Investigators at the University of Michigan and Eli Lilly measured levels of a neurotransmitter called acetylcholine, which is involved in attention and memory, while rats monitored a screen for a signal.
At the end of each trial, the rat had to indicate if a signal had occurred.
Researchers noticed that if a signal occurred after a long period of monitoring or "non-signal" processing, there was a spike in acetylcholine in the rat's right prefrontal cortex. No such spike occurred for another signal occurring shortly afterwards.
Researchers repeated the study in humans using functional magnetic resonance imaging (fMRI), which measures brain activity, and also found a short increase in right prefrontal cortex activity for the first signal in a series.
To connect the findings between rats and humans, they measured changes in oxygen levels, similar to the changes that produce the fMRI signal, in the brains of rats performing the task.
Together, the studies' results provide some of the most direct evidence, so far, linking a specific neurotransmitter response to changes in brain activity in humans.
The findings could guide the development of better treatments for disorders in which people have difficulty switching out of current behaviours and activating new ones.
Repetitive behaviours associated with obsessive-compulsive disorder and autism are the most obvious examples, and related mechanisms may underlie problems with preservative behaviour in schizophrenia, dementia and ageing.
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