title: The Neurocognitive Cost of Enhancing Cognition with Methylphenidate: Improved Distractor Resistance but Impaired Updating.
abstract: A balance has to be struck between supporting distractor-resistant representations in working memory and allowing those representations to be updated. Catecholamine, particularly dopamine, transmission has been proposed to modulate the balance between the stability and flexibility of working memory representations. However, it is unclear whether drugs that increase catecholamine transmission, such as methylphenidate, optimize this balance in a task-dependent manner or bias the system toward stability at the expense of flexibility (or vice versa). Here we demonstrate, using pharmacological fMRI, that methylphenidate improves the ability to resist distraction (cognitive stability) but impairs the ability to flexibly update items currently held in working memory (cognitive flexibility). These behavioral effects were accompanied by task-general effects in the striatum and opposite and task-specific effects on neural signal in the pFC. This suggests that methylphenidate exerts its cognitive enhancing and impairing effects through acting on the pFC, an effect likely associated with methylphenidate's action on the striatum. These findings highlight that methylphenidate acts as a double-edged sword, improving one cognitive function at the expense of another, while also elucidating the neurocognitive mechanisms underlying these paradoxical effects.
authors: Radboud University Donders Institute of Brain, Cognition, and Behavior.|University of Oxford.
authors: Sean James
authors: SJ
authors: Fallon
authors: Radboud University Donders Institute of Brain, Cognition, and Behavior.|Radboud University Nijmegen Medical Centre.
authors: Marieke E
authors: ME
authors: van der Schaaf
authors: Radboud University Nijmegen Medical Centre.
authors: Niels
authors: N
authors: Ter Huurne
authors: Radboud University Donders Institute of Brain, Cognition, and Behavior.|Radboud University Nijmegen Medical Centre.
authors: Roshan
authors: R
authors: Cools
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D056344:Executive Function / Q000187:drug effects*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008774:Methylphenidate / Q000009:adverse effects / Q000494:pharmacology*; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate