title: The Functional Networks of Prepulse Inhibition: Neuronal Connectivity Analysis Based on FDG-PET in Awake and Unrestrained Rats.
abstract: Prepulse inhibition (PPI) is a neuropsychological process during which a weak sensory stimulus ("prepulse") attenuates the motor response ("startle reaction") to a subsequent strong startling stimulus. It is measured as a surrogate marker of sensorimotor gating in patients suffering from neuropsychological diseases such as schizophrenia, as well as in corresponding animal models. A variety of studies has shown that PPI of the acoustical startle reaction comprises three brain circuitries for: (i) startle mediation, (ii) PPI mediation, and (iii) modulation of PPI mediation. While anatomical connections and information flow in the startle and PPI mediation pathways are well known, spatial and temporal interactions of the numerous regions involved in PPI modulation are incompletely understood. We therefore combined [(18)F]fluoro-2-deoxyglucose positron-emission-tomography (FDG-PET) with PPI and resting state control paradigms in awake rats. A battery of subtractive, correlative as well as seed-based functional connectivity analyses revealed a default mode-like network (DMN) active during resting state only. Furthermore, two functional networks were observed during PPI: Metabolic activity in the lateral circuitry was positively correlated with PPI effectiveness and involved the auditory system and emotional regions. The medial network was negatively correlated with PPI effectiveness, i.e., associated with startle, and recruited a spatial/cognitive network. Our study provides evidence for two distinct neuronal networks, whose continuous interplay determines PPI effectiveness in rats, probably by either protecting the prepulse or facilitating startle processing. Discovering similar networks affected in neuropsychological disorders may help to better understand mechanisms of sensorimotor gating deficits and provide new perspectives for therapeutic strategies.
authors: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityMannheim, Germany; Institute of Radiochemistry and Experimental Molecular Imaging, University Hospital of CologneCologne, Germany.
authors: Cathrin
authors: C
authors: Rohleder
authors: In-Vivo NMR Laboratory, Max-Planck-Institute for Metabolism Research Cologne, Germany.
authors: Dirk
authors: D
authors: Wiedermann
authors: Institute of Radiochemistry and Experimental Molecular Imaging, University Hospital of CologneCologne, Germany; Forschungszentrum Jülich GmbH, Institute of Neurosciences and Medicine, INM-5: Nuclear ChemistryJülich, Germany.
authors: Bernd
authors: B
authors: Neumaier
authors: Department of Nuclear Medicine, University Hospital of Cologne Cologne, Germany.
authors: Alexander
authors: A
authors: Drzezga
authors: Department of Neurology, University Hospital of Cologne Cologne, Germany.
authors: Lars
authors: L
authors: Timmermann
authors: Multimodal Imaging of Brain Metabolism, Max-Planck-Institute for Metabolism Research Cologne, Germany.
authors: Rudolf
authors: R
authors: Graf
authors: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany.
authors: F Markus
authors: FM
authors: Leweke
authors: Institute of Radiochemistry and Experimental Molecular Imaging, University Hospital of Cologne Cologne, Germany.
authors: Heike
authors: H
authors: Endepols
keywords: PPI modulation; PPI network; behavioral PET; cerebral glucose consumption; metabolic connectivity