A Neurosurgeon’s Remarkable Plan to Treat Stroke Victims With Stem Cells

Gary Steinberg defied convention when he began implanting living cells inside the brains of patients who had suffered from a stroke.

The day she had a stroke, Sonia Olea Coontz, a 31-year-old from Long Beach, California, was getting ready to start a new career as a dog trainer. She had just wrapped up a week of training, and she and her boyfriend were taking their own dogs to the park. But something strange kept happening: She’d try to say one thing and end up saying another.

By evening, her boyfriend was worriedly telling her that the right side of her face had gone slack. She wasn’t able to focus on anything except the bedroom walls, and she wondered how they’d gotten to be so white. “It was very surreal,” she recalls.

Coontz spent the next six months mostly asleep. One day she attempted to move an arm, but she couldn’t. Then a leg, but she couldn’t move that, either. She tried to call for her boyfriend but couldn’t say his name. “I am trapped in this body,” she remembers thinking.

That was May 2011. Over the next two years, Coontz made only small improvements. She developed a 20-word spoken vocabulary and could walk for five minutes before needing a wheelchair. She could move her right arm and leg only a few inches, and her right shoulder was in constant pain. So when she learned about a clinical trial of a new treatment at Stanford University School of Medicine, she wasn’t fazed that it would involve drilling through her skull.

At Stanford, a magnetic resonance scan showed damage to the left half of Coontz’s brain, an area that controls language and the right side of the body. Ischemic strokes, like Coontz’s, happen when a clot blocks an artery carrying blood into the brain. (Rarer, but more deadly, hemorrhagic strokes are the result of weakened blood vessels that rupture in the brain.) Of the approximately 800,000 Americans who have strokes each year, the majority make their most significant recoveries within six months. After that, their disabilities are expected to be permanent.

On the day of Coontz’s procedure, Gary Steinberg, the chair of neurosurgery, drilled a nickel-size burr hole into Coontz’s skull and injected stem cells around the affected part of her brain. Then everyone waited. But not for long.

Coontz remembers waking up a few hours later with an excruciating headache. After meds had calmed the pain, someone asked her to move her arm. Instead of moving it inches, she raised it over her head.

“I just started crying,” she recalls. She tried her leg, and discovered she was able to lift and hold it up. “I felt like everything was dead: my arm my leg, my brain,” she says. “And I feel like it just woke up.”    

Coontz is part of a small group of stroke patients who have undergone the experimental stem cell treatment pioneered by Steinberg. Conventional wisdom has long maintained that brain circuits damaged by stroke are dead. But Steinberg was among a small cadre of researchers who believed they might be dormant instead, and that stem cells could nudge them awake. The results of his trial, published in June 2016, indicate that he may well be right.

“This important study is one of the first suggesting that stem cell administration into the brain can promote lasting neurological recovery when given months to years after stroke onset,” says Seth Finklestein, a Harvard neurologist and stroke specialist at Massachusetts General Hospital. “What’s interesting is that the cells themselves survived for only a short period of time after implantation, indicating that they released growth factors or otherwise permanently changed neural circuitry in the post-stroke brain.”

Steinberg, a native of New York City, spent his early career frustrated by the dearth of stroke therapies. He recalls doing a neurology rotation in the 1970s, working with a woman who was paralyzed on one side and couldn’t speak. “We pinpointed exactly where in the brain her stroke was,” Steinberg says. But when Steinberg asked how to treat her, the attending neurologist replied, “Unfortunately, there’s no treatment.” For Steinberg, “no treatment” was not good enough.

After earning his MD/PhD from Stanford in 1980, Steinberg rose to become the chair of the school’s neurosurgery department. In 1992, he co-founded the Stanford Stroke Center with two colleagues.

