New study proves absence really does make the heart grow fonder

This is one of countless studies that prove the positive impact of social connection and intimacy while highlighting the negative impact of isolation and separation.

What happens in the human brain when we are reunited with the ones we love?

Image by magic pictures on Shutterstock
  • New research, led by behavioral neuroscience assistant professor Zoe Donaldson explores what drives our mammalian instinct to create lasting bonds - and what exactly happens when we are apart from people we share those bonds with.
  • Studying prairie voles (who fall under the 3-5% of mammals who, along with humans, are monogamous), Donaldson and her team discovered a unique set of cluster cells that light up when reunited with a mate after a period of separation.
  • This study is just the tip of new developing research that could lead to groundbreaking new therapies for individuals who struggle with these types of connections, including people with autism, people who struggle with mood disorders, etc.

Assistant professor of behavioral neuroscience at CU Boulder Zoe Donaldson has recently led a year-long study of prairie voles, who are in the 3-5% of mammals (along with humans) who tend to mate for life.

"In order to maintain relationships over time, there has to be some motivation to be with that person when you are away from them. Ours is the first paper to pinpoint the potential neural basis for that motivation to reunite," explains Donaldson.

What drives the mammalian instinct to create lasting bonds? This was the question Donaldson and her team sought out an answer for. And not an answer based on philosophy or emotion, but an answer based on neuroscience and hard-proof.

        The study

        two prairie voles concept of mating for life monogamous mammals

        This research ground lead to new therapies for individuals who struggle with this kind of emotional connection.

        Photo by torook on Shutterstock

        Donaldson and her team used tiny cameras and a new technology called in-vivo-calcium imaging to analyze the brains of prairie voles at three separate times:

        1. During their first encounter with another vole
        2. Three days after mating with another vole
        3. 20 days after living in the same area as the mate

        When the voles were together in the same area, their brains looked and reacted the same way. However, after separating the voles, it was discovered that a unique cluster of cells in the nucleus accumbens fired up when they were reunited.

        In fact, the study proved that the longer the voles had been paired before being separated, the closer their bond became and the glowing cluster that lit up became stronger during their reunion.

        It's interesting to note that a whole different cluster of cells lit up upon them being introduced to a stranger vole, suggesting that these specific cells may actually be there for the purpose of forming and maintaining bonds with others.

        This study confirms that monogamous mammals (voles and humans alike) are very uniquely hard-wired to mate with others. We have a unique biological drive that urges us to reunite with people we care for, and this drive can be one of the reasons we fall under the 3-5% of mammals that seek out monogamy.

        What does this mean for the future of human behavior studies?

        As far as research goes, this is quite groundbreaking - as this could potentially give us insight into various kinds of therapies for individuals who are autistic or individuals who struggle with severe depression and/or other disorders that make these kinds of emotional connections difficult.

        There is still much to learn about these specific series of events that happens when we're reunited with a mate after a period of separation. For example, it's unclear if this "neuronal code", so to speak, is associated with emotion in humans the same way it is associated with desire in voles.

        According to Donaldson, the research in this department is only just beginning, and the definitive outcome of this study is that mammals are quite literally hardwired to be monogamous mammals.

        Social connection and intimacy is essential to our growth and development

        This isn't the first time a study like this has been conducted, even though this particular study has unveiled new neuronal clusters that had not been previously accounted for.

        There have been many other studies of mammals (from small rodents all the way up to human beings) that suggest we are not only hardwired to seek out intimate connections through monogamy, but that we are also extremely and profoundly shaped by (and perhaps even dependent upon) the experiences we have with those mates.

        Brene Brown, a University of Houston Graduate College of Social Work (who specializes in social connection), explains:

        "A deep sense of love and belonging is an irresistible need of all people. We are biologically, cognitively, physically, and spiritually wired to love, to be loved, and to belong. When those needs aren't met, we don't function as we were meant to."

        This idea is backed up by countless studies, including Dr. Helen Fischer's revolutionary study back in 2005, which included the very first fMRI images of "the brain in love".

        This study concluded that the human brain doesn't just work to amplify positive emotions when we experience romantic love, but that the neural pathways responsible for negative emotions (such as fear and anxiety) are actually deactivated.

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        The surprise reason sleep-deprivation kills lies in the gut

        New research establishes an unexpected connection.

        Reactive oxygen species (ROS) accumulate in the gut of sleep-deprived fruit flies, one (left), seven (center) and ten (right) days without sleep.

        Image source: Vaccaro et al, 2020/Harvard Medical School
        Surprising Science
        • A study provides further confirmation that a prolonged lack of sleep can result in early mortality.
        • Surprisingly, the direct cause seems to be a buildup of Reactive Oxygen Species in the gut produced by sleeplessness.
        • When the buildup is neutralized, a normal lifespan is restored.

