title: Methylene blue modulates functional connectivity in the human brain.
abstract: Methylene blue USP (MB) is a FDA-grandfathered drug used in clinics to treat methemoglobinemia, carbon monoxide poisoning and cyanide poisoning that has been shown to increase fMRI evoked blood oxygenation level dependent (BOLD) response in rodents. Low dose MB also has memory enhancing effect in rodents and humans. However, the neural correlates of the effects of MB in the human brain are unknown. We tested the hypothesis that a single low oral dose of MB modulates the functional connectivity of neural networks in healthy adults. Task-based and task-free fMRI were performed before and one hour after MB or placebo administration utilizing a randomized, double-blinded, placebo-controlled design. MB administration was associated with a reduction in cerebral blood flow in a task-related network during a visuomotor task, and with stronger resting-state functional connectivity in multiple regions linking perception and memory functions. These findings demonstrate for the first time that low-dose MB can modulate task-related and resting-state neural networks in the human brain. These neuroimaging findings support further investigations in healthy and disease populations.
authors.affiliation: Research Imaging Institute, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA. rodriguezp3@uthscsa.edu.|Department of Radiology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Stop 7800, San Antonio, TX, 78229, USA. rodriguezp3@uthscsa.edu.
authors.forename: Pavel
authors.initials: P
authors.lastname: Rodriguez
authors.affiliation: Department of Radiology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Stop 7800, San Antonio, TX, 78229, USA.
authors.forename: Amar P
authors.initials: AP
authors.lastname: Singh
authors.affiliation: Research Imaging Institute, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Malloy
authors.affiliation: Research Imaging Institute, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Barrett
authors.affiliation: Research Imaging Institute, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.
authors.forename: Crystal G
authors.initials: CG
authors.lastname: Franklin
authors.affiliation: Department of Radiology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Stop 7800, San Antonio, TX, 78229, USA.
authors.forename: Wilson B
authors.initials: WB
authors.lastname: Altmeyer
authors.affiliation: Department of Radiology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Stop 7800, San Antonio, TX, 78229, USA.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Gutierrez
authors.affiliation: Research Imaging Institute, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.
authors.forename: Jinqi
authors.initials: J
authors.lastname: Li
authors.affiliation: Research Imaging Institute, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.
authors.forename: Betty L
authors.initials: BL
authors.lastname: Heyl
authors.affiliation: Research Imaging Institute, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.
authors.forename: Jack L
authors.initials: JL
authors.lastname: Lancaster
authors.affiliation: Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: F
authors.initials: F
authors.lastname: Gonzalez-Lima
authors.affiliation: Research Imaging Institute, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA. duongt@uthscsa.edu.
authors.forename: Timothy Q
authors.initials: TQ
authors.lastname: Duong
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D011619:Psychotropic Drugs / Q000494:pharmacology*; D012146:Rest; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D011619:Psychotropic Drugs; D008751:Methylene Blue
keywords: Default mode network; Evoked response; Functional connectivity; Methylene blue; Multimodal fMRI