Going under

Research into human consciousness has crossed from philosophy to neuroscience and medicine

One day this spring, Stanford anesthesiologist Divya Chander, MD, PhD, donned her scrubs, washed her hands, and walked into the operating room for a routine surgery. A resident anesthesiologist-in-training had already stuck flat, round electrodes on the patient’s forehead, and wires snaked from the electrodes to an electroencephalography machine beside the operating table.

Illustration by Jon Han
Illustration by Jon Han

Chander glanced at the machine’s readout, a mountainous terrain of lines pulsing up and down, representing the complexity of information zipping between cells in the brain. These EEG patterns didn’t look like those of an awake person, she thought to herself.

“Oh, have you pushed the anesthetics already?” she asked the resident. He shook his head. Chander frowned, then reached down and shook the patient’s shoulder. Suddenly, the man’s eyes snapped open and the EEG returned to a more expected pattern. He’d been napping.

A decade ago, it’s unlikely that any clinician could glance at the raw squiggly lines of an EEG readout and determine whether a patient was awake or asleep, anesthetized or not. If they had an EEG machine in the operating room at all — a trend that began in the mid-1990s — it likely displayed only some numbers. But now, many neuroscientists and anesthesiologists are tackling an area previously claimed only by philosophers: consciousness. Their research over the past dozen years has begun to illuminate how the brain’s patterns of activity shift as a person’s awareness of their environment changes. By bettering their ability to track consciousness, anesthesiologists hope they can learn how to detect when a patient loses and regains consciousness, fine-tune drug levels to optimize individual patients’ sedation, and develop more effective and safer anesthesia drugs.

Chander is among those who have immersed themselves in the few measures of consciousness available, like EEG, to get a grasp on what changes during sedation. Being under general anesthesia, researchers like Chander have found, closely resembles being in a deep sleep, hence her mistaken assumption in the operating room. In both cases, neurons have slowed their telltale rhythms and fallen into a more stereotyped pattern that prevents one region of the brain from communicating well with other regions.

Consciousness is often defined as being awake, having a sense of self, or an awareness of your surroundings. For doctors, classic measures of consciousness include testing patients’ level of awareness and attention, and asking them whether they know the date and where they are. But historically, the concept of consciousness has also had a more spiritual definition — some believe consciousness is unique to humans; some link it to the idea of a soul.

For many centuries, scientists and philosophers alike saw consciousness as something to ponder and discuss, but not something that could be explicitly measured. For them, consciousness was more than a physical process. They believed that even if one could re-create an entire brain from scratch, a conscious being — with self-awareness and introspection — wouldn’t result because it would be missing a soul. But as neuroscientists have developed new ways to study what happens within brain cells when people engage with their environment, they’ve noticed patterns — like those Chander can see on an EEG readout — linking physical processes in the brain to consciousness. 

“It is not that there was a single, dazzling neurobiological experiment showing that consciousness is a biological phenomenon,” says Patricia Churchland, a neurophilosopher at the University of California-San Diego, who regularly works with neuroscientists and anesthesiologists to probe consciousness. “Instead, there has been an accumulation of important results that collectively render that conclusion fairly obvious.”

Such realizations don’t just have implications in the realm of anesthesia, but could lead to new ways to gauge brain injuries, reverse comas, define sleep problems and treat cognitive disorders.

Tracking consciousness

By any definition of consciousness, there are countless ways to lose it. Epileptic seizures, some recreational drugs and many brain injuries knock people unconscious. But most of those situations that cause diminished consciousness — head trauma, for instance — are both unpredictable and dangerous and can’t be studied in a controlled way in a lab or hospital. Anesthesia, though, provides a perfect testing ground for concepts of consciousness.

“There are very few situations where you can probe human consciousness except when it is depressed,” says Chander. “Anesthesia is one of the best model systems we have because we can both remove and restore consciousness with drugs and we can study the loss of consciousness in the absence of brain damage.”

Typically, anesthesiologists track sedated patients’ levels of consciousness through crude, indirect measures of bodily function — during surgery, they keep an eye on a patient’s blood pressure and heart rate. Although the EEG has been around for the latter half of the 20th century, medical device companies have only recently began promoting the use of EEG in the operating room. In the early 1990s, companies first developed machines designed specifically to monitor anesthetized patients — they each developed their own proprietary formula that analyzes raw EEG readouts and spits out a number indicating a patient’s depth of unconsciousness. But anesthesiologists like Chander think the single number is a poor measure of what’s happening clinically. The number, between 0 and 100 on most systems, involves a complex calculation that can take minutes to generate, making it difficult to use for real-time decision making. It also doesn’t take into consideration the variety of drugs that can be used — and that have varied effects on physiology, Chander says.

“That number doesn’t mean much during critical periods,” she says. “If you relied on the number to make clinical decisions, you’d be in real trouble.” So most anesthesiologists, she says, don’t rely on EEG at all.

