What actually happens in the brain during a hallucination?

A person can experience visual hallucinations for many reasons, including the use of hallucinogenic substances or as a symptom of schizophrenia. But what are the brain mechanisms that explain hallucinations?

The Diagnostic and Statistical Manual of Mental Disorders (DSM-) defines hallucinations as “perceptual-like experiences that occur without an external stimulus” and that “are vivid and clear, with all the force and impact of normal perceptions , though not under voluntary control”.

While we understand some of the circumstances that cause hallucinations, often in the context of substance abuse, mental health conditions, or neurological conditions, we have yet to discover the specifics of how these phenomena manifest in the brain. Recently, a team of researchers at the University of Oregon at Eugene has endeavored to discover more information about how hallucinations affect brain activity.

Their new study, conducted in mouse models, has revealed some surprises that the researchers present in an article that appears in the journal Cell Reports.

Some surprising findings

The researchers worked with mice that were injected with a substance called 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI), a hallucinogenic drug that researchers often use in animal research.

Like other hallucinogens, including LSD, DOI interacts with serotonin 2A receptors, which are involved in the serotonin reuptake process, although they may also perform other, less understood, functions in the brain. Once they gave the mice this drug, the researchers showed them various images on the screen and used various specialized methods to record neural (brain cell) activity in these rodents.

The team found that, unlike what they expected, the mice experienced reduced signaling between neurons in the visual cortex, the region of the brain responsible for interpreting visual information. The timing of the neuron’s firing patterns also changed.

“You might expect neurons in the brain to fire like crazy, or by mismatched signals,” says lead author Cris Niell, who is an associate professor at the University of Oregon.
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“We were surprised to find that a hallucinogenic drug led to reduced activity in the visual cortex,” adds Niell. However, she continues, “in the context of visual processing, it made sense.”

The researchers also saw that the visual signals sent to the visual cortex were similar to the signals sent in the absence of the drug, meaning that the brain still received the same visual information, but was unable to process it correctly.

“Understanding what is happening in the world is a balance between assimilating information and your interpretation of that information. If you’re putting less weight on what’s going on around you but then over-interpreting it, that could lead to hallucinations. ‘

The team admits that studying hallucinations in mouse models is not ideal, since, of course, animals cannot communicate their experience. However, the researchers note that the same types of drugs that cause hallucinations in humans also cause visible movements and behavioral changes in mice.

This, the researchers explain, reasonably suggests that the same drugs alter brain activity in both animals and people. However, future studies should pay more attention to the reactions of animals to visual stimuli in the presence versus the absence of drugs.

“I don’t think we’ve necessarily found the smoking gun for the entire underlying cause of hallucinations, but this is likely part of it,” says Niell.

‘The data we have collected will provide a basis for further future studies. In particular, we plan to use genetic manipulation to study specific parts of this circuit in more detail, ‘adds the lead researcher.

And since previous research has suggested that serotonin 2A receptors, which the researchers also addressed in this study, are involved in schizophrenia, the researcher and the team would also like to know if their current findings can provide new insights regarding treatment of this and other mental disorders.

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