title: Neural mechanisms of placebo anxiolysis.
abstract: The beneficial effects of placebo treatments on fear and anxiety (placebo anxiolysis) are well known from clinical practice, and there is strong evidence indicating a contribution of treatment expectations to the efficacy of anxiolytic drugs. Although clinically highly relevant, the neural mechanisms underlying placebo anxiolysis are poorly understood. In two studies in humans, we tested whether the administration of an inactive treatment along with verbal suggestions of anxiolysis can attenuate experimentally induced states of phasic fear and/or sustained anxiety. Phasic fear is the response to a well defined threat and includes attentional focusing on the source of threat and concomitant phasic increases of autonomic arousal, whereas in sustained states of anxiety potential and unclear danger requires vigilant scanning of the environment and elevated tonic arousal levels. Our placebo manipulation consistently reduced vigilance measured in terms of undifferentiated reactivity to salient cues (indexed by subjective ratings, skin conductance responses and EEG event-related potentials) and tonic arousal [indexed by cue-unrelated skin conductance levels and enhanced EEG alpha (8-12 Hz) activity], indicating a downregulation of sustained anxiety rather than phasic fear. We also observed a placebo-dependent sustained increase of frontal midline EEG theta (4-7 Hz) power and frontoposterior theta coupling, suggesting the recruitment of frontally based cognitive control functions. Our results thus support the crucial role of treatment expectations in placebo anxiolysis and provide insight into the underlying neural mechanisms.
authors.affiliation: Institute for Systems Neuroscience, and Neuroimaging Center Mainz, Focus Program Translational Neuroscience, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany, and benmeyer@uni-mainz.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meyer
authors.affiliation: Institute for Systems Neuroscience, and Neuroimaging Center Mainz, Focus Program Translational Neuroscience, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany, and.
authors.forename: Kenneth S L
authors.initials: KS
authors.lastname: Yuen
authors.affiliation: Department of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany, Department of Neurology and Graduate School for Systemic Neuroscience, University of Munich, 81377 Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ertl
authors.affiliation: Department of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Nenad
authors.initials: N
authors.lastname: Polomac
authors.affiliation: Department of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mulert
authors.affiliation: Institute for Systems Neuroscience, and.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: Institute for Systems Neuroscience, and Neuroimaging Center Mainz, Focus Program Translational Neuroscience, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany, and.
authors.forename: Raffael
authors.initials: R
authors.lastname: Kalisch
mesh_terms: D000328:Adult; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology* / Q000628:therapy*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003463:Cues; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography; D005239:Fear; D005260:Female; D005712:Galvanic Skin Response; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000150:complications / Q000209:etiology / Q000523:psychology; D010147:Pain Measurement; D015990:Placebo Effect; D010919:Placebos / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: D010919:Placebos
keywords: EEG; anxiety; event-related potentials; frontal midline theta; placebo effect