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Anne Churchland

Anne Churchland with former postdoctoral fellow Matt Kaufman at Cold Spring Harbor Laboratory. The microscope is a 2-photon microscope and is one of three techniques used to measure neural activity in the mouse brain. Photo from Margot Bennett

By Daniel Dunaief

Fidgeting, rocking and other movements may have some benefit for thinking. Yes, all those people who shouted to “sit still” may have been preventing some people from learning in their own way.

In a new experiment conducted on mice published in the journal Nature Neuroscience this week, Anne Churchland, an associate professor at Cold Spring Harbor Laboratory, linked idiosyncratic mouse movements to performance in a set of tasks that required making decisions with rewards.

“Moving when deep in thought is a natural thing to do,” Churchland said. “It deeply engages the brain in ways that were surprising to us.”

She suggested that many people believe thinking deeply requires stillness, like the statue of The Thinker created by Auguste Rodin. “Sometimes it does, but maybe not for all individuals,” adding that these movements, which don’t seem connected to the task at hand, likely provide some benefit for cognition.

“We don’t know yet for sure what purpose these movements are serving,” she said.

Margaret Churchland with the lab group at CSHL

Mammals tend to exhibit a process called “optimal motor control.” If a person is reaching out to grab a cup, she tends to move her arm in a way that is energy conserving. Indeed, extending this to her rodent study, Churchland suggests that somehow these ticks, leg kicks or other movements provide assistance to the brain.

In theory, she suggested that these movements may be a way for the brain to recruit movement-sensitive cells to participate in the process. These brain cells that react to movement may then participate in other thought processes that are unrelated or disconnected from the actions themselves.

Churchland offers an analogy to understanding the potential benefit of these extra movements in the sports world. Baseball players have a wide range of stereotyped movements when they step up to the plate to hit. They will touch their shirt, tug on their sleeves, readjust their batting gloves, lift up their helmet or any of a range of assorted physical activities that may have no specific connection to the task of hitting a baseball.

These actions likely have “nothing to do” with the objective of a baseball hitter, but they are a “fundamental part of what it means to go up to bat,” she said.

In her research, Churchland started with adult mice who were novices at the kinds of tasks she and her colleagues Simon Musall and Matt Kaufman, who are the lead authors on the paper, trained them to do. Over a period of months, the mice went from not understanding the objective of the experiment to becoming experts. The animals learned to grab a handle to start a trial or to make licking movements.

These CSHL researchers tracked the behavior and neural activity of the mice every day.

Churchland said a few other groups have measured neural activity during learning, but that none has studied the kind of learning her lab did, which is how animals learn the structure of an environment.

The extra movements that didn’t appear to have any connection to the learned behaviors transitioned from a disorganized set of motions to an organized pattern that “probably reflected, in the animal’s mind, a fundamental part of what it means to make a decision.”

Churchland suggested that some of these conclusions may have a link to human behavior. Each animal, however, has different behaviors, so “we always need to confirm that what we learn in one species is true for another,” she wrote in an email.

Parents, teachers, coaches and guest lecturers often look at the faces of young students who are shaking their legs, rocking in their chair, twiddling their thumbs or spinning their pens between their fingers. While these actions may be distracting to others, they may also play a role in learning and cognition.

The study “suggests that allowing certain kinds of movements during learning is probably very important,” Churchland said. “When we want people to learn something, we shouldn’t force them to sit still. We should allow them to make movements they need to make which will likely help” in the learning process.

Churchland believes teachers already know that some students need to move. These educators also likely realize the tension between allowing individual students to be physically active without creating a chaotic classroom. “Most teachers are working hard to find the right balance,” she explained in an email.

She also suggested that different students may need their own level of movement to stimulate their thinking.

Some adults may have already developed ways to enhance their own thinking about decisions or problems. Indeed, people often take walks that may “finally allow those circuits you need for a decision to kick in.”

Down the road, she hopes to collaborate with other scientists who are working with nonhuman primates, such as marmosets, which are new world monkeys that live in trees and have quick, jerky movements, and macaques, which are old world monkeys and may be familiar from their island perch in an exhibit in the Central Park Zoo.

Churchland said extensions of this research could also go in numerous directions and address other questions. She is hoping to learn more about attention deficit hyperactivity disorder and the brain.

