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Neuroscience, Podcasts, Stanford News

A word with Karl Deisseroth

A word with Karl Deisseroth

Karl D at Breakthrough eventAt 44, Stanford bioengineer/neuroscientist Karl Deisseroth, MD, PhD, has achieved more success and accolades than most scientists receive in their lifetime. Two techniques, optogenetics and CLARITY, which open the brain to deeper and more penetrating explorations of its complexity, are among his seminal achievements. In November, he was awarded the prestigious 2016 Breakthrough Prize in Life Sciences, which comes with a no-strings attached monetary award of $3 million, and I sat down to talk with him for a 1:2:1 podcast shortly after he won.

Great scientific leaps, which optogenetics and CLARITY have been universally hailed as, are often preceded by challenges and detours that ferment doubt in the head of even the most determined researcher. And such was the case with optogenetics. Deisseroth told me there were arched eyebrows and skepticism from others during his quest. And he gave insight on how someone can keep those doubts at bay and remain focused on the endgame when their vision may not be shared or understood by others.

Deisseroth calls the human brain “the most complicated object in the universe.” So complicated, he says, that truly understanding its wiring and why and how it goes awry will take decades. “We don’t know what the finish line will look like,” he told me. “There [are] so many mysteries.”

Deisseroth’s track in neuroscience and medicine began in college, but from early on, as part of a family in which books and reading were venerated, words and creative writing were a strong interest. He told me, “I was just enthralled by how words could make you feel, how the emotions that could come from the words sometimes was independent of their formal meaning… I was so intrigued by their power to sway the mind and to uplift. Without making too sweeping of a claim, I also think that part of what got me interested in the brain is understanding how something like that could happen.”

So why psychiatry? What led him to that path, I asked? He said that he “trudged” into a psychiatry rotation as it was a required part of Stanford’s curriculum, but on the first day a passion was ignited:

There was a patient who was really on the inpatient ward, and really not doing well. This patient more or less accosted me. There was an interaction where there was just a stream of psychotic words and sentences directed at me, rageful, angry, loose in its framing and construction, very hard to understand, but in a way, there was a communicative effect achieved.

Although the words and the sentences didn’t mean anything relating to reality, there was definitely a communication that was achieved. I was so interested in understanding, from that moment, how an otherwise intact person could have a reality that was so different and could communicate in such an unconventional way.

It really hit all parts of me at once. It hit my interest in words and writing, my interest in neuroscience, and my desire to help people in the most direct way I could.

I started to look more into psychiatry, and I saw the opportunities, the depth of the mysteries, the extent of the suffering. It was like all the pieces of a combination lock clicking into place all at once.

We delved into numerous topics during our conversation. Why is the brain such a difficult organ to understand? How were optogenetics and CLARITY adding to the collective wisdom to the field?  Why is the stigma of mental illness so pervasive and persistent? And, if he could answer any one question about the brain and a psychiatric disorder, what would it be? I hope you’ll listen to the podcast and hear his responses.

Previously: Stanford’s Karl Deisseroth talks about the work he was “destined to do”Stanford bioengineer Karl Deisseroth wins 2016 Breakthrough Prize in Life SciencesInside the brain of optogenetics pioneer Karl DeisserothLightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact and An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”
Photo, of Karl Deisseroth receiving his Breakthrough Prize, by Steve Jennings/Getty Images

Neuroscience, Patient Care, Stanford News

Celebrating the new Stanford Neuroscience Health Center

Celebrating the new Stanford Neuroscience Health Center

neuro health center ribbon cutting - 560

The first time Chris Bjornson walked through the infusion area in the new Stanford Neuroscience Health Center, he couldn’t stop smiling. Bjornson, 45, was diagnosed with multiple sclerosis seven years ago. He’s happy with how well his doctor, neuro-immunologist Jeffrey Dunn, MD, has worked with him to control the progress of a disease that has gradually eroded Bjornson’s ability to walk.

