An amphetamine imaging study found that the relationship between brain-signal variability and working-memory performance depended on age and drug-session order. Greater variability was not a universal indicator of better performance.
Garrett and colleagues examined younger and older adults during a letter N-back task under amphetamine and placebo. Functional MRI quantified variability in the blood-oxygenation signal, rather than only its average amplitude. The analysis also considered whether a participant received the drug condition before or after placebo, allowing interactions with task practice to be examined.
Older adults showed lower signal variability on placebo but reached or exceeded younger-adult levels under amphetamine. However, the association with response speed and consistency varied by session order. Older adults receiving amphetamine first tended to improve when variability increased; patterns differed when amphetamine was given second. Counterbalancing order helps control an average sequence effect, but does not make a drug-by-practice interaction disappear.
The findings concern variability of an imaging signal, not variability in a drug concentration and not a direct measurement of dopamine release. A more youthful-looking signal does not automatically demonstrate restored everyday cognition. The experiment also does not establish a treatment for normal aging or an individual impairment threshold. Its practical lesson is methodological: the meaning of a biological change may depend on prior task exposure and population. Omitting those interactions can turn a conditional finding into an unsupported claim that increasing one brain measure always improves function.
See why different structural brain measures should remain separate.