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How the brain handles the unknown

Uncertainty can be hard for humans. It drives anxiety, an emotion neuroscientists are trying to understand and psychologists are trying to better treat.

Why it matters: Under the threat of a virus, job insecurity, election uncertainty, and a general pandemic life-in-limbo that is upending school, holidays and more, people are especially anxious.


  • Before the pandemic, anxiety was already climbing in the U.S., especially among young adults, according to a recent study.
  • Add the pandemic and its many unknowns: 35% of adults in the Household Pulse Survey reported symptoms of anxiety disorder in July. (In the first half of 2019, it was roughly 8%.)

The big picture: "We have anxiety for a reason," says Stephanie Gorka, who studies the neurobiology of anxiety and treatments for anxiety-related disorders and phobias at the Ohio State University.

  • Anxiety alerts people to pay attention to their environment and is key to our survival, but if it is chronic or excessive, it can have negative health consequences, she says.
  • But how exactly the brain responds to uncertainty and leads to anxiety is unclear.

What's new: Recent research suggests the brain circuitry for anxiety and fear, separate emotions long thought to activate different regions in the brain, overlap.

  • Fear is typically a reaction to a certain, immediate threat, whereas anxiety is a prolonged state of worrying about and anticipating an uncertain harm.
  • Both involve many parts and processes of the brain, but fear has been linked to activity in the amygdala and anxiety to a structure called the bed nucleus of the stria terminalis (BNST).

In a study published last week, neuroscientist Alexander Shackman of the University of Maryland and his colleagues presented 99 student participants with "triple threat" stimuli to invoke both emotions.

  • A combination of a painful electric shock, a disturbing image and an aversive recording (a scream, for example) was given either after a countdown (to spur fear) or at an unpredictable time (to invoke anxiety).
  • Whether the subjects experienced fear or anxiety, both the amygdala and the BNST responded.
  • The subjects' brain activity was measured using fMRI, an imaging tool with limitations, and other methods might reveal nuanced differences between the two regions' responses, The Scientist reports.
  • The finding builds on prior research in rodents and meta-analyses of neuroimaging studies that find fear and anxiety look similar in the brain, says Shackman.

The impact: The amygdala-is-fear/BNST-is-anxiety concept has guided research on mental health disorders, says Shackman, who adds that recognizing the connection and overlap between fear and anxiety could possibly lead to better treatments.

What to watch: There is evidence building that another region of the brain — the insula — is key to anticipating threat, says Gorka.

  • The insula essentially reads our internal state, decides the importance of that information, and mobilizes a response to the environment.
  • Gorka has found that individuals who are more sensitive to uncertainty have a greater connectivity between the insula and the dorsal anterior cingulate cortex, an area linked to strategizing and future-planning.
  • Sensitivity in that circuit seems to make someone more vulnerable to anxiety and alcohol use disorders.
  • "Those individual differences in how people tolerate uncertainty are clinically meaningful," says Gorka.

How it works: Psychological tests, including the Intolerance of Uncertainty scale, capture those differences as well.

  • People employ different strategies for copingwith uncertainty — some may avoid it if they are sensitive to it, whereas others may be more flexible.
  • Learning to tolerate uncertainty is key because it can form a vicious and long-lasting cycle with anxiety, psychologist Jack Nitschke of the University of Wisconsin told the Washington Post.
  • Lucy McBride, who practices medicine in D.C., tells her patients that "anxiety is part of the human condition and the survival mechanisms we have," and she stresses the importance of sleep, therapy, minimizing stimulants and other lifestyle modifications.

Keep in mind: Humans are resilient and, as Arthur C. Brooks recently wrote in The Atlantic, difficulty and uncertainty can be "an opportunity for improvement and personal growth, without pushing away the negative emotions that are a natural by-product of hard times."

  • "Uncertainty is inherent in life, so we talk with our clients about the need to tolerate it and build their confidence that you don’t need all the information to have a successful outcome," says Gorka.

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