title: Cholinergic blockade under working memory demands encountered by increased rehearsal strategies: evidence from fMRI in healthy subjects.
abstract: The connection between cholinergic transmission and cognitive performance has been established in behavioural studies. The specific contribution of the muscarinic receptor system on cognitive performance and brain activation, however, has not been evaluated satisfyingly. To investigate the specific contribution of the muscarinic transmission on neural correlates of working memory, we examined the effects of scopolamine, an antagonist of the muscarinic receptors, using functional magnetic resonance imaging (fMRI). Fifteen healthy male, non-smoking subjects performed a fMRI scanning session following the application of scopolamine (0.4 mg, i.v.) or saline in a placebo-controlled, repeated measure, pseudo-randomized, single-blind design. Working memory was probed using an n-back task. Compared to placebo, challenging the cholinergic transmission with scopolamine resulted in hypoactivations in parietal, occipital and cerebellar areas and hyperactivations in frontal and prefrontal areas. These alterations are interpreted as compensatory strategies used to account for downregulation due to muscarinic acetylcholine blockade in parietal and cerebral storage systems by increased activation in frontal and prefrontal areas related to working memory rehearsal. Our results further underline the importance of cholinergic transmission to working memory performance and determine the specific contribution of muscarinic transmission on cerebral activation associated with executive functioning.
authors: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany. bivoss@ukaachen.de
authors: Bianca
authors: B
authors: Voss
authors: Renate
authors: R
authors: Thienel
authors: Martina
authors: M
authors: Reske
authors: Thilo
authors: T
authors: Kellermann
authors: Abigail J
authors: AJ
authors: Sheldrick
authors: Sarah
authors: S
authors: Halfter
authors: Katrin
authors: K
authors: Radenbach
authors: Nadim J
authors: NJ
authors: Shah
authors: Ute
authors: U
authors: Habel
authors: Tilo T J
authors: TT
authors: Kircher
mesh_terms: D000328:Adult; D015536:Down-Regulation / Q000502:physiology; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology*; D016037:Single-Blind Method; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012601:Scopolamine