For our project “The Uncertainty Boom,” we spoke with five experts on the effects of widespread uncertainty on our society, the economy and even the ways we think and act. 

Here, we speak with Jack Nitschke, a clinical psychologist and neuroscientist at the University of Wisconsin School of Medicine and Public Health. Dr. Nitschke discusses how uncertainty affects the architecture of our brains and why it can make us less prepared for the future. This interview has been edited for clarity and length. 

You're a clinical psychologist, a neuroscientist and brain imaging specialist. How did all this come about?

I was interested in clinical psychology, working with individuals to help reduce the suffering in anxiety and depression. I got into research because some of the best clinical training I could receive would be in a research setting. When I started graduate school was actually the year that fMRI [functional magnetic resonance imaging] was founded and that was going to become a major tool of mine throughout my career. 

You’ve focused on how uncertainty affects our brains. We’re going through a period right now in which people seem generally unsure about the economy and unsure whether AI is going to take their jobs. What happens to people under prolonged periods of uncertainty?

The way that neuroplasticity works is that whatever we are spending our time doing — be it healthy behaviors or unhealthy behaviors such as worry — our brains are helping us get really good at them. Specifically, neuroplasticity is building neural connections or reinforcing neural connections through various mechanisms.

Like the famous example of London cab drivers who have enlarged brain areas dedicated to spatial memory?

Exactly. What's happening is that people are building up pathways for uncertainty. Those pathways are just getting more and more attention and more and more activation. And the various components of neuroplasticity are contributing to that uncertainty being strongly represented in a person's brain. The more that we're building these up, the more that we default to those parts of our lives when we’re stressed or even in the middle of the night, when we wake up. 

Let’s discuss some of the specific changes that occur in our brains under uncertainty. You’ve talked about hypervigilance, which is often associated with PTSD.

Hypervigilance is a cardinal feature of PTSD and uncertainty is a piece of that. With PTSD, there has been a breach of safety in the past and essentially what happens with hypervigilance is that people are on the lookout for that, and then how to get through a situation, how to survive. It makes people feel really uncomfortable when they're just sitting in waiting rooms or at restaurants. They have to position themselves to make sure that they see the door so that they can get out. It's all geared toward keeping them safe.

If you were to take someone who has hypervigilance and put him in your fMRI machine, would there be particular areas you'd want to look at?

The big area there that you're interested in is the amygdala, because that is like an early threat detection system in our brain. So you’d see activation in that particular area that indicates that there's danger afoot and that ties right in with the whole safety idea. 

Are there other brain processes involved with safety learning that are negatively affected by uncertainty?

You probably would include the insula, an area that's engaged in moment-to-moment awareness. You would expect to see more activity in the insula, which you often do see in different anxiety disorders. 

Another area of the brain that's more involved is the medial prefrontal cortex, particularly lower down in the prefrontal cortex, called the anterior cingulate cortex, and the ventral medial prefrontal cortex. I know these are big words. The bottom of the prefrontal cortex is known to have direct connections with the amygdala. When a brain is functioning normally, they show a reciprocal relationship. Some work has looked at different species and how that area of the frontal lobe is involved in regulating the amygdala and maybe in that regard it’s important for safety.

Would it be just less active or inactive in people suffering from terrible anxiety?

What's been found is that that area is indeed less active and oftentimes it is not showing the pattern of reciprocal activation with the amygdala, where if that's high, the amygdala is low, 

You also talked about avoidance. Many psychologists believe that worry is actually an adaptive trait. But you say too much worry actually leads to avoidance.

We're not the first ones to talk about this, that worry is in some ways an avoidance strategy. People engage in a lot of worry as opposed to just going out and facing whatever the difficulty is.

Where would you expect to see that reflected?

They're going to have activity in areas of the brain that are involved in verbal mediation. A lot of times worries have a verbal component to it, even if it's all internal monologue. So you would expect in most right-handers, that's going to show up in the left hemisphere because that’s where our language production centers are, what’s called Broca’s area in the left frontal region. 

