(Image caption: This image shows the brain’s default mode network, where memory and sensory information are stored. Credit: Marcus Raichle, Washington University)

What happens to your brain when your mind is at rest?

For many years, the focus of brain mapping was to examine changes in the brain that occur when people are attentively engaged in an activity. No one spent much time thinking about what happens to the brain when people are doing very little.

But Marcus Raichle, a professor of radiology, neurology, neurobiology and biomedical engineering at Washington University in St. Louis, has done just that. In the 1990s, he and his colleagues made a pivotal discovery by revealing how a specific area of the brain responds to down time.

"A great deal of meaningful activity is occurring in the brain when a person is sitting back and doing nothing at all," says Raichle, who has been funded by the National Science Foundation (NSF) Division of Behavioral and Cognitive Sciences in the Directorate for Social, Behavioral and Economic Sciences. "It turns out that when your mind is at rest, dispersed brain areas are chattering away to one another."

The results of these discoveries now are integral to studies of brain function in health and disease worldwide. In fact, Raichle and his colleagues have found that these areas of rest in the brain—the ones that ultimately became the focus of their work—often are among the first affected by Alzheimer’s disease, a finding that ultimately could help in early detection of this disorder and a much greater understanding of the nature of the disease itself.

For his pioneering research, Raichle this year was among those chosen to receive the prestigious Kavli Prize, awarded by The Norwegian Academy of Science and Letters. It consists of a cash award of $1 million, which he will share with two other Kavli recipients in the field of neuroscience.

His discovery was a near accident, actually what he calls “pure serendipity.” Raichle, like others in the field at the time, was involved in brain imaging, looking for increases in brain activity associated with different tasks, for example language response.

In order to conduct such tests, scientists first needed to establish a baseline for comparison purposes which typically complements the task under study by including all aspects of the task, other than just the one of interest.

"For example, a control task for reading words aloud might be simply viewing them passively," he says.

In the Raichle laboratory, they routinely required subjects to look at a blank screen. When comparing this simple baseline to the task state, Raichle noticed something.

"We didn’t specify that you clear your mind, we just asked subjects to rest quietly and don’t fall asleep," he recalls. "I don’t remember the day I bothered to look at what was happening in the brain when subjects moved from this simple resting state to engagement in an attention demanding task that might be more involved than simply increases in brain activity associated with the task.

"When I did so, I observed that while brain activity in some parts of the brain increased as expected, there were other areas that actually decreased their activity as if they had been more active in the ‘resting state,"’ he adds. "Because these decreases in brain activity were so dramatic and unexpected, I got into the habit of looking for them in all of our experiments. Their consistency both in terms of where they occurred and the frequency of their occurrence—that is, almost always—really got my attention. I wasn’t sure what was going on at first but it was just too consistent to not be real."

These observations ultimately produced ground-breaking work that led to the concept of a default mode of brain function, including the discovery of a unique fronto-parietal network in the brain. It has come to be known as the default mode network, whose regions are more active when the brain is not actively engaged in a novel, attention-demanding task.

"Basically we described a core system of the brain never seen before," he says. "This core system within the brain’s two great hemispheres increasingly appears to be playing a central role in how the brain organizes its ongoing activities"

The discovery of the brain’s default mode caused Raichle and his colleagues to reconsider the idea that the brain uses more energy when engaged in an attention-demanding task. Measurements of brain metabolism with PET (positron emission tomography) and data culled from the literature led them to conclude that the brain is a very expensive organ, accounting for about 20 percent of the body’s energy consumption in an adult human, yet accounting for only 2 percent of the body weight.

"The changes in activity associated with the performance of virtually any type of task add little to the overall cost of brain function," he continues. "This has initiated a paradigm shift in brain research that has moved increasingly to studies of the brain’s intrinsic activity, that is, its default mode of functioning."

