Tag: brain

What type of concussion is it? The answer could affect treatment

Joe felt irritable and overwhelmed. Carla had blurry vision and didn’t feel safe to drive. Meg had a pounding headache. But all three of them received the same diagnosis: concussion.

Concussion symptoms vary for different people depending on their medical history, age, degree of injury and other factors. To develop the most effective, personalized treatments, concussion experts across the country are working to learn more about how these variables impact concussion symptoms and recovery.

The researchers — including pediatric emergency medicine physician Angela Lumba-Brown, MD, and neurosurgeon Jamshid Ghajar, MD, PhD, from Stanford’s Brain Performance Center — identified five categories of concussions, which have different symptoms and require different initial treatments:

  • Vestibular — Symptoms include dizziness, fogginess, lightheadedness, nausea, vertigo and disequilibrium. Initially treated with balance and vestibular-ocular training with a physical therapist.
  • Ocular-motor — Symptoms include difficulties with reading and driving, eye strain, problems changing focus between near and far, blurred or double vision, eye pain, vision-derived nausea and photophobia. Initially treated with dynamic vision training with an optometrist. 
  • Headache — Symptoms include different types of headaches, including migraines. Initially treated with headache management.
  • Cognitive — Symptoms include problems with attention, reaction time, working memory, new learning, memory retrieval, organization of thoughts and behavior. Initially treated with neuropsychological assessment and treatments.
  • Anxiety-Mood — Symptoms include nervousness, hypervigilance, ruminative thoughts, depressed mood, anger, irritability, loss of energy, fatigue and feeling more emotional, overwhelmed or hopeless. Initially treated with counseling, including cognitive-behavioral therapies.

The findings appear in Neurosurgery.

However, diagnosing concussions and selecting the correct treatments is a bit more complicated than this list may indicate, Ghajar and Lumba-Brown explained. “These subtypes are not mutually exclusive and they frequently cluster together,” Ghajar said.

This interdependence isn’t all bad news though, because the headache, cognitive and anxiety-mood concussion subtypes often resolve after treating for vestibular and ocular-motor concussion symptoms. Also, early cardiovascular exercise is recommended for all subtypes.

In addition, the experts determined the prevalence of these concussion subtypes in adults and children based on a meta-analysis of previous studies. The most common subtype depends on when a patient is seen, as well as their medical history and age.

“Early on, the headache subtype is the most prevalent for both adult and pediatric populations, and it usually co-exists with the vestibular and ocular-motor subtypes,” said Ghajar. “Weeks to months after injury, the mood subtype with symptoms of anxiety and depression predominates, usually because of inadequate interventions. The prevalence of the vestibular subtype was also very high for pediatric patients.”

The working group also found that sleep disturbance and cervical strain were commonly associated with all five concussion categories. Sleep disturbance symptoms include difficulty falling asleep, frequent awakenings and fatigue, whereas cervical strain symptoms include neck pain, neck stiffness and upper extremity weakness.

According to Lumba-Brown, this work is particularly important because it addresses subtypes in children, a vulnerable subset of patients with unique needs. “Children are expected to go to school daily. They often play sports or engage in risk-taking behaviors. And they often have difficulty expressing their symptoms,” said Lumba-Brown, who recently helped develop clinical guidelines for children with mild traumatic brain injury.

The experts said they hope that a better understanding of the different kinds of concussions and their prevalence will ultimately translate into improved treatment and faster recovery for patients of all ages. The team is now investigating the recovery trajectories for the different subtypes — from the acute period through three months following injury.

They offered clinicians guidance in light of the findings: “Clinicians should assess each subtype of impairment in the acute setting following injury, encourage early cardio exercise and provide prognostic counseling for mood and sleep disturbances.”

Photo by Staff Sgt. Jonathon Fowler/U.S. Air Force

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

Pokémon experts’ brains shed light on neurological development

Photo by Colin Woodcock

Whether parents are dreading or looking forward to taking their kids to see the new “Pokémon” movie may depend on how their brains developed as a child. If they played the video game a lot growing up, a specific region of their visual cortex — the part of the brain that processes what we see — may preferentially respond to Pokémon characters, according to a new research study.

The Stanford psychologists studied the brains of Pokémon experts and novices to answer fundamental questions about how experience contributes to your brain’s development and organization.

Jesse Gomez, PhD, first author of the study and a former neuroscience Stanford graduate student, started playing a lot of Pokémon around first grade. So he realized that early exposure to Pokémon provided a natural neuroscience experiment. Namely, children that played the video game used the same tiny handheld device at roughly the same arm’s length. They also spent countless hours learning the hundreds of animated, pixelated characters, which represent a unique category of stimuli that activates a unique region of the brain.

