Scientists Discover Why Your Brain Can't Block Out Unwanted Thoughts

A new study explains why some people seem to be better than others at ridding their minds of intrusive thoughts.


"Try to pose for yourself this task: not to think of a polar bear, and you will see that the cursed thing will come to mind every minute."

— Fyodor Dostoevsky, Winter Notes on Summer Impressions

Chances are you’ve heard this game before in some form, maybe with a pink elephant instead of a polar bear. And though it’s just a game, the similar phenomenon of being unable to rid your mind of intrusive thoughts can pose serious dangers to mental health, and it’s a hallmark symptom of psychiatric disorders like post-traumatic stress disorder, anxiety, depression, and schizophrenia.

What’s going on in the brain when you’re trying to clear unwanted thoughts from your mind?


Scientists just got much closer to the answer, it seems. A study published in the journal Nature by researchers at the University of Cambridge details how people with higher concentrations of the amino acid neurotransmitter GABA in their brain’s hippocampal region tend to be better at blocking unwanted thoughts, images and memories.

"What's exciting about this is that now we're getting very specific," said study coauthor Michael Anderson to BBC News. "Before, we could only say 'this part of the brain acts on that part', but now we can say which neurotransmitters are likely to be important."

In the study, participants were asked to memorize pairs of unrelated words — for example, moss/north or ordeal/roach. Then the researchers presented participants with two lights: one red, one green. Participants were asked to recall the associated memories when the light was green, and suppress memories when it was red without engaging in any distracting activity or thought pattern. "Whenever a memory intruded into awareness, they were asked to 'push it out of mind.'," write the study authors. 

Meanwhile, participants’ brains were monitored with both functional magnetic resonance imaging (FMRI) and magnetic resonance spectroscopy, which measures chemical changes in the brain.

Results showed that GABA plays a key role in people’s ability to stop thought patterns. functioning as an inhibitory neurotransmitter, GABA effectively tells the cells it comes in contact with not to fire. Without it, nerve cells can fire too often and too easily. Caffeine inhibits the release of GABA in the brain, so one way to conceptualize what a GABA deficiency might feel like is to imagine that jittery, hyperactive feeling when you drink too much coffee.

The study could help improve treatments for rumination and associated psychiatric disorders.

"Most of the focus has been on improving functioning of the prefrontal cortex," Anderson said to BBC News. "Our study suggests that if you could improve GABA activity within the hippocampus, this may help people to stop unwanted and intrusive thoughts."

The Game

The polar bear game listed at the top of the article is similar to a mind game played 24-7 around the world, known simply as The Game. According to its website, there are only three rules to The Game:

  • Rule 1: You are playing The Game. You, along with everyone else in the world, always is, always has been, and always will be playing The Game. Neither awareness nor consent is required to play.
  • Rule 2: Every time you think about The Game, you lose. Loss is temporary; as soon as you forget about The Game you stop losing. The objective of The Game is to forget that it exists. Good luck. 
  • Rule 3: Loss of The Game must be announced. Every time you think about The Game, and hence lose, you must say so. This is the only rule that can be broken, but do you really need to cheat..?
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    Image source: Vaccaro et al, 2020/Harvard Medical School
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    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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