Raichle, whose work on the role of this intrinsic brain activity on facets of consciousness was supported by NSF, is also known for his research in developing and using imaging techniques, such as positron emission tomography, to identify specific areas of the brain involved in seeing, hearing, reading, memory and emotion.

In addition, his team studied chemical receptors in the brain, the physiology of major depression and anxiety, and has evaluated patients at risk for stroke. Currently, he is completing research studying what happens to the brain under anesthesia.

"The brain is capable of so many things, even when you are not conscious," Raichle says. "If you are unconscious, the organization of the brain is maintained, but it is not the same as being awake."

Are Three Brain Imaging Techniques Better than One?

Many recent imaging studies have shown that in children with autism, different parts of the brain do not connect with each other in typical ways. Initially, most researchers thought that the autistic brain has fewer connections between key regions. The most recent studies, however, point to an opposite conclusion: The brains of people with autism exhibit overconnectivity.

To date, almost all studies of autism in children have used a single imaging technique to explore connectivity. None has been able to capture a robust picture of the brain abnormalities associated with autism—until now.

Two new grants from the National Institute of Mental Health (NIMH) will allow San Diego State University Psychology Professor Ralph-Axel Müller to combine three imaging techniques and harness the best of each one in his study of autism.

Techniques in tandem

Although the term “brain imaging” gets thrown around a lot when describing the latest advances in neuroscience and psychology, there are dozens of different brain imaging techniques. Each gives scientists a different view of the inner workings of the brain, and each comes with its own strengths and limitations.

For example, the frequently cited technique of fMRI, or functional magnetic resonance imaging, measures blood flow in different areas of the brain at specific snapshots in time, based on the knowledge that increased blood flow indicates increased activity of nerve cells in that area of the brain. The technique is powerful, but has limitations when it comes to detecting dynamic changes in brain activity that occur very fast, within milliseconds.

EEG (electroencephalography), a much older technique, is actually better at detecting such dynamic changes, although it cannot pinpoint exactly where in the brain the activity occurs. A powerful and more recent technique is MEG, or magnetoencephalography, which can detect dynamic changes in brain activity that happen within a few milliseconds.

Müller looks for disorganized patterns of brain activity that could be responsible for some of the telltale characteristics of autism spectrum disorder, such as inattention to social cues and repetitive and obsessive behaviors. For example, last year, Müller and his colleagues discovered that in children with autism, connectivity was impaired between the cerebral cortex and the thalamus, a deep brain structure that is important for sensorimotor functions and attention.

With $4.2 million in new funding from NIH, Müller—together with collaborators Ksenija Marinkovic at SDSU and Thomas Liu at the University of California, San Diego—will apply fMRI, EEG, and MEG to study both autistic and non-autistic, or typically-developing, children and adolescents during a variety of tests, including language tests designed to tease out activity in various parts of the brain.

Defining the differences

One component of the project will concern the visual system. Previous research has shown that people with autism rely on their visual cortex more than typically- developing people during thought processes, for example, when making a semantic distinction, such as deciding whether a truck is a vehicle. Using the one-two punch of fMRI and MEG together, Müller and his team will be able to determine the dynamic processes in how brain regions work together to come up with a response, and how these processes differ in autism.

The study will also examine brain function during its resting state in order to identify abnormalities in brain network organization. The combined use of EEG and MEG, together with fMRI techniques that reveal brain anatomy, will produce a much more complete picture of abnormal brain organization in autism.

Ultimately, Müller and his colleagues hope to identify biomarkers in the brain that can reliably indicate whether the participant falls on the autism spectrum.

“Autism is a brain-based disorder, but its diagnosis is still based entirely on behavioral observation,” Müller said. “This is inadequate. We need to find brain biomarkers for autism.”

Another goal of the researchers is to find brain biomarkers that can distinguish different subtypes of autism. It is generally suspected that the term “autism” actually covers several different disorders, each of which may be caused by different genetic and environmental risk factors. Eventually, brain biomarkers might be tied to genetic data, giving scientists a better understanding of the origins of autism, as well as new leads for treatment.

