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Bioengineering, In the News, Neuroscience, Stanford News, Technology

New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics

New York Times profiles Stanford's Karl Deisseroth and his work in optogenetics

Rockefeller University neurobiologist Cori Bargmann, PhD, is quoted in today’s New York Times as saying optogenetics is “the most revolutionary thing that has happened in neuroscience in the past couple of decades.” The article is a profile piece of Karl Deisseroth, MD, PhD, the Stanford researcher who helped create the field of optogenetics, and it reveals how a clinical rotation in psychiatry led him to this line of work:

It was eye-opening, he said, “to sit and talk to a person whose reality is different from yours” — to be face to face with the effects of bipolar disorder, “exuberance, charisma, love of life, and yet, how destructive”; of depression, “crushing — it can’t be reasoned with”; of an eating disorder literally killing a young, intelligent person, “as if there’s a conceptual cancer in the brain.”

He saw patient after patient suffering terribly, with no cure in sight. “It was not as if we had the right tools or the right understanding.” But, he said, that such tools were desperately needed made it more interesting to him as a specialty. He stayed with psychiatry, but adjusted his research course, getting in on the ground floor in a new bioengineering department at Stanford. He is now a professor of both bioengineering and psychiatry.

Previously: A federal push to further brain research, An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”, Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, The “rock star” work of Stanford’s Karl Deisseroth and Nature Methods names optogenetics its “Method of the Year
Related: Head lights
Photo in featured-entry box by Linda Cicero/Stanford News Service

Neuroscience, Research, Stanford News

Thoughts light up with new Stanford-designed tool for studying the brain

Thoughts light up with new Stanford-designed tool for studying the brain

A 3d rendered illustration of a nerve cell.

When I talk to neuroscientists about how they study the brain I get a lesson (usually filled with acronyms) in the various ways scientists go about trying to read minds. Some of the tools they use can detect when general regions of the brain are active, but can’t detect individual nerves. Others record the activity of individual nerves, one nerve at a time, but can’t detect networks of nerves firing together. Still another tool can report the afterglow of a signal that has been sent across networks of neurons.

There hasn’t been any one way of seeing when a nerve fires and which neighbors in connects to.

I wrote recently about a new tool to do just that, developed by bioengineer Michael Lin, MD, PhD, and biologist and applied physicist Mark Schnitzer, PhD. They’ve both come up with proteins that light up when a nerve sends a signal. They can put their proteins in a group of nerves in one part of the brain then watch those signals spread across the network of neurons as they interact.

In my story I quote Lin: “You want to know which neurons are firing, how they link together and how they represent information. A good probe to do that has been on the wish list for decades.”

The proteins could be widely used to better understand the brain or develop drugs:

With these tools scientists can study how we learn, remember, navigate or any other activity that requires networks of nerves working together. The tools can also help scientists understand what happens when those processes don’t work properly, as in Alzheimer’s or Parkinson’s diseases, or other disorders of the brain.

The proteins could also be inserted in neurons in a lab dish. Scientists developing drugs, for example, could expose human nerves in a dish to a drug and watch in real time to see if the drug changes the way the nerve fires. If those neurons in the dish represent a disease, like Parkinson’s disease, a scientist could look for drugs that cause those cells to fire more normally.

Now that I’ve written about the invention of this new tool I’m looking forward to hearing more about how scientists start using it to understand our brain or develop drugs.

3D rendered illustration of a nerve cell by Sebastian Kaulitzki/Shutterstock

Aging, Genetics, Neuroscience, Podcasts, Research, Stanford News

The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius

The state of Alzheimer's research: A conversation with Stanford neurologist Michael Greicius

My colleague Bruce Goldman recently wrote an expansive blog entry and article based on research by Mike Greicius, MD, about how the ApoE4 variant doubles the risk of Alzheimer’s for women. I followed up Goldman’s pieces in a podcast with Greicius, who’s the medical director of the Stanford Center for Memory Disorders.

I began the conversation by asking about the state of research for Alzheimer’s: essentially, what do we know? As an aging baby boomer, I’m interested in the differences between normal, age-related cognitive decline versus cognitive declines that signal an emerging disease. Greicius said people tend to begin losing cognitive skills around middle age:

Every cognitive domain we can measure starts to decline around 40. Semantic knowledge – knowledge about the world – tends to stay pretty stable and even goes up a bit. Everything else… working memory, short term memory all tends to go down on this linear decline. The difference with something like Alzheimer’s is that the decline isn’t linear. It’s like you fall off a cliff.