“We don’t know when that strategy [of using movement to trigger or enhance thinking] interferes with the goal,” she said. “Maybe the movements are a symptom of the learner trying to engage, but not being able to do so.”

Ultimately, Churchland expects that different pathways may support different aspects of decision making, some of which can and likely are connected to movement.

From left, Anne Churchland and Tatiana Engel. Photo from CSHL

By Daniel Dunaief

Movies have often used an image of a devil on one shoulder, offering advice, and an angel on another, suggesting a completely different course of action. People, however, weigh numerous factors when making even the simplest of decisions.

The process the brain uses to make decisions involves excitatory and inhibitory neurons, which are spread throughout the brain. Technology has made it possible to study thousands of these important cells on an active mouse, showing areas that are active at the same time.

Anne Churchland, an associate professor at Cold Spring Harbor Laboratory, and Tatiana Engel, an assistant professor at the same facility, are collaborating on a three-year grant from the National Institutes of Health that will study the way neurons interact to understand the patterns that lead to decisions. 

Engel said she, Churchland and another collaborator on the project, Stanford University Professor Krishna Shenoy, applied for the funding in response to a call from the NIH to develop computational methods and models for analyzing large-scale neural activity recordings from the brain.

Churchland and Shenoy will provide experimental data for the computational models Engel’s lab will develop. The data is “huge and complex,” Engel said, and researchers need new methods to understand it. “The simple techniques don’t translate to large-scale recordings,” Engel said.

Churchland and Engel jointly hired James Roach, a postdoctoral researcher who recently earned his doctorate from the University of Michigan and works in both of their labs. 

Churchland’s lab will provide data from the mouse model, while Engel’s lab brings computational expertise.

“Little is known about how these neurons are connected to behavior,” Engel said. Their research will hope to explain the role of inhibitory cells, which may have a more finely tuned function beyond keeping cells from remaining in an excited state.

The prevailing view in the field is that inhibitory neurons provide a balancing input to the network to prevent it from generating too much excitation or creating a seizure. Inhibitors are like the regulators that tap the brakes on a network that’s becoming too active.

Excitatory neurons, by contrast, are the ones that have an important job, representing the decisions individuals make.

Churchland is going to measure neural activity using a 2-photon microscope that allows her to measure the activity of about 600 neurons simultaneously. 

“This provides an incredible opportunity to analyze the data, using tools borrowed from machine learning and dynamical systems,” she explained in an email.

What Churchland’s data has helped show, however, is that the inhibitory neurons are doing more than providing a global braking signal. “They have some dedicated role in the circuit and we don’t know what that role is yet,” Engel said.

The team will build neural circuit models to help understand how the system is wired and what role each type of cell plays in various behaviors.

“We are developing computational frameworks where we can go and analyze activities of large groups of cells and, from the data, determine how individual cells contribute to the activity of the population,” Engel said.

Brains have considerable plasticity, which means that when one area of the brain isn’t functioning for whatever reason — through an injury or a temporary blockage ‒ other areas can compensate. “The whole problem is immensely complicated to figure out what a brain area is doing normally,” she explained. The picture can “completely change when there’s brain damage.”

Research is moving in the direction of understanding and manipulating large neural circuits at once, rather than a single area at a time. 

“Models can extract general principles, which still hold true even in more complex” systems Engel said. The principles include understanding how excitatory and inhibitory cells are balanced. “Models can help you figure out what works and doesn’t work.”

Roach, the current postdoctoral researcher working with Engel and Churchland, will start with modeling and then will develop experiments to test the role of inhibitory cells. He has already worked on computer programs that interpret neurological circuits and laboratory results. He is also receiving laboratory training.

At this point, Engel and Churchland are working on basic science. Engel explained that this type of research is the foundation for translation work that will lead to an improved diagnosis and treatment of neurological disorders. Basic science can, and often does, provide insights and information that help those working to understand or treat disease, she suggested.

Churchland was pleased with her collaboration with Engel.

Engel is “best known for modeling work she did studying neural mechanisms of attention,” Churchland explained in an email. “She is a great addition to Cold Spring Harbor! We work together in the same building and are trying to unravel the mysteries of how large groups of neurons in the brain work together to make decisions.”

A resident of the facilities at Cold Spring Harbor Laboratory, Engel grew up in Vologda, which is over 300 miles north of Moscow. Starting in seventh grade, she attended physics and math schools, first in her home town and then at a boarding school at the Moscow State University.

