Posted tagged ‘neuroscience’

Study shows link between playing football and neurodegenerative disease

July 25, 2017

You’ll likely hear quite a bit this week about a new study that suggests football players have an increased risk of developing chronic traumatic encephalopathy, or CTE, which is a progressive degenerative brain disease associated with repetitive head trauma.

As reported today in JAMA, researchers from the Boston University CTE Center and the VA Boston Healthcare System found pathological evidence of CTE in 177 of the 202 former football players whose brains were donated for research — including 117 of the 119 who played professionally in the United States or Canada. Their study nearly doubles the number of CTE cases described in literature.

The co-first author, Daniel Daneshvar, MD, PhD, is a new resident at Stanford in the orthopaedic surgery’s physical medicine and rehabilitation program, which treats traumatic brain injury and sports injury patients. He recently spoke with me about the study that he participated in while at BU.

“I really enjoyed playing football in high school. I think it’s an important sport for team building, learning leadership and gaining maturity,” he explained. “That being said, I think this study provides evidence of a relationship between playing football and developing a neurodegenerative disease. And that is very concerning, since we have kids as young as 8 years old potentially subjecting themselves to risk of this disease.”

The researchers studied the donated brains of deceased former football players who played in high school, college and the pros. They diagnosed CTE based on criteria recently defined by the National Institutes of Health. Currently, CTE can only be confirmed postmortem.

The study found evidence of mild CTE in three of the 14 former high school players and severe CTE in the majority of former college, semiprofessional and professional players. However, the researchers are quick to acknowledge that their sample is skewed, because brain bank donors don’t represent the overall population of former football players. Daneshvar explained:

“The number of NFL players with CTE is certainly less than the 99 percent that we’re reporting here, based on the fact that we have a biased sample. But the fact that 110 out of the 111 NFL players in our group had CTE means that this is in no way a small problem amongst NFL players.”

The research team also performed retrospective clinical evaluations, speaking with the players’ loved ones to learn their athletic histories and disease symptoms. Daneshvar worked on this clinical component — helping to design the study, organize the brain donations, conduct the interviews and analyze the data. The clinical assessment and pathology teams worked independently, blind to each other’s results.

“It’s difficult to determine after people have passed away exactly what symptoms they initially presented with and what their disease course was,” he told me. “We developed a novel mechanism for this comprehensive, retrospective clinical assessment. I was one of the people doing the phone interviews with the participant’s family members and friends to assess cognitive, behavioral, mood and motor symptoms.”

At this point, there aren’t any clinical diagnosis criteria for CTE, Daneshvar said. Although the current study wasn’t designed to establish these criteria, the researchers are going to use this data to correlate the clinical symptoms that a patient suffers through in life and their pathology at time of death, Daneshvar said. He went on to explain:

“The important thing about this study is that it isn’t just characterizing disease in this population. It’s about learning as much as we can from this methodologically rigorous cohort going forward, so we can begin to apply the knowledge that we’ve gained to help living athletes.”

Daneshvar and his colleagues are already working on a new study to better understand the prevalence and incidence of CTE in the overall population of football players. And they have begun to investigate what types of risk factors affect the likelihood of developing CTE.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

The implications of male and female brain differences: A discussion

July 17, 2017

Photo by George Hodan

Men and women are equal, but they and their brains aren’t the same, according to a growing pile of scientific evidence. So why is most research still performed on only male animals and men? A panel of researchers explored this question and its implications on a recent episode of KALW’s City Visions radio show.

“It’s important to study sex differences because they are everywhere affecting everything,” said panelist Larry Cahill, PhD, a professor of neurobiology and behavior at the University of California, Irvine. “Over the last 20 years in particular, neuroscientists and really medicine generally have discovered that there are sex differences of all sizes and shapes really at every level of brain function. And we can’t truly treat women equally if we continue to essentially ignore them, which is what we’ve been doing.”

Neuropsychiatrist and author Louann Brizendine, MD, went on to say that many prescription medicines are only tested on male animals and men, even birth control pills designed for women. This is because the researchers don’t want the fluctuations of hormones associated with the menstrual cycle to “mess up” the research data, she said.

However, this practice can lead to dangerous side effects for women, she explained. For example, the U.S. Food and Drug Administration determined that many women metabolized the common sleep aid, Ambien, more slowly than men so the medication remained at a high level in their blood stream in the morning, which impaired activities like driving. After reassessing the clinical data on Ambien, Brizendine said, the FDA reset the male dose to 10 mg and the female dose down to 5 mg.