The research team identified this specialized brain response using functional magnetic resonance to image the brains of 11 Pokémon experts and 11 Pokémon novices, who were adults similarly aged and educated. During the fMRI scan, each participant randomly viewed different kinds of stimuli, including faces, animals, cartoons, bodies, pseudowords, cars, corridors and Pokémon characters.

“We find a big difference between people who played Pokémon in their childhood versus those who didn’t,” explained Gomez in the video below. “People who are Pokémon experts not only develop a unique brain representation for Pokémon in the visual cortex, but the most interesting part to us is that the location of that response to Pokémon is consistent across people.”

In the expert participants, Pokémon activated a specific region in the high-level visual cortex, the part of the brain involved in recognizing things like words and faces. “This helped us pinpoint which theory of brain organization might be the most responsible for determining how the visual cortex develops from childhood to adulthood,” Gomez said.

The study results support a theory called eccentricity bias, which suggests the brain region that is activated by a stimulus is determined by the size and location of how it is viewed on the retina. For example, our ability to discriminate between faces is thought to activate the fusiform gyrus in the temporal lobe near the ears and to require the high visual acuity of the central field of vision. Similarly, the study showed viewing Pokémon characters activates part of the fusiform gyrus and the neighboring region called the occipitotemporal sulcus — which both get input from the central part of the retina — but only for the expert participants.

The eccentricity bias theory implies that a different or larger region of the brain would be preferentially activated by early exposure to Pokémon played on a large computer monitor. However, this wasn’t an option for the 20-something participants when they were children.

These findings have applications well beyond Pokémon, as Gomez explained in the video:

“The findings suggest that the very way that you look at a visual stimulus, like Pokémon or words, determines why your brain is organized the way it is. And that’s useful going forward because it might suggest that visual deficits like dyslexia or face blindness might result simply from the way you look at stimuli. And so that’s a promising future avenue.”

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

Researchers investigate fruit flies as a step towards understanding the human brain

Photo by nuzree

Researchers have been trying to map out the brain’s complex neural circuits to understand how diseases like Parkinson’s disrupt healthy brain communication, in hopes of designing better therapies.

That, obviously, is not easy. So a Stanford research team led by biology professor Liqun Luo, PhD, and bioengineer and physicist Stephen Quake, PhD, are instead studying fruit fly brains — yes, those pesky bugs that fly around your bananas.

Specifically, they have mapped out a blueprint for the fruit fly’s olfactory neurons — identifying how specific gene and protein activity correlates with the biological circuitry of different neuronal cell types. The researchers focused on a fruit fly’s sense of smell because the function, physiology and anatomy of its olfactory system are well known, making it a simple and ideal test bed for their research.

They measured the gene expression profiles using a single-cell sequencing technology developed for mice and human cell types, which they modified to work for the smaller and simpler fruit fly cells.

The team determined different types of neurons express genes differently during development, but gene expression between the neuron types becomes indistinguishable as the flies mature, as recently reported in Cell.

“Once the brain is wired up, the fly doesn’t need to express those genes that help them in choosing the connection partners,” said first author and Stanford biology postdoc Hongjie Li, PhD, in a recent news release. “So there is less gene expression in the adult flies.”

The researchers are a long way from using their technique to map the human brain, but they aren’t daunted by the challeng. “By further developing this approach, we hope to one day reverse-engineer and perhaps even repair defective circuitry in the human brain,” Li said in the release.

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

Study shows link between playing football and neurodegenerative disease

Photo by Cpl. Michelle M Dickson

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.

Head injuries alter genes linked to serious brain disorders, new study shows

Photo by geralt

Traumatic brain injuries, like those caused by concussions, are common. But suffering even a mild brain injury boosts the likelihood of developing neurological and psychiatric disorders, such as Alzheimer’s disease and posttraumatic stress disorder, years later. Exactly how and why that happens remains a mystery.

“Very little is known about how people with brain trauma — like football players and soldiers — develop neurological disorders later in life,” said Fernando Gomez-Pinilla, PhD, a University of California, Los Angeles professor of neurosurgery and of integrative biology and physiology, in a recent news release.

Now, Gomez-Pinilla and his colleagues have discovered that a brain injury harms “master” genes that control other genes throughout the body. This triggers the alteration of hundreds of genes, which are linked to disorders like Alzheimer’s disease, Parkinson’s disease, PTSD, attention deficit hyperactivity disorder and depression. Their study was recently published in EBioMedicine.

In the study, the researchers trained 20 rats to navigate through a maze. They then injected a fluid into the brain of half the rats to simulate a concussion-like brain injury. When all the rats were retested in the maze, the rats with a brain injury took about 25 percent longer than the controls to solve the maze — indicating a change in basic cognitive function.

Next, the team investigated how the brain injuries altered the rats’ genes. They analyzed RNA samples from the rats’ white blood cells and hippocampi, the part of the brain that plays a central role in memory processes. In the injured rats, they found almost 300 genes had been altered in the hippocampus and over 1200 genes in the white blood cells.