Getting to his appointments, however, was something else. Many neurological disorders and injuries leave people with less ability to maneuver through crowded hallways, negotiate the changes in texture from one type of floor covering to another or endure going from one place to another to see different specialists. High countertops, narrow bathroom stalls and tight turns at corners become additional obstacles.

Stanford doctors agreed that asking patients to make such a difficult journey for care had to change. They also knew that that change couldn’t be done by renovating the several buildings that now house the Department of Neurology and Neurological Sciences and the Department of Neurosurgery. Only a from-scratch approach would work.

Last week, Stanford Health Care, in partnership with the Stanford School of Medicine, cut the ribbons to officially open the new Stanford Neuroscience Health Center for outpatient care. It’s a five-story, 92,000-square-foot building on the medical school campus. The exterior is, of course, brightly new and sparkling. It is the interior, however, where the center shows its best.

Hallways, floor coverings, lighting, chairs, bathrooms and the building’s floor-by-floor organization all reflect what the Center’s 12-person Patient Advisory Council told Stanford Health Care would eliminate those physical barriers to care — and, as a consequence, their stress. The infusion center that so impressed Bjornson has no dark corners or tiny treatment rooms. Instead, the area is filled with the light and views from three walls of windows.

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Big data, Neuroscience, Research, Videos

An 18-month portrait of a brain yields new insights into connectivity — and coffee

An 18-month portrait of a brain yields new insights into connectivity — and coffee

Coffee changes the brain’s activity. Wait, wait, don’t stop reading, I know you know that. But here’s the cool thing: For 18 months, Stanford psychologist Russell Poldrack, PhD, scanned his brain twice a week. On the days he skipped coffee, the MRI images were quite different, showing, for the first time, how caffeine changes brain connectivity.

A Stanford news release explains:

The connection between the somatosensory motor network and the systems responsible for higher vision grew significantly tighter without caffeine.

“That was totally unexpected, but it shows that being caffeinated radically changes the connectivity of your brain,” Poldrack said. “We don’t really know if it’s better or worse, but it’s interesting that these are relatively low-level areas. It may well be that I’m more fatigued on those days, and that drives the brain into this state that’s focused on integrating those basic processes more.”

Poldrack’s experiment could generate hundreds, or even thousands, of similar insights, once researchers parse through the data, which is open to all. The RNA from his white blood cells was also sequenced once a week to coordinate gene expression with brain function.

Poldrack’s brain remained fairly constant and he admits he’s an even-keeled guy, generally content and rarely sad. But he hopes the approach could reveal differences between healthy brains, like his, and those that suffer from schizophrenia or bipolar disorder.

Previously: Hidden memories: A bit of coaching allows subjects to cloack memories from fMRI detector, Image of the Week: Art inspired by MRI brain scans and From phrenology to neuroimaging: New finding bolsters theory about how brain operates

Bioengineering, Imaging, Neuroscience, Research, Stanford News

Brain radio: Switching nerve circuit’s firing frequency radically alters alertness levels in animal models

Brain radio: Switching nerve circuit's firing frequency radically alters alertness levels in animal models

brain radioIt’s a kick to consider that a part of the brain could act like a radio, with different stations operating at different frequencies, playing different kinds of music and variously attracting or repelling different “listening audiences.” A new study by Stanford neuroscientist Jin Hyung Lee, PhD, and her colleagues has isolated a brain circuit linking just such a “transmission station” in the midbrain to various “listener” regions in the forebrain.

The findings have clear therapeutic potential. In a news release about the research, I wrote:

In a case study published in 2007, [researchers] demonstrated that electrically stimulating the central portion of the thalamus — a deep-brain relay station routing inputs from the senses to myriad cognitive-processing centers throughout the cerebral cortex — could restore consciousness in a patient who’d been in a minimally conscious state for six years.

“But there was no way to know how it worked,” Lee told me.