She learned to appreciate the value of science from the journals her parents subscribed to, including one for children called Kvant magazine. She solved physics problems in that magazine. “I enjoyed the articles and problems in Kvant,” she explained in an email.

As for her work, Engel suggested that there were many discoveries ahead. “It is an exciting and transformative time in neuroscience,” she said.

Anne Churchland. Photo from CSHL

By Daniel Dunaief

Someone is hungry and is walking through a familiar town. She smells pizza coming from the hot brick oven on her left, she watches someone leaving her favorite Chinese restaurant with the familiar takeout boxes, and she thinks about the fish restaurant with special catches of the day that she usually enjoys around this time of year. How does she make her decision?

While this scenario is a simplified one, it’s a window into the decision-making process people go through when their neurons work together. A team of 21 neuroscientists in Europe and the United States recently created a new collaboration called the International Brain Laboratory to explore how networks of brain cells support learning and decision-making.

“We understand the simple motor reflex,” such as when a doctor taps a knee and a foot kicks out, said Anne Churchland, an associate professor at Cold Spring Harbor Laboratory and the American spokesperson for this new effort. Scientists, however, have only a limited understanding of the cognitive processes that weigh sensory details and a recollection of the outcomes from various courses of action that lead to decision-making, Churchland said.

Scientists likened the structure of the new multilaboratory effort to the circuitry involved in the brain itself. The brain is “massively parallel,” said Alexandre Pouget, a professor at the University of Geneva and the spokesperson for the IBL. “We know it’s working on consensus building across areas so, in that respect, the IBL is similar.”

A greater awareness of the decision-making process could provide a step into understanding the brain network problems involved in mental health disorders.

Churchland’s lab is one of three facilities that will house a new behavioral apparatus to study decision-making in mice. The other sites will be in the United Kingdom and in Portugal. Eventually, other labs will use this same technique and house the same apparatus.

An ongoing challenge in this field of research, Churchland said, is that scientists sometimes create their own models to test the neurological basis of behavior. While these approaches may work in their own labs, they have created a reproducibility problem, making it difficult for others who don’t have expertise in their methods to duplicate the results.

Creating this behavioral apparatus will help ensure that the collaborators are approaching the research with a reliable model that they can repeat, with similar results, in other facilities.

While the scientists will all be exploring the brain, they will each be responsible for studying the activity of circuits in different parts. The researchers will collect a wealth of information and will share it through a developing computer system that allows them to maneuver through the mountains of data.

To address this challenge, the IBL is creating a data architecture working group. Kenneth Harris, a professor of quantitative neuroscience at the University College London, is the chair of the effort. He is currently looking to hire additional outside staff to help develop this process.

Harris suggested that the process of sharing data in neurophysiology has been challenging because of the complex and diverse data these scientists share. “In neuroscience, we have lots of different types of measurements, made simultaneously with lots of different experimental methods, that all have to be integrated together,” he explained in an email.

The IBL collaboration will make his job slightly easier than the generic problem of neurophysiology data sharing because “all the labs will be studying how the brain solves the same decision-making task,” he continued.

Harris is looking to hire a data coordinator, a senior scientific programmer and a scientific MATLAB programmer. He has a data management system already running with his lab that he plans to extend to the IBL.

Pouget said there are two milestones built into the funding from the Wellcome Trust and the Simons Foundation for this new collaboration. After two years, the researchers have to have a data sharing platform in place, which will allow them to share data live as they collect it.

Second, they plan to develop standardized behaviors in all 11 of the experimental labs, where the behavior has to be as indistinguishable from one lab to another as possible.

In addition to the experimentalists involved in this initiative, several theoretical neurobiologists will also contribute and will be critical to unraveling the enormous amounts of data, Pouget suggested. “If you’re going to tackle really hard computational problems, you better have people trained in that area,” he said, adding that he estimates that only about 5 percent of neuroscientists are involved in the theoretical side, which is considerably lower than the percent in an area like physics.

Researchers involved in this project will have the opportunity to move from one lab to another, conducting experiments and gaining expertise and insights. The principal investigators are also in the process of hiring 21 postdoctoral students.

Churchland said each scientist will continue to conduct his or her own research while also contributing to this effort. The IBL is consuming between a quarter and a third of her time.

