain anatomy, from the hippocampus to the amygdala. "We've mapped these in exquisite detail," says Arthur Toga, director of the Laboratory of Neuro Imaging at UCLA.

But those maps don't show how the regions connect. And it's this connectivity that enables the complex behaviors our brains perform so seamlessly.

The Human Connectome Project, a $40-million endeavor funded by the National Institutes of Health, aims to plot these connections — both their structure and their function. "It's basically a Manhattan Project to try to establish the wiring diagram," Koroshetz says.

Calling it ambitious would be an understatement. In the 1980s, researchers spent a dozen years mapping 7,000 connections between the 302 neurons inside the worm C. elegans, an animal not exactly known for brainpower. The human brain contains more than 80 billion neurons and trillions of connections. The problem is further complicated by variability: No two brains are exactly alike.

But the payoff could be huge. In addition to gaining a deeper understanding of how normal brains process and store information, researchers also hope to find the root cause of disorders like autism and schizophrenia, which some neuroscientists suspect are the result of faulty connections.

Dr. Helen Mayberg, a professor of psychiatry and neurology at Emory University School of Medicine in Atlanta, has spent the last 20 years probing the neural basis of depression, a difficult-to-treat disorder that affects millions of Americans. Mayberg's goal is to understand precisely what goes wrong in the brains of people who have the illness and, perhaps, relieve the problem by using electrodes to stimulate a particular region of the brain.

The quest began in the late 1990s, when Mayberg and her colleagues started scanning the brains of people with depression, treating them and scanning them again to look for changes in brain activity. The hope was to pinpoint the neural circuits involved in the disorder, and eventually they hit the bull's-eye: When antidepressants worked, the scans invariably showed a decrease in activity in a section of the prefrontal cortex called Brodmann area 25.

Next, Mayberg needed a way to block the activity of area 25. So she turned to a technique called deep brain stimulation, a therapy that helps calm the shaking that plagues people with Parkinson's disease. A neurosurgeon implants small electrodes that deliver a faint but steady stream of electricity that stimulates the deep reaches of the brain while calming down the trouble spot. A battery pack implanted under the skin near the collarbone provides the power source.

Deep brain stimulation isn't a magic bullet. It doesn't work for everyone, and the therapy requires brain surgery, which comes with a variety of risks.

But small studies conducted over the last several years suggest the therapy holds promise, and 2012 started with new validation. In January, Mayberg and her team published a placebo-controlled study that examined the approach for both major depression and bipolar disorder. After two years of stimulation, seven out of 12 subjects were in remission, according to the report in Archives of General Psychiatry.

"People didn't just get better, they were well," Mayberg says. Now the device's manufacturer has launched a randomized clinical trial to test the therapy in even more patients.

Other research groups are looking at stimulating different areas of the brain to treat depression and other disorders. In 2009, the Food and Drug Administration approved the technology for use in people with extreme obsessive-compulsive disorder.

Neurofeedback is another futuristic brain therapy that is already producing real results. Here's the premise: Functional magnetic resonance imaging machines, which watch changes in blood flow in the brain, can monitor brain activity in near real time. And if patients can see their brains working, maybe they can control the activity.

In an experiment published in 2005 in Proceedings of the National Academy of Sciences, researchers placed eight patients with chronic pain in state-of-the-art FMRI machines. A screen inside the machine displayed a flame that was linked to activity in the part of the brain that senses pain. When the pain center fired up, the flame grew. When that area got quiet, the flame shrank. The researchers asked study subjects to change the size of the flame by trying different strategies — for example, by imagining themselves relaxing on the beach. Overall, the group experienced a 64% drop in self-reported pain.

One of the study's authors launched a company called Omneuron to develop the technology.

"It's not entirely possible to predict exactly where this is all going," says lead author Sean Mackey, chief of Stanford University's Pain Management Division. Brain scanning is expensive. Perhaps researchers can figure out how to provide the same feedback using a less expensive EEG machine, Mackey says. Or perhaps patients could ultimately learn how to control pain without a machine.

Researchers are also investigating neurofeedback as a possible treatment for depression, attention deficit hyperactivity disorder, addiction and more.

Brain breakthroughs are already changing lives in amazing ways. Dr. Leigh Hochberg, a neurologist at Providence VA Medical Center in Rhode Island, is working to perfect an implanted device that has allowed a handful of paralyzed patients to control a robotic arm with only their thoughts. The device, called BrainGate, collects information from the motor cortex, the part of the brain that controls voluntary movement.

The system still needs to be refined and tested further, but Hochberg already has loftier goals in mind. "The dream is to one day reconnect brain to limb," giving paralyzed people the ability to use their own arms and legs, he says.

Even as these therapies progress, scientists are trying to dig deeper to understand exactly why they work. For instance, the electrodes in Mayberg's studies stimulate area 25, but they may be acting on other areas of the brain, too, through a complex web of connections that researchers are just starting to understand.
One thing seems clear: New discoveries in neuroscience tend to prompt new questions. Each time researchers manage to wrestle open a locked door, they find themselves facing another doorway.

As Koroshetz put it: "You thought you knew everything, and you were just in one room of the building."