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Everyone knows that the brain influences the heart.
Stressful thoughts can set the heart pounding, sometimes with such deep force that we worry people can hear it. Anxiety can trigger the irregular skittering of atrial fibrillation. In more extreme and rarer cases, emotional turmoil from a shock — the death of a loved one, a cancer diagnosis, an intense argument — can trigger a syndrome that mimics a heart attack.
But not everyone knows that the heart talks back.
Powerful signals travel from the heart to the brain, affecting our perceptions, decisions and mental health. And the heart is not alone in talking back. Other organs also send mysterious signals to the brain in ways that scientists are just beginning to tease apart.
A bodywide perspective that seeks to understand our biology and behavior is relatively new, leaving lots of big, basic questions. The complexities of brain-body interactions are “only matched by our ignorance of their organization,” says Peter Strick, a neuroscientist at the University of Pittsburgh.
Exploring the relationships between the heart, other organs and the brain isn’t just fascinating anatomy. A deeper understanding of how we sense and use signals from inside our bodies — a growing field called interoception — may point to new treatments for disorders such as anxiety.
“We have forgotten that interactions with the internal world are probably as important as interactions with the external world,” says cognitive neuroscientist Catherine Tallon-Baudry of École Normale Supérieure in Paris.
These internal signals, most of which we are wholly unaware of, may even hold clues to one of the grandest scientific puzzles of all — what drives human consciousness.
The heart pulls the brain’s strings
Coalitions of cells in the brain exert exquisite control over the heart. In some parts of the brain, more than 1 in 3 nerve cells influence the heart’s rhythm, Tallon-Baudry and her colleagues reported in 2019 in the Journal of Neuroscience. One of these brain regions, the entorhinal cortex, is famous for its role in memory and navigation. It makes sense that these two jobs — physically moving through the world and influencing heart rate — would fall to the same neurons; the tasks of seeing a jogging path and priming the heart for running are linked.
The brain bosses the heart around. But that’s not the whole story — not even close. Scientists are finding that information from the heart can boss around our brains and our behavior, too.
Each heartbeat serves as a little signal to the brain. It’s an event, much like seeing an apple or hearing the first note of a song. But unlike those external events, the heartbeat signals come from inside the body. The brain senses these internal signals. Each heartbeat prompts a reliable and measurable neural reaction that scientists call a heartbeat-evoked response, or HER.
And though this heart-initiated, neural thrumming is only on the inside, it can influence what we see in the outside world, Tallon-Baudry and colleagues have found. In one study of 17 people, messages from the heart sharpened eyesight. When certain areas of the brain responded strongly to heartbeat, creating a large HER, people were more likely to see faint gray lines around a red dot. When the HER was weaker, people were less likely to see the lines, the researchers reported in 2014 in Nature Neuroscience.
Seeing with heartbeats
Study participants were asked to look out for a hard-to-see gray circle (stimulus), while scientists measured their heartbeats (left, bottom) and brain activity (right, bottom) in the same moment (gray arrows). When the brain responded strongly to the heart rhythm, people were more likely to report seeing the gray circle.
H.D. Park. Et al/Nature Neuroscience 2014H.D. Park. Et al/Nature Neuroscience 2014Signals from the heart also appear to play a role in memory. In lab experiments, people were shown brief blips of words on a screen. When a word showed up as the heart was contracting, a squeezing phase called systole, people were more likely to forget the word on later memory tests, neuroscientist Sarah Garfinkel and colleagues reported in 2013 in Psychophysiology.
There are hints that the heart can influence intuitions, decision making and emotions. People who were better able to feel their hearts’ rhythms reacted more intensely to emotional images than people who were worse at sensing their heartbeat, for instance.
These results and others suggest the tantalizing possibility that our brains are taking in and using information from the heart — and perhaps other interoceptive awareness — to help us make sense of the world. But findings from people are often correlational. It’s been hard to know whether beating hearts caused the effects or whether they just happened at the same time.
A recent study in mice got around this problem in an unexpected way (SN: 3/14/23). The experiment relied on a powerful technique that can control neuron behavior with light, developed in part by neuroscientist Karl Deisseroth at Stanford University. Called optogenetics, the method uses specific wavelengths of light to force cells to fire an electrical impulse (SN: 6/18/21). Along with Deisseroth, bioengineer Ritchie Chen used the technique to control mice’s heartbeats with exquisitely precise timing. “We can target a specific cell without ever touching it,” says Chen, of the University of California, San Francisco.
With each flash of a light, delivered through a fabric vest worn by the mice, muscles in the heart ventricles contracted, slamming blood out of the heart and into the body. “It was incredibly exciting to see these really precise heart contractions being evoked with light just delivered through the skin,” Chen says.
The researchers then studied the brains and behaviors of mice whose hearts were set racing. An artificially fast heartbeat didn’t always affect mouse behavior, the team was surprised to learn. In some situations, the mice didn’t seem to notice. But when they encountered danger — an exposed area, where in the wild the mice would be vulnerable to predators, or a sip of water that could come with a shock — the mice behaved more anxiously when their hearts were forced to race than when their hearts beat normally.
