Nav: Home

New study uncovers vivid patterns of neural activity in the resting mouse brain

December 12, 2016

NEW YORK -- Columbia scientists have traced the origins of mysterious signals in the brain that have captivated the functional magnetic resonance imaging (fMRI) community for the last decade. Using a recently developed imaging technique in mice, the Columbia team revealed synchronized, network-like neural activity coursing around the brain, even when the mouse was 'at rest.' The researchers further demonstrated that this neural activity could predict slowly changing patterns of blood flow in the brain, connecting their findings to the enigmatic signals detected in so-called 'resting-state' fMRI. Taken together, this research provides a tantalizing new view of brain-wide neural activity that could lead to a better understanding of how distinct brain regions interact with each other, and how these connections -- and the way they change with disease -- can be studied in the human brain using fMRI.

The researchers published their findings today in the Proceedings of the National Academy of Sciences.

"Our results should reassure scientists in the resting-state fMRI community who have long believed that they were detecting patterns of neural activity," said Elizabeth Hillman, PhD, principal investigator at Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute, associate professor of biomedical engineering and radiology at Columbia's Fu Foundation School of Engineering and Applied Science and the paper's senior author. "At the same time, our results may come as a surprise for those who have remained skeptical that -- first of all -- this type of underlying neural activity even exists, but also that such activity can be accurately represented by fMRI signals."

Within a few years of the first demonstration of fMRI, scientists noticed that, even without an external stimulus, fluctuating signals could be detected in the brains of humans. Despite appearing to be random, analysis of these signals identified regions located on opposite sides of the brain that were synchronously singing the same random song. This synchrony was taken as evidence of interconnected functional networks throughout the brain. Moreover, properties of these networks were found to distinguish subtle signs of disease that are otherwise undetectable. However, these resting-state fMRI signals have proved challenging to interpret, in large part because fMRI works not by tracking the activity of neurons in the brain, but by tracking changes in blood flow as a proxy for that activity. As a result, it has been difficult to reconcile this high-level view of the brain with how scientists think of neurons interacting with each other individually.

To address this, Dr. Hillman and her team employed a wide-field, optical imaging method that allowed them to visualize both changes in blood flow and neural activity simultaneously across the surface of the mouse brain. Much to their surprise, they saw patterns of neural activity that flickered and swirled around the brain in elegant symmetric patterns.

"First, we only looked at small areas of the brain, seeing what seemed to be flashes and random activity,"said Dr. Hillman. "But when we zoomed out to view both sides of the brain at once, we saw that this activity wasn't random -- it was symmetrical, organized and composed of repeating patterns. We immediately thought of resting-state fMRI."

They then compared these patterns to changes in blood flow. And while these blood-flow changes at first appeared sluggish compared to the neural activity, further analysis revealed that the fluctuations did in fact represent a cumulative effect; each small neural signal was triggering a small, slow increase in blood flow.

"In essence, these findings tell us that resting-state fMRI is probably picking up a representation of these underlying neural signals," said Ying Ma, a doctoral candidate at Columbia and the paper's first author. "What is great about our data is that it lets us uncover how these signals get blurred and distorted in fMRI, and whether there are any additional changes in blood flow -- or cellular activity -- that are also occurring but that aren't accounted for by normal neural activity. We hope that this will help to improve how fMRI data is analyzed and interpreted."

The team has already begun working with fMRI researchers to help in the development of more robust methods of drawing information out of resting-state fMRI scans in the healthy human brain, and to explore how and why networks appear to change in disease states.

Moving forward, Dr. Hillman and her team are also expanding their studies of brain-wide neural activity to include more complex methods that, she hopes, will provide fundamental insights into how and why this resting-state neural activity is generated.

"Our high-speed imaging methods are giving us an entirely new view of what the brain is doing, one that we hadn't seen before," said Dr. Hillman. "We are eager to understand how this brain-wide activity fits with classic descriptions of the brain's underlying circuitry.

"Moreover," she added, "we can follow the lead of resting-state fMRI and understand why these activity patterns are affected by disease, this could be the first step to developing new treatments."
-end-
This paper is titled: "Resting state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons." Additional contributors include Mohammad Shaik, Mariel Kozberg, PhD, Sharon Kim, Jacob Portes and Dmitry Timmerman.

