Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.
RATIONALE
Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans.


OBJECTIVES
Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity.


METHODS
Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later.


RESULTS
Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity.


CONCLUSIONS
Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.
['Wagner|Isabella C|IC|', 'van Buuren|Mariët|M|', 'Bovy|Leonore|L|', 'Morris|Richard G|RG|', 'Fernández|Guillén|G|']
D000293:Adolescent D000328:Adult D002395:Catecholamines D004311:Double-Blind Method D006624:Hippocampus D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D008568:Memory D057567:Memory, Long-Term D008774:Methylphenidate D009483:Neuropsychological Tests D013702:Temporal Lobe D055815:Young Adult
Systems consolidation Dopamine Norepinephrine Ritalin Synaptic tagging and capture fMRI