A pounding heart “wasn’t this primal circuit to induce panic,” Chen says. The mice were integrating signals from their heart and signals from their environment to arrive at a course of action. “And that was exciting to us because it meant that the brain was involved.”
Further experiments turned up a key player in the brain: the insula. The human insula, one on each side of the brain, has been shown to have a role in emotions, internal sensations and pain. Shutting down neuron activity in the mice’s insula silenced the racing heart’s influence on behavior, the team found.
“Being able to manipulate the heart in this way,” Tallon-Baudry says, “opens all sorts of ways to look at things that are much more subtle and might not be related to anxiety at all.” The precise control of optogenetics could help researchers investigate the heart’s influence on perceptions, decisions and memory — some of the key attributes that shape how a thinking, remembering, feeling person experiences the world.
Wiring diagrams are missing
In Chen’s study, how signals moved from the heart to the insula and beyond isn’t clear. “We are very much at the beginning of circuit dissection between the brain and the body,” he says.
Still, scientists know some of the routes signals can take as they move from the heart to the brain. The textbook version goes something like this: Muscles in the heart ventricles contract, squeezing blood out. Cells in nearby blood vessels, including the aorta and carotid artery, sense the change and relay it to nerves. One of those nerves is the vagus nerve, a rambling superhighway to the brain that sends missives about heart rates, digestion and breathing (SN: 11/13/15). Once the information arrives at the brain, it bounces from spot to spot in unknown ways. Our knowledge of these biological daisy chains is woefully incomplete, Tallon-Baudry says. “The full story is not so easy to get.”
Strick, the neuroscientist at the University of Pittsburgh, shares the same lament: “There are nerves that speak to the organs, and the organs speak to the brain, but we don’t know anything about the wiring diagram,” how and where these bits of crucial information actually get exchanged. And that’s an important thing to be missing. “You can say, “Who is driving whom?’ But we’re even more primitive than that. We don’t have a wiring diagram,” he says.
One way of scoping out the wiring involves, of all things, rabies virus. Years ago, Strick realized that he could use the virus to trace cell connections in the brain and body thanks to the virus’ very unusual trick: Rabies virus can hop backward from neuron to neuron, from message receiver to message sender. When designed to carry a fluorescent molecule, the virus can illuminate entire neural circuits in an animal.
That’s what Strick and colleagues have done with various organs — stomach and kidney, for instance — and the brain. Some of the most tantalizing connections he has found are between the adrenal glands, which pump out fight-or-flight hormones in an emergency, and specific brain regions, especially neural locales that control muscles.
And that’s what Strick would like to do with the heart as well. So far, he has a single glimpse of that data from a monkey. “We have one successful heart injection, and the data’s amazing,” Strick says. “The regions of the cerebral cortex that control the heart are mind-blowing. But it’s an n of 1.” This preliminary result needs to be confirmed in more animals, Strick emphasizes.
Tracing these paths would illuminate anatomical connections that undoubtedly exist. Strick and his colleagues are keen to explore more of the body, including the immune system’s spleen and the pancreas.
But another project has raised the possibility of a shortcut that jumps from heart to brain, and it was discovered by accident. Neuroscientist Veronica Egger of the University of Regensburg in Germany and colleagues were curious about the connections between nerve cells that process odors. To get a good look at the behavior of these cells, the team co-opted an ultrasimple system: a rat’s olfactory bulb, which is a part of the brain that handles smells, and the single blood vessel that supplies it with nutrients. In the experiment, an artificial pump sent fluid through the vessel.
But the experiment yielded a worrisome signal: rhythmic, collective activity in the nerve cells that seemed to be created by the pump. “Every neuroscientist knows pump artifacts and hates them,” Egger says.
But this signal, it turned out, was no artifact. It was the real deal. On a hike, Egger had a flash of insight that led to the discovery. Perhaps, she thought, the neurons were sensing the pressure caused by the pump directly.
This direct sensing is a cellular possibility. In 2021, neuroscientist Ardem Patapoutian, a Howard Hughes Medical Institute Investigator at Scripps Research in La Jolla, Calif., had received a Nobel Prize for the discovery of mechanical sensors called PIEZO1 and PIEZO2, present in many animals including humans. These sensors, which sit in cell membranes and look like three-bladed propellers, can detect pressure changes, including the inflating of lungs that comes after a deep breath, the stretch of a full bladder and the pressure of blood moving through a vessel.
Propeller-shaped proteins called PIEZO channels sit in cell membranes and serve as mechanical sensors. Forces, such as the pressure changes created by pulsing blood vessels, can alter the channels’ shape, alerting the cell to the change.M. Szczot ET AL/Annu. Rev. Biochem. 2021
Poised on neurons in the olfactory bulb, these sensors might be detecting when the pump had pushed fluid. When Egger and her colleagues analyzed the system, they found that the neurons were in fact responding to the pressure changes from the pump. Blood pushing through vessels in mice’s brains also influenced the firing activity of nerve cells elsewhere, further experiments revealed. That included the hippocampus, which is involved in memory, and the prefrontal cortex.
