Scientists are hunting loneliness to help us better understand the cost of social isolation.Long before the world heard about COVID-19, Professor Kei Tai, a neuroscientist, decided to answer a question that took on a new resonance in an era of social distancing. When people feel lonely, do they yearn for social interactions in the same way a hungry person craves food? Can she and her colleagues detect and measure this "hunger" in the neural circuits of the brain?
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In recent years, a lot of scientific literature has appeared that links loneliness with depression, anxiety, alcoholism and drug abuse. A growing body of epidemiological research demonstrates that loneliness increases the likelihood of getting sick. It appears to induce a chronic release of hormones that suppress healthy immunity. Biochemical changes due to loneliness can accelerate the spread of cancerous tumors, hasten the development of heart disease, and simply deprive even the healthiest of people of the will to live. The ability to measure and detect it will help identify those at risk and set the stage for new interventions.
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According to Tai, loneliness is essentially a subjective thing. You can spend the whole day in complete isolation and meditate in silence, and feel uplifted. Or feel alienated and distressed in a crowd, in the middle of a big city, among friends and family. To take a more modern example: participate in a Zoom video call with loved ones from another city and feel a deep connection; or, on the contrary, after the call to feel even more lonely than before.
This inaccuracy explains why Tai got interesting results when, before publishing the first scientific paper on the neuroscience of loneliness in 2016, he tried to search for other papers on the topic. She found research on loneliness in the psychological literature, but the number of papers containing the words "cells", "neurons" and "brain" was zero.
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Tai hopes to change things and create a new field: aimed at analyzing and understanding how our sensory perception, previous experience, genetic predisposition and life situation, together with the environment, produce a specific, measurable biological state called loneliness. And she wants to define what this ineffable experience looks like when activated in the brain.
If Tai succeeds, it will lead to new tools for identifying and monitoring those who are at risk of illness aggravated by loneliness. It could also provide more effective ways to deal with the health crisis caused by the COVID-19 pandemic.
Looking for the neurons of loneliness
Ty has tracked a specific population of neurons in the rodent brains that appear to be associated with a measurable need for social interaction. It's like "hunger" that can be controlled by directly stimulating the neurons themselves. To pinpoint these populations, Ty relied on a technique she developed as a postdoctoral fellow at Karl Deisseroth's laboratory at Stanford University.
Deisseroth was a pioneer of optogenetics. For this technique, genetically modified light-sensitive proteins are implanted into brain cells; the researchers can then turn individual neurons on and off by shining through a fiber optic cable. This method is too invasive to be used in humans. In addition to injecting proteins into the brain, it requires a fiber optic cable to be passed through the skull and directly into the brain. However, it allows researchers to regulate the neurons of living, free-moving rodents, and then observe their behavior.
Ty began using optogenetics in rodents to track the neural circuits involved in emotion, motivation, and social behavior. She found that by activating a neuron and identifying other parts of the brain that respond to its signal, it can trace individual chains of cells that work together to perform specific functions. Tai has carefully traced connections from the amygdala: a group of almond-shaped neurons believed to be the center of fear and anxiety in rodents and humans.
Kei Tai, a neuroscientist at the Salk Institute of Biological Sciences, tries to detect and measure loneliness in the neural circuits of the brain
Scientists have long known that if you stimulate the amygdala entirely, you can make the animal cringe in fear. But by tracing the labyrinth of connections between the parts of the amygdala, Ty was able to show that the "fear circuit" in the brain is capable of giving sensory stimuli much more nuance than previously thought. In fact, it also modulates courage.
By the time Ty opened her lab at MIT's Picower Institute for Learning and Memory in 2012, she was tracing neural connections from the amygdala to places like the prefrontal cortex, which controls brain function, and the hippocampus, where episodic memory is stored. The goal was to build maps of the brain's neural connections that we rely on to understand the world, make sense of current experiences, and respond to different situations.
She began to study loneliness by sheer luck. While looking for new postdocs, Ty stumbled upon the work of Gillian Matthews. A graduate student at Imperial College London, Matthews made an unexpected discovery when she separated mice from each other during her experiments. Social isolation - the fact of loneliness - changed the so-called DRN-neurons, which indicated their involvement in the process.
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Ty realized that if she and Matthews could map the “chain of loneliness,” they would be able to answer in the lab exactly the questions she hoped to explore: How does the brain fill social isolation with meaning? In other words, how and when does the objective experience of not being among people turn into a subjective feeling of loneliness? The first step is to better understand what role DRN neurons play in this.
Shown here are DRN neurons in the dopamine system.
One of the first things Ty and Matthews noticed when they stimulated these neurons was that the mice were more likely to socialize with each other. In a later experiment, they showed that animals, when given a choice, actively avoided areas of the cell that triggered neuronal activation. This suggests that their search for social interaction was motivated more by a desire to avoid pain than to enjoy, an experience that mimics the "repulsive" feeling of loneliness.