An evolutionary scientist might say that these traits must be adaptive in some way. Isn’t there something useful about anxiety? 

It certainly makes sense to talk about these traits as having potential adaptive qualities to them. So even something like worry, it brings your attention to something in the future that might be good to plan for. There might be an adverse outcome, and if you do something about it, you might be able to prevent that from happening, so you could talk about that as being adaptive.

But we know that 90 percent of what we worry about actually never comes to pass. So we're spending a lot of mental energy and building up neural pathways using these potentially helpful strategies for events that are not ever going to happen.

How have these kinds of insights changed how you deal with patients?

Patients have found it really helpful when I explain what's going on in terms of neuroplasticity and in terms of building up neural connections, for them to realize, “Oh my gosh, I've been worrying about this for 20 years. I'm just a worrier.” OK, well, you know what? You've got neural pathways in your brain that are really well developed for worry. And what we're really wanting to do in treatment now is actually build up another set of neural pathways for approaching problems of life and our approach to the future in a different manner. 

So you're creating a sort of rival system to sort of take over because there’s no way to break down the previous system?

Yeah, there is no way because they built it up so strongly, so much has been invested in it with new neurons, new synapses being made and then what's called long-term potentiation. That's the strengthening of the synaptic synapses over time to support the worry. And once that's been done, that neural circuitry is not going anywhere.

This is the bad news about the neuroplasticity story. We can't do anything about all those neural pathways that you built with all the worry from the last 20 years. But what we can do is let that neural circuitry lie dormant. We don't have to fire those neurons. Those neural pathways can just sit there. So we have to build up the neural pathways for those different strategies, which is going to take a bit of time to do and needs a concerted effort. 

What kind of strategies do you suggest?

Utilizing mindfulness. Mindfulness is all about being in the present moment and that can be very helpful for somebody struggling with what might happen in the future. So getting people to switch over from those worry pathways in the brain to the present-focused mindfulness pathways. 

How does that help? Does it create greater tolerance for the uncertainty?

They get some specific instruction about concepts such as acceptance that there is uncertainty. Mindfulness can very much contribute to the development of the tolerance of uncertainty. People make some really good progress on that. Then there's a big stressful event in their life and all of a sudden they can't sleep well at night. They're going back to the old stuff and they're like, “God, this has been much better for the last six months and now I feel like I'm just back down to ground zero.” To which I can say, you are not back at ground zero because you now have the new neural circuit that you've been building over the last six months that you found really helpful. All we have to do now is switch over and start to activate that again.

Take someone who's been under your care for a long time and has been very successful at treatment. If you put them under the fMRI machine, what changes would you expect to see?

It depends. With an fMRI, you always have to have some sort of stimulation. But, for some sort of anticipation of a negative event, you might see less activation of the amygdala, maybe certain other parts of the brain that generally show larger response when there is anxiety. 

We are, for the first time in history, able to describe what's going on when we do psychotherapy for our patients. Just the way that a cardiologist can explain to their patient who just had a cardiac event and needs triple bypass surgery, he can point out onto a model exactly what's going to happen. We can't just point to some area of the brain and say, “That's anxiety.” But what we can do is to examine some of the symptoms of anxiety and point to how these neural pathways get built up over time, and then how the kinds of treatments that we do, like cognitive behavior therapy, for example, or exposure-based therapy, are leading to the building up a new neural connections that support healthier, adaptive responses. 

Explore other Uncertainty Boom interviews:

Jill Lepore, the Harvard historian, talks about her new book examining how technology is affecting our liberal democracy.

George W. Casey, a retired four-star US Army general, discusses leadership under uncertainty and the lessons he learned taking over the multinational force in Iraq in 2004.

Nicholas Bloom, an economist at Stanford University, discusses economic uncertainty: what it is, how it is measured and how it affects companies, countries, investors and consumers.

Kate Sweeny, a research psychologist, studies how uncertain outcomes affect our behavior and sometimes prompt poor decision-making.