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Neurological Brain Science


February 14, 2017

10 Years of Brain Science = 10 Ideas


Scientific American MIND reflects on the major discoveries of the past decade that have transformed how we think about the brain


Scientist and author Lyall Watson once remarked: “If the brain were so simple we could understand it, we would be so simple we couldn't.” The chaotic networks of billions of electrically pulsating neurons in our skulls have perplexed scientists for centuries. Yet in the last 10 years, our understanding of this mysterious organ has exploded. Prodigious advances in diagnostic and molecular techniques have laid bare some of the brain’s complexity, and scientists are just beginning to parse how these revelations translate into everyday behavior, let alone disease. “I feel really sorry for the people who retired five years ago,” says Michael Stryker, a neuroscientist at the University of California, San Francisco. “Neuroscience now is a completely different world from how it used to be.” In celebration of its 10-year anniversary, Scientific American Mind looks back at 10 significant branches of brain research and the meaningful contributions each has made.


1. Neurogenetics


The woman at the Human Genome exhibit at the National Museum of Natural History in Washington, D.C. Credit: Flickr/Pickering

Neurogenetics

To diagnose neurological disorders merely two decades ago, doctors performed costly or intrusive procedures such as brain scans, spinal taps, and biopsies. Parents of children with hereditary diseases often worried whether they would pass the same genetic abnormality onto their next child. Today, many such evaluations—including those of select degenerative disorders, epilepsies, and movement disorders—can be performed with a quick and simple blood test. These assessments were made possible by the Human Genome Project (HGP), which sequenced and mapped our genes in 2001. In its wake a flood of new sequencing technologies allowed scientists to boost our understanding of the genetic pathways that spawn neurological and psychiatric disorders.

Other research has not yet yielded diagnostic tests but is nonetheless turning up much-needed insight into several challenging conditions. Scientists have homed in on bits of genetic material that swirl in the blood of patients with schizophrenia, Alzheimer’s disease, depression, and autism, among other disorders. The quick identification of clusters of disease-related genes will likely transform the way we identify and treat brain disorders in the future.


2. Brain Mapping


A top-down 3-D view of the cortico-connections originating from multiple distinct cortical areas, visualized as virtual tractography using Allen Institute Brain Explorer software. Credit: Allen Institute for Brain Science


Philanthropist Paul Allen gathered experts in the early 2000s with the lofty goal of understanding how the human brain works. On the heels of the completed HGP, they formed the Allen Institute for Brain Science in 2003. The Seattle-based organization began mapping regions of gene activity in the mouse brain and pooling results into online databases, or atlases, which now also include data on human and nonhuman primates. Free, comprehensive maps of genetic activity help researchers engineer mice that express specific cell types or discover genes relevant to certain diseases or behaviors. Today the institute continues to build atlases and it recently launched a 10-year plan to examine not only where specific genes are active but how these genetic circuits process the vast flow of information into the brain. As a major participant in the White House BRAIN Initiative, the National Institutes of Health just granted the project $8.7 million to plot the trillions of neural connections in mouse and human brains. The ultimate goal is to revamp the way we approach brain diseases and disorders.


3. The Malleable Brain


Scientists long viewed the adult brain as a relatively static organ, Stryker says. As recently as 15 years ago, they believed that the brain was highly malleable in infancy and early childhood but resistant to change thereafter. Although the brain is most pliable early in life, “what’s really new this decade is the widespread appreciation, realization, and exploitation of adult plasticity,” Stryker says. Brain training software developed by companies such as Lumosity and popular games such as Nintendo’s Big Brain Academy Wii Degree has penetrated popular culture. R. Douglas Fields, a senior investigator at the NIH, credits the emergence of better imaging techniques and new ways to label cells to make them fluorescent, which have made it possible to observe the brain as it learns new information. “The ability to see brain cells operate alive inside the brain of an experimental animal is what has revealed the mechanisms of plasticity.”


4. Knowing Our Place


Scientists have long pondered our innate ability to navigate from one place to another. In 1971 John O’Keefe of University College London made the first steps toward deciphering it with the discovery of “place cells,” neurons that fire only when an animal is in one specific place but not any other location. The cells, which lie in the hippocampus, a brain region heavily involved in memory, seemed to explain much about our spatial reasoning skills.