“For decades, research teams studying autism have specialized in one or another scientific technique, often without understanding well what other techniques can reveal. Our study combining several of the major imaging techniques will be one step toward a more comprehensive account of how the autistic brain differs from the typically developing one – and what may be done about it,” Müller said.

Scientists use lasers and carbon nanotubes to look inside living brains

Some of the most damaging brain diseases can be traced to irregular blood delivery in the brain. Now, Stanford chemists have employed lasers and carbon nanotubes to capture an unprecedented look at blood flowing through a living brain.

The technique was developed for mice but could one day be applied to humans, potentially providing vital information in the study of stroke and migraines, and perhaps even Alzheimer’s and Parkinson’s diseases. The work is described in the journal Nature Photonics.

Current procedures for exploring the brain in living animals face significant tradeoffs. Surgically removing part of the skull offers a clear view of activity at the cellular level. But the trauma can alter the function or activity of the brain or even stimulate an immune response. Meanwhile, non-invasive techniques such as CT scans or MRI visualize function best at the whole-organ level; they cannot visualize individual vessels or groups of neurons.

The first step of the new technique, called near infrared-IIa imaging, or NIR-IIa, calls for injecting water-soluble carbon nanotubes into a live mouse’s bloodstream. The researchers then shine a near-infrared laser over the rodent’s skull.

The light causes the specially designed nanotubes to fluoresce at wavelengths of 1,300-1,400 nanometers; this range represents a sweet spot for optimal penetration with very little light scattering. The fluorescing nanotubes can then be detected to visualize the blood vessels’ structure.

Amazingly, the technique allows scientists to view about three millimeters underneath the scalp and is fine enough to visualize blood coursing through single capillaries only a few microns across, said senior author Hongjie Dai, a professor of chemistry at Stanford. Furthermore, it does not appear to have any adverse affect on innate brain functions.

"The NIR-IIa light can pass through intact scalp skin and skull and penetrate millimeters into the brain, allowing us to see vasculature in an almost non-invasive way," said first author Guosong Hong, who conducted the research as a graduate student in Dai’s lab and is now a postdoctoral fellow at Harvard. "All we have to remove is some hair."

The technique could eventually be used in human clinical trials, Hong said, but will need to be tweaked. First, the light penetration depth needs to be increased to pass deep into the human brain. Second, injecting carbon nanotubes needs approval for clinical application; the scientists are currently investigating alternative fluorescent agents.

For now, though, the technique provides a new technique for studying human cerebral-vascular diseases, such as stroke and migraines, in animal models. Other research has shown that Alzheimer’s and Parkinson’s diseases might elicit – or be caused in part by – changes in blood flow to certain parts of the brain, Hong said, and NIR-IIa imaging might offer a means of better understanding the role of healthy vasculature in those diseases.

"We could also label different neuron types in the brain with bio-markers and use this to monitor how each neuron performs," Hong said. "Eventually, we might be able to use NIR-IIa to learn how each neuron functions inside of the brain."

(Image caption: Brain image showing activity in the amygdala, the area of the brain involved with emotion. The amydgala was more active during the graphic scenarios only when the harm being described was intentional. Credit: Marois Lab / Vanderbilt)

Fault trumps gruesome evidence when it comes to meting out punishment

Issues of crime and punishment, vengeance and justice date back to the dawn of human history, but it is only in the last few years that scientists have begun exploring the basic nature of the complex neural processes in the brain that underlie these fundamental behaviors.

Now a new brain imaging study – published online Aug. 3 by the journal Nature Neuroscience – has identified the brain mechanisms that underlie our judgment of how severely a person who has harmed another should be punished. Specifically, the study determined how the area of the brain that determines whether such an act was intentional or unintentional trumps the emotional urge to punish the person, however gruesome the harm may be.

