title: Effects of sedation, stimulation, and placebo on cerebral blood oxygenation: a magnetic resonance neuroimaging study of psychotropic drug action.
abstract: The effects of pharmacologic depression and stimulation of cerebral activity were investigated in seven healthy young volunteers using blood oxygenation-sensitive MRI at 2.0 T. Dynamic gradient-echo imaging (7 min) was performed before, during and after the intravenous application of 10 mg diazepam and 15 mg metamphetamine as well as of the corresponding drug placebos (isotonic saline) in a brain section covering frontotemporal gray matter, subcortical gray matter structures, and cerebellum. The MRI responses were significantly different for the two drugs applied (p = 0.01). Relative to signal strength during injection, metamphetamine elicited a signal increase of 0.97 +/- 0.03% (mean +/- SD, p = 0.02) within the whole section 4-5 min after injection. Similarly, both placebo conditions led to a small signal increase, i.e. 0.50 +/- 0. 03% (n.s.) for the metamphetamine placebo and 0.40 +/- 0.07% (p = 0. 03) for the diazepam placebo. Diazepam abolished this signal increase. A topographic analysis revealed the metamphetamine-induced signal increase to be more pronounced in subcortical gray matter structures (p = 0.01) and cerebellum (p = 0.02) than in frontotemporal cortical gray matter (p = 0.04). This finding is in agreement with the hypothesis that pertinent responses not only reflect global cerebral hemodynamic adjustments, but also localized perfusion changes coupled to alterations in synaptic activity. The occurrence of a placebo response is best explained by expectancy and may provide a confounding factor in the design of functional activation experiments.
authors.affiliation: Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, D-37070 Göttingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kleinschmidt
authors.forename: H
authors.initials: H
authors.lastname: Bruhn
authors.forename: G
authors.initials: G
authors.lastname: Krüger
authors.forename: K D
authors.initials: KD
authors.lastname: Merboldt
authors.forename: G
authors.initials: G
authors.lastname: Stoppe
authors.forename: J
authors.initials: J
authors.lastname: Frahm
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D010919:Placebos
chemical_list: D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D010919:Placebos; D008694:Methamphetamine; D003975:Diazepam; D010100:Oxygen