Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia.
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.
Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Peipeng
P
Liang
Anna
A
Manelis
Xiaonan
X
Liu
Howard J
HJ
Aizenstein
Ferenc
F
Gyulai
Joseph J
JJ
Quinlan
Lynne M
LM
Reder
D000293:Adolescent; D000328:Adult; D020324:Amnesia, Anterograde / Q000503:physiopathology / Q000523:psychology*; D001931:Brain Mapping; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply; D018592:Cross-Over Studies; D003463:Cues; D004311:Double-Blind Method; D018755:GABA Agonists / Q000494:pharmacology*; D006801:Humans; D008568:Memory / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects; D008874:Midazolam / Q000494:pharmacology*; D013113:Spin Labels; D014705:Verbal Behavior / Q000187:drug effects; D055815:Young Adult
D018755:GABA Agonists; D013113:Spin Labels; D008874:Midazolam