Greicius’ most recent research looks at the certain increased Alzheimer’s risk ApoE4 confers on women. As described by Goldman:

Accessing two huge publicly available national databases, Greicius and his colleagues were able to amass medical records for some 8,000 people and show that initially healthy ApoE4-positive women were twice as likely to contract Alzheimer’s as their ApoE4-negative counterparts, while ApoE4-positive men’s risk for the syndrome was barely higher than that for ApoE-negative men.

In addition to the increased risk of Alzheimer’s for women with the ApoE4 variant, I asked Greicius how he advises patients coming into the clinic who ask about staving off memory loss. At this point, he concedes, effective traditional medication isn’t really at hand. “Far and away our strongest recommendations bear on things like lifestyle and particularly exercise,” he said. “We know, in this case from good animal models, that physical exercise, particularly aerobic exercise, helps brain cells do better and can stave-off various insults.” So remember, a heart smart diet along with aerobic exercise.

One last question for Greicius: What about those cognitive-memory games marketed to the elderly and touted as salves for memory loss – do they have any benefit? He’s riled now: “I get asked that all the time, and smoke starts coming out of my ears.” He says the games are nothing more than snake oil.  His advice when he gets asked the question: “Give that money to the Alzheimer’s Association or save it and get down on the floor with your grandkids and build Legos. That’s also a great cognitive exercise and more emotionally rewarding.”

Previously: Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s and Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor

Neuroscience, Research, Technology, Videos

Using Google Glass to improve quality of life for Parkinson’s patients

Using Google Glass to improve quality of life for Parkinson's patients

Researchers at Newcastle University are exploring ways that Google Glass could improve Parkinson’s patients’ quality of life by assisting them in placing phone calls, reminding them to take their medications or giving them behavioral prompts, such as speaking louder. In the video above, Roisin McNaney, a PhD student in the university’s Digital Interaction Group, explains how using Glass could ease patients’ anxiety about encountering a symptom-related problem while in public, raise patients’ confidence and, ultimately, make them more independent.

Previously: Abraham Verghese uses Google Glass to demonstrate how to begin a patient exam, Revealed: The likely role of Parkinson’s protein in the healthy brain and Stanford study identifies molecular mechanism that triggers Parkinson’s
Via Medgadget

In the News, Neuroscience, Technology

Facial expression recognition software could predict student engagement in learning

Facial expression recognition software could predict student engagement in learning

bored faceTest day approaching? Get your game face on. A study of a computer program that recognizes and interprets facial expressions has found that identifying students’ level of engagement while learning may predict their performance in the class. Computer scientists at the University of California, San Diego and Emotient, a San Diego-based company that developed the facial-recognition software used in the study, teamed with psychologists at Virginia Commonwealth and Virginia State universities to look at “when and why students get disengaged,” study lead author Jacob Whitehill, PhD, researcher in UC San Diego’s Qualcomm Institute and Emotient co-founder, said in a release.

The authors write in the study, which was published in an early online version in the journal IEEE Transactions on Affective Computing:

In this paper we explore approaches for automatic recognition of engagement from students’ facial expressions. We studied whether human observers can reliably judge engagement from the face; analyzed the signals observers use to make these judgments; and automated the process using machine learning.

“Automatic engagement detection provides an opportunity for educators to adjust their curriculum for higher impact, either in real time or in subsequent lessons,” Whitehill said in the release. ”Automatic engagement detection could be a valuable asset for developing adaptive educational games, improving intelligent tutoring systems and tailoring massive open online courses, or MOOCs.”

Previously: Looks of fear and disgust help us to see threats, study showsProviding medical, educational and technological tools in Zimbabwe and Whiz Kids: Teaching anatomy with augmented reality
Photo by Jesús Gorriti

Aging, Genetics, Men's Health, Neuroscience, Research, Stanford News, Women's Health

Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men

Having a copy of ApoE4 gene variant doubles Alzheimer's risk for women but not for men

brain cactus - smallSince the early 1990s, when Duke University neurologist Allen Roses, MD, first broke the news, it’s been known that a person carrying the gene variant known as ApoE4 is at elevated risk of getting Alzheimer’s disease. To this day ApoE4 is the strongest known single genetic risk factor for Alzheimer’s, a progressive neurological syndrome that robs its victims of their memory and reasoning ability.

But only now is it looking certain that the increased Alzheimer’s risk ApoE4 confers is largely restricted to women. Men’s fates don’t seem to be altered nearly as much by the genetic bad penny that is ApoE4, according to a new Annals of Neurology study led by Mike Greicius, MD, medical director of the Stanford Center for Memory Disorders.

Accessing two huge publicly available national databases, Greicius and his colleagues were able to amass medical records for some 8,000 people and show that initially healthy ApoE4-positive women were twice as likely to contract Alzheimer’s as their ApoE4-negative counterparts, while ApoE4-positive men’s risk for the syndrome was barely higher than that for ApoE-negative men.

