A woman with major depression lies as motionless as she can, her head inside the doughnut hole of an MRI scanner that clangs, beeps, chirps and buzzes as it captures images of her brain’s neural activity. She’s wearing headphones so she can listen to Pandora. However, brain mappers can see on their computer screens what’s going on in her head. They are measuring her brain’s structure, shape, chemistry and function before treating her with electroconvulsive therapy (ECT). A few days after the treatment, they’ll map her again, to compare the before and after.

Two hundred miles per hour is the top speed of signals that pass between active neurons, the cells that process and transmit information through electrical and chemical signals. Billions of them are at work in our heads, many firing off at any given time. At the UCLA Ahmanson-Lovelace Brain Mapping Center (ALBMC), scientists map the paths those neurons take and the networks they form with high-tech scanners, enabling the study of a vast array of processes going on in our brains. These include — among many others — sleep, learning, aging and memory, and the aberrant activities caused by such afflictions as schizophrenia, Alzheimer’s and Parkinson’s diseases, autism, clinical depression and brain injuries.

Brain mapping was named one of this decade’s “10 Big Ideas of Brain Science” by Scientific American Mind, and UCLA has been in the forefront since the beginning. In 1993, John Mazziotta, now vice chancellor of UCLA Health Sciences, proposed what became the ALBMC. Today, the center is a global resource for studying the human brain through state-of-the-art equipment, experienced technicians and a talented faculty with expertise that ranges from the clinic to the physics of instrumentation to computer science and algorithm development.

“ALBMC is the ideal place for studying the human brain using the most modern equipment, but more importantly for providing vivid interaction with world-leading staff scientists and experienced technicians,” says Karl Zilles, senior professor of brain research at the Institute of Neuroscience and Medicine at the Forschungszentrum Jülich in Germany, who has collaborated with scientists at the center. He says ALBMC is “one of the few leading centers worldwide, and an indispensable place for research and collaboration among neuroscientists.”

Brain mapping can be likened to tracking a skyful of jets in flight from one airline hub to another. The more detailed the map, the more visible are the patterns that develop in the flight paths and, particularly, the way the patterns change during peaks of activity. The overall patterns of activity are what brain mappers try to understand because they indicate the effects of such things as electrical stimulation, drugs, disease and diet on neural activity.

ALBMC’s Mayank Mehta, professor of physics and astronomy, neurology and neurobiology, cites three key challenges that mappers face in determining these changes. “The first,” he says, “is the ability to get suitably high spatial resolution images of the active neurons at high speed, about a thousandth of a second; the second is in translating this vast and complex data using mathematics to make sense of it; and the third is linking all this to behavior.”

Roger Woods, ALBMC’s director, paints a picture of this process: “You can have a person in the scanner and give them some task to do and then identify, by the changes in the picture, the parts of the brain that are engaged in that task. With each succeeding generation of high-tech scanners, researchers can go back and revisit some disease, some problem that maybe they saw nothing of when they did an MRI or CT scan 20 years ago. And now something can be revealed. It’s what lets us ask new questions we could never begin to ask before.”

Answers Beget Questions

As with other forays into the unknown, the deeper the look into the brain, the more there is to be discovered. The scope, specificity and overlay of the various studies in-progress require teamwork. And there is a line-up of highly specialized teams engaged in research at ALBMC, such as one that develops novel algorithms for processing magnetic resonance imaging data. Without that, no maps.

One of the teams that Mehta leads has tackled several problems by following their neural pathways. “A key brain region, called the hippocampus, is implicated in several disorders such as Alzheimer’s, epilepsy, schizophrenia and depression,” he says. “The question is how. To solve this, we are mapping hippocampal circuit and developing sophisticated mathematical techniques to decipher the data.”

Mehta has also pioneered the use of virtual reality in mapping, which led to a surprising discovery. “We’ve found that 60 percent of the hippocampus neurons shut down when we map the brain of a subject navigating in a virtual reality world, and learning-related brain rhythms are altered. This has profound implications,” he says.

