title: Practice and difficulty evoke anatomically and pharmacologically dissociable brain activation dynamics.
abstract: Brain activation is adaptive to task difficulty and practice. We used functional MRI to map brain systems activated by an object-location learning task in 24 healthy elderly volunteers each scanned following placebo and two of four active drugs studied. We distinguished a fronto-striatal system adaptive to difficulty from a posterior system adaptive to practice. Fronto-striatal response to increased cognitive load was significantly attenuated by scopolamine, sulpiride and methylphenidate; practice effects were not modulated by these drugs but were enhanced by diazepam. We also found enhancement by methylphenidate, and attenuation by sulpiride, of load response in premotor, cingulate and parietal regions comprising a spatial attention network. Difficulty and practice evoke anatomically and pharmacologically dissociable brain activation dynamics, which are probably mediated by different neurotransmitter systems in humans.
authors.affiliation: University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ. etb23@cam.ac.uk
authors.forename: Ed
authors.initials: E
authors.lastname: Bullmore
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.forename: Fernando
authors.initials: F
authors.lastname: Zelaya
authors.forename: Chris
authors.initials: C
authors.lastname: Long
authors.forename: Garry
authors.initials: G
authors.lastname: Honey
authors.forename: Laurence
authors.initials: L
authors.lastname: Reed
authors.forename: Carol
authors.initials: C
authors.lastname: Routledge
authors.forename: Virginia
authors.initials: V
authors.lastname: Ng
authors.forename: Paul
authors.initials: P
authors.lastname: Fletcher
authors.forename: John
authors.initials: J
authors.lastname: Brown
authors.forename: Steve C R
authors.initials: SC
authors.lastname: Williams
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000368:Aged; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D018757:GABA Modulators / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010296:Parietal Lobe / Q000187:drug effects / Q000502:physiology; D011214:Practice, Psychological; D012601:Scopolamine / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018492:Dopamine Antagonists; D018757:GABA Modulators; D018727:Muscarinic Antagonists; D008774:Methylphenidate; D013469:Sulpiride; D012601:Scopolamine; D003975:Diazepam