Introduction: Lisdexamfetamine (LDX) is a drug used to treat ADHD/impulsive patients.
Impulsivity is known to affect inhibitory, emotional and cognitive function. On the other hand, smell
and odor processing are known to be affected by neurological disorders, as they are modulators of addictive
and impulsive behaviors specifically. We hypothesize that, after LDX ingestion, inhibitory
pathways of the brain would change, and complementary behavioral regulation mechanisms would
appear to regulate decision-making and impulsivity.
Methods: 20 children were studied in an aleatory crossover study. Imaging of BOLD-fMRI activity,
elicited by olfactory stimulation in impulsive children, was performed after either LDX or placebo ingestion.
Results: Findings showed that all subjects who underwent odor stimulation presented activations of
similar intensities in the olfactory centers of the brain. This contrasted with inhibitory regions of the
brain such as the cingulate cortex and frontal lobe regions, which demonstrated changed activity patterns
and intensities. While some differences between the placebo and medicated states were found in
motor areas, precuneus, cuneus, calcarine, supramarginal, cerebellum and posterior cingulate cortex,
the main changes were found in frontal, temporal and parietal cortices. When comparing olfactory
cues separately, pleasant food smells like chocolate seemed not to present large differences between
the medicated and placebo scenarios, when compared to non-food-related smells.
Conclusion: It was demonstrated that LDX, first, altered the inhibitory pathways of the brain, secondly
it increased activity in several brain regions which were not activated by smell in drug-naïve patients,
and thirdly, it facilitated a complementary behavioral regulation mechanism, run by the cerebellum,
which regulated decision-making and impulsivity in motor and frontal structures.