2-Minute Neuroscience: Vagus Nerve (Cranial Nerve X)

The vagus nerve is a long cranial nerve that stretches from the brainstem to the colon and is involved in an extensive list of functions. In this video, I summarize the main functions of the vagus nerve, talk about the nuclei associated with the nerve, and discuss some of the symptoms that can appear when the vagus nerve is damaged.

The disturbing story of the first use of electroconvulsive therapy

Image credit: University of Liverpool Faculty of Health & Life Sciences

If you were able to glance inside a certain room on the first floor of the Clinic for Mental and Nervous Diseases in Rome on the morning of April 11th, 1938, it might have looked like a small group of physicians was about to commit a murder.

The doctors were congregated around a bed in a large, isolated laboratory, and on the bed lay a middle-aged man with a surgically-shaved head. The nervousness of the physicians would have been difficult to ignore. They were abnormally quiet—the type of uncomfortable silence that can only be created by extreme tension. Despite the cool temperature of the room, their foreheads were beaded with perspiration. One of them repeatedly walked out the door to look up and down the hallway, just to make sure no one was around.

They had good reason to be uneasy. They were preparing to send an amount of electricity that far exceeded what was considered safe at the time coursing through their patient’s brain. Indeed, at least some in the room must have feared they were about to be complicit in an execution.

On top of that, the patient hadn’t quite consented to be their guinea pig. The police had brought him into the clinic after they had found him wandering the streets of Rome in a delusional state. He was unable to provide simple information about where he was from or whether he had any family; in fact his “speech” was mostly gibberish. The police thought he was just another schizophrenic vagrant, and they probably believed they were being compassionate by bringing him somewhere he could get treatment.

But little did they know that a handful of physicians at the clinic had been waiting for a patient whose life was perhaps a bit more expendable than the rest. This man who had descended into a seemingly irreversible state of mental discord, who had no family, friends, or home to return to—he was deemed the perfect type to test an experimental, potentially life-threatening treatment on. He would be the first human to undergo what was originally called electroshock therapy.


A dangerous idea

As reckless as this might all sound, the scientists who spearheaded the experiment weren’t doing it on a whim. They had been conducting similar experiments with animals for years before building up the confidence to try the procedure with humans.

The idea had started with the director of the experiment, Ugo Cerletti. Cerletti was a respected Italian neurologist who was passionate about finding treatments for psychiatric disorders. At the time (the 1930s), mental illness was often considered irreversible, and successful therapies were difficult to come by.

Cerletti had not shied away from extreme treatments in the past. In 1937, he had begun using a stimulant drug called Cardiazol (aka Metrazol) to treat schizophrenia. When given in high doses, Cardiazol would induce seizures. This sounds like an undesirable—and potentially horrifying—side effect, but to schizophrenia researchers, it was exactly what they wanted to happen. For the thinking at the time was that there was something about the convulsions of a seizure that could counteract the effects of disorders like schizophrenia on the brain.

The use of Cardiazol to cause seizures quickly became popular, due mostly to the fact that physicians didn’t have many other options when it came to schizophrenia. But Cardiazol had a few “unpleasant” side effects. For some patients, the drug caused apprehension bordering on terror from the time it was injected until the time the seizure began. This intense dread was not simply a fear of the oncoming seizure, but seemed instead to be a psychological side effect of the medication. The behavior of patients after the seizure could be problematic as well. Some became unpredictable, irrational, and—in rare cases—even suicidal.

These factors, combined with a paucity of evidence to suggest that Cardiazol actually was having an effect that was specific to schizophrenia (it actually seemed that Cardiazol could jolt almost any patient out of a stuporous state—whether they suffered from schizophrenia, depression, mania or something else), caused Cerletti to tenaciously seek other treatments. But as he continued to test alternative therapies, he couldn’t stop thinking about electricity.

After all, everyone knew that large doses of electricity could cause convulsions. Maybe, then, electricity could also be used to induce the type of convulsions that were thought to have potential in treating schizophrenia.

When Cerletti began testing this idea on dogs, however, he realized how dangerous the approach might be: about half of the animals subjected to electrical shock died of cardiac arrest. What’s more, Cerletti’s group was using stimulation of around 125 volts to cause convulsions in dogs—and death in humans had been reported after as low as 40 volts.

Every week for almost a year, the local dog catcher dropped off an unfortunate collection of dogs at Cerletti’s lab, and the researchers there immediately began experimenting on them. They soon learned that the original placement of the electrodes (one in the mouth and one in the anus) was a large reason dogs were dying after electrical stimulation. This configuration caused the current to cross the heart, which (not surprisingly) sometimes caused cardiac arrest.

When the electrodes were moved to the head, pulses of electricity produced convulsions—but rarely death. Cerletti’s group replicated their experiments with pigs, and similarly found that electrical current applied for short periods to the head convulsed, but didn’t kill. After many tests on canine and porcine subjects, Cerletti was confident that electrical stimulation to the head was not a fatal procedure. It was time for the ultimate test: a human.


The birth of “electroshock”

Which brings us back to the morning of April 11th, 1938. Cerletti was surrounded by a small group of other physicians, a nurse, and an assistant. They had sequestered themselves in a laboratory that had a bed in it, originally installed so the director of the laboratory could rest between experiments.

But now on the bed was a homeless schizophrenic patient with a circular metal apparatus placed on his head. Wires ran from the apparatus to a device on a table nearby.

Lucio Bini—a psychiatrist who had helped to develop the electrical device being used—was watching for Cerletti’s signal to turn the machine on. Everyone else stared intently at the patient, eagerly but apprehensively waiting for something to happen.

