Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain

Published Online:Jun 28 2016https://doi.org/10.1148/radiol.2016152893

Abstract

Low-dose methylene blue increased functional MR imaging activity during sustained attention and short-term memory tasks and potentiated memory retrieval.

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.

Article History

Received December 30, 2015; revision requested February 17, 2016; revision received March 4; accepted March 22; final version accepted April 5.
Published online: June 28 2016
Published in print: Nov 2016

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Vol. 281, No. 2

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Funding/Support

Supported by National Center for Advancing Translational Sciences (UL1TR001120) and Julio C. Palmaz, MD, Endowment for Excellence in Radiology Research.

Abbreviations

Abbreviations:
ANOVA	analysis of variance
BOLD	blood oxygen level dependent
CBF	cerebral blood flow
CVR	cerebrovascular reactivity
PANAS	positive and negative affect schedule
PCASL	pseudo-continuous arterial-spin labeling

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