Niaro Shah, MD, PhD, a professor of psychiatry and behavioral sciences and of neurobiology at Stanford, said this action by the FDA was a sign of progress. “Decisions like what were made about Ambien represent people starting slowly to wake up and realize that we’ve been assuming that we don’t have to worry fundamentally about sex. And in not worrying about it, we are disproportionally harming women. Bare in mind, women absolutely, clearly and disproportionally bear the brunt of side effects of drugs and medicine.” In fact, he explained, eight out of ten drugs are withdrawn from the market due to worse side effects in women. He later added, “This issue is deeply affecting medical health, especially for women.”

So why are most researchers still studying only male animals or men?

According to Cahill, researchers have a deeply ingrained bias against studying sex differences, believing that sex differences aren’t fundamental because they aren’t shared by both men and women. He also said that resistance to this research boils down to the implicit and false assumption that equal has to mean the same. “If a neuroscientist shows that males and females (be that mice or monkeys or humans) are not the same in some aspect of brain function, then [many people think] the neuroscientist is showing that they are not equal — and that is false.”

Cahill offered advice for consumers: “You can go to the FDA website and for almost any approved drug you can get the essentials on how the testing was done. You’re going to find a mixed bag. For some drugs, you’re going to find there is pretty darn good evidence that the drug probably has roughly equal effects in men and women. On the other hand, you’re going to find a lot of cases when the testing was done mostly or exclusively in males and basically people don’t know [the effects in women].”

“You should be discerning and do your homework,” Brizendine agreed.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Unable to smell? One Stanford researcher is working to improve therapies

February 13, 2017

I don’t often think about my sense of smell, unless I’m given a fragrant flower or walk past someone smoking. But the ability to smell is both critical and underappreciated, according to Zara Patel, MD, a Stanford assistant professor of otolaryngology, head and neck surgery.

A smell begins when a molecule — say, from a flower — stimulates the olfactory nerve cells found high up in the nose. These nerve cells then send information to the brain, where the specific smell is identified. Anything that interferes with these processes, such as nasal congestion or damage to the nerve cells, can lead to a loss of smell.

I recently spoke with Patel about the loss of the sense of smell, a condition known as anosmia.

How does losing the sense of smell impact patients?

“If asked which sense they’d give up first, most people would likely choose their sense of smell. It’s only after the loss of olfaction that its significant impact on our lives is appreciated. Our sense of smell plays a key role in a vast array of basic human interactions, such as what attracts us to sexual partners, what keeps us in committed relationships and how maternal bonding occurs with newborns. It’s also one of our most basic protective mechanisms that allows us to wake up in the midst of a fire and prevents us from eating spoiled food. And importantly — keeping in mind that our ability to taste is highly dependent on our ability to smell — the inability to enjoy food and related social activities often causes social isolation, depression and malnutrition.”

What causes olfactory loss?

“There are over 100 reasons why people can lose their sense of smell. However, the majority of people lose it from sinonasal inflammatory disease, post-viral infections, traumas or tumors. Unfortunately, olfactory loss is often of “idiopathic” origin, meaning we just don’t know what caused it. That is why research in this area is so important.

It’s also important to be treated as early as possible. It is always frustrating to see someone who lost their sense of smell over a year ago, but they weren’t referred to me at the time or were told that nothing could be done. Those are missed opportunities that will negatively impact those patients for the rest of their lives.”

How do you treat patients who can no longer smell?

“The treatment really depends on the reason for loss, and may include surgery or medications. For those who lose the ability to smell after trauma, post-viral infection or when we don’t know why it happened, olfactory training can be used, which is a very simple protocol that patients can do at home. The patients smell several essentials oils in a structured way twice a day, every day, over a long period of time. The oils — rose, eucalyptus, clove and lemon —stimulate different types of olfactory receptor cells in the nose. Although it does not help everyone, it has been shown to be effective in 30 to 50 percent of patients, across multiple origins of loss.

We don’t have an exact understanding of how and why it works. However, a study using functional MRI observed a change in how the brain responds to odors before and after olfactory training. Before the training, there was a chaotic array of random areas lighting up in the brain. After the training, the images showed a renewed pathway to the olfaction center in the brain. We also know that the olfactory nerve has an inherent ability to regenerate. We’re trying to take advantage of this fact and ‘switch on’ those regenerative cells.

I have many patients who have benefited from olfactory training, including some who need their sense of smell for their livelihood — such as chefs or wilderness guides. Being able to get that sense back has allowed them to continue doing what they’re passionate about and has increased their quality of life.”