Cerletti gave a nod, and Bini flipped the switch to send 80 volts of current surging across the patient’s temples. A flat, mechanical hum emanated from the device, and the muscles throughout the patient’s body contracted spasmodically one time, lifting him up slightly from the bed. Then, his body just as suddenly fell back down—limp, but alive. Upon questioning, the patient didn’t seem to have any recollection of what had just happened.

That was the first proof a human could tolerate this type of controlled electrical stimulation to the head. But Cerletti wasn’t satisfied. He wanted to see convulsions reminiscent of a seizure, not just one spasm. He ordered another shock be given—this time at 90 volts.

The patient’s body convulsed once again, but this spasm lasted a bit longer. The patient stopped breathing—his diaphragm remained contracted—and he began to turn pale. The asphyxia continued for a few seemingly interminable seconds, but then the patient suddenly let out a deep breath. He lay silent for about a minute, then abruptly sat up in bed and began to sing a bawdy song that was popular at the time. The song—as unusual as it was in the moment—elicited a collective sigh of relief from the experimenters, who had naturally begun to wonder if the second shock had been too much.

But again, the whole point was to see if they could prompt a seizure, not just one convulsion. Cerletti wanted to attempt the procedure one more time—with 110 volts.

At this point, according to Cerletti, some of those involved became uneasy, and urged him to stop. Someone suggested the patient be given time to rest; someone else thought it would be better to wait until the next day to continue testing. Then, the patient unexpectedly chimed in with an ominous warning: “Be careful; the first one was a nuisance, the second one was deadly.” Cerletti took in all of these recommendations and simply responded with, “Let’s proceed.”

Bini set the machine for the maximum voltage of 110 volts. When the switch was flipped, that dull humming noise briefly filled the room again. The patient’s muscles contracted in a spasm. But this time, they did not relax immediately afterward. His body began convulsing with the rhythmic shaking of a seizure.

As his body shook, his face began to turn pale due to lack of breathing. Then, it took on a bluish-purple hue—a clear sign of oxygen deprivation. Bini was timing the asphyxia with his watch. It got up to twenty seconds, then thirty….then forty. Surely many in room feared they had finally gone too far. But at 48 seconds, the patient exhaled violently and fell back to the bed—fast asleep. His vitals were normal. Cerletti declared “electroshock” safe to use on humans.


The aftermath through today

Cerletti’s group ended up giving their patient regular electroshock treatments over the next two months, and eventually they claimed he was completely cured. It turned out that he was not just a vagrant. He had a wife who had been searching desperately for him, and eventually they were reunited—providing a nice conclusion to a success story that was uncomfortably close to being a tragedy.

The use of electroshock therapy—which would eventually come to be known as electroconvulsive therapy, or ECT—spread rapidly. Over time, like any other treatment, the technique was refined, and best practices were established for “dose,” duration of the electrical impulse, and placement of the electrodes.

More substantial changes were made as well. Initially, the convulsions evoked by ECT were violent enough to sometimes cause fractures (often spinal fractures) along with other injuries. So, practitioners started administering muscle relaxing drugs before ECT to reduce the severity of the convulsions. This created another issue: the muscle relaxants temporarily induced complete paralysis, which was often terrifying for patients. Thus, physicians began using anesthesia before the procedure, which allowed patients to remain unaware of the paralysis (or any other unpleasant aspect of the period of time surrounding the seizure).

With these and other modifications, ECT today is considered a safe practice. Serious complications are rare, and memory disturbances are the most problematic side effect. Typically, these memory problems fade with time—although there have been cases where they’ve persisted and had a substantial negative effect on patients’ lives.

The safety of the procedure, however, doesn’t jibe with the perception many people still have about ECT as a dangerous, or even barbaric, method. This perception was created in large part by negative portrayals of ECT in movies and television shows—a classic example being the use of ECT as a disciplinary measure in a psychiatric hospital in the 1975 movie One Flew Over the Cuckoo’s Nest (based on Ken Kesey’s novel of the same name).

ECT has been used in an abusive and/or unscrupulous manner at times, so some of these portrayals may have a grain of truth to them. But ECT today is typically only administered with the full consent of the patient, and the procedure now is much less distressing—for the patient and observer alike—than these fictional depictions suggest.

And, although it’s still not understood how ECT might act on the brain to produce its therapeutic effects, it’s difficult to dispute that it is effective for some conditions. It didn’t end up being the remedy for schizophrenia that Cerletti had hoped (it does seem to be useful in certain cases of schizophrenia, but most studies generally find antipsychotic drugs to be more effective), but it is surprisingly effective in its most common application today: the treatment of depression.

In fact, many argue that ECT is among the most potent treatments we have for depression. A number of studies have found it to be as effective as—or more effective than—antidepressant medication, causing some to argue that it’s an extremely underutilized therapeutic approach. Regardless, a number of factors ranging from cost to its potential impact on memory cause ECT to remain more of a “last resort” for depression treatment.

Nevertheless, ECT has found its way back onto the list of respectable therapies in the eyes of most doctors and researchers. And given its somewhat ignominious beginnings as a dangerous experiment with a non-consenting patient, this is quite an achievement.


References (in addition to linked text above):

Accornero F. An Eyewitness Account of the Discovery of Electroshock. Convuls Ther. 1988;4(1):40-49.

Cerletti U. Old and new information about electroshock. Am J Psychiatry. 1950 Aug;107(2):87-94.

Payne NA, Prudic J. Electroconvulsive therapy: Part I. A perspective on the evolution and current practice of ECT. J Psychiatr Pract. 2009 Sep;15(5):346-68. doi: 10.1097/01.pra.0000361277.65468.ef.