In the years that followed, two treatments emerged for acute stroke patients. Tissue plasminogen activator, or tPA, was approved by the FDA in 1996. Delivered by catheter into the arm, it could dissolve clots, but it needed to be administered within a few hours of the stroke and caused hemorrhaging in up to 6 percent of patients. Mechanical thrombectomy emerged about a decade later: By inserting a catheter into an artery in the groin and snaking it into the brain, doctors could break up a clot with a fluid jet or a tiny suction cup. But that treatment could only be delivered within six hours of a stroke and couldn’t be used in every case. After the window closed, doctors could offer nothing but physical therapy.

When Steinberg started looking into stem cell therapy for stroke patients, in the early 2000s, the idea was still unorthodox. Stem cells start off unspecialized, but as they divide, they can grow into particular cell types. That makes them compelling to researchers who want to create, for example, new insulin-producing cells for diabetics. But stem cells also help our bodies repair themselves, even in adulthood. “And that’s the power that Steinberg is trying to harness,” says Dileep Yavagal, a professor of clinical neurology and neurosurgery at the University of Miami.

Steinberg began testing this in a small trial that ran between 2011 and 2013. Eighteen volunteers at Stanford and the University of Pittsburgh Medical Center agreed to have the cells—derived from donor bone marrow and cultured by the Bay Area company SanBio—injected into their brains.

Sitting in his office, Steinberg boots up footage of a woman in her 70s wearing a NASA sweatshirt and struggling to wiggle her fingers. “She’s been paralyzed for two years. All she can do with her hand, her arm, is move her thumb,” says Steinberg. “And here she is—this is one day later,” he continues. Onscreen, the woman now touches her fingers to her nose. “Paralyzed for two years!” Steinberg repeats jubilantly.

His staff calls this woman and Coontz their “miracle patients.” The others improved more slowly. For example, a year after their surgery, half of the people who participated in a follow-up exam gained 10 or more points on a 100-point assessment of motor function. Ten points is a meaningful improvement, says Steinberg: “That signifies that it changes the patient’s life.” His team hadn’t expected this. “It changes the whole notion—our whole dogma—of what happens after a stroke,” he says.

But how did the stem cells jump-start those dormant circuits? “If we understood exactly what happened,” he says wryly, “we’d really have something.” Here’s what didn’t happen: The stem cells didn’t turn into new neurons. In fact, they died off within a month.

Steinberg thinks the circuits in question were somehow being inhibited. He’s not exactly sure why, but he thinks chronic inflammation could be one reason. He has a clue: After the procedure, 13 of his patients had temporary lesions in their brains. Steinberg thinks these indicated a helpful immune response. In fact, the size of the lesions after one week was the most significant predictor of how much a patient would recover.

For all 18 patients, Steinberg also thinks the cells secreted dozens, perhaps hundreds, of proteins. Acting in concert, these proteins influenced the neurons’ environment. “Somehow,” Steinberg reflects, “it’s saying, ‘You can act like you used to act.’”

Some of the participants had adverse reactions to the surgery, but not to the cells themselves. (A small European study published later also indicated that stem cells are safe for stroke sufferers.) And Steinberg says his patients’ recovery “was still sustained on all scales at two years.”

He’s now collaborating with Yavagal on a randomized controlled study that will include 156 stroke patients. Key questions await future researchers: How many cells should doctors use? What’s the best way to administer them? And are the cells doing all the work, or is the needle itself contributing? Could the death of the cells be playing a role?

Steinberg thinks stem cell therapy might help alleviate Parkinson’s, Lou Gehrig’s disease, maybe even Alzheimer’s. His lab is also testing its effects on traumatic brain and spinal cord injuries. Even though these conditions spring from different origins, he thinks they might all involve dormant circuits that can be reactivated. “Whether you do it with stem cells, whether you do it with optogenetics, whether you do it with an electrode, that’s going to be the future for treating neurologic diseases.”

