Brain regions active when our minds wander may hold a key to understanding neurological disorders and even consciousness itself
• Neuroscientists have long thought that the brain’s circuits are turned off
when a person is at rest.
• Imaging experiments,however, have shown that there is a persistent level
of background activity.
• This default mode, as it is called, may be critical in
planning future actions.
• Miswiring of brain regions involved in the default mode may lead to disorders
ranging from Alzheimer’s to schizophrenia.
Imagine you are almost dozing in a lounge chair outside, with a magazine on your lap. Suddenly,a fly lands on your arm. You grab the magazine and swat at the insect. What was going on in your brain after the fly landed? And what was
going on just before?
Many neuroscientists have long assumed that much of the neural activity inside
your head when at rest matches your subdued,somnolent mood. In this view, the activity
in the resting brain represents nothing more than random noise, akin to the snowy pattern on the
television screen when a station is not broadcasting.
Then, when the fly alights on your forearm,he brain focuses on the conscious task of squash.
ing the bug. But recent analysis produced by neuro imaging technologies has revealed something
quite remarkable: a great deal of meaningful activity is occurring in the brain when a person is
sitting back and doing nothing at all.
It turns out that when your mind is at rest when you are daydreaming quietly in a chair,
say, asleep in a bed or anesthetized for surgery dispersed brain areas are chattering away to one
another. And the energy consumed by this ever active messaging, known as the brain’s default
mode, is about 20 times that used by the brain when it responds consciously to a pesky fly or
another outside stimulus. Indeed, most things we do consciously, be it sitting down to eat dinner
or making a speech, mark a departure from the baseline activity of the brain default mode.
Key to an understanding of the brain’s default mode has been the discovery of a heretofore unrecognized
brain system that has been dubbed the brain’s default mode network (DMN). The
exact role of the DMN in organizing neural activity is still under study, but it may orchestrate
the way the brain organizes memories and various systems that need preparation for future
events: the brain’s motor system has to be revved and ready when you feel the tickle of a fly on
The DMN may playa critical role in synchronizing all parts of the brain so that, like
racers in a track competition, they are all in the proper “set” mode when the starting gun goes
off. If the DMN does prepare the brain for conscious activity, investigations of its behavior may
provide clues to the nature of conscious experience.
Neuroscientists have reason to suspect,moreover, that disruptions to the DMN may underlie
simple mental errors as well as a range of complex brain disorders, from Alzheimer’s disease
Probing Dark Energy
The idea that the brain could be constantly busy is not new. An early proponent of that notion
was Hans Berger, inventor of the familiar electroencephalogram,which records electrical
activity in the brain with a set of wavy lines on a graph. In seminal papers on his findings, pub-
lished in 1929, Berger deduced from the ceaseless electrical oscillations detected by the device
that “we have to assume that the central nervous system is always, and not only during wakefulness,
in a state of considerable activity.”
But his ideas about how the brain functions were largely ignored, even after noninvasive imaging
methods became a fixture in neuroscience laboratories. First, in the late 1970s, came positron-
emission tomography (PET), which measures glucose metabolism, blood flow and oxygen
uptake as a proxy for the extent of neuronal activity, followed in 1992 by functional magnetic
resonance imaging (fMRI), which gauges brain oxygenation for the same purpose. These technologies
are more than capable of assaying brain activity, whether focused or not, but the design
of most studies inadvertently led to the impression that most brain areas stay pretty quiet until
called on to carry out some specific task.
Typically neuroscientists who run imaging experiments are trying to pinpoint the brain regions
that give rise to a given perception or behavior.
The best study designs for defining such regions simply compare brain activity during
two related conditions. If researchers wanted to see which brain areas are important during reading
words aloud (the “test” condition) as opposed to viewing the same words silently (the
“control” condition), for instance, they would look for differences in images of those two conditions.
And to see those differences clearly, they would essentially subtract the pixels in the passive-
reading images from those in the vocal image;
activity of neurons in the areas that remain “lit up” would be assumed to be the ones necessary
for reading aloud. Any of what is called intrinsic activity, the constant background activity,
would be left on the cutting-room floor. Representing data in this way makes it easy to
envision areas of the brain being “turned on,”during a given behavior, as if they were inactive
until needed by a particular task.
Over the years, however, our group, and others,became curious about what was happening
when someone was simply resting and just letting the mind wander. This interest arose from
a set of hints from various studies that suggested the extent of this behind-the-scenes activity.
One clue came from mere visual inspections of the images. The pictures showed that areas in
many regions of the brain were quite busy in both the test and the control conditions. In part
because of this shared background “noise,” differentiating a task from the control state by looking at the separate raw images is difficult if not impossible and can be achieved only by applying sophisticated computerized image analysis.
Further analyses indicated that performing a particular task increases the brain’s energy consumption
by less than 5 percent of the underlying baseline activity. A large fraction of the overall
activity-from 60 to 80 percent of all energy used by the brain-occurs in circuits unrelated
to any external event. With a nod to our astronomer colleagues, our group came to call this intrinsic
activity the brain’s dark energy, a reference to the unseen energy that also represents
the mass of most of the universe.