Yet in 2005 the married scientists May-Britt and Edvard Moser of Norwegian University of Science and Technology added a new discovery: the existence of “grid cells” in the nearby cortex. By eavesdropping on the electrical activity of individual brain cells as a rodent moves around a box, they discerned that certain cells fire in a gridlike pattern to track the animal’s updated location. They work in concert with place cells to tell an animal where it is. “This discovery is one of the most remarkable findings in the history of single-unit recordings of brain activity,” wrote James Knierim, professor of neurobiology at the University of Texas Medical School at Houston, in an article for Scientific American MIND in 2007. The three scientists were awarded the 2014 Nobel Prize in Physiology or Medicine in October.


5. Funny Things with Memory


One of the great mysteries of the brain is that we still cannot pin down exactly what a memory is—that is, how neural circuitry stores a given recollection. Yet in the last decade, we have learned a lot about memory’s limitations. Memories are not necessarily written into our brains like ink on paper. Think of them instead as inscribed in clay, suggests André Fenton, a neuroscientist at New York University’s Center for Neural ScienceEvery time you access a memory, the message can get smudged, just as a clay tablet might if you were to pick it up and run your fingers over its surface. Ongoing biochemical processes cause memories to shift over time.


Further, our mindsets and emotions can influence what we pay attention to and thus remember. Scientists are tinkering with experimental chemicals that, when injected, can interfere with memory-forming proteins and erase certain types of maladaptive feelings, such as an addict’s desire for drugs. Researchers have even managed to trick mice into forming entirely false memories. Memory formation and recollection are an evolving, active, and plastic process that involves many different working parts of the brain, and scientists are just beginning to piece together how they coalesce into such a complex machine.



6. Advances in Therapy


A spate of therapeutic techniques that target the mind-body connection has gained traction in the past decade. Of particular note is cognitive behavior therapy (CBT), a type of talk therapy that examines how one’s thoughts and feelings influence behavior and then introduces strategies to nix those maladaptive beliefs. When CBT first emerged in the 1960s and 1970s, it was mainly used to treat phobias and anxiety disorders, according to Mary Alvord, a clinical psychologist based in Maryland. Yet in the decades since, CBT has expanded to encompass a wide range of maladies. A 2012 meta-analysis of over 100 studies found CBT to be a scientifically sound strategy for combating not only anxiety disorders but also bulimia, anger, stress, and mental illnesses that cause pain.


Other behavioral techniques that have grown in popularity include mindfulness meditation, which encourages practitioners to be in tune with the present moment, and dialectical behavior therapy. This latter treatment is grounded in CBT but adds new strategies to address serious mental health issues, such as suicidal thoughts, by emphasizing emotional regulation. Alvord hopes that these therapies may one day be as effective as pharmaceuticals. “Medications don’t change your lifestyle or teach you how to get along better with other people,” Alvord says. “[These therapies] are kind of like an empowerment movement. They’re giving people hope.”


7. Optogenetics


Mouse with optogenetic tools in operation, including implanted fiberoptic and light-sensitive molecules produced in the brain, all representing technologies developed in the Deisseroth lab at Stanford University by graduate students Raag Airan, Feng Zhang, Ed Boyden, and Lief Fenno. Credit: Raag Airan, Feng Zhang, Ed Boyden, and Lief Fenno


When Stanford scientists presented a technique for switching individual neurons on or off with light in 2005, researchers were thrilled. “This has totally changed everything,” U.C.S.F.’s Stryker says. Before optogenetics standard methods of activating and silencing neural networks were crude. “You had no idea what cells you were stimulating,” he explains. To probe how a certain class of neurons helps mice navigate mazes, for example, scientists would insert electrodes into brain tissue and stimulate thousands of neurons at a time. Now scientists can tuck light-sensitive molecules into specific brain cells to manipulate only those selected neuron types or networks. Shining a light makes those neurons either more or less active and can elucidate their role in behavior or disease.

Neuroscience labs worldwide have now embraced the technique. “Over the past decade hundreds of research groups have used optogenetics to learn how various networks of neurons contribute to behavior, perception, and cognition,” wrote Ed Boyden, a co-inventor of optogenetics, in an article in the November/December 2014 Scientific American MIND. In the future optogenetics will allow us to decipher both how various brain cells elicit feelings, thoughts, and movements—as well as how they can go awry to produce psychiatric disorders.


8. New Roles for Glial Cells


Glial cells have gotten a bad rap. Unlike neurons, they do not communicate electrically, and for centuries scientists dismissed these abundant brain cells as a mere packaging material that performed the brain’s housekeeping functions. “They were thought to be unimportant and dull compared to exciting neurons,” the NIH’s Fields says. Yet new imaging methods have finally created opportunities for scientists to interrogate these brain cells, and they are finding that glia is pivotal to many key brain functions, including memory and learning. “It really is a new frontier. They’re not at all like neurons, they’re far more complicated and diverse,” he says. “The fact that they’re doing something different from neurons means that we have to understand them.”


