title: Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex.
abstract: Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
authors.forename: Susanna A
authors.initials: SA
authors.lastname: Walter
authors.affiliation: Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Forsgren
authors.affiliation: Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Lundengård
authors.affiliation: Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Rozalyn
authors.initials: R
authors.lastname: Simon
authors.affiliation: The National Board of Forensic Medicine and Linköping University, Linköping, Sweden.
authors.forename: Maritha
authors.initials: M
authors.lastname: Torkildsen Nilsson
authors.affiliation: Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.|Radiation Physics, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Söderfeldt
authors.affiliation: Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.|Radiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Lundberg
authors.affiliation: Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Engström
mesh_terms: D000328:Adult; D000494:Allosteric Regulation; D003975:Diazepam / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018757:GABA Modulators / Q000493:pharmacokinetics / Q000494:pharmacology*; D006179:Gyrus Cinguli / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood*; D055815:Young Adult
chemical_list: D018757:GABA Modulators; D003975:Diazepam; D010100:Oxygen