Neuroimaging analysis of an anesthetic gas that blocks human emotional memory

Abstract

It is hypothesized that emotional arousal modulates long-term memory consolidation through the amygdala. Gaseous anesthetic agents are among the most potent drugs that cause temporary amnesia, yet the effects of inhalational anesthesia on human emotional memory processing remain unknown. To study this, two experiments were performed with the commonly used inhalational anesthetic sevoflurane. In experiment 1, volunteers responded to a series of emotional and neutral slides while under various subanesthetic doses of sevoflurane or placebo (no anesthesia). One week later, a mnemonic boost for emotionally arousing stimuli was evident in the placebo, 0.1%, and 0.2% sevoflurane groups, as measured with a recognition test. However, the mnemonic boost was absent in subjects who received 0.25% sevoflurane. Subsequently, in experiment 2, glucose PET assessed brain-state-related activity of subjects exposed to 0.25% sevoflurane. Structural equation modeling of the PET data revealed that 0.25% sevoflurane suppressed amygdala to hippocampal effective connectivity. The behavioral results show that 0.25% sevoflurane blocks emotional memory, and connectivity results demonstrate that this dose of sevoflurane suppresses the effective influence of the amygdala. Collectively, the findings support the hypothesis that the amygdala mediates memory modulation by demonstrating that suppressed amygdala effectiveness equates with a loss of emotional memory.

Fig. 1.

The number of pictures rated as either neutral or emotional for their arousal reaction is shown (mean ± SEM). Placebo subjects rated the same number of items neutral as emotional. Subjects that received sevoflurane (SEVO) rated significantly more items as neutral vs. emotional. There was no significant effect of increasing dose from 0.2% to 0.25% on how subjects rated the pictures, as shown by the dose × emotionality interaction. NS, not significant.

Fig. 2.

The dose-dependent changes in recall memory performance are shown (mean ± SEM). The expected mnemonic boost for emotionally arousing items is evident in the placebo and the 0.1% sevoflurane groups. The mnemonic boost is not seen in the 0.2% or 0.25% groups. There was no significant effect of increasing dose from 0.2% to 0.25% on recall performance related to emotionality of the items, as shown by the dose × emotionality interaction. NS, not significant.

Fig. 3.

The Pr for recollection memory is shown (mean ± SEM). A mnemonic boost for emotional pictures is noted in the placebo, 0.1%, and 0.2% sevoflurane groups. The mnemonic advantage of emotional material fails to occur in subjects exposed to 0.25% sevoflurane. There was a significant effect of increasing dose from 0.2% to 0.25% on recollection related to arousal intensity of the items, as shown by the dose × emotionality interaction. NS, not significant.

Fig. 4.

The cerebral metabolic effects of 0.25% sevoflurane are shown. (A) Representative high-resolution PET scans. (B) Absolute (mean ± SD) regional metabolic changes (white bars, placebo, no anesthesia; dark bars, 0.25% sevoflurane; marked with * for P < 0.05, Bonferroni corrected, paired t test). (C) Relative percent decreases of regional metabolism. (D) Regional SPM results of sevoflurane induced metabolic suppression (Upper, sagittal; Lower, axial). E shows the regional thalamic finding (brain center) on a colorized MRI. The SPM effects are significant at P < 0.001, uncorrected; displayed at P < 0.005, with a 500-voxel extent.

Fig. 5.

Path diagrams for baseline (placebo, no anesthesia, A) and 0.25% sevoflurane (B) are shown. Positive influences of one region onto another are shown as solid lines and negative influences are shown as dotted lines. Line width represents the magnitude of the effective influence, larger widths indicating a larger influence, according to the scale shown. The numerical difference in path weights between conditions is shown in C. Paths that significantly contribute to the network model more in the placebo state vs. the anesthesia state are highlighted; all other paths are shown grayed out. A large change in path weights is noted for the effective influence of the amygdala and the nucleus basalis of Meynert (NBM) on the hippocampus during sevoflurane. Thal, thalamus; Amyg, amygdala; LC, locus coeruleous; Hipp, hippocampus.