Pouget suggested that Churchland was “instrumental in representing the International Brain Laboratory to the Simons Foundation,” where she is the principal investigator on that grant. “Her role has been critical to the organization,” he said.

Churchland said the effort is progressing rapidly. “It’s moving way faster” than expected. “This is the right moment, with an incredible team of people, to be working together. Everyone is dedicated to the science.”

Harris indicated that he believes this effort could be transformative for the field. “Neuroscience has lagged behind many other scientific domains” in creating large-scale collaborations, he explained. “If we can show it works, we will change the entire field for good.”

Christopher Fetsch (far left) and Anne Churchland (second from right) with a group of neuroscientists at a conference last month. Photo from Anne Churchland

When she’s having trouble understanding something she’s reading, Anne Churchland will sometimes read the text out loud. Seeing and hearing the words often helps.

An associate professor at Cold Spring Harbor Laboratory, Churchland recently published research in the Journal of Neurophysiology in which she explored how people use different senses when thinking about numbers.

She asked nine participants in her study to determine whether something they saw had a larger or smaller number of flashes of light, sequences of sounds or both compared to another number.

To see whether her subjects were using just the visual or auditory stimuli, she varied the  clarity of the signal, making it harder to decide whether a flash of light or a sound counted.

The people in her study used a combination of the two signals to determine a number compared to a fixed value, rather than relying only on one type of signal. The subjects didn’t just calculate the average of sight and sound clues but took the reliability of that number into account. That suggests they thought of the numbers with each stimuli within a range of numbers, which could be higher or lower depending on other evidence.

Churchland describes this process as the probabilistic method. It would be the equivalent of finding two sources of information online about Gertrude Ederle, the first woman to swim across the English Channel. In the first one, someone might have posted a brief entry on his personal Web page, offering some potentially interesting information. In the second, a prize-winning biographer might have shared an extensive view of her long life. In a probabilistic strategy, people would weigh the second source more heavily.

Funded by an educational branch of the National Science Foundation, Churchland said this is the kind of study that might help teachers better understand how people’s brains represent numbers.

Young children and people with no formal math training have some ability to estimate numbers, she said. This kind of study might help educators understand how people go from an “innate to the more formalized math.”

This study might have implications for disorders in which people have unusual sensory processing. “By understanding the underlying neural circuitry” doctors can “hopefully develop more effective treatments,” Churchland said.

Churchland is generally interested in neural circuits and in putting together a combination of reliable and unreliable signals. Working with rodents, she is hoping to see a signature of those signals in neural responses.

Churchland runs a blog in which she shares developments at her lab. Last month, she attended a conference in which she and other neuroscientists had a panel discussion of correlation versus causation in experiments.

She cautioned that a correlation — the Knicks lose every time a dog tracks mud in the house — doesn’t imply causation.

The group studied a lighthearted example, viewing the relationship between chocolate consumption and the number of Nobel Prizes in various countries, with Switzerland coming out on top of both categories. “In the chocolate case, correlation does imply causation because I like to eat chocolate and was looking for excuses,” she joked.

Christopher Fetsch, a postdoctoral research fellow at the Department of Neuroscience at Columbia University, worked with Churchland for several months in 2010. In addition to teaching him how to do electrical microstimulation and serving as a “terrific role model,” Fetsch described Churchland as “an innovator with a high degree of technical skill and boundless energy.” Fetsch, who attended the same conference last month, lauded Churchland’s ability to bring together experts with a range of strengths.

Churchland created a website, www.Anneslist.net, which is a compilation of women in neuroscience. She said it began for her own purposes, as part of an effort to find speakers for a computational and systems neuroscience meeting. The majority of professors in computational neuroscience are men, she said. “It is important to have a field that is open to all,” she said. “That way, the best scientists [can] come in and do the best work.” The list has since gone viral and people from all over the world send her emails.

A resident of the housing at Cold Spring Harbor Laboratory, Churchland lives with her husband, Michael Brodesky, and their two children.

Churchland has collaborated with her brother Mark, an assistant professor at the Department of Neuroscience at Columbia University. Her parents, Patricia and Paul, are well-known philosophers. Her mother has appeared on “The Colbert Report.” She said her family members can all be contentious when discussing matters of the mind.

“The dinner table is lively,” she said.