Six years after her stroke, Coontz now speaks freely, although her now-husband sometimes has to help her find words. Her shoulder pain is gone. She goes to the gym, washes dishes with both hands and takes her infant son on walks in the stroller. For Coontz, motherhood is one of the greatest joys of post-stroke life. During her pregnancy, she worked out five times a week so she would be able to hold and bathe and deliver the baby. After so many medical procedures she couldn’t control, this time, she felt, “I am awake, I can see, I know how I want this to be.”

Her son is now 1 year old. “My husband picks him up and holds him way over his head, and obviously I can’t do that,” she says. “But I will. I don’t know when, but I will. I guarantee it.”

This article originally appeared on smithsonianmag.com and was written by Kara Platoni

What Happens in the Brain When We Feel Fear?

And why some of us just can’t get enough of it?

Fear may be as old as life on Earth. It is a fundamental, deeply wired reaction, evolved over the history of biology, to protect organisms against perceived threat to their integrity or existence. Fear may be as simple as a cringe of an antenna in a snail that is touched, or as complex as existential anxiety in a human.

Whether we love or hate to experience fear, it’s hard to deny that we certainly revere it – devoting an entire holiday to the celebration of fear.

Thinking about the circuitry of the brain and human psychology, some of the main chemicals that contribute to the “fight or flight” response are also involved in other positive emotional states, such as happiness and excitement. So, it makes sense that the high arousal state we experience during a scare may also be experienced in a more positive light. But what makes the difference between getting a “rush” and feeling completely terrorized?

We are psychiatrists who treat fear and study its neurobiology. Our studies and clinical interactions, as well as those of others, suggest that a major factor in how we experience fear has to do with the context. When our “thinking” brain gives feedback to our “emotional” brain and we perceive ourselves as being in a safe space, we can then quickly shift the way we experience that high arousal state, going from one of fear to one of enjoyment or excitement.

When you enter a haunted house during Halloween season, for example, anticipating a ghoul jumping out at you and knowing it isn’t really a threat, you are able to quickly relabel the experience. In contrast, if you were walking in a dark alley at night and a stranger began chasing you, both your emotional and thinking areas of the brain would be in agreement that the situation is dangerous, and it’s time to flee!

But how does your brain do this?

**********

Fear reaction starts in the brain and spreads through the body to make adjustments for the best defense, or flight reaction. The fear response starts in a region of the brain called the amygdala. This almond-shaped set of nuclei in the temporal lobe of the brain is dedicated to detecting the emotional salience of the stimuli – how much something stands out to us.

For example, the amygdala activates whenever we see a human face with an emotion. This reaction is more pronounced with anger and fear. A threat stimulus, such as the sight of a predator, triggers a fear response in the amygdala, which activates areas involved in preparation for motor functions involved in fight or flight. It also triggers release of stress hormones and sympathetic nervous system.

This leads to bodily changes that prepare us to be more efficient in a danger: The brain becomes hyperalert, pupils dilate, the bronchi dilate and breathing accelerates. Heart rate and blood pressure rise. Blood flow and stream of glucose to the skeletal muscles increase. Organs not vital in survival such as the gastrointestinal system slow down.

A part of the brain called the hippocampus is closely connected with the amygdala. The hippocampus and prefrontal cortex help the brain interpret the perceived threat. They are involved in a higher-level processing of context, which helps a person know whether a perceived threat is real.

For instance, seeing a lion in the wild can trigger a strong fear reaction, but the response to a view of the same lion at a zoo is more of curiosity and thinking that the lion is cute. This is because the hippocampus and the frontal cortex process contextual information, and inhibitory pathways dampen the amygdala fear response and its downstream results. Basically, our “thinking” circuitry of brain reassures our “emotional” areas that we are, in fact, OK.

**********

Being attacked by a dog or seeing someone else attacked by a dog triggers fear. (Jaromir Chalabala/Shutterstock.com)

Similar to other animals, we very often learn fear through personal experiences, such as being attacked by an aggressive dog, or observing other humans being attacked by an aggressive dog.

