Some time before the COVID-19 pandemic shut down much of the world, a neuroscientist named Dr. Kay Tye was studying the impact of human loneliness on the brain — a phenomenon that would soon become all too relevant in a world of social distancing. Tye knew that the overwhelming majority of people knew what it meant to be lonely and that 60 percent of people in the United States alone report suffering from loneliness — roughly three in five Americans. What she wanted to understand as a neuroscientist and researcher was how people felt loneliness. Was craving human contact similar to how people crave food when they’re hungry? With her colleagues at the Salk Institute of Biological Sciences, she set out to see if it was possible to detect this hunger in the brain’s circuitry, and determine if it was possible to measure it with modern technology
Tye is hardly the first person to be interested in the phenomenon of human loneliness. There’s already a substantial body of scientific literature that makes a correlation between loneliness and depression, as well as anxiety, alcoholism, and drug abuse. It’s even become commonly accepted that increased feelings of loneliness can make you more prone to getting sick, supported by epidemiological research. Somehow, loneliness prompts the release of hormones that help your immune system to function normally. The biochemical changes released in the brain from loneliness can also speed up the spread of cancer, and the rates of heart disease and Alzheimer’s. Therefore, Tye’s research has the potential to unlock a great deal of knowledge that could help health care workers in stemming the tide and morbidity of some of the worst diseases plaguing the modern world.
After nearly half a year of lockdowns, mental health experts are preparing for another epidemic apart from the coronavirus — with potential rising rates of suicide and drug overdoses due to spending long periods in isolation. Even rates of anxiety and chronic stress alone could be significant, as many countries undergo what some psychiatrists are seeing as months of a traumatic experience. “The recognition of the impact of social isolation on the rest of mental health is going to hit everyone really soon,” says Tye, with a sense of urgency added to her research. “I think the impact on mental health will be pretty intense and pretty immediate.”
Unfortunately, being able to identify loneliness can be a daunting task on its own, making it somewhat difficult to recruit test subjects. Quantifying how much of it an individual feels is even more difficult, which is one reason why Tye’s colleagues have not been pursuing the issue for very long. While it might seem like a literal definition to some — a person who spends their life largely isolated, living alone and having room with their own thoughts, even if that person largely feels content. Another individual could live in the middle of a large city and have a consistent network of friends or be an active member of a large social circle, and yet still secretly feel emotionally detached from everyone. This is one reason why Zoom conference calls seem like a poor substitute for going to live events and connecting in person.
To begin her search for the loneliness neurons, Tye looked to lab rats whose brains consist of specific populations of neurons that become active when they socialize. She had previously studied the neural circuits used in emotion and motivation during her postdoc research at the Stanford University lab of Dr. Karl Deisseroth, who pioneered the technology of implanting light sensitive proteins in brain cells. By flickering lights on and off through fiber optic cables reaching into the skull, Tye was able to trace the rodents’ fearful reactions to the brain’s amygdala, the region typically associated with fear and anxiety. What she uncovered, however, is that the amygdala is more than that — and the signals produced by the amygdala are much more nuanced than scientists had previously suspected, as the amygdala seemed to formulate courage responses as well.
While recruiting new postdoc researchers for her learning and memory lab at MIT years later, she learned of the work of a graduate student named Gillian Matthews from Imperial College London who studied isolated lab mice. The isolation apparently led to changes in brain cells known as dorsal raphe nucleus (DRN) neurons, leading them to a map of what a potential loneliness circuit in the brain would look like.
When Tye and Matthews stimulated the DRN neurons with light, they noticed the lab mice were more eager to interact with their fellow mice. They then isolated the mice in solitary confinement for a 24 hour period and then rereleased them in their shared enclosure. As expected, the mice became more sociable than usual. They then used optogenetics to silence the DRN neuron signals and put the group back into solitary. When they returned the mice to their enclosure the next day, they showed no interest in their roommates, as if they lost their need to interact.
Researchers have long known that the human brain has an ability to gauge the quantity of our basic needs to fulfill — measuring things like hunger, thirst, and levels of tiredness, and the DRN neurons seem to play the same role for social interactions in mice. The trouble is that optogenetics are too invasive to apply to people at present, so now Tye is collaborating with MIT professor of cognitive neuroscience, Dr. Rebecca Saxe to explore further.
A year ago, Saxe along with her postdoc Dr. Livia Tomova, found 40 volunteers who described themselves as having large social networks and reported low levels of loneliness. Tomova confined them to an isolated room in the lab where they were not allowed any contact with other people for 10 hours. The same subjects were invited back to the lab after their session for another 10 hours of interacting with fellow participants but no food was served.
When each session concluded, the subjects were placed under an functional MRI scanner and shown different images: one set of photos contained people making nonverbal social cues, and another consisted of pictures of food. The scanner focused on portions of the midbrain where substantial amounts of dopamine were produced — to answer a question: Would people who were hungry respond to the food pictures the same way people craved attention would respond to nonverbal cues?
After experiencing social isolation, the participants’ brains showed considerably more activity when they were exposed to nonverbal cues than when they saw pictures of food, and the reverse reaction was true of the group that spent a 10-hour session socializing but denied food.
“Whether it’s the drive for social contact or the drive for other things like food, it seems to be represented in a very similar way,” says Tomova.
Their next objective is to further determine the role social isolation in the brain plays when it comes to illness. It’s not yet clear if depression causes the feelings of loneliness, or if loneliness brings about depression, for example. Looking deeper into the DRN neurons could finally give us further clues. It could also shed light on addiction and singling out the individuals who are most at risk for it.
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