“A fundamental aspect of the human experience is the desire to punish harmful acts, even when the victim is a perfect stranger. Equally important, however, is our ability to put the brakes on this impulse when we realize the harm was done unintentionally,” said Rene Marois, the Vanderbilt University professor of psychology who headed the research team. “This study helps us begin to elucidate the neural circuitry that permits this type of regulation.”

The study

In the experiment, the brains of 30 volunteers (20 male, 10 female, average age 23 years) were imaged using functional MRI (fMRI) while they read a series of brief scenarios that described how the actions of a protagonist named John brought harm to either Steve or Mary. The scenarios depicted four different levels of harm: death, maiming, physical assault and property damage. In half of them, the harm was clearly identified as intentional and in half it was clearly identified as unintentional.

Two versions of each scenario were created: one with a factual description of the harm and the other with a graphic description. For example, in a mountain climbing scenario where John cuts Steve’s rope, the factual version states, “Steve falls 100 feet to the ground below. Steve experiences significant bodily harm from the fall and he dies from his injuries shortly after impact.” And the graphic version reads, “Steve plummets to the rocks below. Nearly every bone in his body is broken upon impact. Steve’s screams are muffled by thick, foamy blood flowing from his mouth as he bleeds to death.”

After reading each scenario the participants were asked to list how much punishment John deserved on a scale from zero (no punishment) to nine (most severe punishment the subject endorsed).

Analysis of the responses

When the responses were analyzed, the researchers found that the manner in which the harmful consequences of an action are described significantly influences the level of punishment that people consider appropriate: When the harm was described in a graphic or lurid fashion then people set the punishment level higher than when it was described matter-of-factly. However, this higher punishment level only applied when the participants considered the resulting harm to be intentional. When they considered it to be unintentional, the way it was described didn’t have any effect.

“What we’ve shown is that manipulations of gruesome language leads to harsher punishment, but only in cases where the harm was intentional. Language had no effect when the harm was caused unintentionally,” summarized Michael Treadway, a post-doctoral fellow at Harvard Medical School and lead author of the study.

According to the researchers, the fact that the mere presence of graphic language could cause participants to ratchet up the severity of the punishments suggests that photographs, video and other graphic materials sampled from a crime scene is likely to have an even stronger impact on an individual’s desire to punish.

“Although the underlying scientific basis of this effect wasn’t known until now, the legal system recognized it a long time ago and made provisions to counteract it,” said Treadway. “Judges are permitted to exclude relevant evidence from a trial if they decide that its probative value is substantially outweighed by its prejudicial nature.”

Underlying neuroanatomy

The fMRI scans revealed the areas of the brain that are involved in this complex process. They found that the amygdala, an almond-shaped set of neurons that plays a key role in processing emotions, responded most strongly to the graphic language condition. Like the punishment ratings themselves, however, this effect in the amygdala was only present when harm was done intentionally. Moreover, in this situation the researchers found that the amygdala showed stronger communication with the dorsolateral prefrontal cortex (dlPFC), an area that is critical for punishment decision-making. When the harm was done unintentionally, however, a different regulatory network – one involved in decoding the mental states of other people – became more active and appeared to suppress amygdala responses to the graphic language, thereby preventing the amygdala from affecting decision-making areas in dlPFC.

“This is basically a reassuring finding,” said Marois. “It indicates that, when the harm is not intended, we don’t simply shunt aside the emotional impulse to punish. Instead, it appears that the brain down-regulates the impulse so we don’t feel it as strongly. That is preferable because the urge to punish is less likely to resurface at a future date.”

Seeing the inner workings of the brain made easier by new technique

Last year Karl Deisseroth, a Stanford professor of bioengineering and of psychiatry and behavioral sciences, announced a new way of peering into a brain – removed from the body – that provided spectacular fly-through views of its inner connections. Since then laboratories around the world have begun using the technique, called CLARITY, with some success, to better understand the brain’s wiring.