In the next experiment, the researchers placed some mice in solitary confinement for 24 hours and then reintroduced them to social groups of other mice. As you might expect, the animals sought and spent an unusually long time interacting with other animals as if they were "alone." Ty and Matthews then isolated the same mice again, this time using optogenetics to silence DRN neurons after a period of solitary stay. This time, the animals lost their desire for communication. As if social isolation hadn't checked into their brains.
Scientists have long known that the brain contains the biological equivalent of a car's fuel sensor - a sophisticated homeostasis system that allows our gray matter to track our basic biological needs, including food, water, and sleep. The purpose of the system is to induce us to behave in order to maintain or restore our natural state of balance.
It looks like the researchers have found an analogue of the homeostatic regulator for the basic social needs of rodents.
The next question is: what do these discoveries mean for people?
Thirst for a smile
To answer this question, Ty works with researchers in the laboratory of Rebecca Sachs, a professor of cognitive neuroscience at MIT who specializes in the study of human social cognition and emotion.
Planning human experiments is more difficult because brain surgery required for optogenetics is not an option. Instead, you can show lonely people pictures of friendly people showing social cues - such as a smile - and then track and record changes in blood flow in different parts of the brain using MRI scans. Previous experiments in mice have given scientists an idea of which area of the brain to look for.
Last year, Livia Tomova, the postdoc who led research at the Sachs lab, recruited 40 volunteers. They identified themselves as social media users with low levels of loneliness. Tomova left her test subjects in a room in the laboratory and forbade any contact with people for 10 hours. In comparison, Tomova asked the same participants to return for a second 10-hour session, which had a lot of social interaction but no food.
Tomova and Sachs used MRI to measure the brain's response to food and social interaction after periods of fasting and isolation. Right scan shows reward-related midbrain activity
At the end of each session, subjects were placed in an MRI scanner, where they were shown different images. Some featured people sending non-verbal social cues, while others contained images of food.
Unlike Ty and Matthews, Tomova was unable to isolate individual neurons. But it tracked changes in blood flow in larger scan areas known as voxels; each voxel displayed the varying activity of individual populations of several thousand neurons. Tomova focused on areas of the midbrain known to be rich in neurons associated with the production and processing of the neurotransmitter dopamine.
These areas have already been associated in other experiments with feelings of "desire" or "craving" for something. These are areas that “light up” in response to images of food when a person is hungry, or images of drugs in people with addiction. Will they do the same with single people who are shown pictures with smiles?
The answer was clear: After social isolation, brain scans of the subjects showed much more activity in the midbrain when presented with images of social cues. When subjects were hungry but not socially isolated, they showed the same consistent response to food cues, but not social cues.
“Whether it’s the pursuit of social contact or the pursuit of other things, such as food, it seems to be presented in a very similar way,” says Tomova.
Pandemic as an experiment
Understanding how social hunger is created in the brain will allow a deeper study of the role of social isolation in certain diseases.
Objectively measuring loneliness in the brain can provide some clarity to the relationship between depression and loneliness, which is not achieved by asking people how they are feeling. Which comes first: does depression cause loneliness or loneliness causes depression? And can timely social intervention help fight depression?
Understanding the loneliness chain in the brain may shed light on addictions that isolated animals are more prone to, according to some studies. The evidence is especially compelling for adolescent animals, which are even more sensitive to the effects of social isolation than older or younger animals. People between the ages of 16 and 24 are most likely to report feeling lonely, and it is at this age that many mental health disorders first begin to manifest. Is there a connection here?
Understanding the "loneliness chain" in the brain can shed light on addictions.
But the most obvious current need has to do with the social isolation caused by the COVID-19 pandemic. There has been no overall increase in loneliness since the start of the pandemic, according to some online surveys . What about the people most at risk for mental disorders? When they are isolated, at what point does it start to threaten their psychological and physical well-being? What measures can protect them from this danger? When we can measure loneliness, we begin to learn - and this will make it much easier to design targeted interventions.
"A vital question for future research is how many and what types of positive social interaction are sufficient to satisfy this basic need and thus eliminate neural cravings," Tomova and Tai write in a preprint of their forthcoming article posted at the end of the last Martha. The pandemic "highlighted the need for a better understanding of human social needs, as well as the neural mechanism that underlies social motivation."
"This study provides a first step in this direction."
This, in restrained scientific terms, signals the birth of an entirely new field of research. You don't often see this, let alone be part of the phenomenon.
“It’s so exciting to me because we’ve heard about all these concepts about a million times in psychology. For the first time, we actually have brain cells that we can connect to the system, says Tai. - And when you have one cell, you can trace its connections backward, you can trace its connections forward; you can understand what is higher and what the neighboring neurons are doing, what 'messages' are being sent. "
"Now you can find the whole chain and know where to start."
