To see how the two gene versions affect the living human brain, the NIMH researchers scanned 24 healthy young adults twice using PET (positron emission tomography), which uses radioactive tracers to visualize brain function. The first scan measured subjects' overall brain activity while they performed working memory tasks. The second scan used a dopamine tracer to reveal the synthesis of the neurotransmitter in the midbrain.
Frontal cortex activity increased as midbrain dopamine activity increased in subjects with val, but decreased in those who had inherited two copies of the met COMT gene.
This "trait-like characteristic" of COMT gene type fits a model in which the prefrontal cortex functions optimally when dopamine activity is neither too low nor too high, corresponding to the top of an upside-down "U" (see diagram below). In this model, people with val fall on the left (rising) slope, with lower dopamine levels, while those with met fall on the right (falling) slope, with higher dopamine levels.
The findings suggest that dopamine "tunes" prefrontal neurons (brain cells) to achieve an optimal signal-to-noise ratio, much like a fine-tuning dial on a radio. For the clearest signal, the "dial" must be turned in opposite directions, depending on which version of the COMT gene one inherits: up with val, down with met. In people with val and schizophrenia, which is marked by too little prefrontal and too much midbrain dopamine, the dial is turned "way up," the NIMH researchers speculate.
"We expected that there would be different regulatory mechanisms be