Safely Switching Consciousness Off and On Again

We take it for granted that any kind of surgical procedure, whether extracting a wisdom tooth or replacing a heart valve, will be painless and won't leave any bad memories. Every year tens of millions of patients worldwide remember being prepared for an operation?then nothing, until they wake up in the recovery room. This is the magic of general anesthesia, which safely knocks out that most precious of life's possessions, conscious experience, then reliably restores it without any lasting consequences. Of course, it was not always thus. Until the discovery of nitrous oxide as an anesthetic in the mid-19th century, surgery was an extreme and dangerous intervention of last resort whose effects could, at best, be blunted by opium or alcohol.

Today anesthesiologists can choose from an astonishing variety of chemicals to separately and independently eliminate pain (analgesia), memory (amnesia), mobility, and responsiveness to the cutting, scraping, drilling or cauterizing of the surgical procedure, and, most important from the point of view of the patient, awareness (loss of consciousness). Two types of anesthetics exist: intravenous agents that are injected into the bloodstream for the rapid induction and maintenance of anesthesia, such as barbiturates, propofol and ketamine, and inhalation agents, such as laughing gas (nitrous oxide) or vapors of volatile liquids, including isoflurane and sevoflurane.

Much is known about the molecular action of these substances. With the singular exception of the dissociative ketamine (abused at low doses as a street drug known as vitamin K or special K and not further discussed here), anesthetics strengthen neuronal inhibition either by activating inhibitory chemical synapses, which constrain activity in the neurons they are connected to, or by binding to membrane proteins that keep the electrical activity of neurons?and therefore their ability to transmit information and command?in check. Their net effect is to reduce overall brain activity. Every functional brain-imaging study carried out to date proves this point. For anesthesiologists, the technique of choice is positron emission tomography (PET), in which a small amount of radioactive tracer is injected into the bloodstream of the subject. Brain regions that are more or less active than neighboring areas consume metabolic resources in the same ratio. This metabolic activity can be reliably measured in a PET device, albeit with a crude temporal (on the order of tens of seconds) and spatial (on the order of the size of a pea) resolution.

PET imaging demonstrates that essentially all anesthetics decrease global cerebral metabolism in a dose-dependent manner. The more of the anesthetic dispensed, the bigger the activity reduction in regions of the brain stem responsible for promoting wakefulness and in the neocortex and the closely allied thalamus underneath it. The neocortex is the most recently evolved part of the cerebral cortex, the folded layers of neurons that constitute the proverbial gray matter. It occupies most of the forebrain and is a unique hallmark of mammals. The thalamus is a quail egg?size structure in the middle of the brain that regulates all input into the neocortex and receives massive feedback from it.

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