A new understanding of brain activity when we ‘read the minds’ of others

Imagine you are about to confront a friend about a hurtful comment she made and are trying to predict her response. Depending on what you know about your friend, you might infer that she will understand where you’re coming from and apologize, get defensive, or respond with a criticism of you.

This process of trying to predict other people’s beliefs, intentions, and emotions is known as mentalizing, and the dorsal medial prefrontal cortex (DMPFC) is one of the key brain regions that make up what is known as the “mentalizing network.” Studies have shown that the network is more engaged during mentalizing than when people make other kinds of inferences, such as about objects—like the comfortability of a chair—or human physical traits.

But new research from psychologists at the University of Pennsylvania challenges the interpretation of these findings by highlighting a confounding variable in DMPFC activation: uncertainty.

They found that the region was engaged not only when people tried to resolve uncertainty in order to form assessments about what others were thinking and feeling, but also when they faced uncertainty about objects and human physical traits. Their study—one of the few to directly examine relationships between uncertainty and social cognition—is published in the Journal of Neuroscience.

“Our work points to uncertainty as an important factor that might help explain differences in how people think and behave in social compared to nonsocial contexts,” says senior author Adrianna (Anna) Jenkins, an associate professor of psychology in the School of Arts & Sciences. She and postdoctoral researcher Dilara Berkay, the paper’s first author, note that DMPFC activation seems to be driven by uncertainty, which is often elevated in social contexts—hence why previous research indicates activation is higher because of the social context.

Their findings came from scanning the brains of 46 participants using functional magnetic resonance imaging (fMRI) as they made inferences about one mental domain and two nonmental domains: human minds, human bodies, and physical objects.

To determine whether brain activity is driven by differences in domain or by differences in level of uncertainty, the researchers varied the level of uncertainty in each of the three conditions, Berkay explains. To measure levels of uncertainty, they ran an online pilot study before the fMRI scanning in which they asked participants to rate from 1 to 100 how informative one characteristic is for their assessment of another.

Then, during fMRI scanning, participants were asked how likely one characteristic was to describe the same personality, human body, or piece of furniture as another. For example, given that a person is compassionate, how likely is it they are sincere? Knowing a person is redheaded, how likely is it they are short? They found that uncertainty was associated with DMPFC activation across all three categories.

Their findings open avenues for better understanding conditions with atypical mentalizing, such as autism spectrum disorder and social anxiety. Berkay notes that autism is associated with atypical mentalizing despite typical performance on nonsocial tasks, and that it is also associated with higher levels of intolerance to uncertainty.

“Our findings provide a unifying framework for understanding these seemingly separate findings by suggesting that the atypical performance we observe in autistic individuals during mental tasks might be due to differences in responses to uncertainty, or strategies of uncertainty reduction, and therefore has implications for potential interventions that can be fruitful,” Berkay says.

Jenkins adds, “This is one of the future directions about which we’re most excited. We’re especially curious to see if it’s possible to get new traction on understanding autism and other ‘social’ conditions by reconceptualizing aspects of atypical social cognition as atypical uncertainty cognition.”

This study focused on uncertainty about people and objects, but Jenkins and Berkay note that the question of whether DMPFC plays a role in uncertainty reduction about other things is one for future experiments.

Looking ahead, the researchers are working on characterizing different types of uncertainty—such as reducible and irreducible uncertainty—including how they relate to DMPFC activation and disorders of social function. Other future directions for research include characterizing how different people process uncertainty, understanding whether certain kinds of uncertainty are especially prevalent in people’s lives, and distinguishing the strategies people use to reduce uncertainty in social and nonsocial contexts.

Adrianna (Anna) Jenkins is an associate professor of psychology in the School of Arts & Sciences at the University of Pennsylvania.

Dilara Berkay is a postdoctoral fellow in the Jenkins Lab at Penn Arts & Sciences.

This research is supported by the University of Pennsylvania University Research Foundation.