title: Cerebellar cortex and cerebellar nuclei are concomitantly activated during eyeblink conditioning: a 7T fMRI study in humans.
abstract: There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortex may be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages. As yet, human studies have provided little to resolve this question. In the present study, we established a setup that allows ultra-high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar cortex and interposed cerebellar nuclei simultaneously during delay eyeblink conditioning in humans. Event-related fMRI signals increased concomitantly in the cerebellar cortex and nuclei during early acquisition of conditioned eyeblink responses in 20 healthy human subjects. ANOVAs with repeated-measures showed significant effects of time across five blocks of 20 conditioning trials in the cortex and nuclei (p < 0.05, permutation corrected). Activations were most pronounced in, but not limited to, lobules VI and interposed nuclei. Increased activations were most prominent at the first time the maximum number of conditioned responses was achieved. Our data are consistent with a simultaneous and synergistic two-site model of learning during acquisition of classically conditioned eyeblinks. Because increased MRI signal reflects synaptic activity, concomitantly increased signals in the cerebellar nuclei and cortex are consistent with findings of learning related potentiation at the mossy fiber to nuclear cell synapse and mossy fiber to granule cell synapse. Activity related to the expression of conditioned responses, however, cannot be excluded.
authors.affiliation: Departments of Neurology, University Clinic Essen, Erwin L. Hahn Institute for MRI, and.
authors.forename: Markus
authors.initials: M
authors.lastname: Thürling
authors.affiliation: Departments of Neurology, University Clinic Essen.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kahl
authors.affiliation: Erwin L. Hahn Institute for MRI, and.
authors.forename: Stefan
authors.initials: S
authors.lastname: Maderwald
authors.affiliation: Departments of Neurology, University Clinic Essen, Erwin L. Hahn Institute for MRI, and.
authors.forename: Roxana M
authors.initials: RM
authors.lastname: Stefanescu
authors.affiliation: Diagnostic and Interventional Radiology and Neuroradiology, University Clinic Essen, University of Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schlamann
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Boele
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands, The Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
authors.affiliation: Institute of Cognitive Neuroscience, University College London, WC1N 3AR London, United Kingdom, and.
authors.forename: Jörn
authors.identifier: http://orcid.org/0000-0003-0264-8532
authors.initials: J
authors.lastname: Diedrichsen
authors.affiliation: Erwin L. Hahn Institute for MRI, and Division of Medical Physics in Radiology (E020), German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ladd
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: Sebastiaan K E
authors.initials: SK
authors.lastname: Koekkoek
authors.affiliation: Departments of Neurology, University Clinic Essen, dagmar.timmann-braun@uni-due.de.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Timmann
mesh_terms: D000328:Adult; D001767:Blinking / Q000502:physiology; D002525:Cerebellar Cortex / Q000502:physiology*; D002529:Cerebellar Nuclei / Q000502:physiology*; D003215:Conditioning, Eyelid / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000502:physiology; D055815:Young Adult
keywords: acquisition; cerebellum; eyeblink conditioning; fMRI; human; interposed nuclei