What are you working on now?

“Although olfactory training has allowed us to help more patients, 30 to 50 percent improvement is still quite low and certainly not the final answer. That’s why the research I’m currently doing has me excited about the potential of using both stem cells and neurostimulation to advance this field. I hope to soon be able to offer alternative interventions to these patients.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Stanford researchers map brain circuitry affected by Parkinson’s disease

February 2, 2017

In the brain, neurons never work alone. Instead, critical functions of the nervous system are orchestrated by interconnected networks of neurons distributed across the brain — such as the circuit responsible for motor control.

Researchers are trying to map out these neural circuits to understand how disease or injury disrupts healthy brain cell communication. For instance, neuroscientists are investigating how Parkinson’s disease causes malfunctions in the neural pathways that control motion.

Now, Stanford researchers have developed a new brain mapping technique that reveals the circuitry associated with Parkinson’s tremors, a hallmark of the disease. The multi-disciplinary team turned on specific types of neurons and observed how this affected the entire brain, which allowed them to map out the associated neural circuit.

Specifically, they performed rat studies using optogenetics to modify and turn on specific types of neurons in response to light and functional MRI to measure the resulting brain activity based on changes in blood flow. These data were then computationally modeled to map out the neural circuit and determine its function.

The research was led by Jin Hyang Lee, PhD, a Stanford electrical engineer who is an assistant professor of neurology and neurological sciences, of neurosurgery and of bioengineering. A recent Stanford News release explains the results:

“Testing her approach on rats, Lee probed two different types of neurons known to be involved in Parkinson’s disease — although it wasn’t known exactly how. Her team found that one type of neuron activated a pathway that called for greater motion while the other activated a signal for less motion. Lee’s team then designed a computational approach to draw circuit diagrams that underlie these neuron-specific brain circuit functions.”

“This is the first time anyone has shown how different neuron types form distinct whole brain circuits with opposite outcomes,” Lee said in the release.

Lee hopes their research will help improve treatments for Parkinson’s disease by providing a more precise understanding of how neurons work to control motion. In the long run, she also thinks their new brain mapping technique can be used to help design better therapies for other brain diseases.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Dr. B’s brain collection helps local students learn anatomy

November 21, 2016
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Photo courtesy of Donna Bouley

Most of the time, veterinary pathologist Donna Bouley, DVM, PhD, provides pathology support for Stanford researchers and clinicians who work with animals.

But she also has an unusual hobby: Bouley, known to all as Dr. B, collects animal brains. Since 1997, she and others have taken “Dr. B’s Brain Collection” to local schools for a variety of science programs. Fascinated by this idea, I contacted her to learn more.

What inspired you to create your brain collection? What does it include?

“When I first started as faculty at Stanford, there were some preserved brains in the necropsy [animal autopsy] lab. I decided to start collecting more brains from animals that came to necropsy, when we didn’t need their brains to make our diagnosis. The word somehow got out that such a resource existed on campus. Now, I actually have two collections that are almost identical, because multiple labs were interested in borrowing the collection at the same time.

In each collection, I try to have at least one of the following brains: sheep, pig, dog, macaque, squirrel monkey, rabbit, owl, rat, mouse, cyclid (fish), and Xenopus laevis (an African Clawed frog). The brains are preserved and sealed in ‘seal-a-meal’ style bags or jars.

If any new species come through necropsy, I try to get brains from those animals. I also have to replace damaged ones each year, since the enthusiasm of middle schoolers can often result in the rough handling of my bagged brains. My necropsy tech keeps a close watch over the condition of the collections and replaces brains as needed or when available.”

How do you use the collection at Stanford?

“I teach a freshman seminar called Comparative Anatomy and Physiology of Mammals that tends to have several pre-vet and pre-med students each year. I use these brains to demonstrate various features that are similar or different between them, such as overall size, location of the cerebellum or the extent of brain surface folds and ridges. For instance, in lower mammals such as rodents — that survive mainly on instinct rather than cognitive processing — the brain has a very smooth surface. In mammals such as a pig, dog, or macaque that are higher functioning and quite intelligent, the brain surface is highly folded or convoluted. And dolphins and elephants have even more convolutions in their brains than humans!

I also have colleagues that teach Comparative Neuroanatomy at the graduate level and they borrow the brains.

I can only speak about my own college student reactions to exposure to this field and tell you in general they are amazed and in awe. They never look at animals the same after taking my class.”

How do others use the brain collection?

