Inside the search for a universal signature of unconsciousness

Picture a calm, flat ocean dotted with countless buoys. A few start bobbing, rippling the glassy water. Suddenly, clusters of buoys begin jumping and splashing back down in unison, sending out waves. Others join in. Then more. The ocean becomes a torrent of rolling hills. Is there some sort of pattern? 

You notice the waves seem to be influencing the buoys’ frenzied activity. The waves the buoys created seem to move with purpose, a seemingly coordinated spectacle. But this is no chaotic ocean storm. What you’re witnessing is an improvisational, sapient dance.

Now, imagine the ocean is your brain. The buoys are neurons. The waves are electrical activity. And their mysterious, patterned movements? That’s consciousness.

To better understand consciousness, neuroscience has traditionally focused on neurons, considered the primary carriers of information in the brain. But neuroscientists like Earl K. Miller argue that the brain’s coordinated waves do the real work — carrying, combining, and transforming information — perhaps even creating consciousness.

Miller’s recent research explores that idea in a counterintuitive way — by studying how chemically distinct anesthetics alter the brain’s wave patterns in similar ways, leading to the same vanishing point: unconsciousness. The hope is that watching how consciousness unravels may reveal what holds it together.

A universal signature

One of science’s greatest mysteries is why we experience the world subjectively. It’s a grand, controversial, and intellectually seductive question. But it’s not what interests Miller, the Picower Professor of Neuroscience at MIT and a member of the Picower Institute for Learning and Memory. “That’s something for philosophers to consider,” he says. “I’m interested in how the brain produces consciousness — the mechanisms and fundamental principles.”

To study those, Miller and the members of his laboratory regularly probe unconsciousness. Examining unconsciousness enables researchers to explore the factors in the brain that permit consciousness to emerge in the first place. “You shut the whole thing off — now you can ask what has changed about the brain,” says Daniel Toker, a neuroscientist at UCLA, who is also researching consciousness via unconsciousness.

The most reliable way to do so is through anesthesia. Inhalable drugs such as sevoflurane, desflurane, and isoflurane — along with more powerful injectable ones like propofol, ketamine, and dexmedetomidine — disrupt brain activity to such a degree that the organ loses its ability to process and integrate information. Your subjective experience goes black.

Surprisingly, scientists only recently learned how anesthetics trigger unconsciousness. In a study published last year, Miller and his colleagues explained in detail how the leading drug propofol causes consciousness to vanish. “The brain has to operate on this knife’s edge between excitability and chaos,” Miller explained. “It’s got to be excitable enough for its neurons to influence one another, but if it gets too excitable, it spins off into chaos. Propofol seems to disrupt the mechanisms that keep the brain in that narrow operating range.”

Generalized seizures also tip the brain into unconsciousness, but in a different way than anesthesia. “When you’re anesthetized, you go into this unstable, chaotic regime,” Toker says. “Whereas in generalized seizures, the brain becomes this super predictable metronome.”

Miller and his team are having far more success probing unconsciousness via anesthesia. In a study published in May, he and Alexandra Bardon, a graduate student, administered two distinct anesthetics, ketamine and dexmedetomidine, to macaques while recording the animals’ brain activity. With both drugs, the alignment of brain waves shifted in similar ways as the animals’ consciousness waned and then winked out. 

This easily measurable shift may serve as a universal signature of unconsciousness: a neural pattern that reliably signals when consciousness disappears, no matter the cause. “Our study suggests that anesthetics are all triggering unconsciousness the same way,” Miller says. “They may arrive there by different routes, but … they’re altering your brain waves in very specific ways.”

Riding the (brain) wave

The results deepen Miller’s long-running metaphor of the brain as an ocean — waves of electrical activity rising and interacting across the cortex. These waves, he believes, may do more than reflect neural firing. They might help stitch consciousness together.

While the major theories of consciousness differ in many ways, most agree that consciousness arises when enough of the brain’s cortex — the outermost layer, responsible for high-level functions such as thought and memory — hums in coordinated harmony. “Brain waves are a great way to do that,” Miller says, “because how else do you coordinate millions of neurons across your cortex?”

Waves offer an elegant solution to that problem. As simple functions, they provide an efficient way to coordinate and structure patterns of activity across the brain. “It’s a great, tractable way for the brain to produce self-organization,” Miller says.

For much of the 20th century, neuroscientists believed that neurons performed the heavy lifting of producing conscious experience through a process called spiking, which involves transmitting a signal via an electrical impulse known as an action potential. Most neuroscientists considered it mystical to suggest that brain waves could be the drivers of consciousness. After all, it was unclear whether brain wave patterns were simply useful biomarkers or whether their alterations could reveal something deeper about consciousness itself. “Is consciousness going away because the brain waves are changing like this, or is this just some weird read-out that functionally means nothing?” Toker says.