Now, in a set of experiments published in eLife, she and her associates have used precisely targeted stimulation and recording techniques to show that forcing a set of nerve cells in the central thalamus to fire at 40 or 100 times a minute induces a state of arousal: Rats that were fast asleep wake up and start roving around and exploring their environments. Switch the same nerve cells to a firing frequency of 10 times a minute, and the same rats immediately go into a state of deep unconsciousness more akin to a coma or a petit mal seizure (a transient state of behavioral arrest) than to restful sleep.

In addition to these behavioral effects, forcing those central-thalamic nerve cells to fire at different rates causes distinct structures elsewhere in the brain to rev up or slack off. In a sense, firing at 100 times a minute was like blasting heavy-metal music – some forebrain regions leapt into the mosh pit, some ran for cover – while 10 times a minute (the easy-listenin’ channel?) variously appealed to or turned off different brain areas.

You can’t do that with a drug.

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Cancer, Neuroscience, Research, Science, Stanford News

“Chemobrain” studied by researchers at Stanford, MD Anderson

"Chemobrain" studied by researchers at Stanford, MD Anderson

5490361039_7af0ae216b_zIt’s an unfortunate fact that even successful cancer treatment can leave lasting scars. Surgeries are sometimes needed to remove tumors, skin can be permanently damaged from radiation therapy and powerful chemotherapy drugs can wreak havoc throughout the body.

One of the least understood lasting effects, however, is a cognitive deficit that some survivors describe as “chemobrain.” The difficulties they experience in focusing and remembering are attributed to the neurotoxic effects of chemotherapy. But it’s not been clear whether some drugs are worse than others in this regard.

Now Stanford oncologist Douglas Blayney, MD, and former Stanford faculty member Shelli Kesler, PhD, have published a study in JAMA Oncology assessing cognitive defects in a group of 62 breast cancer patients treated between 2008 and 2014. About one-third of the patients had received a class of chemotherapy drugs that are anthracycline-based, like doxorubicin; one-third received other chemotherapy drugs that were non-anthracycline-based; and the remainder received no chemotherapy at all.

As Blayney explained in an email to me:

Chemotherapy for breast cancer is often associated with cognitive problems in patients. However, it is unclear whether certain treatment regimens are associated with greater cognitive difficulties than others. In a small study, we showed that women treated with anthracycline-based chemotherapy had lower verbal memory, including immediate recall and delayed recall, compared with non-anthracycline chemotherapy treated breast cancer patients, and breast cancer patients not treated with chemotherapy.

Kesler, who has published before on chemobrain in breast cancer patients, is now at MD Anderson Cancer Center in Texas.

Although their results are intriguing, Blayney cautions that the study was relatively small and it’s too soon to start ruling out one type of chemotherapy over another. But it’s important to begin these types of analyses. He writes:

Patient-reported outcomes of cognitive dysfunction and psychological distress were elevated in both groups of women treated with chemotherapy compared with patients treated without chemotherapy.  Our study is hypothesis generating, involves small numbers of patients, there is no dose-response information available, and it is way too soon to abandon doxorubicin adjuvant treatment, which remains a valuable chemotherapeutic agent.  We are currently enrolling in a larger, longitudinal study of women measuring cognitive functioning before any treatment, after completion of systemic treatment, and one year later.

Previously: Wellness after cancer: Stanford opens clinic to address survivors’ needs,  A look at stem cells and “chemobrain” and Stanford study shows effects of chemotherapy and breast cancer on brain function
Image by Steve Snodgrass

Behavioral Science, Neuroscience, Research, Stanford News

Like or dislike? Brain scans reveal source of initial preferences

Like or dislike? Brain scans reveal source of initial preferences

3228273137_020ba1b3c1_oJust seconds into an interview with a potential babysitter, I had already formed a slightly unfavorable opinion. She had excellent reviews — five stars across the board. She was polite and paid attention to my baby. Why didn’t I like her?