“Graduate students from Stanford psychology or neurobiology labs generally take a brain collection to nearby middle schools, where they work with students during a science class. They most likely also bring some human brains that they compare to the animal brains. Having unique visual teaching tools — real brains, not models or pictures — helps the middle schoolers gain insight into the complexity of the nervous system. Learning about anatomy from a truly comparative aspect is incredibly valuable, because it demonstrates the similarities as well as the unique differences between humans and other mammals.

I’m sure that ‘Dr. B’s Brains’ provide a very lasting impression on students.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Alzheimer’s researchers call on citizen scientists to play an online game

November 7, 2016
Image by geralt

Image by geralt

Many people, like me, have helplessly watched a loved one suffer and die from dementia. Now there is something you can do to help accelerate Alzheimer’s research — play a game.

The game, called Stall Catchers, is part of the EyesOnALZ project that uses citizen scientists to analyze Alzheimer’s research data. The game was developed by the Human Computation Institute, in collaboration with scientists from Cornell University, MIT and the University of California, Berkeley. The research team is trying to understand the association between reduced blood flow in the brain and Alzheimer’s disease.

The game features movies of real blood vessels in live mouse brains. Players must search for clogged vessels where blood flow is blocked, or stalled. Each movie is seen by many citizen scientists and then checked by a research scientist in order to quickly and accurately identify the stalls.

Past research has shown that Alzheimer’s is associated with the accumulation of beta amyloid proteins that clump together into sticky, neurotoxic aggregates called amyloid plaques. These proteins are normally cleared by the blood stream, but the formation of amyloid plaques slows down this clearance process.

Recent animal studies, performed by the Schaffer-Nishimura Lab at Cornell, suggest that improving blood flow in the brain may help reduce the devastating effects of amyloid accumulation. The researchers discovered that up to two percent of capillaries in the brains of Alzhiemer’s-affected mice were clogged — 10 times more than usual — and this caused up to a 30 percent decrease in overall blood flow in the brain.

“Advanced optical techniques have allowed us to peer into the brain of mice affected by Alzheimer’s disease,” said Chris Schaffer, PhD, the principal investigator in the Schaffer-Nishimura Lab, in a recent news release. “For the first time, we were able to identify the mechanism that is responsible for the significant blood flow reduction in Alzheimer’s, and were even able to reverse some of the cognitive symptoms typical to the disease.”

Now the main challenge for the Cornell researchers is the time-consuming process of manually analyzing all the brain movies to identify the stalled vessels. They need to study up to a thousand vessels for each animal. That’s why they collaborated with the experienced citizen teams at UC Berkeley and MIT to create the Stall Catchers game to get help from the public.

“Today, we have a handful of lab experts putting their eyes on the research data,” said Pietro Michelucci, PhD, the EyesOnALZ principal investigator, in a news story. “If we can enlist thousands of people to do that same analysis by playing an online game, then we have created a huge force multiplier in our fight against this dreadful disease.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

 

Researchers discover “brain signature” for fibromyalgia using brain scans

October 27, 2016

portrait-1006703_1280Millions of patients suffering from fibromyalgia often experience widespread musculoskeletal pain, sleep disturbances, fatigue, headaches and mood disorders. Many also struggle to even get diagnosed, since there are currently no laboratory tests for fibromyalgia and the main symptoms overlap with many other conditions. However, new research may help.

Scientists from the University of Colorado, Boulder may have found a pattern of brain activity that identifies the disease. They used functional MRI (fMRI) scans to study the brain activity of 37 fibromyalgia patients and 35 matched healthy controls, while the participants were exposed to a series of painful and non-painful sensations.

As reported recently in the journal PAIN, the research team identified three specific neurological patterns correlated with fibromyalgia patients’ hypersensitivity to pain.

Using the combination of all three patterns, they were able to correctly classify the fibromyalgia patients and the controls with 92 percent sensitivity and 94 percent specificity — meaning that their test accurately identified 92 percent of those with and 94 percent of those without the disease.

Tor Wager, PhD, senior author and director of the school’s Cognitive and Affective Control Laboratory, explained the significance of the work in a recent news release:

“Though many pain specialists have established clinical procedures for diagnosing fibromyalgia, the clinical label does not explain what is happening neurologically and it does not reflect the full individuality of patients’ suffering. The potential for brain measures like the ones we developed here is that they can tell us something about the particular brain abnormalities that drive an individual’s suffering. That can help us both recognize fibromyalgia for what it is – a disorder of the central nervous system – and treat it more effectively.”

More research is needed, but this study sheds a bit of light on this “invisible” disease.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.


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