Methylene Blue Shows Promise for Improving Short Term Memory

Summary: According to researchers, a single dose of methylene blue could enhance short-term memory and attention.

Source: RSNA.

A single oral dose of methylene blue results in an increased MRI-based response in brain areas that control short-term memory and attention, according to a new study published online in the journal Radiology.

Methylene blue is used to treat methemoglobinemia, a blood disorder in which oxygen is unable to release effectively to body tissues, and as a surgical stain.

Animal studies have shown a single low dose of methylene blue enhances long-term contextual memory–the conscious recall of the source and circumstances of a specific memory–and extinction memory, a process in which a conditioned response from stimuli gradually diminishes over time.

“Although the memory-enhancing effects of methylene blue were shown in rodents in the 1970s, the underlying neuronal changes in the brain responsible for memory improvement and the effects of methylene blue on short-term memory and sustained-attention tasks have not been investigated,” said study author Timothy Q. Duong, Ph.D., from the University of Texas Health Science Center at San Antonio, Texas. “Our team decided to conduct the first multi-modal MRI study of methylene blue in humans.”

Twenty-six healthy participants, between the ages of 22 and 62, were enrolled in a double-blinded, randomized, placebo-controlled clinical trial to measure the effects of methylene blue on the human brain during working-memory and sustained-attention tasks. This study was approved by the local ethical committee.

Image shows brain scans.
Delayed match-to-sample task. Repeated-measures ANOVA results of the delayed match-to-sample task (colors indicate P values of significant voxels, cluster-based P ? .05; K ? 10) superimposed to a standard brain template. A, Probability map overlays show positive drug X time interactions in favor of a methylene blue effect in the bilateral inferior frontal gyri during the encoding phase, B, in the right superior frontal gyrus, left middle frontal gyrus, and posterior cerebellum during the maintenance phase, and, C, in the right inferior frontal gyrus and cuneus during the retrieval phase (n = 26, with 24 degrees of freedom). D, Representative blocks from the delayed match-to-sample task show the encoding, maintenance, retrieval, feedback, and rest phases as demarcated by set times. NeuroscienceNews.com image is adapted from the RSNA press release.

The participants underwent functional MRI (fMRI) before and one hour after low-dose methylene blue or placebo administration to evaluate the potential effects of methylene blue on cerebrovascular reactivity during tasks. Mean cerebral blood flow was measured pre- and post-intervention.

The results showed methylene blue increased response in the bilateral insular cortex, an area deep within the brain associated with emotional responses, during a task that measured reaction time to a visual stimulus. The fMRI results also showed an increased response during short-term memory tasks involving the brain’s prefrontal cortex, which controls processing of memories, the parietal lobe, primarily associated with the processing of sensory information, and the occipital cortex, the visual processing center of the brain. In addition, methylene blue was associated with a 7 percent increase in correct responses during memory retrieval.

The findings suggest that methylene blue can regulate certain brain networks related to sustained attention and short-term memory after a single oral low dose.

“This work certainly provides a foundation for future trials of methylene blue in healthy aging, cognitive impairment, dementia and other conditions that might benefit from drug-induced memory enhancement,” Dr. Duong said.

About this memory research article

Funding: The funding was provided by NIH/National Center for Advancing Translational Sciences.

Source: Linda Brooks – RSNA
Image Source: This NeuroscienceNews.com image is adapted from the RSNA press release.
Original Research: Full open access research for “Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain” by Pavel Rodriguez, Wei Zhou, Douglas W. Barrett, Wilson Altmeyer, Juan E. Gutierrez, Jinqi Li, Jack L. Lancaster, Francisco Gonzalez-Lima, and Timothy Q. Duong in Radiology. Published online June 28 2016 doi:10.1148/radiol.2016152893

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]RSNA. “Methylene Blue Shows Promise for Improving Short Term Memory.” NeuroscienceNews. NeuroscienceNews, 28 June 2016.
<https://neurosciencenews.com/memory-methylene-blue-4586/>.[/cbtab][cbtab title=”APA”]RSNA. (2016, June 28). Methylene Blue Shows Promise for Improving Short Term Memory. NeuroscienceNew. Retrieved June 28, 2016 from https://neurosciencenews.com/memory-methylene-blue-4586/[/cbtab][cbtab title=”Chicago”]RSNA. “Methylene Blue Shows Promise for Improving Short Term Memory.” https://neurosciencenews.com/memory-methylene-blue-4586/ (accessed June 28, 2016).[/cbtab][/cbtabs]


Abstract

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

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.

“Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain” by Pavel Rodriguez, Wei Zhou, Douglas W. Barrett, Wilson Altmeyer, Juan E. Gutierrez, Jinqi Li, Jack L. Lancaster, Francisco Gonzalez-Lima, and Timothy Q. Duong in Radiology. Published online June 28 2016 doi:10.1148/radiol.2016152893

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