What's the buzz: Neural Inertia

Getting your wisdom teeth removed? Most people wouldn't think twice about requesting general anaesthesia; in fact it is estimated that 25 million patients per year in the U.S undergo surgeries using general anaesthesia. However, we're still not sure how exactly anaesthesia interacts with the central nervous system to produce its effects. A group of researchers at the University of Pennsylvania School of Medicine, led by Dr. Max Kelz, MD, PhD, assistant professor of Anesthesiology and Critical Care recently conducted a study to try to understand how the brain comes out of its anaesthetized state and back to consciousness. 

The prevailing theory about how anaesthesia works is that going under- or the induction of anaesthesia- is commonly attributed to drug-induced modifications of neuronal function, while coming back up- or emergence from anaesthesia- is thought to be a passive process, as the drug is eliminated from its sites of action in the central nervous system. If this is the case, then it follows that induction and emergence are the same process, just in different directions. Consequently, one would expect that the concentrations of the anaesthetic in the central nervous system would be the same during induction and emergence. However, using dose response data from animal models, the group of researchers were able to demonstrate that induction and emergence are actually not identical; in fact the concentration of the anaesthetic is lower at emergence than at induction. More interestingly, the researchers observed  their animal subjects exhibited resistance when returning to the wakeful state during emergence. They explain this observation by introducing the concept of "neural inertia", which they describe as the tendency of the central nervous system to resist behavioral state transitions between conscious and unconscious states. 

Intuitively, neural inertia seems useful in terms of keeping the patient unconscious as the body recovers from a surgery. I was terrified to learn that 1 in 1000 cases of patients undergoing surgery under general anaesthesia report experiencing wakefulness during the procedure. At the other extreme however, patients with neurological disorders like narcolepsy can take hours to emerge from anaesthesia-induced unconsciousness. Thus, elucidating the actual circuits underlying neural inertia will give anaesthesiologists better control of the effects of anaesthesia on patient. 

The concept of neural inertia is also fascinating in terms of understanding how people wake up from comas. A recent report in the New York Times Magazine described a significant number of cases where doctors were able to wake up coma patients after years of unresponsiveness (find the article here). The first of such incidents happened in 1999 in South Africa. The patient, who had been in a coma for 3 years, was given a drug called zolpidem to improve sleep quality. Miraculously, just within a few hours of being given the drug, the patient began to stir and when he woke, he immediately recognized his mother, who was waiting eagerly by his bedside. Over the next few hours and days, his speech, movement and cognition all slowly revived. Since this case, there has been a growing number of successful 'awakenings' using zolpidem. No one really understands how this drug is working, but Kelz says that "this line of research may one day help us to develop novel anesthetic drugs and targeted therapies for patients who have different forms of sleep disorders or who have the potential to awaken from coma but remain stuck in comatose states for months or years."