The question of the existence of neural dark energy also arose when observing just how little
information from the senses actually reaches the brain’s internal processing areas. Visual information,
for instance, degrades significantly as it passes from the eye to the visual cortex.
Of the virtually unlimited information available in the world around us, the equivalent of 10
billion bits per second arrives on the retina at the back of the eye. Because the optic nerve attached
to the retina has only a million output connections, just six million bits per second can
leave the retina, and only 10,000 bits per second make it to the visual cortex.
After further processing, visual information feeds into the brain regions responsible for forming
our conscious perception. Surprisingly, the amount of information constituting that conscious
perception is less than 100 bits per second.
Such a thin stream of data probably could not produce a perception if that were all the
brain took into account; the intrinsic activity must playa role.
Yet another indication of the brain’s intrinsic processing power comes from counting the number
of synapses, the contact points between neurons.
In the visual cortex, the number of synapses devoted to incoming visual information is less
than 10 percent of those present. Thus, the vast majority must represent internal connections
among neurons in that brain region.
Discovering the Default Mode
These hints of the brain’s inner life were well established. But some understanding was needed
of the physiology of the brain’s intrinsic activity and how it might influence perception and
behavior. Happily, a chance and puzzling observation made during PET studies, later corroborated
with fMRI, set us on a path to discovering the DMN.
In the mid-1990s we noticed quite by accident that, surprisingly, certain brain regions experienced
a decreased level of activity from the baseline resting state when subjects carried out some
task. These areas-in particular, a section of the medial parietal cortex (a region near the middle
of the brain involved with remembering personal events in one’s life, among other things)-registered
this drop when other areas were engaged in carrying out a defined task such as reading
aloud. Befuddled, we labeled the area showing the most depression MMPA, for “medial mystery
A series of PET experiments then confirmed that the brain is far from idling when not engaged
in a conscious activity. In fact, the MMP A as well as most other areas remains constantly
active until the brain focuses on some novel task,at which time some areas of intrinsic activity decrease.
At first, our studies met with some skepticism.
In 1998 we even had a paper on such findings rejected because one referee suggested that
the reported decrease in activity was an error in our data. The circuits, the reviewer asserted,
were actually being switched on at rest and switched off during the task. Other researchers,
however, reproduced our results for both the medial parietal cortex-and the medial prefrontal
cortex (involved with imagining what other people are thinking as well as aspects of our
emotional state). Both areas are now considered major hubs of the DMN.
The discovery of the DMN provided us with a new way of considering the brain’s intrinsic activity.
Until these publications, neurophysiologists had never thought of these regions as a system
in the way we think of the visual or motor system-as a set of discrete areas that communicate
with one another to get a job done. The idea that the brain might exhibit such internal activity
across multiple regions while at rest had escaped the neuroimaging establishment. Did the
DMN alone exhibit this property, or did it exist more generally throughout the brain? A surprising
finding in the way we understand and analyze fMRI provided the opening we needed to
answer such questions.
The fMRI signal is usually referred to as the blood oxygen level-dependent, or BOLD, signal
because the imaging method relies on changes in the level of oxygen in the human brain induced
by alterations in blood flow. The BOLD signal from any area of the brain, when observed in a
state of quiet repose, fluctuates slowly with cycles occurring roughly every 10 seconds. Fluctuations this slow were considered to be mere noise,and so the data detected by the scanner were simply eliminated to better resolve the brain activity
for the particular task being imaged.
The wisdom of discarding the low-frequency signals came into question in 1995, when Bharat
Biswal and his colleagues at the Medical College of Wisconsin observed that even while a subject
remained motionless, the “noise” in the area of the brain that controls right-hand movement fluctuated
in unison with similar activity in the area on the opposite side of the brain associated with
left-hand movement. In the early 2000s Michael Greicius and his co-workers at Stanford University
found the same synchronized fluctuations in the DMN in a resting subject.
Because of the rapidly accelerating interest in the DMN’s role in brain function, the finding by
the Greicius group stimulated a flurry of activity in laboratories worldwide, including ours, in
which all of the noise, the intrinsic activity of the major brain systems, was mapped. These remarkable
patterns of activity appeared even under general anesthesia and during light sleep, a
suggestion that they were a fundamental facet of brain functioning and not merely noise.
It became clear from this work that the DMN is responsible for only a part, albeit a critical
part, of the overall intrinsic activity-and the notion of a default mode of brain function extends
to all brain systems. In our lab, discovery of a generalized default mode came from first examining
research on brain electrical activity known as slow cortical potentials (SCPs), in which groups of neurons fire every 10 seconds or
so. Our research determined that the spontaneous fluctuations observed in the BOLD images
were identical to SCPs:the same activity detected with different sensing methods.
