title: Acetylcholine modulates human working memory and subsequent familiarity based recognition via alpha oscillations.
abstract: Working memory (WM) can be defined as the ability to maintain and process physically absent information for a short period of time. This vital cognitive function has been related to cholinergic neuromodulation and, in independent work, to theta (4-8Hz) and alpha (9-14Hz) band oscillations. However, the relationship between both aspects remains unclear. To fill this apparent gap, we used electroencephalography (EEG) and a within-subject design in healthy humans who either received the acetylcholinesterase inhibitor galantamine (8mg) or a placebo before they performed a Sternberg WM paradigm. Here, sequences of sample images were memorized for a delay of 5s in three different load conditions (two, four or six items). On the next day, long-term memory (LTM) for the images was tested according to a remember/know paradigm. As a main finding, we can show that both theta and alpha oscillations scale during WM maintenance as a function of WM load; this resembles the typical performance decrease. Importantly, cholinergic stimulation via galantamine administration slowed down retrieval speed during WM and reduced associated alpha but not theta power, suggesting a functional relationship between alpha oscillations and WM performance. At LTM, this pattern was accompanied by impaired familiarity based recognition. These findings show that stimulating the healthy cholinergic system impairs WM and subsequent recognition, which is in line with the notion of a quadratic relationship between acetylcholine levels and cognitive functions. Moreover, our data provide empirical evidence for a specific role of alpha oscillations in acetylcholine dependent WM and associated LTM formation.
authors.affiliation: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; Department of Psychology, Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Cindy
authors.initials: C
authors.lastname: Eckart
authors.affiliation: Department of Psychology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
authors.forename: Agata
authors.initials: A
authors.lastname: Woźniak-Kwaśniewska
authors.affiliation: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Nora A
authors.initials: NA
authors.lastname: Herweg
authors.affiliation: Cognition and Brain Plasticity Group, [Bellvitge Biomedical Research Institute] IDIBELL, L'Hospitalet de Llobregat, Barcelona 08097, Spain; Department of Cognition, Development and Educational Psychology, Faculty of Psychology, and Institute of Neuroscience, University of Barcelona, Barcelona 08035, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Fuentemilla
authors.affiliation: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; Department of Psychology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany. Electronic address: nico.bunzeck@uni-luebeck.de.
authors.forename: Nico
authors.initials: N
authors.lastname: Bunzeck
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D000513:Alpha Rhythm / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology*; D055815:Young Adult
chemical_list: D000109:Acetylcholine