Delusions—beliefs that can seem bizarre and appear unsupported by evidence—are a hallmark of the most severe mental illnesses.

Yale investigators used brain imaging to probe the persistence of delusions, which often endure in the face of contradicting evidence. The results of their study, published in the journal PLOS ONE, suggest that being in a delusional state can strengthen the formation of both positive and negative memories.

In the current experiment, healthy subjects were shown pictures that predicted either a negative or a positive memory—an unpleasant loud noise or a sip of sweet fruit juice, respectively.

The next day, researchers induced a brief and reversible delusional state among a subset of those individuals. While in this state, individuals were shown the picture again.

The following day, the scientists measured the individual's response to the picture. Compared to memories that were not reactivated and memories that were reminded under a placebo infusion (salty water with no delusional effects), the scientists found that the delusional state made the reactivated memory stronger.

"Our study suggests important and previously unknown features of delusions," said Philip Corlett, PhD, assistant professor of psychiatry at Yale School of Medicine, and the study's lead author. He continued, "The more we can learn about these puzzling symptoms, the more likely we will be able to develop new and novel treatments for a number of psychiatric disorders."

The researchers had previously observed that activity in the brain's right dorsolateral prefrontal cortex predicted delusion severity in patients with psychosis. Having developed this neural marker of the processes underlying delusions, the researchers sought to explore whether that activity related to the memory strengthening effect. They measured the healthy subjects’ brain responses a month before the memory study and found that the brain response predicted the memory strengthening effect of the induced delusional state.

Corlett added, "The brain response we measured is an index of surprise. When we are surprised, we bring memories to mind to explain away the surprise. We hypothesize that patients with delusions are surprised too much which makes them hold odd beliefs. This new work suggests that the surprise signal also makes those beliefs fixed."

This research was supported by the Wellcome Trust, which unites researchers from the Yale Department of Psychiatry and the University of Cambridge Departments of Psychology and Psychiatry.