Chander — who already had a PhD in neuroscience before choosing anesthesia as her clinical specialty — thinks the time is ripe, though, to start turning to raw EEG data to get a more nuanced view of how consciousness changes during anesthesia. A few years ago, on the suggestion of a mentor and colleague, she started displaying the raw waves of data rather than the processed index number on the EEG machines of every patient she puts under, a change that takes the simple click of a button but is rare outside of research labs.

Over time, she began noticing particular patterns of brain activity as a patient drifted in and out of consciousness and as she administered different drugs. Now, she’s organizing those observations into more concrete data on consciousness. Chander is interested in understanding what changes take place in neural networks during changes in level of consciousness. If she can see them in real time on the EEG in the operating room, that information may ultimately be used by clinicians to monitor anesthetic depth. She and her colleagues are also finding that the way in which people emerge from anesthesia may influence how they feel after surgery. “Some people have a very gentle, easy wake-up from anesthesia and feel great,” she says. “Other people are very agitated, disoriented or in pain.”

But even if Chander nails down exactly what happens in the brain as an anesthetic causes a patient to lose consciousness, or as the patient emerges back to consciousness again, there’s no guarantee that the same changes occur when a person is made unconscious through other means.

“It’s clear that there’s no one switch that flips to go from conscious to unconscious,” says Stanford anesthesiologist Bruce MacIver, PhD. “All the ways you can lose consciousness — falling asleep or getting anesthesia or a head injury — all have different underlying mechanisms.”

To aid in understanding the neural basis for some of these consciousness state-switches, Chander has worked with Stanford professor of psychiatry and of bioengineering Karl Deisseroth, MD, PhD, a developer of a technique called optogenetics, and Stanford associate professor of psychiatry Luis de Lecea, PhD, who uses optogenetics to study sleep. Using genetically engineered mice with special light-sensitive proteins in their brain cells, researchers can control when different neurons fire by shining light on them. Chander is using optogenetics to control areas of the brain that she suspects might play a role in consciousness. She can test whether firing certain neurons makes a mouse go from an unconscious to conscious state — or vice versa.

“Optogenetics is the way I control the system, and EEG is the readout device,” says Chander. The patterns she observes in patients during anesthesia help inform which areas she studies in mice. She hasn’t published results yet, but thinks that combining clinical data with the latest molecular approaches — like optogenetics — will be key to discovering which neural networks support the consciousness state of the brain.

Building better anesthetics

As far back in history as ancient Egypt, healers searched for drugs — from alcohol to opium to other herbs — that would ease patients’ suffering during surgical procedures. By the early 19th century, doctors had discovered mixtures of natural compounds that would not only ease pain, but induce temporary states of paralysis and unconsciousness. The use of chloroform and barbital to sedate patients soon followed. Through chance and happenstance, trial and error, the field has settled on a handful of drugs that put patients into a deep, but reversible, state of unconsciousness — somewhere between a normal night’s sleep and a coma.

Many of today’s drugs are derivatives of the compounds that have been used for centuries, and none is as effective nor as safe as doctors would like. One in 1,000 patients remembers parts of their surgery afterward, indicating that they had some level of consciousness during it. And for some patients, anesthetics cause plummeting blood pressure and the risk of death. “Not a single one of these drugs has been designed rationally to achieve any known mechanism or desired effect in the brain,” MacIver says.

He thinks that by uncovering what defines consciousness and unconsciousness he can design better anesthetics and improve the tracking of a patient’s state while they’re under. Anesthesiologists, he says, want to ensure that every patient remains unconscious for the duration of a procedure, but using the least amount of anesthetic possible. “There’s increasing evidence that the lighter we keep patients, the better their speed of recovery,” he says.

To characterize different anesthetics and how to detect the right dosage, MacIver’s lab administers the drugs to rats, and uses EEG to observe what happens. They’ve pinpointed a few key changes to the EEG that tend to happen at the exact moment that rats from go from being able to respond to a stimulus to being unresponsive.

But applying these data to the operating room is tricky. Interpreting the pulsating lines of raw EEG data on the spot is a skill that few clinicians have. “An EEG is this weird, random, squiggly line that changes quite a bit from moment to moment,” MacIver says. And like Chander, MacIver doesn’t put much weight in the processed index numbers that EEG machines display in most operating rooms. But while Chander thinks one solution is to teach more anesthesiologists to read the raw form of the EEG data, MacIver and Chander are also teaming up on another solution: an entirely new way to display EEG data. “We’re using the exact same data that’s been recorded for decades,” MacIver explains. “But we’re finding new ways to visualize it.”

His EEG visualizations look like balls of yarn — the more spherical they are, the more chaotic the brain’s signals are. And chaos, in this case, means consciousness. “When a rat is awake,” he says, “it’s a perfect sphere.” When a rat is unconscious, rather than a tight sphere, lines project far outward from an oblong ball.