What the heck is ApoE4 for, anyway? In my release on the new study, I wrote:

The ApoE gene is a recipe for a protein important for shuttling fatty substances throughout the body. This is particularly important in the central nervous system, as brain function depends on rapid rearrangement of such fatty substances along and among nerve cell membranes. The ApoE gene comes in three varieties — ApoE2, ApoE3 and ApoE4 — depending on inherited variations in the gene’s sequence. As a result, the protein that the gene specifies also comes in three versions, whose structures and fatty-substance-shuttling performance differ. Most people carry two copies of the ApoE3 gene variant (one from each parent). But about one in five people carries at least one copy of ApoE4, and a small percentage have two ApoE4 copies. Numerous studies … have confirmed that ApoE4 is a key risk factor for Alzheimer’s disease, with a single copy of ApoE4 increasing that risk twofold or fourfold. Carrying two copies confers 10 times the risk of Alzheimer’s.

Early hints in the medical literature that the ApoE4 variant exerted differential effects on women’s versus men’s brains were largely ignored until now, says Greicius. He says that’s because most of the seminal ApoE4/Alzheimer’s genetics research was conducted as case-control studies: The ApoE4 gene version’s frequency in people with Alzheimer’s was compared to its frequency in people without the disease. (About half of those with Alzheimer’s, but only about 15 percent without it, are positive for ApoE4.)

But that method has limitations, says Greicius: “About 10-15 percent of ‘normal’ 70-year-olds will develop Alzheimer’s if you wait five or ten years.” Their lurking in the “normal” group dilutes the results. Moreover, Greicius says,“these kinds of genetic studies are looking for needles in a haystack, so they require large numbers of subjects – thousands – to achieve statistical significance. If you want to further examine male/female differences, you have to double the sample size.” That’s costly.

And that’s how come the large government- and industry-supported repositories to which Greicius and his team resorted are such a great idea.

Previously: Estradiol – but not Premarin – prevents neurodegeneration in women at heightened dementia risk, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s, Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor and A one-minute mind-reading machine? Brain-scan results distinguish mental states
Photo by Sean Michael Ragan

Humor, Neuroscience, Research, Stanford News

Looking at how a child’s sense of humor takes its shape

Looking at how a child's sense of humor takes its shape

girl2Where does a child’s sense of humor come from? That depends on how you define humor and where you look to find it. A recent blog post from the Cognitive Neuroscience Society reports:

Humor can be a very complex and hard concept for some kids to grasp, said [Jessica Black, PhD,] of the Graduate School of Social Work Boston College, speaking yesterday about her poster on this new work at the CNS meeting in Boston. It requires people to both detect and resolve incongruities and to find amusement – involving many regions of the brain, including those that process cognitive computations and those that process emotions.

Black and others, including Allan Reiss, MD, the study’s director, and Pascal Vrticka, PhD, both of Stanford, studied how different brain regions were activated as children watched a video with funny, positive or neutral content. Twenty-two children ages 6 to 13 were asked to rate their ability to create and appreciate humor. Then, researchers examined their brain activity using fMRI scans.

The CNS blog post continues:

In general, the researchers found greater brain activity in children who rated themselves low on the sense of humor scale. The systems related to detecting incongruities and those involved in language and working memory had to ramp up to process the funny videos, as did the arousal network that is usually more active when processing negative emotional information. Interestingly, the brain activity related to social processing was lower in these children, suggesting perhaps more difficulty in being able to think about the mental state of others.

Their results suggest that children with a low sense of humor may require more cognitive effort to process humor, Black said. The data also imply that children with a low sense of humor may experience stress and increased levels of arousal during social interactions involving humor.

Previously: A closer look at the way our brains process humorHumor as a mate selection strategy for women? and Making kids laugh for science: Study shows how humor activates children’s brains
Photo by Maria del Carmen Gomez

Autism, Genetics, Neuroscience, Research, Videos

Building a blueprint of the developing human brain

Building a blueprint of the developing human brain

In an effort to identify and better understand how genes turned on or off before birth influence early brain development, scientists at the Allen Institute for Brain Science have created a comprehensive three-dimensional map that illustrates the activity of some 20,000 genes in 300 brain regions during mid-prenatal development.

A post on the NIH Director’s blog discusses the significance of the project, known as the BrainSpan Atlas of the Developing Human Brain:

While this is just the first installment of what will be an atlas of gene activity covering the entire course of human brain development, this rich trove of data is already transforming the way we think about neurodevelopmental disorders.

