title: Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Kapittelweg 29, Nijmegen, 6525 EN, The Netherlands. isabella.c.wagner@gmail.com.
authors.forename: Isabella C
authors.initials: IC
authors.lastname: Wagner
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Kapittelweg 29, Nijmegen, 6525 EN, The Netherlands.
authors.forename: Mariët
authors.initials: M
authors.lastname: van Buuren
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Kapittelweg 29, Nijmegen, 6525 EN, The Netherlands.
authors.forename: Leonore
authors.initials: L
authors.lastname: Bovy
authors.affiliation: Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Morris
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Kapittelweg 29, Nijmegen, 6525 EN, The Netherlands.
authors.forename: Guillén
authors.initials: G
authors.lastname: Fernández
mesh_terms: D000293:Adolescent; D000328:Adult; D002395:Catecholamines / Q000378:metabolism*; D004311:Double-Blind Method; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects*; D057567:Memory, Long-Term / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology*; D009483:Neuropsychological Tests; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
chemical_list: D002395:Catecholamines; D008774:Methylphenidate
keywords: Dopamine; Norepinephrine; Ritalin; Synaptic tagging and capture; Systems consolidation; fMRI