However, an evolutionarily unique and fascinating way of learning in humans is through instruction – we learn from the spoken words or written notes! If a sign says the dog is dangerous, proximity to the dog will trigger a fear response.

We learn safety in a similar fashion: experiencing a domesticated dog, observing other people safely interact with that dog or reading a sign that the dog is friendly.

**********

Fear creates distraction, which can be a positive experience. When something scary happens, in that moment, we are on high alert and not preoccupied with other things that might be on our mind (getting in trouble at work, worrying about a big test the next day), which brings us to the here and now.

Furthermore, when we experience these frightening things with the people in our lives, we often find that emotions can be contagious in a positive way. We are social creatures, able to learn from one another. So, when you look over to your friend at the haunted house and she’s quickly gone from screaming to laughing, socially you’re able to pick up on her emotional state, which can positively influence your own.

While each of these factors - context, distraction, social learning - have potential to influence the way we experience fear, a common theme that connects all of them is our sense of control. When we are able to recognize what is and isn’t a real threat, relabel an experience and enjoy the thrill of that moment, we are ultimately at a place where we feel in control. That perception of control is vital to how we experience and respond to fear. When we overcome the initial “fight or flight” rush, we are often left feeling satisfied, reassured of our safety and more confident in our ability to confront the things that initially scared us.

It is important to keep in mind that everyone is different, with a unique sense of what we find scary or enjoyable. This raises yet another question: While many can enjoy a good fright, why might others downright hate it?

**********

Any imbalance between excitement caused by fear in the animal brain and the sense of control in the contextual human brain may cause too much, or not enough, excitement. If the individual perceives the experience as “too real,” an extreme fear response can overcome the sense of control over the situation.

This may happen even in those who do love scary experiences: They may enjoy Freddy Krueger movies but be too terrified by “The Exorcist,” as it feels too real, and fear response is not modulated by the cortical brain.

On the other hand, if the experience is not triggering enough to the emotional brain, or if is too unreal to the thinking cognitive brain, the experience can end up feeling boring. A biologist who cannot tune down her cognitive brain from analyzing all the bodily things that are realistically impossible in a zombie movie may not be able to enjoy “The Walking Dead” as much as another person.

So if the emotional brain is too terrified and the cognitive brain helpless, or if the emotional brain is bored and the cognitive brain is too suppressing, scary movies and experiences may not be as fun.

**********

All fun aside, abnormal levels of fear and anxiety can lead to significant distress and dysfunction and limit a person’s ability for success and joy of life. Nearly one in four people experiences a form of anxiety disorder during their lives, and nearly 8 percent experience post-traumatic stress disorder (PTSD).

Disorders of anxiety and fear include phobias, social phobia, generalized anxiety disorder, separation anxiety, PTSD and obsessive compulsive disorder. These conditions usually begin at a young age, and without appropriate treatment can become chronic and debilitating and affect a person’s life trajectory. The good news is that we have effective treatments that work in a relatively short time period, in the form of psychotherapy and medications.

This article was originally published on The Conversation.

image: https://counter.theconversation.com/content/85885/count.gif

Arash Javanbakht, Assistant Professor of Psychiatry, Wayne State University

Linda Saab, Assistant Professor of Psychiatry, Wayne State University

Read more: https://www.smithsonianmag.com/science-nature/what-happens-brain-feel-fear-180966992/#EWEYT3vFG19mf7P4.99
 

Why Does Your Body Twitch As You're Falling Asleep?

If you’ve ever found yourself drifting off to sleep only to be woken by a vigorous, full-body twitch or jerk, then do not feel alarmed. You’re among the estimated 60 - 70 % of Americans who regularly experience a phenomenon known as a hypnic jerk—also known as a hypnagogic jerk, or sleep start—which strikes as a person falls into a deep sleep. Here’s what to know about it.

What do sleep jerks feel like?