However, Deisseroth said that with two technological fixes CLARITY could be even more broadly adopted. The first problem was that laboratories were not set up to reliably carry out the CLARITY process. Second, the most commonly available microscopy methods were not designed to image the whole transparent brain. “There have been a number of remarkable results described using CLARITY,” Deisseroth said, “but we needed to address these two distinct challenges to make the technology easier to use.”

In a Nature Protocols paper published June 19, Deisseroth presented solutions to both of those bottlenecks. “These transform CLARITY, making the overall process much easier and the data collection much faster,” he said. He and his co-authors, including postdoctoral fellows Raju Tomer and Li Ye and graduate student Brian Hsueh, anticipate that even more scientists will now be able to take advantage of the technique to better understand the brain at a fundamental level, and also to probe the origins of brain diseases.

This paper may be the first to be published with support of the White House BRAIN Initiative, announced last year with the ambitious goal of mapping the brain’s trillions of nerve connections and understanding how signals zip through those interconnected cells to control our thoughts, memories, movement and everything else that makes us us.

"This work shares the spirit of the BRAIN Initiative goal of building new technologies to understand the brain – including the human brain," said Deisseroth, who is also a Stanford Bio-X affiliated faculty member.

Eliminating fat

When you look at the brain, what you see is the fatty outer covering of the nerve cells within, which blocks microscopes from taking images of the intricate connections between deep brain cells. The idea behind CLARITY was to eliminate that fatty covering while keeping the brain intact, complete with all its intricate inner wiring.

The way Deisseroth and his team eliminated the fat was to build a gel within the intact brain that held all the structures and proteins in place. They then used an electric field to pull out the fat layer that had been dissolved in an electrically charged detergent, leaving behind all the brain’s structures embedded in the firm water-based gel, or hydrogel. This is called electrophoretic CLARITY.

The electric field aspect was a challenge for some labs. “About half the people who tried it got it working right away,” Deisseroth said, “but others had problems with the voltage damaging tissue.” Deisseroth said that this kind of challenge is normal when introducing new technologies. When he first introduced optogenetics, which allows scientists to control individual nerves using light, a similar proportion of labs were not initially set up to easily implement the new technology, and ran into challenges.

To help expand the use of CLARITY, the team devised an alternate way of pulling out the fat from the hydrogel-embedded brain – a technique they call passive CLARITY. It takes a little longer, but still removes all the fat, is much easier and does not pose a risk to the tissue. “Electrophoretic CLARITY is important for cases where speed is critical, and for some tissues,” said Deisseroth, who is also the D.H. Chen Professor. “But passive CLARITY is a crucial advance for the community, especially for neuroscience.” Passive CLARITY requires nothing more than some chemicals, a warm bath and time.

Many groups have begun to apply CLARITY to probe brains donated from people who had diseases like epilepsy or autism, which might have left clues in the brain to help scientists understand and eventually treat the disease. But scientists, including Deisseroth, had been wary of trying electrophoretic CLARTY on these valuable clinical samples with even a very low risk of damage. “It’s a rare and precious donated sample, you don’t want to have a chance of damage or error,” Deisseroth said. “Now the risk issue is addressed, and on top of that you can get the data very rapidly.”

Fast CLARITY imaging in color

The second advance had to do this rapidity of data collection. In studying any cells, scientists often make use of probes that will go into the cell or tissue, latch onto a particular molecule, then glow green, blue, yellow or other colors in response to particular wavelengths of light. This is what produces the colorful cellular images that are so common in biology research. Using CLARITY, these colorful structures become visible throughout the entire brain, since no fat remains to block the light.

But here’s the hitch. Those probes stop working, or get bleached, after they’ve been exposed to too much light. That’s fine if a scientist is just taking a picture of a small cellular structure, which takes little time. But to get a high-resolution image of an entire brain, the whole tissue is bathed in light throughout the time it takes to image it point by point. This approach bleaches out the probes before the entire brain can be imaged at high resolution.

