title: Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.
abstract: Purpose To investigate the sustained-attention and memory-enhancing neural correlates of the oral administration of methylene blue in the healthy human brain. Materials and Methods The institutional review board approved this prospective, HIPAA-compliant, randomized, double-blinded, placebo-controlled clinical trial, and all patients provided informed consent. Twenty-six subjects (age range, 22-62 years) were enrolled. Functional magnetic resonance (MR) imaging was performed with a psychomotor vigilance task (sustained attention) and delayed match-to-sample tasks (short-term memory) before and 1 hour after administration of low-dose methylene blue or a placebo. Cerebrovascular reactivity effects were also measured with the carbon dioxide challenge, in which a 2 × 2 repeated-measures analysis of variance was performed with a drug (methylene blue vs placebo) and time (before vs after administration of the drug) as factors to assess drug × time between group interactions. Multiple comparison correction was applied, with cluster-corrected P < .05 indicating a significant difference. Results Administration of methylene blue increased response in the bilateral insular cortex during a psychomotor vigilance task (Z = 2.9-3.4, P = .01-.008) and functional MR imaging response during a short-term memory task involving the prefrontal, parietal, and occipital cortex (Z = 2.9-4.2, P = .03-.0003). Methylene blue was also associated with a 7% increase in correct responses during memory retrieval (P = .01). Conclusion Low-dose methylene blue can increase functional MR imaging activity during sustained attention and short-term memory tasks and enhance memory retrieval.©RSNA, 2016 Online supplemental material is available for this article.
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Pavel
authors.initials: P
authors.lastname: Rodriguez
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Barrett
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Wilson
authors.initials: W
authors.lastname: Altmeyer
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Juan E
authors.initials: JE
authors.lastname: Gutierrez
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Jinqi
authors.initials: J
authors.lastname: Li
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Jack L
authors.initials: JL
authors.lastname: Lancaster
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Francisco
authors.initials: F
authors.lastname: Gonzalez-Lima
authors.affiliation: From the Research Imaging Institute (P.R., W.Z., J.L., J.L.L., T.Q.D.) and Department of Radiology (P.R., W.A., J.E.G.), The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229; and Department of Psychology and Institute for Neuroscience, The University of Texas at Austin, Austin, Tex (D.W.B., F.G.L.).
authors.forename: Timothy Q
authors.initials: TQ
authors.lastname: Duong
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001288:Attention; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D011446:Prospective Studies; D011597:Psychomotor Performance / Q000187:drug effects*; D013647:Task Performance and Analysis
chemical_list: D004791:Enzyme Inhibitors; D008751:Methylene Blue