But recent research has reignited interest in brain waves. In 2012, a Miller-led research team at MIT, along with a group at Boston University, correlated brain wave activity with different thoughts in monkeys’ brains. Six years later, scientists at Yale showed that at the precise moment of conscious awareness of stimuli, a wave of electrical activity flows from the visual cortex located at the rear of the brain to the frontal lobes. 

The result: Scientists have realized that neuron firing isn’t solely responsible for consciousness. In fact, researchers have discovered that neurons spend about 80% of their time not spiking. During these periods, they still communicate with other brain cells through subtle electrical influences. Those influences — waves — travel around the brain 5,000 times faster than the slower signaling of synaptic spikes, and they’re being sent out all the time.

Scientists have also discovered that astrocytes — star-shaped glial cells that comprise up to 40% of all cells in the brain — do more than just support neurons structurally, remove waste products, and provide nutrients. Like neurons, they also oscillate and spread electrical influences. In May, a team led by Thomas Papouin, an assistant professor of neuroscience at Washington University in St. Louis, found that a brain chemical associated with alertness, attention, and learning alters brain connectivity and function by acting on astrocytes, not neurons. As he put it in a statement, “This is the type of discovery that profoundly reshapes our understanding of how the brain works.”

Your mind is not a MacBook

For decades, neuroscientists assumed the brain functioned like a digital computer, a living, breathing MacBook Pro. Spikes of neurons were seen as ones and zeros, and these were considered the carriers of information.

But Miller is nurturing another hypothesis that fits with the idea that brain waves, not neurons, drive consciousness: The mind actually functions more like an analog computer. These machines solve problems by representing quantities as models — think voltages or mechanical positions — rather than the ones and zeros used in digital computers.

In the analog brain, waves could easily serve as those models, Miller says. Computation could emerge from how waves interact, adding together or canceling out depending on their phases. And because these waves ripple across the brain’s layered, three-dimensional structure, they could support enormously complex computations. (Unlike digital ones and zeros, waves can take on all the values in between.)

Miller points to the human brain’s meager use of power — just 20 watts — as evidence that its computational approach must be vastly more efficient than today’s energy-hungry digital supercomputers. Although their demands reach into the tens of megawatts, supercomputers still don’t match the raw computing power of the human brain.

“Biology solves problems in an energy-efficient way,” says Miller. “Plus, your brain is constantly creating the raw materials for [analog computing] — these oscillating waves that are traveling in your cortex. If evolution didn’t take advantage of that — this obvious, powerful, highly efficient solution — [then] I don’t understand evolution.”

Automating anesthesia

For Miller, understanding the fundamental mechanism of consciousness via anesthesia isn’t just an abstract scientific goal. It’s one with real-world benefits. Along with his MIT colleague and practicing anesthesiologist Emery N. Brown, he hopes to bring them to mainstream clinical practice.

In most operating rooms today, anesthesiologists monitor a patient’s heart rate, blood pressure, and physical movements to ensure they aren’t feeling pain or regaining consciousness. They rarely track brain activity with electroencephalograms (EEGs). Miller and Brown argue that EEGs should become a standard tool because they offer a more direct and reliable window into the brain’s actual state under anesthesia. “It makes perfect sense to me that you should monitor the thing that’s going unconscious, and that’s the brain,” Miller says. “But to do that, you need to know what the neural signatures of consciousness are.”

Building on his recent study of macaques, Miller’s goal is to conclusively identify a brain wave signature of unconsciousness in humans. Knowing this key marker, anesthesiologists could deliver to patients the necessary amount of medication to reach unconsciousness and no more. Miller and his team have already built a prototype machine that automates the administration of anesthesia and works very well in animal models.

What would be the benefit of this sort of machine? For one, it could greatly reduce the number of patients who regain consciousness during major surgical procedures. It’s estimated that in roughly one or two of every 1,000 surgeries under general anesthesia, the patient regains consciousness. They likely don’t experience any pain, but the experience can be upsetting.

More importantly, an automated anesthesia machine based on a brain wave signature of consciousness could prevent surgery patients from being overmedicated with anesthesia. Anesthetics are powerful and can impart lasting deleterious effects, particularly on the very young and the elderly. The lower the amount, the better. For those over 65, anesthesia can cause short-term and long-term cognitive decline. Anesthesia also exacerbates dementia, Alzheimer’s disease, and almost every mental illness, Miller says.

Toker also stresses the real-world benefits of probing unconsciousness. The ultimate aim of his research is to find ways to awaken people affected by disorders of consciousness. Many of these patients live in either a vegetative or barely conscious state, in which they are fully “awake” but unaware, or only minimally aware, of their surroundings. As many as 300,000 Americans are imprisoned in these gray zones of consciousness, often hidden away from public sight.

“Studying consciousness is interesting, but if we think about, ‘What is the point of doing this kind of research?’ then for me, it’s really about helping patients who can’t perceive anything consciously,” Toker says. “If we can study what’s going wrong in their brains, then it’s not only helpful for the general science of consciousness, but might also help wake some people up.”