John M. Talmadge, M.D.

A Blog Covering Many Topics

New Brain Discovery? Lymph!

Although we don't know for certain that new treatments are just over the horizon, here's some potentially exciting news. Scientists at the University of Virginia have discovered previously unknown lymphatic vessels in the outer layers of the brain. These vessels appeared to link the brain and spinal cord with the rest of the body’s immune system. This study used mice and human samples, vessel structure was investigated in the mice, and the observations followed up in the human samples. This was an animal study using mice to investigate the structure and function of lymphatic vessels in the brain. In fact, this story has been circulating for awhile, but recently it's been highlighted in several stories. The good news is that this may mean that the original studies are standing up to scrutiny by other scientists.

The discovery may require a reassessment of our assumptions about lymph drainage in the brain and its role in diseases involving brain inflammation or degeneration, such as Alzheimer’s disease and multiple sclerosis. The study was published in the peer-reviewed scientific journal Nature.

When I was in medical school, we were taught that the central nervous system (brain and spinal cord) did not have a typical lymphatic drainage system. Lymph is the immune fluid that circulates through the body, containing white blood cells to fight infection and destroy abnormal cells. This study aimed to look at the circulation of lymph in the mouse brain, but mice and humans do not have identical biology, so the findings may not be directly applicable. 

The study involved complex laboratory techniques, using a fluorescent antibody to assess the alignment of cells within the brain, examination for markers associated with a lymphatic drainage system and looking at the functional capacity of identified vessels to carry lymphatic fluid to and from the brain. 
Human samples taken from the brain at autopsy were used to investigate any structures found in mice.

The scientists found that the outer protective layers of the mouse brain showed cells that were clearly lined up, which suggested that these were vessels with a unique function. These cells showed the characteristic features of functional lymphatic vessels. These vessels appeared able to carry both fluid and immune cells from the fluid surrounding the brain and spinal cord (the cerebrospinal fluid), and were connected to the lymph nodes in the neck. The location of these vessels may have been the reason they have not been discovered before, thereby causing the belief that there is no lymphatic drainage system in the brain.

This may mean current thinking about how the brain works needs to be reassessed. The researchers go on to say it could be the malfunction of these vessels that could be the cause of a variety of brain disorders, such as multiple sclerosis and Alzheimer’s disease.

Summary: This mouse study has examined the circulation of lymph in the brain. It discovered previously unknown lymphatic vessels in the outer layers of the mouse brain. If accurate, the findings may call for a review of how the immune system in the brain functions, and shed new light on its role in brain diseases involving brain inflammation or degeneration. Though animal research can give a good insight into biological and disease processes, and how they may work in humans, the processes in humans and mice are not identical. Further studies are needed to confirm these findings and to assess whether this knowledge is transferable to humans. As such, it is too early to say whether the findings could one day have any implications for the treatment of degenerative brain conditions such as multiple sclerosis or Alzheimer’s.  

The original article in Nature can be found here.

Aging Brain? Not So Bad...

From Harvard Health Publications at Harvard Medical School comes some exciting news about the aging brain.

At middle age, the brain begins to draw on more of its capacity for improved judgment and decision making.
If you forget a name or two, take longer to finish the crossword, or find it hard to manage two tasks at once, you’re not on the road to dementia.
What you’re experiencing is your brain changing the way it works as you get older. And in many ways it’s actually working better. Studies have shown that older people have better judgment, are better at making rational decisions, and are better able to screen out negativity than their juniors are.
Although it may take you a little longer to get to the solution, you’re probably better at inductive and spatial reasoning at middle age than you were in your youth.

The brain changes as we get older, and in some ways it works better as we get older.

How is it possible for older people to function better even as their brains slow? “The brain begins to compensate by using more of itself,” explains Dr. Bruce Yankner, professor of genetics and co-director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School. He notes that MRIs taken of a teenager working through a problem show a lot of activity on one side of the prefrontal cortex, the region we use for conscious reasoning. In middle age, the other side of the brain begins to pitch in a little. In seniors, both sides of the brain share the task equally. The cooperative effort has a payoff. “Several studies suggest that seniors who can activate both sides of the brain actually do better on tasks, while those who can’t do worse,” Dr. Yankner says.

If you’ve found that it’s a little harder to carry on a conversation while searching your bag for your keys, MRI studies offer some clues. They show that in younger people, the area of the brain used to do a task goes dark immediately once the task is completed, while in older people it takes longer to shut down. As a result, it’s harder for the older brain to take on several tasks, because not only do you need to use more of the brain for any single task, but the brain also has a harder time letting go of a task. So even after you fish out your keys, you may have trouble getting back into the conversation.
What about the moments when you find yourself driving down the street without any recollection of having passed the last few blocks? Or the times you’ve locked the car door with your keys in the ignition? On those occasions your brain may have slipped into the default mode, which controls processes like remembering and daydreaming that are not required for a directed task. Imaging studies show that interconnected regions of the brain dubbed the “default network” grow more active with age, indicating that as we age we spend more time daydreaming.