To test the powers of the new atlas, researchers decided to use the database to explore the activity of 319 genes, previously linked to autism, during the mid-prenatal period. They discovered that many of these genes were switched on in the developing neocortex—a part of the brain that is responsible for complex behaviors and that is known to be disrupted in children with autism. Specifically, these genes were activated in newly formed excitatory neurons, which are nerve cells that send information from one part of the brain to another. The finding provides more evidence that the first seeds for autism are planted at the time when the cortex is in the midst of forming its six-layered architecture and circuitry.

In the above video, Ed Lein, PhD, an Allen Institute investigator, talks about the atlas and explains how it will allow researchers to examine genes that have been associated with a range of neurodevelopmental disorders and pinpoint when and where that gene is being used.

Previously: NIH announces focus of funding for BRAIN initiative, Brain’s gain: Stanford neuroscientist discusses two major new initiatives and Co-leader of Obama’s BRAIN Initiative to direct Stanford’s interdisciplinary neuroscience institute

Neuroscience, Patient Care, Stanford News, Videos

Treating intractible epilepsy

Treating intractible epilepsy

In this new Stanford Medicine video, patient Laura Koellstad tells the story of how her life changed with her first seizure and a diagnosis of intractible epilepsy, and then turned around following treatment at Stanford. Josef Parvizi, MD, PhD, associate professor of neurology and neurological sciences, and Robert Fisher, MD, PhD, director of the Stanford Comprehensive Epilepsy Program, explain the functional mapping and surgical procedures used to treat Koellstad’s condition, allowing her to return to work and regain her ability to drive.

Previously: The brain whisperer: Stanford neurologist talks about his work, shares tips with aspiring doctorsHow epilepsy patients are teaching Stanford scientists more about the brain and Implanting electrodes to treat epilepsy, better understand the brain

Events, Medical Education, Medicine and Society, Neuroscience, Stanford News

The brain whisperer: Stanford neurologist talks about his work, shares tips with aspiring doctors

The brain whisperer: Stanford neurologist talks about his work, shares tips with aspiring doctors

Parvizi at MS 101 - smallJosef Parvizi, MD, PhD, knows firsthand how art can influence medicine. While at a concert featuring music created by digitizing space sounds, he was inspired: “Why can’t we make music by digitzing brain waves?”

Parvizi, a neurologist who specializes in epilepsy, told local high-school students attending Stanford’s Med School 101 recently that the beauty of being a physician-researcher at Stanford is that you’re “surrounded by brilliant people in all areas.” So he took his literal brainstorm to Chris Chafe, PhD, in Stanford’s music department, and the result is a newly patented “brain stethoscope” that can translate brainwaves into music. Parvizi demonstrated the difference between normal brainwave music and the music produced by a brain experiencing a seizure in this YouTube video about the research.

In addition to the brain stethoscope, Parvizi has developed a procedure utilizing electrodes to detect the exact area of the brain that is causing the seizure, and then working with brain surgeons to operate on the affected area. At last week’s event he told the story of a patient who for 20 years had seizures that caused her leg to flail out to the side, greatly limiting her ability to do the things we take for granted every day, like driving or taking a shower. Showing a picture of the happy patient in her car holding up her driver’s license, Parvizi said, “This patient has been seizure-free for six years, driving and enjoying life like never before.”

Parvizi described being a physician-researcher this way: “Like riding two horses standing up with one foot on each horse, you have to keep your balance and it takes some skill.” But, he says, being a physician-researcher allows you to help thousands of patients with your research, and one patient at a time with the application of that research.

He advised the students to “do work you are excited about,” and in looking for a mentor, “be persistent, not pushy.” Parvizi told the story of how as a medical student he contacted the pioneering cognitive neuroscientist Antonio Damasio, MD, PhD, after reading his ground-breaking book, Descartes’ Error. “This was before the Internet, so I wrote to him and sent him faxes. I finally called him and told him I would be coming to the States and would like to meet with him. He told me he would give me 15 minutes. I told him, ‘I am coming all the way from Norway,’ and he said, ‘I will give you 15 minutes.’” That meeting set the course for Parvizi’s career, a career he clearly relishes.

“It took me 22 years of school and training, and that sounds like a lot, but it went by fast because everything is so interesting and exciting,” Parvizi told the group. Snapping his fingers and smiling, he said, “It went by just like that.”

Jacqueline Genovese is assistant director of the Arts, Humanities, and Medicine Program within the Stanford Center for Biomedical Ethics. Parvizi and Chafe will be demonstrating their brain stethoscope on April 29 from 5:30-7 PM at the Center for Computer Research in Music and Acoustics, as part of  the program’s Recombinations series.

Previously: At Med School 101, teens learn that it’s “so cool to be a doctor”, How epilepsy patients are teaching Stanford scientists more about the brainImplanting electrodes to treat epilepsy, better understand the brain and Ask Stanford Med: Neurologist answers your questions on drug-resistant epilepsy
Photo by Norbert von der Groeben

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