More than 100 of these altered genes have counterparts in humans that are linked to neurological and psychiatric disorders. The researchers concluded that concussive brain injury reprograms key genes and this reprogramming could make neurological and psychiatric disorders more likely.

In addition, almost two dozen of the altered genes occurred in both the hippocampus and white blood cells. The researchers hope this genetic signature can be used to develop a gene-based blood test that determines whether a brain injury has occurred and whether future neurological disorders are likely.

They also hope their identification of master genes can give scientists new targets to develop better pharmaceuticals for brain disorders. However, more research is needed to fully understand the role of these master genes. Gomez-Pinilla said he now plans to study the phenomenon in people who have suffered a traumatic brain injury.

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

Curious about concussions? A Stanford researcher reflects on current research, outstanding questions

Photo by Steve - Body Slam
Photo by Steve – Body Slam

Football season has begun, reviving concern and discussion over sports-related concussions.

The American Academy of Pediatrics defines a concussion as a direct hit to the head or jarring blow to the body that gets transmitted to the head, resulting in a rapid onset of short lived impairment of neurological function. However, some controversy surrounds even this definition. So I reached out to Jessica Little, PhD, director of clinical research and operations at the Stanford Concussion and Brain Performance Center, to learn more about concussion research and Stanford’s clinical study of teenage athletes.

What should we know about concussions?

“I think it is important to note that concussions are still not well understood. There are hundreds of different definitions of ‘what is a concussion’ and there is currently no single evidence-based consensus on how to identify and treat concussions.

Research has shown that one of the biggest risk factors for sustaining a concussion is a history of having a prior concussion. There is a ‘window of vulnerability’ — the concept that a person experiencing symptoms of concussion is more vulnerable to incurring a second concussion during this time, as the brain has not yet fully recovered. If a truly concussed athlete has problems paying attention or is not coordinated, they can then be vulnerable to another injury. Protocols are often used to track signs and symptoms of concussion, and athletes are not allowed to return to play until these have resolved. However, it would be helpful to have more precise ways to measure attention and coordination on the sidelines to keep impaired athletes out of contact sports until those skills recover.

The vast majority of people with a concussion recover fully after the injury, though not all symptoms may improve at the same rate and everyone recovers a little differently.”

Describe your clinical study for athletes between 12-17 years of age.

“Our study just closed recruitment and we’re prepping all the data for analysis, so it is an exciting time. The study was called EYE-TRAC Advance, short for Eye-Tracking Rapid Attention Computation. Our lab used a specific type of eye-tracking called ‘circular smooth pursuit’ where an athlete follows a dot that moves at predictable speed around a circle. The eye-tracking was in the form of custom-designed portable “goggles,” using built-in cameras and infrared pupil detection.

Our hypothesis is that people without a concussion can ‘sync-up’ with the way the dot is moving pretty easily, while a person with a concussion has a disruption in their ability to focus and pay attention. You often hear people saying that they feel “off” or “out of sync” following a concussion, and we’re trying to quantify that experience. For the study, we baseline tested athletes (before sports participation) with the eye-tracking, as well as other neurocognitive tests that measured things like attention and reaction time. If the athlete later got a concussion, we tested them again as soon as possible and again at 1, 3 and 12 months after the injury. In this way, we’re able to get a clear picture of how their brain recovered over time.

Overall, we reached out to over 60 different organizations and recruited over 1,400 people. We had a specially outfitted ‘mobile testing center’ RV. This allowed us to literally drive up to the side of an athletic field and perform the testing on-site at the school or organization, which really reduced common barriers to participating in a research study, such as the costs and time associated with transportation to and from appointments.”

Can technology play a significant role in preventing concussions?

“A lot of current technologies focus on diagnosing a concussion, but there are far fewer that actually focus on preventing concussions. There are some technologies that measure an athlete’s gait and vestibular-balance ability. If there are impairments, the athletes can be provided skill training to improve any deficits, thus reducing the risk of injury. Other technologies, such as helmet technologies, may be helpful in reducing the instance of skull fractures and other serious injuries, but they haven’t yet proved effective at preventing a concussion — that is caused more by brain rotation, which a helmet can’t fully protect against. One possible preventative solution could come from a neck device that stabilizes the rotational forces while still allowing neck movement at low accelerations, so athletes can move about freely until it senses a potentially dangerous level of force.”

Are there issues with under-reporting concussions?

“Historically, there have been some issues with individuals under-reporting symptoms that would lead to a diagnosis of a concussion. This is often motivated by the idea that they should ‘suck it up,’ ‘don’t want to let the team down’ or the fact that their ability to perform athletically is tied to keeping an athletic scholarship. There is research happening in the field right now trying to figure out the best way to dismantle these types of beliefs and make it more likely that athletes can be properly identified, given the treatment they need, and hopefully continue to safely engage in their sport.”

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

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