The second advance of the new paper addresses this issue, making it easier to image the entire brain without bleaching the probes. “We can now scan an entire plane at one time instead of a point,” Deisseroth said. “That buys you a couple orders of magnitude of time, and also efficiently delivers light only to where the imaging is happening.” The technique is called light sheet microscopy and has been around for a while, but previously didn’t have high enough resolution to see the fine details of cellular structures. “We advanced traditional light sheet microscopy for CLARITY, and can now see fine wiring structures deep within an intact adult brain,” Deisseroth said. His lab built their own microscope, but the procedures are described in the paper, and the key components are commercially available. Additionally, Deisseroth’s lab provides free training courses in CLARITY, modeled after his optogenetics courses, to help disseminate the techniques.

Brain imaging to help soldiers

The BRAIN Initiative is being funded through several government agencies including the Defense Advanced Research Projects Agency (DARPA), which funded Deisseroth’s work through its new Neuro-FAST program. Deisseroth said that like the National Institute of Mental Health (NIMH, another major funder of the new paper), DARPA “is interested in deepening our understanding of brain circuits in intact and injured brains to inform the development of better therapies.” The new methods Deisseroth and his team developed will accelerate both human- and animal-model CLARITY; as CLARITY becomes more widely used, it will continue to help reveal how those inner circuits are structured in normal and diseased brains, and perhaps point to possible therapies.

Other arms of the BRAIN Initiative are funded through the National Science Foundation (NSF) and the National Institutes of Health (NIH). A working group for the NIH arm was co-led by William Newsome, professor of neurobiology and director of the Stanford Neurosciences Institute, and also included Deisseroth and Mark Schnitzer, associate professor of biology and of applied physics. That group recently recommended a $4.5 billion investment in the BRAIN Initiative over the next 12 years, which NIH Director Francis Collins approved earlier this month.

In addition to funding by DARPA and NIMH, the work was funded by the NSF, the National Institute on Drug Abuse, the Simons Foundation and the Wiegers Family Fund.

Brain imaging reveals clues about chronic fatigue syndrome

A brain imaging study shows that patients with chronic fatigue syndrome may have reduced responses, compared with healthy controls, in a region of the brain connected with fatigue. The findings suggest that chronic fatigue syndrome is associated with changes in the brain involving brain circuits that regulate motor activity and motivation.

Compared with healthy controls, patients with chronic fatigue syndrome had less activation of the basal ganglia, as measured by fMRI (functional magnetic resonance imaging). This reduction of basal ganglia activity was also linked with the severity of fatigue symptoms.

According to the Centers for Disease Control and Prevention, chronic fatigue syndrome is a debilitating and complex disorder characterized by intense fatigue that is not improved by bed rest and that may be worsened by exercise or mental stress.

The results are scheduled for publication in the journal PLOS One.

"We chose the basal ganglia because they are primary targets of inflammation in the brain," says lead author Andrew Miller, MD. "Results from a number of previous studies suggest that increased inflammation may be a contributing factor to fatigue in CFS patients, and may even be the cause in some patients."

Miller is William P. Timmie professor of psychiatry and behavioral sciences at Emory University School of Medicine. The study was a collaboration among researchers at Emory University School of Medicine, the CDC’s Chronic Viral Diseases Branch, and the University of Modena and Reggio Emilia in Italy. The study was funded by the CDC.

The basal ganglia are structures deep within the brain, thought to be responsible for control of movements and responses to rewards as well as cognitive functions. Several neurological disorders involve dysfunction of the basal ganglia, including Parkinson’s disease and Huntington’s disease, for example.

In previous published studies by Emory researchers, people taking interferon alpha as a treatment for hepatitis C, which can induce severe fatigue, also show reduced activity in the basal ganglia. Interferon alpha is a protein naturally produced by the body, as part of the inflammatory response to viral infection. Inflammation has also been linked to fatigue in other groups such as breast cancer survivors.

