A brain region called the medial prefrontal cortex (mPFC) maintains a structured map of a person's social circles, based on closeness. People that struggle with loneliness often perceive a gap between themselves and others. This gap is reflected by the activity patterns of the mPFC.

Courtney and Meyer used functional magnetic resonance imaging to examine participants' brain activity while they thought about the self, close friends, acquaintances, and celebrities. Thinking about someone from each category corresponded to a different activity pattern in the mPFC: one for the self, one for the social network (both friends and acquaintances), and one for celebrities. The closer the relationship, the more the pattern resembled the pattern seen when thinking about the self.

These brain patterns differed for lonelier individuals. Activity related to thinking about the self was more different from activity related to thinking about others, while the activity from thinking about others was more similar across social categories. In other words, lonelier people have a "lonelier" neural representation of their relationships.