Imagine sitting alone in an empty movie theater. Just before the film starts, another person comes in and takes the seat right next to you, even though there are plenty of other seats available.

How would you react?

Presumably, you wouldn’t be very comfortable. It would probably be difficult to concentrate on the movie. Your fight or flight response might even kick in.

How would your reaction differ if you were in a crowded theater, and the same person took the seat next to you because it was the only one left? In that context, it seems much more reasonable.

We have similar unspoken rules about making eye contact. Too much eye contact can seem threatening or flirtatious, while too little can make the other person think you are bored or disinterested.

Most of us manage these behaviors by instinct. But what happens when the brain circuitry driving them misfires? When the simple act of making brief eye contact causes the same burning sensation as if someone is staring right at you, or when your personal space bubble becomes so enlarged that others can make you uncomfortable without realizing it?

Two researchers at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital are using brain imaging technology to gain new insights into how the brain systems that typically manage personal space and eye contact work differently in individuals with schizophrenia and autism.

Daphne Holt, MD, PhD, is exploring how perceptions of personal space differ in individuals with schizophrenia, and how these differences contribute to symptoms such as isolation and withdrawal. Nouchine Hadjikhani, MD, PhD, is studying how individuals with autism respond to eye contact, and how this can influence their behavior and social interactions.

Their findings could revolutionize the way we understand, treat and assess those who suffer from these disorders.

The Story Behind the Science

Functional magnetic resonance imaging, or fMRI, is a method of measuring brain activity by detecting changes in blood flow. While the technology is now used widely across the globe, the concept can be traced back to two papers published in the early 1990s by Martinos Center investigators Kenneth Kwong, PhD, and the late Jack Belliveau, PhD.

Dr. Holt and her team are using fMRI to measure the activity in the parietal frontal network of the brain, which is tasked with monitoring objects in close proximity to us.

The team created a study where participants were presented with a series of images that appear to be progressively coming closer. They first ran the test in healthy participants, which confirmed that this part of the brain was activated by approaching objects, and that the activation was greatest when the approaching images were human faces.

They then conducted the same study in individuals with schizophrenia, where they saw significantly higher levels of network activation, particularly when the participants looked at approaching faces.

The team then compared these results to a set of symptoms experienced by schizophrenic individuals that are known collectively as “negative symptoms." Negative symptoms include social withdrawal, isolation and demonstrating a lack of interest in other people or activities.

They found that the study participants who showed the largest spike in brain activity when shown images of approaching faces were also the ones who had the pronounced negative symptoms.

The results suggest that individuals with schizophrenia are more reactive to perceived intrusions into their personal space, and that this sensitivity could contribute to behaviors such as withdrawal and isolation.

Dr. Hadjikhani uncovered a similar pattern of excessive brain activity in individuals with autism in the context of making eye contract.

Using fMRI scans, Hadjikhani and her team compared the activity of a region of the brain called the subcortical face-processing network in individuals with autism and control subjects when both groups were shown short movies of human faces.

Both groups displayed similar levels of brain activity when allowed to gaze freely at the movies without having their focus directed to a specific area. But when the test was altered to narrow the focus to the eyes of the people in the videos, the team saw significantly higher levels of brain activation in the participants with autism, particularly in areas involved with the processing of threats.

“This helps to explain why one of the first things you notice in someone with autism is an unusual way of making eye contact,” Hadjikhani says.

She explains that many autistic individuals describe making eye contact as extremely bothersome. It can feel like their eyes are burning, or produce such a sensory overload that they essentially shut down, which makes it hard for them to listen to what the other person is saying.

This creates a lot of social challenges. For one thing, humans perceive a lot of subtle emotional cues by looking directly at someone. Without that information to help guide behavior, it becomes much more difficult to interact with others.

While Holt and Hadjikhani have been conducting their research separately, they can see clear connections. “There is a genetic overlap between autism and schizophrenia, so we may be talking about the same or a similar thing biologically,” Holt says.

Encouraging Progress

More work still needs to be done before Holt and Hadjikhani can translate their findings into the clinic, but both researchers have been encouraged by their recent progress.

“I think we’re really getting somewhere,” Holt says, noting that the lack of scientifically validated biomarkers for schizophrenia has made it difficult to develop treatments for the negative symptoms of the disease. “We’re close to being able to use this science to actually help people, so I’m looking forward to that.”

Hadjikhani is pleased that her work is helping to explain why autistic individuals act in certain ways. Many mistakenly perceive a lack of eye contact as signs of boredom or disinterest, rather than as a protective measure against sensory overload, she explains.

“What motivates me is when I publish a paper and get all these emails from people with autism or their parents or caregivers, who say, ‘Now it makes sense,’” Hadjikhani says. “You feel so happy if you can help those who struggle with this condition to be better understood.”