Investigators at Massachusetts General
Hospital (MGH) and Massachusetts Institute of Technology (MIT) have
identified for the first time a pattern of brain activity that
appears to signal exactly when patients lose consciousness under
general anesthesia. Although their study only involved use of one
anesthetic drug, propofol, the researchers believe that their
findings will apply to other forms of general anesthesia and could
lead to better ways of monitoring anesthetized patients.
"How anesthetics produce unconsciousness
is a major scientific mystery, so this finding is very important
because it suggests a specific mechanism for how propofol, one of
the most widely used anesthetic drugs, works," says Patrick Purdon,
PhD, senior author of the report appearing in PNAS Plus. "The
pattern that we found marks a new brain state in which neurons in
different areas become inactivated at different times, impairing
communication between different brain regions." Purdon is an
Instructor in Anesthesia in the MGH Department of Anesthesia,
Critical Care and Pain Medicine at Harvard Medical School.
The current hypothesis on the nature of
unconsciousness is that it represents a loss of communication
functions throughout the brain. Animal studies of the effects of
general anesthesia cannot accurately determine when consciousness is
lost.
The current study measured the activity of both single neurons and
neuronal networks in three patients who previously had electrodes
implanted into their brain to help diagnose epilepsy. At the outset
of surgical procedures to remove the electrodes, patients were asked
to press a button whenever they heard a tone, which was generated
every four seconds.
When a patient failed to respond to two tones in a row, the
five-second period defined by those tones was identified as the
point when consciousness was lost.
Measurement of the activity of single
neurons showed a drop in overall activity but not until up to 30
seconds after consciousness had been lost. But the time when
consciousness was lost did coincide with a significant change in the
overall structure of brain activity.
While electrical activity in the conscious brain appears to be
disorganized with no apparent regular patterns, at the point when
study participants lost consciousness, their brain activity began to
show regular oscillations between states of activation and
deactivation.
"These deactivated or silent periods of
brain activity occur at different times in different brain regions,
so communication between regions is interrupted" says Laura Lewis,
co-lead author of the report. "It's as if one brain region is in
Boston and the other is in Singapore – they can't make phone calls
to each other because one is asleep when the other is awake."
While this slow oscillation pattern has been previously observed in
humans who are asleep or under ansethesia, this is the first study
to record neuronal activity during the transition to
unconsciousness, so it is the first to match the onset of this
pattern with the loss of consciousness, she adds. Lewis is a
graduate student in the MIT Department of Brain and Cognitive
Sciences, working with Purdon and with Emery Brown, MD, PhD, the
Warren M. Zapol Professor of Anaesthesia at MGH and Harvard Medical
School and professor in the MIT Department of Brain and Cognitive
Sciences.
Purdon explains, "Previously, the brain
wave patterns and brain physiology indicating unconsciousness were
not clear, so anesthesiologists did not have a principled way to
monitor the brain during general anesthesia. Without this knowledge,
existing anesthetic brain monitors are highly inaccurate. Now that
we have identified a specific physiological marker associated with
unconsciousness, we can develop systems that accurately indicate
patients' level of consciousness and help anesthesiologists
determine the best drug dosage to use. Having that information could
both prevent the rare instances when patients regain consciousness
during surgery and avoid anesthesia overdoses."
Lewis's co-lead author is Veronica
Weiner, also an MIT graduate student working with Purdon and Brown.
In addition to Brown, the other co-authors on this paper are Emad
Eskandar, MD, MGH Neurosurgery; Sydney Cash, MD, PhD, and Leigh
Hochberg, MD, PhD, MGH Neurology; Eran Mukamel, PhD, University of
California, San Diego; and Jacob Donoghue, Harvard-MIT Division of
Health Sciences and Technology; Joseph Madsen, MD, Boston Children's
Hospital; and William Anderson, MD, Brigham and Women's Hospital.
The study was supported in part by an NIH Director’s New Innovator
Award, an NIH Director’s Pioneer Award, a fellowship from the
Canadian Institutes of Health Research, and a grant from the
National Institute of Neurological Disorders and Stroke.
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