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.

 
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1. Neurogenetics

10 Years
Woman at the Human Genome exhibit at the National Museum of Natural History in Washington, D.C. Credit: Flickr/vpickering

1.

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.

 
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Introduction
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2. Brain Mapping

10 Years
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

1.

Brain Mapping
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 announced by Pres. Barack Obama, 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.

 
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3. The Malleable Brain

10 Years
Credit: Flickr/National Library of Australia

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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 have penetrated popular culture. Oprah magazine now gives tips on how to “improve” your brain and make it “smarter.” 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.”

 
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4. Knowing Our Place

10 Years
Credit: Flickr/CIAT

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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.

 
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5. Funny Things with Memory

10 Years
Credit: Flickr/Joyce Kaes

1.

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 mind sets 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 is 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.

 
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6. Advances in Therapy

10 Years
Credit: Flickr/A&M-Commerce

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Advances in Therapy
A spate of therapeutic techniques that target the mind–body connection have 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.”

 
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7. Optogenetics

10 Years
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

1.

Optogenetics
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 a 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.

 
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8. New Roles for Glial Cells

10 Years
Stained astrocyte cell from a rat brain. Credit: Wikimedia Commons/GerryShaw

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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 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 are 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.”

 
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9. Neural Implants

10 Years
Electrode array positioned on the retina. Credit: Second Sight

1.

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.

 
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10. Decision Making

10 Years
Credit: Flickr/Julia Manzerova

1.

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 backwards. 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.””

 
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9. Neural Implants
10. Decision Making