title: Acetylcholine mediates behavioral and neural post-error control.
abstract: Humans often commit errors when they are distracted by irrelevant information and no longer focus on what is relevant to the task at hand. Adjustments following errors are essential for optimizing goal achievement. The posterior medial frontal cortex (pMFC), a key area for monitoring errors, has been shown to trigger such post-error adjustments by modulating activity in visual cortical areas. However, the mechanisms by which pMFC controls sensory cortices are unknown. We provide evidence for a mechanism based on pMFC-induced recruitment of cholinergic projections to task-relevant sensory areas. Using fMRI in healthy volunteers, we found that error-related pMFC activity predicted subsequent adjustments in task-relevant visual brain areas. In particular, following an error, activity increased in those visual cortical areas involved in processing task-relevant stimulus features, whereas activity decreased in areas representing irrelevant, distracting features. Following treatment with the muscarinic acetylcholine receptor antagonist biperiden, activity in visual areas was no longer under control of error-related pMFC activity. This was paralleled by abolished post-error behavioral adjustments under biperiden. Our results reveal a prominent role of acetylcholine in cognitive control that has not been recognized thus far. Regaining optimal performance after errors critically depends on top-down control of perception driven by the pMFC and mediated by acetylcholine. This may explain the lack of adaptivity in conditions with reduced availability of cortical acetylcholine, such as Alzheimer's disease.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Montessorilaan 3, 6525 HR Nijmegen, the Netherlands; Max Planck Institute for Neurological Research, Gleueler Strasse 50, 50931 Cologne, Germany; Department of Neuropsychology, Otto-von-Guericke-Universität, Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: c.danielmeier@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Danielmeier
authors.affiliation: Department of Biological and Medical Psychology, University of Bergen, Jonas Liesvei 91, 5009 Bergen, Norway; The Mind Research Network, 1101 Yale Boulevard NE, Albuquerque, NM 87106, USA.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Allen
authors.affiliation: Center for Behavioral Brain Sciences, Otto-von-Guericke-Universität, Universitätsplatz 2, 39106 Magdeburg, Germany; Faculty of Economics and Management, Otto-von-Guericke-Universität, Universitätsplatz 2, 39106 Magdeburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jocham
authors.affiliation: Department of Neurology, University Hospital Cologne, Kerpener Strasse 62, 50937 Cologne, Germany; Institut für Neurowissenschaften und Medizin, Research Center Jülich, Leo-Brandt-Strasse, 52425 Jülich, Germany.
authors.forename: Oezguer A
authors.initials: OA
authors.lastname: Onur
authors.affiliation: Department of Biological and Medical Psychology, University of Bergen, Jonas Liesvei 91, 5009 Bergen, Norway; The Mind Research Network, 1101 Yale Boulevard NE, Albuquerque, NM 87106, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Eichele
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Montessorilaan 3, 6525 HR Nijmegen, the Netherlands; Max Planck Institute for Neurological Research, Gleueler Strasse 50, 50931 Cologne, Germany; Department of Neuropsychology, Otto-von-Guericke-Universität, Universitätsplatz 2, 39106 Magdeburg, Germany; Center for Behavioral Brain Sciences, Otto-von-Guericke-Universität, Universitätsplatz 2, 39106 Magdeburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ullsperger
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D001519:Behavior / Q000502:physiology*; D001712:Biperiden; D003071:Cognition / Q000502:physiology*; D005625:Frontal Lobe / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D014793:Visual Cortex / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001712:Biperiden; D000109:Acetylcholine