between general anesthesia and coma
in the Dec. 30 New England Journal of
Schiff, a neurologist who helps brain-injured patients recover consciousness,
is poring over the EEG patterns seen in
anesthesia cases looking for common
links to those found in patients recovering from coma. Such commonalities may
point to a “signature” for awareness that
could be detected with EEG.
While he has yet to find such a marker,
Schiff has identified brain behaviors that
are similar in the two groups. As drugs
administered to patients undergoing
general anesthesia begin to take effect,
activity between neurons may actually
increase for a short period. (The same
effect can explain the excitable feeling
you get after a single glass of wine.) As
more medication is given, patients give
in to sedation.
Schiff sees similar patterns of temporary excitability in some brain-injured
patients. Those who are “minimally
conscious” — meaning they show only
occasional awareness of themselves
and their surroundings — can respond to
low doses of sedative drugs by waking up.
Here, the anesthetic drugs “kick-start”
the brain, helping it to turn itself back on.
“Patients might start to speak, or suddenly gain the ability to stand or walk or
chew or swallow,” Schiff says.
Over time, with repeated doses, the
mere act of being alert can help the
underactive brain make gains toward
recovery, Schiff says. In the January
2010 Trends in Neurosciences, he suggests
that a switching mechanism explaining
this excitatory effect may rely on links
between the thalamus, the cortex and t wo
brain regions — the globus pallidus and
the striatum — that help regulate activity
between the cortex and thalamus.
Back in the operating room
While Schiff looks for a signature of
awareness for patients in coma, other
labs are looking for markers that might
help anesthesiologists track surgery
By correlating the squiggly EEG signals of anesthetized brains to images
Mathematician leonhard euler proved in the
18th century that there was no journey through
königsberg, Prussia, that would take a walker
across each of the city’s bridges once and
only once. By simplifying the city’s layout —four
land areas connected via seven bridges (as
shown) —into a series of nodes connected
via paths, euler established the foundations
for modern network theory. Today researchers
study the brain by similarly reducing it to an architecture of nodes and paths.
neurons or groups of neurons are königsberg’s landmasses, and connections
between those neurons are the city’s bridges. recent work suggests anesthe-
sia can disrupt the brain by interfering with the system in two ways —changing
the layout of the nodes and altering the efficiency of the pathways.
showing changes in blood flow in specific
brain regions, Purdon and Brown hope
to identify patterns that could be used
in the operating room.
“Once you know that connection, you
can then identify specific EEG patterns
and make inferences about what different brain systems are doing when you
see that pattern,” Purdon says.
Mashour and University of Michigan physicist UnCheol Lee are taking
advantage of graph theory, a mathematical approach used to study networks,
to link the EEG patterns seen in anesthetized patients to knowledge about
the underlying brain networks. Ideally,
such a system could be set up to track
the moment-to-moment changes seen
in patients during surgery.
The team has already found that clinicians may get more information on
patient awareness by gluing the EEG
monitors farther back on the head, rather
than on the forehead. In the April
Anesthesiology, Mashour’s team showed that
networks in the parietal region display
greater levels of disruption during anesthesia than those in the front of the brain.
“The parietal lobe may be an important
hub or point of convergence for information processing in the brain,” he says.
Such studies may allow anesthesiologists to fine-tune their procedures during
surgery, knowing exactly where to steer
the brain to balance drugs’ main effects
against a host of potential side effects.
“Certain brain areas, if activated, can
cause nausea and vomiting. Others can
adversely affect your respiratory sys-
tem,” Brown says. “If I can have a drug
avoid going there, I’d love to do that.”
Michael Alkire, who studies the neural
biology of anesthesia at the University of
California, Irvine, says that by knowing
how anesthetics affect different brain
areas, researchers may be able to develop
new therapies or find ways to customize
treatments. He foresees a day when a
patient’s genes are analyzed before sur-
gery to determine sensitivity to drugs or
potential to suffer certain side effects. “If
you know that a patient is very anxious,
and maybe that anxiety is related to the
amygdala function in the brain, you might
want to use a different agent or anesthetic
for that case,” he says.
Understanding how anesthetics work
in the brain could also lead to entirely
new ways of creating anesthetic states.
Future anesthesia may rely on Star Trek–
like devices with energy fields capable of
disrupting key circuits, for example.
In such a scenario, patients wouldn’t
need to take any type of medication at
all, meaning side effects would be minimal, Alkire says. “But first,” he says, “we
have to figure out the anesthetics.” s
s e.n. Brown et al. “General anesthesia,
sleep, and coma.” New England Journal
of Medicine. December 30, 2010.