Hypnic jerks—involuntary twitches or jolts which occur during the night—can affect people in different ways. Many people will sleep right through them, but for others, they are vigorous enough to wake them up.

Although there is no definite explanation for what causes hypnic jerks, people are more likely to suffer from them when they’re sleep deprived or anxious, or when they do sleep-impairing habits before going to bed, like drinking caffeine or doing exercise close to bedtime, says James Wilson, a U.K.-based sleep behavior and sleep environment expert. “For people who suffer from hypnic jerks, it’s awful,” he adds. “They worry about it before they go to bed, which makes it worse.”

Jacqui Paterson, who is 44 and lives in the U.K., says she has experienced these kinds of twitches on an almost-nightly basis for about three years.

“When I was about 41, I started getting insomnia, which I’d never had in my life before,” she says. “Initially, I was staying awake all night, but I now get these annoying jerks which wake me up exactly an hour after I fall asleep, like someone has set an alarm in my head. I seem to have replaced one evil with another.”

Paterson says the jerks come more regularly when she feels concerned or preoccupied. If she worries about them happening before she goes to bed, then it “almost guarantees” that she will suffer from them that night.

The jerks feel like a jolt or an electric shock, Paterson says. “I’ve heard people talk about getting a falling sensation when they drop off to sleep,” she says. “To me, the feeling is like that but on steroids. It’s like someone has come and slapped me. It’s a really shocking feeling, like jumping into freezing cold water. I always wake up feeling totally alert.”

What causes hypnic jerks?

Put simply, hypnic jerks are caused when one part of the brain tries to go to sleep more quickly than other parts of the brain.

“The complexity of going to sleep and waking up is incredible, and sometimes—particularly when we are sleep deprived—our brain doesn’t shut down normally, which means we get this sort of jerking movement when we’re in a light sleep,” says Wilson. Often, he adds, the brain tries to make sense of it, “which is when we imagine ourselves falling off the sidewalk, a cliff or in a hole.”

The reason why some people experience the twitches at such a predictable time is due to their circadian rhythm, or body clock, Wilson says. “Normally when we go to sleep, about half an hour later we go into a deep stage of sleep during which we wouldn’t get these hypnic jerks,” he says. “If someone is sleep deprived, as they go through the process of falling asleep, the brain will get stuck at the same point in time. Usually if we can help people address their sleep deprivation, the instances decrease or disappear altogether.”

How can you prevent sleep jerks from happening?

There are ways to limit the effects, particularly by making a conscious effort to sleep better. “Try and get in a good routine around sleep,” Wilson says. “Wake up at the same time every day, and wind down properly before going to bed, making sure the activities you do in the hour before going to sleep are relaxing to you. Like most issues surrounding sleep, preventing hypnic jerks is all about trying to solve that sleep deprivation.”

Wilson also suggests that if a person suffers from them at the same time every night, they could ask a housemate or family member to disturb their sleep about five minutes before the jerks tend to occur, either by encouraging them to turn over in bed or rustling something near them. Often, that will help stop the twitches from happening, he says.

This article originally appeared on time.com and was written by Kate Samuelson

A Dan­cer’s Brain De­vel­ops in a Unique Way

Music activates our deeper brain areas, but what happens in a dancer’s brain? Movement can trigger a flow state which makes way for an intuitive neural network.

As technology takes over more areas of our lives, interest in more natural ways of life has also increased massively. One example of this desire to reconnect with nature is the upsurge of yoga and meditation retreats.

Music and dance have been fundamental parts of the human experience for millennia. They have enabled interaction which has given rise to close communities and rich cultures. 

Neuroscience has studied music for decades. It has been found to activate the deeper brain areas in a unique way. Deep brain areas are primarily responsible for emotions, memory and social interaction.  They evolved in the human brain much earlier than the cognitive functions in the cortex. 

Deep brain areas are primarily responsible for emotions, memory and social interaction.