But neither Chander nor MacIver has achieved a perfect method to track consciousness. Based on his data from rats, “we can get about 80 or 90 percent accuracy in humans for loss of consciousness,” MacIver says. “But we’d like that to be 100 percent. Already by tracking vital signs we can get better than 90 percent accuracy.”

One step toward getting better, they say, is having the chance to put patients under anesthesia at a much slower rate than is usual during surgery. MacIver and Chander are currently recruiting participants for a study that will observe subtle EEG changes in their brains as they’re very slowly anesthetized.

Digging deeper in the brain

A few years ago, Brett Foster, PhD, was a graduate student in Australia trying to understand how different anesthetics and sedatives influence brain activity in different ways and can make the EEG index numbers hard to interpret. Time and time again, his results and his literature searches pointed toward the importance of the midline parietal lobe — a region of the brain sandwiched in the center, between the two halves, called hemispheres. But EEG can’t accurately record the activity in the midline of the brain.

“Where the two hemispheres of the brain push up against each other, the brain curves down between them,” Foster explains. “When you’re using electrodes on the scalp to record activity, this valley is too deep. Any signal gets smeared and smoothed out before it reaches the electrodes.”

But Foster learned that Stanford neurologist Josef Parvizi, MD, PhD, was more accurately recording the activity in this area of the brain in patients with epilepsy. In select patients with especially severe seizures, doctors implant electrodes in their brains to determine where seizures are originating and whether surgery can treat their epilepsy. But Parvizi, an associate professor of neurology, was also taking advantage of the deep placement of these electrodes to study — with the patients’ permission — broader questions about brain activity. With the electrodes, he could either stimulate select neurons or record their activity. Foster saw Parvizi’s work as a perfect inroad to the parietal lobe’s potential role in consciousness and memory and joined his lab at Stanford as a postdoctoral researcher.

Parvizi and Foster can’t knock their epilepsy patients unconscious, but they can study the activity in the brain’s midline as these patients perform simple tasks, recall events, tell stories or go about their daily activities in the hospital. One aspect of consciousness that they’re trying to study has to do with attention — part of being conscious has to do with paying attention to your surroundings. Someone who is zoning out in class can be said to have a different level of consciousness than someone listening to the professor’s every word — though both are quite conscious. Parvizi and Foster are observing how activity deep in the brain is different when someone notices a stimulus compared with when they don’t. Another aspect relates to memory — why does the midline light up when someone is recalling the past, and how does that relate to the fact that patients have no memory of their time spent under anesthesia?

“For us, this is an opportunity to get measurements from this hard-to-access part of the brain,” Foster says. “But what we need to do is build up from very basic questions.”

Parvizi says the implanted electrodes offer far more detail than previous methods, but technology still limits scientists’ understanding of the brain. “We know that consciousness is likely mediated by many regions of the brain and controlled by how those regions are interacting,” he says. “Right now, we can’t simultaneously record from all over the brain at once. We have to pick and choose what to look at.” But a new grant they’ve received will let them focus on how the midline parietal lobe communicates with other areas.

Humans: conscious machines?
If consciousness is viewed as a spectrum, then the study of consciousness doesn’t just mean finding a single line that people cross from conscious to unconscious. People in a coma are less conscious than those asleep for the night; people who are hyper-alert to their surroundings are more conscious than people sleep-walking. Determining how to comparatively measure such different states of awakeness and awareness in the brain would give scientists an unprecedented look into what it means for a person to be a living human being.

Some philosophers, Churchland says, remain skeptical that consciousness can be gauged in such a concrete, physical way. But she prefers to think about the limits of science to study consciousness as a known unknown. “We cannot be sure whether we’re up against a solvable or an unsolvable problem,” she says. “But when philosophers claim we’ll never understand the brain basis of consciousness, they are making a rash prediction about the future of science. Against that prediction is the significant progress that has already been made. The fact is, the naysayers cannot really know what science will discover.”

Much of the drive to understand consciousness comes from basic human curiosity: What makes us tick? What makes you have a different view on the world than me? Can we download someone’s memories from their brain? But there are also more practical questions that the science can lend a hand in answering: How can we measure consciousness in patients who appear to be in comas? How can we develop better anesthetics?

“What I’m always hoping is that hearing about this kind of work makes people ask more questions about what it means when they themselves enter different states,” says Chander. She challenges people to pay attention to what’s happening in their brain when their state of attention, or awareness about the world around them, changes.

“Some people still think consciousness can’t be accessed by scientific methods,” says Parvizi. “But that’s a very unfortunate view.” Scientists are already there, he says, getting at the heart of consciousness every day.

Sarah C.P. Williams

Sarah C.P. Williams is an award-winning science writer based in Hawaii, covering biology, chemistry, translational research, medicine, ecology, technology and anything else that catches her eye.

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