At The Center for BrainHealth, as at Harvard, we are discovering that the more mature brain actually has advantages over its younger counterpart. These findings came as a surprise to many people, who were accustomed to seeing “senior moments”—groping for the right word or taking longer to articulate your thoughts—as a sign that the brain was on the skids. Yet even in professions where youth is valued, testing has shown that maturity has advantages.

For example, in a study of air-traffic controllers and airline pilots, those between ages 50 and 69 took longer than those under 50 to master new equipment, but once they had, they made fewer mistakes using it. (Keep this in mind when you’re trying to conquer a new computer program or adapt to a new car!) The mastery that comes with maturity is due to changes in your glands as well as your brain. Declining levels of testosterone—even in women—result in better impulse control. The end of the hormonal roller coaster of menopause may also contribute to emotional stability. After midlife, people are less likely to have emotional issues like mood swings and neuroses that interfere with cognitive function.

Most importantly, the wealth of knowledge from decades of learning and life experience enables you to better assess new situations. At midlife, most people are more adept at making financial decisions and getting to the heart of issues than they were when they were younger.

In most people, these abilities improve with age:

Inductive reasoning. Older people are less likely to rush to judgment and more likely to reach the right conclusion based on the information. This is an enormous help in everyday problem solving, from planning the most efficient way to do your errands to managing your staff at work.

Verbal abilities. In middle age, you continue to expand your vocabulary and hone your ability to express yourself.

Spatial reasoning. Remember those quizzes that require you to identify an object that has been turned around? You are likely to score better on them in your 50s and 60s than you did in your teens. And you may be better at some aspects of driving, too, because you are better able to assess the distance between your car and other objects on the road.

Basic math. You may be better at splitting the check and figuring the tip when you’re lunching with friends, simply because you’ve been doing it for so many years.

Accentuating the positive. The amygdala, the area of the brain that consolidates emotion and memory, is less responsive to negatively charged situations in older people than in younger ones, which may explain why studies have shown that people over 60 tend to brood less.

Attaining contentment. Years ago, researchers were surprised to find that people seem to be more satisfied with their lives as they age, despite the losses that accumulate with passing years. This is probably because they tend to minimize the negative, accept their limitations and use their experience to compensate for them, and set reasonable goals for the future. Dr. Yankner notes that this trait may be innate, because it is prevalent even in the United States and other Western nations, which tend to value youth over age.

Genetics, Weird Facts, & Placebos

There are times when the practice of medicine is the most fascinating possible kind of work. For example, consider the placebo effect.

A placebo is anything that seems to be a "real" medical treatment -- but isn't. It could be a pill, a shot, or some other type of "fake" treatment. What all placebos have in common is that they do not contain an active substance meant to affect health. Younger physicians won't remember this, but years ago it was considered okay for doctors to prescribe placebos. Surgeons fairly often would substitute saline (salt water) injections when they worried that patients were asking for too many narcotic shots after an operation. There was a preparation called Gevrabon that was essentially sherry wine with some vitamins added, and it could be given by prescription "for relaxation at bedtime." Over the years, for obvious reasons, experts in medical ethics began to question whether these practices—essentially deceiving patients, but with good intentions—were proper and permissible.

In addiction medicine, I've seen college students come into the emergency room looking drunk, only to discover (with lab verification) that the "drug" they had tried was simply a vitamin pill. Similar findings have emerged at The University of Texas Austin, where one of the research labs has a full-fledged bar (i.e. a saloon) set up to simulate the settings where college students drink. Click here to see the Sahara Bar in the Department of Psychology. Study subjects sometimes get tipsy even when their margarita or manhattan contains no alcohol at all.

In 1996, scientists assembled a group of students and told them that they were going to take part in a study of a new painkiller, called "trivaricaine". Trivaricaine was a brown lotion to be painted on the skin, and smelled like a medicine. But the students were not told that, in fact, trivaricaine contained only water, iodine, and thyme oil – none of which are painkilling medicines. It was a fake – or placebo – painkiller. Read an abstract of the study: Mechanisms of Placebo Pain Reduction. With each student, the trivaricaine was painted on one index finger, and the other left untreated. In turn, each index finger was squeezed in a vice. The students reported significantly less pain in the treated finger, even though trivaricaine was a fake.

In this example, expectation and belief produced real results. The students expected the "medicine" to kill pain: and, sure enough, they experienced less pain. This is the placebo effect.

