Study in mice, people offers new approach to investigating mental illnesses
Researchers at Washington University School of Medicine in St. Louis devised a rigorous approach to study how hallucinations are produced in the brain in a study that shows there are important links between human and mouse minds in how they function and malfunction.
To study how hallucinations occur, the researchers set up a computer game that could be completed by both people and mice. The researchers played a particular sound, and subjects indicated that they'd heard it by clicking a button (people) or poking their noses into a port (mice).
The task was made challenging by obscuring the sound with background noise. People in the study rated how confident they felt that they'd accurately identified a real sound by moving a slider on a scale; mice indicated their confidence by how long they waited for a reward. When a subject confidently reported that he or she had heard a sound that was not actually played, the researchers labeled that a hallucination-like event.
While simple in design, the task appeared to tap into the brain circuits underlying hallucinations. People with more hallucination-like events during the experiment also were more likely to experience spontaneous hallucinations, as measured by questionnaires designed to evaluate psychiatric symptoms in the general population, even though no participants were diagnosed with a psychiatric condition.
To test whether mice also can be primed the same way, the researchers manipulated the mice's expectations by adjusting how frequently the sound was played. When the sound was played frequently, the mice were even more likely to confidently but wrongly report that they'd heard it, similar to people.
To better connect mouse and human experience, the researchers used a drug, ketamine, that induces hallucinations. Mice that were given ketamine before performing the task also reported more hallucination-like events.
Having established these crucial similarities between mice and people, the researchers then investigated the biological roots of hallucinations.
When studying mice, the researchers observed that elevations in dopamine levels preceded hallucination-like events and that artificially boosting dopamine levels induced more hallucination-like events. These behavioral effects could be blocked by administering the antipsychotic drug haloperidol, which blocks dopamine.
"There seems to be a neural circuit in the brain that balances prior beliefs and evidence, and the higher the baseline level of dopamine, the more you rely on your prior beliefs," said senior author Adam Kepecs, a professor of neuroscience and of psychiatry. "We think that hallucinations occur when this neural circuit gets unbalanced, and antipsychotics rebalance it. Our computer game probably engages this same circuit, so hallucination-like events reflect this circuit imbalance."
The study was published Friday in the journal Science.
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