Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia

Peipeng Liang, Anna Manelis, Xiaonan Liu, Howard J. Aizenstein, Ferenc Gyulai, Joseph J. Quinlan, Lynne M. Reder

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


While our previous work suggests that the midazolam-induced memory impairment results from the inhibition of new association formation, little is known about the neural correlates underlying these effects beyond the effects of GABA agonists on the brain. We used arterial spin-labeling perfusion MRI to measure cerebral blood flow changes associated with the effects of midazolam on ability to learn arbitrary word-pairs. Using a double-blind, within-subject cross-over design, subjects studied word-pairs for a later cued-recall test while they were scanned. Lists of different word-pairs were studied both before and after an injection of either saline or midazolam. As expected, recall was severely impaired under midazolam. The contrast of MRI signal before and after midazolam administration revealed a decrease in CBF in the left dorsolateral prefrontal cortex (DLPFC), left cingulate gyrus and left posterior cingulate gyrus/precuneus. These effects were observed even after controlling for any effect of injection. A strong correlation between the midazolam-induced changes in neural activity and memory performance was found in the left DLPFC. These findings provide converging evidence that this region plays a critical role in the formation of new associations and that low functioning of this region is associated with anterograde amnesia.

Original languageEnglish (US)
Pages (from-to)113-117
Number of pages5
JournalNeuroscience Letters
Issue number2
StatePublished - Aug 1 2012
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the National Natural Science Foundation of China 61105118 (to Peipeng Liang), the National Institutes of Health to L. Reder: 5R01MH052808 and T32MH019983 (supported A. Manelis). We would like to thank C. Tanase for help with the analyses and J. Detre for advice using ASL.


  • Arterial spin labeling
  • Associative memory
  • Dorsolateral prefrontal cortex


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