9. Neural Implants


When injury, disease, or a stroke cripples an essential component of the brain, a neural implant may be the only option for restoring lost function. The first implantable brain device to gain widespread adoption was the cochlear implant, an in-ear device that became available in the 1980s. In the past decade the quality of their sound has improved dramatically, in large part due to advances in semiconductor manufacturing, says Satinderpall Pannu, director of Lawrence Livermore National Laboratory's Center for Bioengineering. Now a retinal implant promises to do for vision what the cochlear implant has done for the hearing of more than a quarter-million individuals worldwide. The first retinal implant passed clinical trials in 2011 and debuted on the market in 2013 for patients with degenerative eye conditions.


Other implantable therapies such as deep-brain stimulation and vagus nerve stimulation have brought relief to individuals suffering from otherwise intractable brain disorders, most notably Parkinson’s disease and epilepsy. Recently researchers have been exploring the use of these techniques in major depression, obsessive-compulsive disorder, addiction, and pain, among other conditions. Currently, neural implants alter the electrical activity in targeted areas of the brain, yet Pannu forecasts that future versions will also release chemicals to fix imbalances that cause disorders, such as depression.


10. Decision Making


Making a choice can be an anxiety-inducing endeavor. Sometimes an act as simple as figuring out what to wear in the morning can send a person into a tailspin. Dozens of books and hundreds of research articles in the last 10 years have sought to tease apart the psychological factors influencing our decisions, yet none has had the broad impact of psychologist and Nobelist Daniel Kahneman’s 2011 book, Thinking Fast and Slow. His account, which summarized decades of work on cognitive biases, popularized the notion that the brain has two distinct mechanisms for committing to a course of action: an automatic, unconscious way of thinking known as “system 1,” and a more deliberate and measured approach dubbed “system 2.” System 1 drives quick reactions, such as jumping out of the way of a speeding motorcycle; whereas system 2 helps us solve complicated math problems or recite a string of letters backward. By drawing attention to our brain’s strengths and weaknesses, Kahneman helped readers dodge common errors and make better choices. As reviewer Glenda Cooper wrote about the book in the Telegraph, “Having sold over a million copies, it’s been described as a “masterpiece” and a “landmark book in social thought,” while Kahneman himself has been called the “most important psychologist alive.” By Julia Calderone 

DNA - DIET


Do DNA-based diets work?

The ability to customize diet and exercise plans based on an individual’s genetics may be the next frontier in nutrition counselling.


June 18, 2020

By Kristin Kirkpatrick


Will you succeed or fail on a ketogenic diet? Will exercise be more important than food choices if you want to lose weight? The answer to these questions may lie within your genes. Genetic analysis is contributing to a growing area of nutritional medicine that offers dietary prescriptions — including personalized diet plans based on nutrigenomics — to help people make more informed decisions about their lifestyle habits and health.

The Cleveland Clinic has been providing personalized nutrigenomic testing for several years. As a dietitian there, I can see firsthand the benefits it provides to patients. It’s especially useful for patients who have found themselves “stuck” in their weight-loss efforts. Having a genetic insight into the types of diet that work best for them often increases both compliance and sustainability.

I pinpoint about five of the most important genes to focus on with my patients based on their goals. This may involve changing the type of workout they are doing, altering the percentages of fat and protein in their diet, suggesting specific supplements, like methylated folate or vitamin B12 and increasing certain nutrients from food, like vitamin A or iron. Often, my recommendations are in line with supplemental laboratory data for the patient as well.


What is nutrigenomics?


A relatively new scientific discipline, nutrigenomics focuses on the relationship between genes, nutrition and health. It seeks to explain how our bodies respond to what we eat and drink — and how we can use that knowledge to promote activity in our “good” genes and suppress it in “bad” genes. Diet plans based on nutrigenomics rely on an analysis of your genetic makeup to inform dietary recommendations that meet your personal nutritional and health needs and help prevent nutrition-related chronic diseases.

“The ultimate goal of nutrigenomic testing is to identify sub-groups of populations who may respond to diets differently or show distinct intolerances to foods or susceptibility to diseases,” Dr. Lu Qi, an adjunct professor of nutrition in the Harvard T.H. Chan School of Public Health’s nutrition department told TODAY in an email. “Such a goal is promising and increasingly supported by scientific evidence, including those from our studies,” Qi explained that this type of personalized approach is expected to improve the efficacy of dietary recommendations. However, he said, “the research of nutrigenomics is still in its infancy. At this stage, it’s more important to accumulate evidence than to generate recommendations.”