Well, I may not consciously know, but perhaps the answer lies deep in my brain, new research from Stanford’s Department of Psychology suggests.

A team led by Jeanne Tsai, PhD, associate professor of psychology, showed volunteers faces that varied by gender, ethnicity and emotion and monitored their reactions using functional magnetic resonance imaging (fMRI), a recent Stanford News article details:

In the study, Tsai and her colleagues examined whether cultural values could drive neural responses and preferences for different positive facial expressions – like excited versus calm faces…

“Within cultures, European Americans responded similarly to excited and calm faces, but Chinese showed greater activity in the ventral striatum in response to calm versus excited expressions,” Tsai said.

The ventral striatum is part of the brain involved in emotional responses, particularly those related to the anticipation of pleasure. “This pattern held regardless of the ethnicity or gender of the face,” Tsai added.

This finding reflects the cultural preference in China for calm expressions, Tsai said, and it could have implications for employment decisions as well as mate selection.

Previously: Hidden memories: A bit of coaching allows subjects to cloak memories from fMRI detector, Thinking about “culture” as part of global well-being and From phrenology to neuroimaging: New finding bolsters theory about how brain operates
Photo by Dar’ya Sip

Behavioral Science, Neuroscience, Podcasts

Advice for changing health behavior: “Think like a designer”

Advice for changing health behavior: "Think like a designer"

When listening to our latest 1:2:1 podcast, featuring a conversation with Kyra Bobinet, MD, MPH, two things jumped out at me. First, Bobinet, an expert in design thinking and behavioral change who says she “leads by my curiosity,” has a very cool personal story, and second: We shouldn’t be so hard on ourselves when we struggle to make positive health changes. In short, it’s not us – it’s a design flaw.

The interests of Bobinet, CEO and founder of a design firm using neuroscience to change behavior, can be traced back to medical school, when she was exposed to a program that taught health education in juvenile hall. “I became fascinated by the behavioral patterns of gang members who had violent pasts and came in and out of the system,” she says. These gang members vowed to stay out of jail when they were released but yet “two days later they were immersed” in their old lives and back in trouble. “Why is that happening? And how is that different than me saying I don’t want to eat french fries during Lent but then doing so the second day?” she wonders aloud.

Not long after, an experience with a patient wound up changing the trajectory of her career. During residency she saw a man with gout who had taken meth just three days prior. Bobinet had only ten minutes in clinic with him, and he only mentioned the drug use during the tail end of their conversation, before she had a chance to probe into it. “He changed my life,” she says. “I was so interested in the behavior that led to the medical condition – I [realized I] didn’t want to write prescriptions for the condition anymore, I wanted to focus on the behavior.” She went on to public health school from there.

In the podcast, Bobinet, who also teaches courses on patient engagement and empowerment in the Stanford AIM Lab with Larry Chu, MD, goes on to talk a lot more about behavior and what she has learned through extensive research of patients and caregivers. She talks about her new book, Well Designed Life, which lays the groundwork for those looking to design the changes they want to see in their life, and she offers more advice and words of encouragement for people who are struggling to, say, stay on a diet or quit smoking. “Think like a designer,” she says. Your failed attempt at making positive change “was just a version, just a protoptype… That was something that didn’t work – but it’s not you, it’s the design… And you have to redesign what will grab your attention now.”

Previously: Designing behavior for better health

Addiction, Behavioral Science, Neuroscience

Decisions, decisions: How evolution shaped our decision-making

Decisions, decisions: How evolution shaped our decision-making

Research in neuroscience, psychology, business and economics tells us that a plethora of influences can alter the decisions we make. The author explored some of these factors in a Worldview Stanford course and wrote about them in a Stanford story package, Decisions, Decisions. This post is the last in a series on what she learned. 

evolution

Our brains evolved to get the reward now and worry about consequences later. That, according to Stanford’s Keith Humphreys, PhD, is in part why addiction treatment programs so often fail.