We then went on to examine the purpose of SCPs as they relate to other neural electrical signals.
As Berger first showed and countless others have since confirmed, brain signaling consists
of a broad spectrum of frequencies, ranging from the low-frequency SCPs through activity in
excess of 100 cycles per second. One of the great challenges in neuroscience is to understand how
the different frequency signals interact.
It turns out that SCPs have an influential role.
Both our own work and that of others demonstrate that electrical activity at frequencies above
that of the SCPs synchronizes with the oscillations,or phases, of the SCPs. As observed recently
by Matias Paiva and his colleagues at the University of Helsinki, the rising phase of an
SCP produces an increase in the activity of signals at other frequencies.
The symphony orchestra provides an apt metaphor,with its integrated tapestry of sound arising
from multiple instruments playing to the same rhythm. The SCPs are the equivalent of the
conductor’s baton. Instead of keeping time for a collection of musical instruments, these signals
coordinate access that each brain system requires to the vast storehouse of memories and
other information needed for survival in a complex,ever changing world. The SCPs ensure that
the right computations occur in a coordinated fashion at exactly the correct moment.
But the brain is more complex than a symphony orchestra. Each specialized brain system one
that controls visual activity, another that actuates muscles-exhibits its own pattern of
SCPs. Chaos is averted because all systems are not created equal. Electrical signaling from some
brain areas takes precedence over others. At the top of this hierarchy resides the DMN, which
acts as an tiber-conductor to ensure that the cacophony of competing signals from one system
do not interfere with those from another. This organizational structure is not surprising, because
the brain is not a free-for-all among independent systems but a federation of interdependent
At the same time, this intricate internal activity must sometimes give way to the demands of
the outside world. To make this accommodation,SCPs in the DMN diminish when vigilance
is required because of novel or unexpected sensory inputs: you suddenly realize that you promised
to pick up a carton of milk on the drive home from work. The internal SCP messaging
revives once the need for focused attention dwindles.
The brain continuously wrestles with the need to balance planned responses and the immediate
needs of the moment.
Consciousness and Disease
The ups and downs of the DMN may provide insight into some of the brain’s deepest mysteries.
It has already furnished scientists with fascinating insights into the nature of attention, a
fundamental component of conscious activity.
In 2008 a multinational team of researchers reported that by watching the DMN, they could
tell up to 30 seconds before a subject in a scanner was about to commit an error in a computer
test. A mistake would occur if, at that time, the default network took over and activity in areas
involved with focused concentration abated.
And in years to come, the brain’s dark energy may provide clues to the nature of consciousness.
As most neuroscientists acknowledge, our conscious interactions with the world are just a
small part of the brain’s activity. What goes on below the level of awareness-the brain’s dark
energy, for one-is critical in providing the context for what we experience in the small window
of conscious awareness.
Beyond offering a glimpse of the behind-the scenes events that underlie everyday experience,
study of the brain’s dark energy may provide new leads for understanding major neurological
maladies. Mental gymnastics or intricate movements will not be required to complete the exercise.
A subject need only remain still within the scanner while the DMN and other hubs of dark
energy whir silently through their paces.
Already this type of research has shed new light on disease. Brain-imaging studies have
found altered connections among brains cells in the DMN regions of patients with Alzheimer’s,
depression, autism and even schizophrenia. Alzheimer’s,in fact, may one day be characterized
as a disease of the_DMN. A projection of the brain regions affected by Alzheimer’s fits neatly
over a map of the areas that make up the DMN.
Such patterns may not only serve as biological markers for diagnosis but may also provide deeper
insights into causes of the disease and treatment strategies.
Looking ahead, investigators must now try to glean how coordinated activity among and within
brain systems operates at the level of the individual cells and how the DMN causes chemical
and electrical signals to be transmitted through brain circuits. New theories will then be needed
to integrate data on cells, circuits and entire neural systems to produce a broader picture of how
the brain’s default mode of function serves as a master organizer of its dark energy. Over time
neural dark energy may ultimately be revealed as the very essence of what makes us tick .•
by Marcus E. Raichle
is professor of radiology and neurology at the Washington University School of
Medicine in St. louis. For many years Raichle has led a team that investigates human brain function using positron-emission tomography and functional magnetic resonance imaging. He was elected to the Institute of Medicine in 1992
and to the National Academy of Sciences in 1996,
MORE TO EXPLORE
Spontaneous Fluctuations in Brain Activity Observed with Functional
Magnetic Resonance Imaging.
Michael D. Fox and Marcus E. Raichle in Nature Reviews Neuroscience, Vol.
8, pages 700-711; September 2007.
Disease and the Brain’s Dark Energy.
Dongyang Zhang and Marcus E. Raichle in Nature Reviews Neurology,
Vol. 6, pages 15-18; January 2010.
Two Views of Brain Function.
Marcus E. Raichle in Trends in Cognitive Science (in press).
SOURCE SCIENTFIC AMERICAN 2010