Personalized diet plans are not a new concept. They started gaining traction about 20 years ago with an approach that helped people lose weight by eating and exercising according to their blood type. The blood type diet garnered a lot of interest but lacked strong scientific backing. Nutrigenomics emerged in the early 2000s after the Human Genome Project (HPG) was completed. Though scientists were aware for decades that genes played a role in health, the HPG helped them gain new insights into the connection between bioactive compounds in food and their impact on genes — and on people’s health. They discovered that lifestyle choices could direct genes to either work to the body’s advantage, or to its detriment.

The science behind personalized testing

Multiple studies have shown that genetics come into play with our eating habits. Research also suggests that knowledge of our genetics can influence how well we comply with dietary prescriptions. For example, a 2014 randomized controlled trial showed that participants who possessed the risk variant of the ACE gene (a gene that directs the body on blood pressure levels) were able to significantly reduce their sodium intake compared to the control group; they also maintained their lower sodium intake one year later.

Another study published last month in the British Medical Journal demonstrated that individuals who are given nutrigenomics-guided dietary advice for total fat and saturated fat intake significantly reduced their long-term intake compared to gold-standard population-based interventions.

Other studies, however, have suggested that gene-based dietary interventions may not be as promising as once thought. The results of a randomized clinical trial that followed more than 600 overweight adults for a period of 12 months found that a genotype eating approach was not “associated with the dietary effects of weight loss.”

While the concept may have potential, more research is needed to affirm the efficacy of gene-based diets. Qi underscored that a balanced diet, exercise and adequate sleep benefit everyone, regardless of their genomic makeup, but he suggested that certain sub-groups are likely to be more sensitive to different diets — a low-fat vs. a high-fat diet, for example, or certain specific exercise regimens. “However, current evidence is still far from sufficient (for doctors or dietitians) to provide practical guidelines,” he said, “and the personalized recommendations will be built on accumulating data in the future.”


The potential benefits of a DNA-based diet

The ability to customize diet and exercise plans based on an individual’s genetics may be the next frontier in nutrition counselling. A personalized dietary plan may help increase compliance, as well as help you target dietary and physical activity goals that are more in line with what works for your body.

“While food and nutrition guidelines set by government agencies are important to follow, evidence has demonstrated that those one-size-fits-all nutrition recommendations can be inefficient and often ineffective,” said Dr. Ahmed El-Sohemy, a professor and Canada research chair in nutrigenomics at the University of Toronto and founder and chief science officer of Nutrigenomix, Inc., a company that does genetic testing for personalized nutrition.

Dr. Christopher Lynch, the director of the Office of Nutrition Research at the National Institute of Diabetes and Digestive and Kidney Diseases, told TODAY in an email that the NIDDK’s new 2020-2030 Strategic Plan for NIH Nutrition Research is centered on the unifying theme of precision nutrition, which focuses on personalized eating plans based on DNA and includes nutrigenomics. “There are many factors that affect individual responses to diet, including diet-gene interactions, that need to be taken into account when developing comprehensive and dynamic nutritional recommendations relevant to both individual and population health,” he said. Lynch also stressed that “more research is needed to fully understand the impact of these factors and their interrelationships.”


Is nutrigenomic testing right for you?


“Genetic variation is an important component of why people differ from one another in their metabolism,” Dr. Steven Zeisel, the director of the Nutrition Research Institute at the University of North Carolina and founder of SNP Therapeutics, told TODAY in an email. “Genetic testing and nutrigenetics have a lot to offer, but may not be ready yet to tell someone which diet will make them lose weight.”

Aside from the fact that the research is still in its early phases, nutrigenomic testing isn’t cheap, so the cost can be a concern. The price for a test and analysis starts at about $300. Privacy is another common concern. “Some individuals may worry that their genetic information could be used to discriminate against them in their job or with their health insurance coverage,” said El-Sohemy. But he also noted that the “Genetic Information Non‐discrimination Act (GINA) was signed into law in May of 2008 and offers federal protection against such discrimination.”

There are dozens of tests on the market that provide analysis on the genes involved in nutrient metabolism and response, including Ancestry and 23andMe, but once you receive the results, you still need to seek out a specialist to analyze the raw data and make recommendations. If you’re interested in learning more about DNA-based diets, speak to your doctor about getting a referral to a reputable medical group that offers nutrigenomic testing.

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