Another team of scientists from the ALBMC and UCLA’s Division of Digestive Diseases collaborated to discover that bacteria ingested in food have an impact on brain function. They found that dietary changes can alter the signals from the intestines to the brain. This knowledge is expected to help scientists develop new prevention and treatment strategies for digestive, mental and neurological disorders. Future research aims to answer whether people with bloating, abdominal pain and altered bowel movements show improvements in their symptoms that correlate with changes in brain response.

Another technology being very actively researched is transcranial magnetic stimulation (TMS), the use of magnets to affect neural patterns. Scientists know that it works, but understanding how, they say, will likely be of great benefit to people with movement disorders. The initial research progressed so rapidly that the Food and Drug Administration approved TMS as a treatment for severe depression in 2008. Now, an ALBMC team is studying its use in treating Parkinson’s disease, atypical Parkinsonism syndromes and dystonia. Because it’s noninvasive, TMS is considered a possible future alternative to deep brain stimulation surgery for Parkinson’s patients. If it proves to be so, brain mapping will have played a major role in the achievement.

Depression: Underdiagnosed, Undertreated

Depression is the research province of Katherine Narr Ph.D. ’02, associate professor of neurology, psychiatry and biobehavioral sciences. One of her quests is to identify the biomarkers of treatment response. Studying changes in the brain — as well as in gene expression, immune response and inflammation — she and her team focus on understanding why and how some people respond to treatment, while others don’t.

“Depression has been underdiagnosed and undertreated,” she says. “That’s changing, because we are now identifying biomarkers that may not only predict who will be treatment-responsive, but also help us design more effective treatments to improve the lives of patients and their families.”

She points to then-and-now time factors in mapping the brain’s structure. “Five years ago, to get a quality picture of it, I would have someone in a scanner for half an hour. Now, I get an even better quality result in five minutes,” she says. It used to take twice as long to set all the gradients needed to map a brain’s connections. The ever-increasing speed of scanners is also expected to significantly reduce health care costs.

Wide Open to Exploration

With so many goals being pursued, Woods takes a long pause before citing an example. “One that’s on our agenda is trying to get into a situation where we can image people with implanted brain stimulators, like those being used in Parkinson’s research, so we can see, specifically, what the stimulator is doing. It’s very black-box right now.”

So much concerning the exploration and mapping of the mind is not yet known. But that proverbial “black box,” in which so many mysteries were once hopelessly locked, is now opening at UCLA.

Dean Buonomano: Debugging the Brain

“Neuroscience is arguably the most complex and interdisciplinary field of all scientific endeavors,” says Dean Buonomano, professor of neurobiology and psychology in UCLA’s Interdepartmental Ph.D. Program for Neuroscience (NS-IDP). “It involves molecular biology, biochemistry, computer science, electrical engineering and physics. It’s hard to get a grasp on all its different aspects. Our goal is to communicate the niches we work on to the public, which is a challenge.”

That was Buonomano’s objective with his first book, 2011’s Brain Bugs: How the Brain’s Flaws Shape Our Lives, in which he offers insights into why we humans have biases in our decision-making, why memories are fallible and why we don’t always remember everything we’d like to at a mechanistic level. The follow-up to Brain Bugs, tentatively titled Time Machine: The Neuroscience and Physics of Time, is due for release in 2016.

Time Machine will explore the brain’s ability to tell time as an inherent, intrinsic property of neural circuits. Topics will range from how we tell time and think about it to the very nature of time. “In many ways, the brain is a type of time machine — it allows us to not only tell time, but to travel in time,” says Buonomano. “You can reminisce about your past or dream about your potential future. That’s one of the most unique aspects of the human brain.”

Buonomano’s curiosity drove him to pursue an interest in neuroscience as a child. “There’s just this fascination with an organ that essentially is made out of the same composition as the heart or liver, yet allows us to carry on conversations, laugh, or recognize someone by their gait, face and voice,” he says.

Add the curious neuroscientist’s interest in the nature of time, and mysteries such as “predicting the future” unfold. “Really, one of the brain’s main functions is to predict what is about to happen next,” Buonomano says. “The degree to which we can do that translates into the currency of evolutionary fitness. How that’s achieved is a mystery, and a fundamental mystery at that.” — Bekah Wright