"A number of previous studies have suggested that responses to viruses may underlie some cases of CFS," Miller says. "Our data supports the idea that the body’s immune response to viruses could be associated with fatigue by affecting the brain through inflammation. We are continuing to study how inflammation affects the basal ganglia and what effects that has on other brain regions and brain function. These future studies could help inform new treatments."

Treatment implications might include the potential utility of medications to alter the body’s immune response by blocking inflammation, or providing drugs that enhance basal ganglia function, he says.

The researchers compared 18 patients diagnosed with chronic fatigue syndrome with 41 healthy volunteers. The 18 patients were recruited [not referred] based on an initial telephone survey followed by extensive clinical evaluations. The clinical evaluations, which came in two phases, were completed by hundreds of Georgia residents. People with major depression or who were taking antidepressants were excluded from the imaging study, although those with anxiety disorders were not.

For the brain imaging portion of the study, participants were told they’d win a dollar if they correctly guessed whether a preselected card was red or black. After they made a guess, the color of the card was revealed, and at that point researchers measured blood flow to the basal ganglia.

The key measurement was: how big is the difference in activity between a win or a loss? Participants’ scores on a survey gauging their levels of fatigue were tied to the difference in basal ganglia activity between winning and losing. Those with the most fatigue had the smallest changes, especially in the right caudate and the right globus pallidus, both parts of the basal ganglia.

Ongoing studies at Emory are further investigating the impact of inflammation on the basal ganglia, including studies using anti-inflammatory treatments to reduce fatigue and loss of motivation in patients with depression and other disorders with inflammation including cancer.

Your brain on speed: Walking doesn’t impair thinking and multitasking

When we’re strolling down memory lane, our brains recall just as much information while walking as while standing still—findings that contradict the popular science notion that walking hinders one’s ability to think.

University of Michigan researchers at the School of Kinesiology and the College of Engineering examined how well study participants performed a very complex spatial cognitive task while walking versus standing still.

"We’re saying that at least for this task, which is fairly complicated, walking and thinking does not compromise your thinking ability at all," said Julia Kline, a U-M doctoral candidate in biomedical engineering and first author on the study, which appears online in Frontiers in Human Neuroscience.

The finding surprised researchers, who expected to see decreased thinking performance with increased walking speed, Kline said. The 2011 best-selling book “Thinking Fast and Slow” suggests that because walking requires mental effort, walking may hinder our ability to think when compared to standing still.

"Past studies that have compared mental performance at a slow walking speed and standing have not found any differences, but our study is the first to show that the walking speed doesn’t matter," said Daniel Ferris, professor of kinesiology and biomedical engineering and senior author of the paper.

"Given the health benefits of walking, we should not discourage people from walking and thinking when they want."

Ferris offered one caveat: previous research has shown that walking performance can be impaired in the elderly when they dual-task during gait.

Ferris, Kline and Katherine Poggensee of U-M’s Human Neuromechanics Laboratory measured the ability of young, healthy participants to memorize numbers and their placement on a grid, and then enter those numbers correctly with a keypad while walking different speeds and standing still.

"Think of filling numbers one through nine on a tic-tac-toe grid and then remembering where they all are," Ferris said. "At every walking speed and standing still, participants entered about half the numbers correctly."

While speed didn’t change task performance, people took wider steps when performing the task than when they were only walking, which may be to compensate and stay balanced while concentrating, Kline said.

All participants showed increased activity in areas of the brain associated with spatial relationships and short-term memory during the cognitive task. In keeping with the U-M findings, a recent Stanford study suggested that walking fueled creativity.

In addition to good news for treadmill-desk users or people who like to think on the move, the study provides a useful scientific tool by demonstrating that it’s possible to collect accurate EEG data on moving subjects, Kline said.

This is important to researchers who study the brain and are concerned about getting accurate results when the subjects aren’t perfectly still. U-M researchers achieved their EEG results by applying different signal-processing techniques to eliminate the movement “noise” from the EEG signal.