These effects, described in the Feb. 2 Science, aren’t large; they’re quite subtle, Egger says. “We haven’t seen this before because it’s a very weak effect.” Still, the effect seems to indicate that neurons throughout these rodents’ brains have their fingers on the body’s literal pulse — an immediate signal that doesn’t need to travel through nerves from the heart.
“It is extremely likely that human brains do this,” Egger says, though that remains to be shown. Also unclear is what the brain might do with this pulse information or how it might be used to take measure of the body’s internal state. “What the brain needs this fast pathway for is completely unknown,” she says. “We just know that it happens.”
Message delivered
Brain cells can take the heart’s pulse directly. When heart muscles squeeze (left), blood is pumped out into vessels, including those in the brain (rat brain shown, middle). In the olfactory bulb, specialized nerve cells called mitral cells (right) sense and respond to the pressure change, connecting the three rhythms (bottom lines).
Why should we listen to the heart?
With all these lines of research, the field of interoception is energized in a way it hasn’t been before, says Garfinkel, of University College London. “It’s blown my mind how much the field has changed, and how much people are embracing the idea.”
One of the reasons for the momentum is that body-brain communications might point to ways to treat disorders such as anxiety. “I do think it opens a window in understanding more about the fundamental etiology of these conditions,” Garfinkel says. “Looking at the brain, you’re looking at part of the story.”
Though Garfinkel was focused on study participants’ brain activity initially, she saw that their bodies were also responding, with racing hearts and other signs of panic. “Interoceptive numbing,” in which a person is less able to accurately sense their bodily signals, has been linked to suicide attempts. And a lessened awareness of heart activity has been tied to a poorly understood kind of seizure.
These days, Garfinkel is listening in on people’s heart-brain conversations and testing whether training people to better detect their own heartbeat could alleviate anxiety. Anyone can experience anxiety, but autistic people have higher than average rates of anxiety. In 2021 in eClinical Medicine, Garfinkel and colleagues reported that after undergoing rounds of training to better sense the rhythm of their hearts, people with autism reported being less anxious.The training procedure asked people to say whether a steady beat they listened to was the same or different from their own internal heartbeat. Over six training sessions, each lasting about half an hour, people’s accuracy improved. And their anxiety scores went down.
Garfinkel and her colleagues have since found similar results in people without autism, though those results have not yet been published.
It’s not at all clear why this training procedure might alleviate anxiety, Garfinkel says. But still, the link may point to ways to treat anxiety. In many ways, the body is easier to change than the brain, Garfinkel says. “Rather than hit people with heavy medications that change their brain, it’s intriguing and exciting to think there’s an easier route — to change the body.”
Understanding interoception may yield insights that go beyond alleviating anxiety. Some scientists, including Tallon-Baudry, suspect that signals from inside our bodies collectively help give rise to consciousness. The concept that consciousness requires a body that can be sensed and an organism striving to stay alive isn’t new, but recent interoception results have added evidence to support the idea that the body’s drive to monitor itself may be more important than previously thought.
Tallon-Baudry and her colleagues studied 68 people who had been fully unconscious. Their goal was to split these people into two groups: Those who still have no signs of consciousness, and those who had signs of consciousness in their brains. The team used HER signals, when a heartbeat prompts a neural thrum, to predict which people may have fleeting moments of consciousness but are unable to show it. “This is the moment when we do find the brain is responding to the heartbeat,” she says. These results, published in 2021 in the Journal of Neuroscience, highlight just how rich and powerful signals from the heart to the brain can be, she says.
All together now
Pacemaker cells in the heart, stomach and brain stem (controlling the lungs) and cells that can sense mechanical changes (mechanoreceptors) generate signals that can be used by the brain. These various body rhythms may contribute to a range of tasks, from perceptions to consciousness itself.
T. Engelen et al/Nature Neuroscience 2023T. Engelen et al/Nature Neuroscience 2023And remember that study she did that linked the HER thrum to whether a person saw a faint grid? She says that the people’s perception of the grid had a lot to do with the eyes, the visual system, but it also depended on having a perspective — a point of view. But the perception also requires a person to experience the vision, interpret it and have that point of view — the “I” in the simple sentence, “I see it.”
Interoceptive signals, and not just those from the heart, but also from the lungs, stomach, muscles, skin and more, may help create a person’s sense of self — their “I,” their identity as a conscious, aware entity with a point of view. Tallon-Baudry and colleagues described last year in Nature Neuroscience how rhythmic signals from the heart, the lungs and the stomach all converge in the brain. That review also advanced the idea that a sense of self relies on internal body signals.
Without a body and a beating heart, a stomach that can rumble and lungs that fill, the brain would be adrift. We navigate the world by seeing, hearing and touching too. We make choices to stay alive. Perhaps the real magic of consciousness comes from the combinations — of heart and brain, of the outside world and inside world, as mysterious as it may yet be.
