I was feeling lonely one recent weekend. I craved company, but friends and family all seemed to be on vacation or busy. So I arranged to chat with a friend who lives in another city, signed up for a group kayak outing, and decided I’d take myself to Sunday brunch at a new restaurant nearby.

Then I canceled my plans, ignored my phone when it rang and read for two days. It didn’t make me less lonely. I was relieved Monday morning when the rhythm of work started up again.

Many lonely people wish they had social plans or a bigger network of friends to call upon. But sometimes, even when they do, they avoid contact. And this can lead to a downward spiral of more loneliness.

Now, two new studies by the husband and wife research team John and Stephanie Cacioppo, psychologists at the University of Chicago and leading authorities on the psychology and neuroscience of loneliness, show that this may be because people’s brains operate differently when they are lonely.

The researchers found that the electrical activity in the brains of lonely people occurred faster and was more extreme than that of non-lonely people when shown negative social cues. They believe that this means lonely people are constantly and subconsciously guarding against social threats.

“If I feel lonely, my brain is already in this attentive state,” says John Cacioppo, professor of psychology, psychiatry and behavioral neuroscience and director of the Center for Cognitive and Social Neuroscience at the University of Chicago.

For this reason, it is important to combat the urge to isolate when you already feel lonely—or expect that you might soon be.

In the first study, published online in July in the journal Cortex, 70 participants were recruited—38 who were very lonely and 32 who weren't lonely. Researchers then used electroencephalography (EEG) to assess the brain activity changes of the subjects as they were given a Stroop test, in which they were shown words written in different colors and asked to identify the color, not the meaning of the word. One-quarter of the words were social and positive (pal, admired), one-quarter were social and negative (disliked, unwanted), one-quarter were emotionally positive but nonsocial (joy, happy) and one-quarter were emotionally negative and nonsocial (angry, vomit).

In the next study, published online in August in Cognitive Neuroscience, 19 participants, 10 of whom were lonely, were shown 28 pictures while their brain activity was assessed using an EEG. Seven of the pictures were social and positive (for instance, people celebrating together), seven were social and negative (someone being mocked), seven were nonsocial and positive (pleasant scenery) and seven were nonsocial and negative (snakes).

Of course, loneliness isn't the same as being alone. You can be quite content being alone. Loneliness is what happens when you feel socially isolated, when there is a disconnect between your desired social relationships and your actual social relationships.

It is important to be self-aware about what loneliness does to your brain—that it primes it to be hypervigilant to threats and go into self-preservation mode. Feeling lonely might mean you need to reinterpret your view of your social interactions, says Dr. Cacioppo. For example, if you feel a friend has slighted you, ask yourself if you were actually hostile and in an isolation mode first and your friend is reacting to your behavior. “You need to understand that you may be responsible,” says Dr. Cacioppo.

This is called social cognitive retraining. Dr. Cacioppo suggests four steps to combat loneliness, which he describes by the acronym EASE:

Extend Yourself. “You cannot connect if you isolate yourself—or if you only connect online where many people present a non-authentic self,” Dr. Cacioppo says. Accept social invitations, even if you don’t feel like going out.

Develop an action plan. It isn’t enough to rely on random invites. Get your calendar out and map out your social life. Make sure your week is scattered with social activities. If you don’t have any, take the initiative to plan something and invite others to join you.

Share good times with people who have similar interests. The best way to not be lonely is to spend time with folks who share your interests, values and attitudes. If you don’t have people in your life who fit the bill, it is time to make a plan to meet more, which will require going to the right place. Love to read? Join a book club. Love to run? Join a runner’s group.

Expect the best. When you get lonely you may read other people’s actions wrong. Did your friend really blow you off? Or was she overwhelmed with work and children and truly too busy to call? “Give the other person the benefit of the doubt,” Dr. Cacioppo says. “Friends don’t mean their actions as negative as they sometimes appear.”

My new anti-loneliness antidote? I adopted a puppy. Scout demands that we get out of the house—multiple times a day. She happily makes friends with everyone she meets. And if the people we meet like Scout, it is a pretty good bet I will like them.

Write to Elizabeth Bernstein at elizabeth.bernstein@wsj.com or follow her on Twitter or Facebook at EBernsteinWSJ