My doctoral dissertation developed methods for understanding the processes that dance generates in the cortex. 

I compared the brain functions of professional dancers and musicians to people with no experience of dance or music as they watched recordings of a dance piece. The brain activity of the dancers was different from that of musicians and the control group during sudden changes in the music, long-term listening of music and the audio-visual dance performance. 

These results support the earlier findings indicating that the auditory and motor cortex of dancers develops in a unique way. In my study, the dancers’ brains reacted more quickly to changes in the music than those of musicians or members of the control group. The change is apparent in the brain as a reflex, before the dancer is even aware of it at a conscious level.

I also found that dancers displayed stronger synchronisation at the low theta frequency. Theta synchronisation is linked to emotion and memory processes which are central to all interpersonal interaction and self-understanding.

In dance, the basic elements of humanity combine in a natural way.

Touch and cooperation are integral elements of dance – without them, there can be no dance. They are as important to dance as movement and music. 

However, the neuroscience of dance is still a young field. Consequently, the brain processes of touch and cooperation have not yet been studied through dance specifically. 

We do know that in dance, the basic elements of humanity combine in a natural way. It combines creative act, fine-tuned movement and collaboration, much like playing music. The movement involves the whole body, like in sports. There is touch, like in gentle interaction. 

Dancing is also associated with “flow”, a well-researched phenomenon in which the person becomes fully immersed in an activity. Flow experiences have been found to increase the general contentment and productivity of the person as well as the quality of the activity. It reduces the activation of the neural network which is responsible for logical deduction and detailed observation. 

This makes room for the creative neural network which also has an important role in generating a relaxed state of mind.

Practicing an instrument requires extreme precision. It has been found to shape motor processes in the brain in many ways. Meanwhile, studies conducted on dancers reveal how their brains have specialised to process dance motion. 

Certain areas of dancers’ brains have specialised precisely to observe dance movements. The brain structures of musicians and dancers have also been found to differ from the general population in the areas responsible for processing movement and sound.

Brain synchronisation enables seamless cooperation.

Studies on producing music and movement show how during cooperation, the brains of two people become attuned to the same frequency. This is apparent in how the low-frequency brain waves of the participants become synchronised. 

Brain synchronisation enables seamless cooperation, and is necessary for creating both harmonic music and movement. The ability to become attuned to another person’s brain frequency is essential for the function of any empathetic community.

Lately, researchers have gained fantastic results regarding the role of exercise as a mood enhancer. In addition to drug treatment and psychotherapy, exercise is currently even being recommended as a form of treatment for depression. Exercise releases hormones that create a sense of wellbeing, which in turn boosts positive emotional processes in the brain. It also lowers the activation of the amygdala, the brain’s fear and stress centre. 

Finding the right dance style can make dancers euphoric, and make them forget the drudgery of official exercise recommendations and step counters.

Dancers who pursue graceful movement must practice being aware of their bodies and (being aware) of wordless communication. These skills are particularly important today, when we spend so much time sitting and in virtual realities. Our way of life has taken us further from our own physical experiences and the understanding of the wordless emotional messages of others.

For example, contact improvisation makes the dancers to listen attentively to the body of their partner. Touch is known to reduce pain, fear and anxiety. 

Functional brain imaging has shown that these effects of touch are also apparent in the brain. In one study, a touch from a significant other reduced the intensity of the pain activation in the brain during an electric stimulus when compared with pain experienced alone.

Pain, stress and anxiety often go hand in hand with depression. Dance, music and related expressive forms of therapy could help lessen mental fluctuations even before the onset of full depression. Promising results have been gained from treating depression through music therapy. 

Dance therapy can help with many disorders of the mind and body, from anxiety to dementia and Parkinson’s disease.

Dance is a highly subjective experience. However, neuroscience can help us understand how people can use dance to feel more connected to each other in our technology-filled world.

This article originally appeared on www.helsinki.fi

AUTHOR HANNA POIKONEN