This research was supported by the National Institutes of Health (1R01NS063226, 1R01NS076628), the National Science Foundation (CAREER 0954796), the Human Frontier Science Foundation and the Kavli Foundation. The authors report no financial or other conflicts of interest.

Columbia University's Mortimer B. Zuckerman Mind Brain Behavior Institute brings together an extraordinary group of world-class scientists and scholars to pursue the most urgent and exciting challenge of our time: understanding the brain and mind. A deeper understanding of the brain promises to transform human health and society. From effective treatments for disorders like Alzheimer's, Parkinson's, depression and autism to advances in fields as fundamental as computer science, economics, law, the arts and social policy, the potential for humanity is staggering. To learn more, visit: zuckermaninstitute.columbia.edu.

Columbia University's Fu Foundation School of Engineering and Applied Science, founded in 1864, offers programs in nine departments to both undergraduate and graduate students. With facilities specifically designed and equipped to meet the laboratory and research needs of faculty and students, Columbia Engineering is home to NSF-NIH funded centers in genomic science, molecular nanostructures, materials science, and energy, as well as one of the world's leading programs in financial engineering. These interdisciplinary centers are leading the way in their respective fields while individual groups of engineers and scientists collaborate to solve some of modern society's more difficult challenges. engineering.columbia.edu.

The Zuckerman Institute at Columbia University

Related Blood Flow Articles:

Blood flow monitor could save lives
A tiny fibre-optic sensor has the potential to save lives in open heart surgery, and even during surgery on pre-term babies.
Changes in blood flow tell heart cells to regenerate
Altered blood flow resulting from heart injury switches on a communication cascade that reprograms heart cells and leads to heart regeneration in zebrafish.
Blood flow command center discovered in the brain
An international team of researchers has discovered a group of cells in the brain that may function as a 'master-controller' for the cardiovascular system, orchestrating the control of blood flow to different parts of the body.
Researchers closer to new Alzheimer's therapy with brain blood flow discovery
By discovering the culprit behind decreased blood flow in the brain of people with Alzheimer's, biomedical engineers at Cornell University have made possible promising new therapies for the disease.
In vitro grafts increase blood flow in infarcted rat hearts
Advances in stem cell research offer hope for treatments that could help patients regrow heart muscle tissue after heart attacks, a key to patients achieving more complete recoveries.
Balloon-guided catheters provide better blood flow following stroke interventions
Patients who have experienced a stroke as a result of blockages of the arteries in the brain have better outcomes with the use of balloon-guided catheter surgery as compared to having a conventional guided catheter procedure.
Scientists developed new contactless method of measuring blood flow in hands
Russian researchers proposed a new contactless method for measuring blood flow in the upper limbs.
Researchers investigate correlation between blood flow and body position
For the first time ever, an international research group detected alterations in capillary blood flow around the face caused by body position change.
Restoring blood flow may be best option to save your life and limb
Amputation for severe blockages in the lower limbs has a lower survival rate than other treatment options that restore blood flow.
Blood flow in the heart revealed in a flash
Researchers at Linköping University have for the first time been able to use information from computer tomography images to simulate the heart function of an individual patient.
More Blood Flow News and Blood Flow Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#542 Climate Doomsday
Have you heard? Climate change. We did it. And it's bad. It's going to be worse. We are already suffering the effects of it in many ways. How should we TALK about the dangers we are facing, though? Should we get people good and scared? Or give them hope? Or both? Host Bethany Brookshire talks with David Wallace-Wells and Sheril Kirschenbaum to find out. This episode is hosted by Bethany Brookshire, science writer from Science News. Related links: Why Climate Disasters Might Not Boost Public Engagement on Climate Change on The New York Times by Andrew Revkin The other kind...
Now Playing: Radiolab

Breaking Bongo
Deep fake videos have the potential to make it impossible to sort fact from fiction. And some have argued that this blackhole of doubt will eventually send truth itself into a death spiral. But a series of recent events in the small African nation of Gabon suggest it's already happening.  Today, we follow a ragtag group of freedom fighters as they troll Gabon's president - Ali Bongo - from afar. Using tweets, videos and the uncertainty they can carry, these insurgents test the limits of using truth to create political change and, confusingly, force us to ask: Can fake news be used for good? This episode was reported and produced by Simon Adler. Support Radiolab today at Radiolab.org/donate.