Placebo medicine has even been shown to cause stomach ulcers to heal faster than they otherwise would. These amazing results show that the placebo effect is real, and powerful. They mean that fake or placebo treatments can cause real improvements in health conditions: improvements we can see with our own eyes. Experiencing the placebo effect is not the same as being "tricked", or being foolish. The effect can happen to everyone, however intelligent, and whether they know about the placebo effect or not.

An article in Harvard Magazine describes Harvard Professor Dr.Ted Kaptchuk’s first randomized clinical drug trial, where nearly a third of his 270 subjects complained of awful side effects. All the patients had joined the study hoping to alleviate severe arm pain: carpal tunnel, tendinitis, chronic pain in the elbow, shoulder, wrist. In one part of the study, half the subjects received pain-reducing pills; the others were offered acupuncture treatments. And in both cases, people began to call in, saying they couldn’t get out of bed. The pills were making them sluggish, the needles caused swelling and redness; some patients’ pain ballooned to nightmarish levels. “The side effects were simply amazing,” Kaptchuk explains; curiously, they were exactly what patients had been warned their treatment might produce. But even more astounding, most of the other patients reported real relief, and those who received acupuncture felt even better than those on the anti-pain pill. These were exceptional findings: no one had ever proven that acupuncture worked better than painkillers. But Kaptchuk’s study didn’t prove it, either. The pills his team had given patients were actually made of cornstarch; the “acupuncture” needles were retractable shams that never pierced the skin. The study wasn’t aimed at comparing two treatments. It was designed to compare two fakes.

Dr. Kaptchuk and his colleagues have found that placebo treatments—interventions with no active drug ingredients—can stimulate real physiological responses, from changes in heart rate and blood pressure to chemical activity in the brain, in cases involving pain, depression, anxiety, fatigue, and even some symptoms of Parkinson’s. His work was also featured in a New Yorker article, "The Power of Nothing," that can be found here.

Here are four fascinating (and weird) facts about placebos and the placebo effect:

1. It doesn't have to be a secret. Some believe that a placebo can only work if the recipient is unaware they are taking one. But there's evidence that people with irritable bowel syndrome who knowingly receive a placebo do better than those who are left untreated.

2. It works better if it's expensive. The pain-killing power of a placebo pill is greater among people who are told they are taking a full-price version, compared to those told that the pill is on sale for a discounted price.

3. It's not just us, animals can get it too. A 2012 study found that between 30 and 40 per cent of rats experienced pain relief when their morphine injections were swapped for inactive saline solution.

4. It has an evil twin. The nocebo effect makes people undergoing treatment more likely to suffer from side-effects if they are warned about them by their doctor.

For the full New Scientist journal article on the subject, click here.

Slowly, over the past decade, researchers have begun to tease out the strands of the placebo response. The findings, while difficult to translate into medicine, have been compelling. In most cases, the larger the pill, the stronger the placebo effect. Two pills are better than one, and brand-name pills trump generics. Capsules are generally more effective than tablets, and injections produce a more pronounced effect than either. There is even evidence to suggest that the color of medicine influences the way one responds to it: colored pills are more likely to relieve pain than white pills; blue pills help people sleep better than red pills; and green capsules are the best bet when it comes to anxiety medication.

Change Your Brain

And now…a word or two about good science and having a healthy brain. We offer a range of programs at the Brain Performance Institute to help people of all ages and conditions improve and extend peak brain performance throughout their lives. By evaluating brain fitness and applying proven brain-training methods, the Brain Performance Institute will train individuals to think smarter and exploit their greatest natural resources — their brains.

A unique cognitive assessment that measures cognitive reserve in pivotal areas of higher-order mental functioning, all of which rely on robust frontal lobe function. It is just as essential to measure and monitor brain fitness as it is to measure and monitor physical fitness. Get a benchmark of your brain’s health.

The high performance brain training program, Strategic Memory Advanced Reasoning Training (SMART®Winking, was developed by Center for BrainHealth cognitive neuroscientists and is based on more than 25 years of scientific study. The training program targets improvement in the frontal lobe of the brain and is based on cognitive neuroscience principles of how to build strategic thinking, advanced reasoning and innovative problem-solving skills. SMART sessions include personalized training materials and integrated practice sessions.

I joined the staff at The Center for BrainHealth and BPI after extensive contact with the scientists and clinicians there. Over a period of months I found myself returning at least once or twice weekly to attend a lecture, to discuss research, or to interact with my friends on The Warrior Team, a powerful resource for veterans. I remember the day in November 2014 when I spoke with Dr. Sandra Chapman, the CEO, and she asked me whether I was enjoying my visits. "Are you kidding me?" I said, "I want to be more than a visitor—I want to work here!" Needless to say, I was both honored and extremely delighted when, early in 2015, I got the call and the invitation to be Senior Medical Advisor for CBH and BPI.