“An alcoholic person will always choose the swift and certain rewards of a drink now over the possible threat of punishment at some future time,” he says.

In my story about how evolution shaped our decisions, I describe a program that allows people with drunken driving arrests to keep driving as long as they prove twice a day that they are sober:

Punishment is mild – a night in jail – but swift and certain if they are caught with alcohol in their bloodstream. And, according to a 2013 study, repeat offenses were down 12 percent where that policy was in effect.

Humphreys said he’d written about this program, to some skepticism. But when he explained evolutionary theory to an assembled group of law enforcement and lawyers he was surprised at how receptive they were.

“The rest of the conference everyone kept telling me that they had never thought about the neurological basis of why addicted offenders do what they do and why criminal justice systems which ignore this reality fail over and over again,” he said.

The story has more about a new initiative within the Stanford Neurosciences Institute in which Humphries and other faculty members are hoping to use neuroscience to influence addiction policies.

Previously: Decisions, decisions: How group dynamics alters decisionsKeith Humphreys: Drug-addiction treatment programs for military families are outdated and “24/7 Sobriety” program may offer a simple fix for drunken driving
Photo from Shutterstock

Behavioral Science, Neuroscience, Stanford News

Decisions, decisions: How group dynamics alters decisions

Decisions, decisions: How group dynamics alters decisions

Research in neuroscience, psychology, business and economics tells us that a plethora of influences can alter the decisions we make. The author explored some of these factors in a Worldview Stanford course and wrote about them in a Stanford story package, Decisions, Decisions. This post is part of a series on what she learned. 

Are you a leader? A follower? Are you charismatic? Knowledgeable? All of these factors will alter your role in a group, and eventually the decisions that the group makes.

Lindred Greer, PhD, with the Stanford Graduate School of Business, studies the way power structures effect group decisions. “If you put people with high power together, it’s a clash of egos like no other,” she said. “They are busier maintaining power than in making good decisions.”

In her work, she has found that hierarchical teams make faster decisions, but teams of equals produce the most creative solutions. Ultimately, the pressure is on the group leader to figure out what kind of decision is needed and to make sure the group functions effectively.

“The leader really does have the onus to be the most competent person in the room and we always forget that,” she said.

There’s more in my story about the qualities that make a good leader and the perils of choosing a bad one.

Previously: Decisions, decisions: How emotions alter our decisionsDecisions, decisions: The way we express a decision alters the outcome and Decisions, decisions: How our decision making changes with age
Video courtesy of Worldview Stanford

Behavioral Science, Mental Health, Neuroscience, Stanford News

Decisions, Decisions: How mental-health issues alter decision-making

Decisions, Decisions: How mental-health issues alter decision-making

Research in neuroscience, psychology, business and economics tells us that a plethora of influences can alter the decisions we make. The author explored some of these factors in a Worldview Stanford course and wrote about them in a Stanford story package, Decisions, Decisions. This post is part of a series on what she learned. 

Here’s something truly unfair. People with mental-health issues have changes in their brains that make it harder for them to make decisions that will benefit their health.

Just when you need good decision-making the most, it fails you.

Child psychiatrist Kathleen Fitzpatrick, MD, works with kids who have anorexia. She said that in those people, their risk/reward pathways are aligned so that not eating is rewarding and eating is cause for anxiety. And, like anyone, they decide in favor of the rewarding experience.

Fitzpatrick put it like this, “I will work for the reward of a cupcake. They will work for the reward of removing all cupcakes.”

In my story I also talk with psychiatrist Manpreet Singh, MD, who says people with depression face similar issues. That’s in part why mental-health conditions are so hard to treat. They change a person’s brain in ways that make it even harder to recover.

Previously: Decisions, Decisions: How emotions alter our decisionsDecisions, Decisions: The way we express a decision alters the outcome and Decisions, Decisions: How decisions change with age
Video courtesy of Worldview Stanford

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