        We don't have to tell you what it feels like when you don't get enough sleep. A night or two of that can be miserable; long-term sleeplessness is out-and-out debilitating. Though we know from personal experience that we need sleep — our cognitive, metabolic, cardiovascular, and immune functioning depend on it — a lack of it does more than just make you feel like you want to die. It can actually kill you, according to study of rats published in 1989. But why?

        A new study answers that question, and in an unexpected way. It appears that the sleeplessness/death connection has nothing to do with the brain or nervous system as many have assumed — it happens in your gut. Equally amazing, the study's authors were able to reverse the ill effects with antioxidants.

        The study, from researchers at Harvard Medical School (HMS), is published in the journal Cell.

        An unexpected culprit

        The new research examines the mechanisms at play in sleep-deprived fruit flies and in mice — long-term sleep-deprivation experiments with humans are considered ethically iffy.

        What the scientists found is that death from sleep deprivation is always preceded by a buildup of Reactive Oxygen Species (ROS) in the gut. These are not, as their name implies, living organisms. ROS are reactive molecules that are part of the immune system's response to invading microbes, and recent research suggests they're paradoxically key players in normal cell signal transduction and cell cycling as well. However, having an excess of ROS leads to oxidative stress, which is linked to "macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging." To prevent this, cellular defenses typically maintain a balance between ROS production and removal.

        "We took an unbiased approach and searched throughout the body for indicators of damage from sleep deprivation," says senior study author Dragana Rogulja, admitting, "We were surprised to find it was the gut that plays a key role in causing death." The accumulation occurred in both sleep-deprived fruit flies and mice.

        "Even more surprising," Rogulja recalls, "we found that premature death could be prevented. Each morning, we would all gather around to look at the flies, with disbelief to be honest. What we saw is that every time we could neutralize ROS in the gut, we could rescue the flies." Fruit flies given any of 11 antioxidant compounds — including melatonin, lipoic acid and NAD — that neutralize ROS buildups remained active and lived a normal length of time in spite of sleep deprivation. (The researchers note that these antioxidants did not extend the lifespans of non-sleep deprived control subjects.)

        fly with thought bubble that says "What? I'm awake!"

        Image source: Tomasz Klejdysz/Shutterstock/Big Think

        The experiments

        The study's tests were managed by co-first authors Alexandra Vaccaro and Yosef Kaplan Dor, both research fellows at HMS.

        You may wonder how you compel a fruit fly to sleep, or for that matter, how you keep one awake. The researchers ascertained that fruit flies doze off in response to being shaken, and thus were the control subjects induced to snooze in their individual, warmed tubes. Each subject occupied its own 29 °C (84F) tube.

        For their sleepless cohort, fruit flies were genetically manipulated to express a heat-sensitive protein in specific neurons. These neurons are known to suppress sleep, and did so — the fruit flies' activity levels, or lack thereof, were tracked using infrared beams.

        Starting at Day 10 of sleep deprivation, fruit flies began dying, with all of them dead by Day 20. Control flies lived up to 40 days.

        The scientists sought out markers that would indicate cell damage in their sleepless subjects. They saw no difference in brain tissue and elsewhere between the well-rested and sleep-deprived fruit flies, with the exception of one fruit fly.

        However, in the guts of sleep-deprived fruit flies was a massive accumulation of ROS, which peaked around Day 10. Says Vaccaro, "We found that sleep-deprived flies were dying at the same pace, every time, and when we looked at markers of cell damage and death, the one tissue that really stood out was the gut." She adds, "I remember when we did the first experiment, you could immediately tell under the microscope that there was a striking difference. That almost never happens in lab research."

        The experiments were repeated with mice who were gently kept awake for five days. Again, ROS built up over time in their small and large intestines but nowhere else.

        As noted above, the administering of antioxidants alleviated the effect of the ROS buildup. In addition, flies that were modified to overproduce gut antioxidant enzymes were found to be immune to the damaging effects of sleep deprivation.

        The research leaves some important questions unanswered. Says Kaplan Dor, "We still don't know why sleep loss causes ROS accumulation in the gut, and why this is lethal." He hypothesizes, "Sleep deprivation could directly affect the gut, but the trigger may also originate in the brain. Similarly, death could be due to damage in the gut or because high levels of ROS have systemic effects, or some combination of these."

        The HMS researchers are now investigating the chemical pathways by which sleep-deprivation triggers the ROS buildup, and the means by which the ROS wreak cell havoc.

        "We need to understand the biology of how sleep deprivation damages the body so that we can find ways to prevent this harm," says Rogulja.

        Referring to the value of this study to humans, she notes,"So many of us are chronically sleep deprived. Even if we know staying up late every night is bad, we still do it. We believe we've identified a central issue that, when eliminated, allows for survival without sleep, at least in fruit flies."

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