Brain Scams: Don't Buy the MRI

Neuroimaging, or the use of functional magnetic resonance imaging to study the brain, is a powerful research tool. At The Center for Brain Health our scientists are doing amazing work in unraveling what goes on in the human brain, and imaging studies are essential to their research. However, fMRI studies do not enable us to diagnose or treat psychiatric disorders more effectively. There is quite a gap between the research lab and the clinic. Nonetheless, entrepreneurs have started marketing brain scans to consumers, and some doctors are making claims not supported by the science. These claims have been widely criticized and condemned, but the average consumer is easily duped. My distinguished colleague Daniel Carlat, M.D. wrote a brilliant article which you can find here in Wired magazine. There is also extensive discussion of the subject on Quackwatch, as well as on the Science Based Medicine Blog.

Dr. Carlat writes: "My journey through the land of functional neuroimaging has helped me to understand how spectacularly meaningless these images are likely to be. Most neuromarketers are using these scans as a way of sprinkling glitter over their products, so that customers will be persuaded that the pictures are giving them a deeper understanding of their mind. In fact, imaging technologies are still in their infancy. And while overenthusiastic practitioners may try to leapfrog over the science, real progress, which will take decades, will be made by patient and methodical researchers, not by entrepreneurs looking to make a buck."

If a person has a brain tumor, a brain aneurysm, or a stroke, then brain imaging can be helpful. However, brain imaging makes no difference (and makes no sense) in the treatment of problems like depression, anxiety, ADD/ADHD, alcoholism, addictions, or other commonly seen psychiatric disorders.

Brain imaging is very expensive, and the brain is exposed to radiation during a scan. This is an unnecessary risk, and a very expensive procedure, for anyone with a psychiatric disorder.

Changing the Brain

Current neuroscience reveals that both psychotherapy and psychiatric medications produce positive changes in the brain. Research at UCLA demonstrates that people who suffered from depression had abnormally high activity in the prefrontal cortex.  Psychotherapy patients who improved show more nearly normal brain activity in this hyperactive region. For obsessive-compulsive disorder, OCD, cognitive behavior therapy (CBT) was associated with a decrease in the hyperactivity of the caudate nucleus, and the effect was most evident in people who had a good response to CBT.  In other words, the better the therapy seemed to work, the more the brain activity changed.
People with chronic fatigue syndrome (CFS) tend to have a decrease in a type of brain tissue called grey matter in the prefrontal cortex of the brain.  OCD researchers in the Netherlands provided 16 sessions of CBT, and found significant increases in gray matter volume in the prefrontal cortex.  This seems to suggest that the CFS patients were able to “recover” some gray matter volume after CBT.

The bottom line: Although medication and psychotherapy appear to work their magic in difference places, the results are positive for both. The mechanism of action remains unclear, but studies also show that the combination of psychotherapy and the right medication (getting it right is very important!) is an excellent approach for many individuals. As the brain changes, we see the production of new proteins, which change our brains through neuroplasticity.   In selecting a treatment strategy, sometimes medication works best, sometimes psychotherapy is the best option, and sometimes it’s a combination of the two. 

Neuroscience of Belief

In the current issue of New Scientist I came across a good article on the neuroscience of belief. Graham Lawton writes, in part: Beliefs define how we see the world and act within it; without them, there would be no plots to behead soldiers, no war, no economic crises and no racism. There would also be no cathedrals, no nature reserves, no science and no art. Whatever beliefs you hold, it's hard to imagine life without them. Beliefs, more than anything else, are what make us human. They also come so naturally that we rarely stop to think how bizarre belief is.
In 1921, philosopher Bertrand Russell put it succinctly when he described belief as "the central problem in the analysis of mind". Believing, he said, is "the most 'mental' thing we do" – by which he meant the most removed from the "mere matter" that our brains are made of. How can a physical object like a human brain believe things? Philosophy has made little progress on Russell's central problem. But increasingly, scientists are stepping in.
The neuroscientific investigation of belief began in 2008, when Sam Harris (Harris, S., Sheth, S. A. and Cohen, M. S. (2008), Functional neuroimaging of belief, disbelief, and uncertainty. Ann Neurol., 63: 141–147) at the University of California, Los Angeles, put people into a brain scanner and asked them whether they believed in various written statements. Some were simple factual propositions, such as "California is larger than Rhode Island"; others were matters of personal belief, such as "There is probably no God". Harris found that statements people believed to be true produced little characteristic brain activity – just a few brief flickers in regions associated with reasoning and emotional reward. In contrast, disbelief produced longer and stronger activation in regions associated with deliberation and decision-making, as if the brain had to work harder to reach a state of disbelief. Statements the volunteers did not believe also activated regions associated with emotion, but in this case pain and disgust.

To read the full article, click here.