Department of Anesthesiology

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Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects.

TitleEffect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects.
Publication TypeJournal Article
Year of Publication2015
AuthorsPryor KO, Root JC, Mehta M, Stern E, Pan H, Veselis RA, Silbersweig DA
JournalBr J Anaesth
Volume115 Suppl 1
Paginationi104-i113
Date Published2015 Jul
ISSN1471-6771
KeywordsAdolescent, Adult, Amygdala, Anesthetics, Intravenous, Emotions, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory, Oxygen, Propofol, Reaction Time, Receptors, GABA-A
Abstract

BACKGROUND: Subclinical doses of propofol produce anterograde amnesia, characterized by an early failure of memory consolidation. It is unknown how propofol affects the amygdala-dependent emotional memory system, which modulates consolidation in the hippocampus in response to emotional arousal and neurohumoral stress. We present an event-related functional magnetic resonance imaging study of the effects of propofol on the emotional memory system in human subjects.

METHODS: Thirty-five healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 μg ml(-1), or placebo. During drug infusion, emotionally arousing and neutral images were presented in a continuous recognition task, while blood-oxygen-level-dependent activation responses were acquired. After a drug-free interval of 2 h, subsequent memory for successfully encoded items was assessed. Imaging analysis was performed using statistical parametric mapping and behavioural analysis using signal detection models.

RESULTS: Propofol had no effect on the stereotypical amygdalar response to emotional arousal, but caused marked suppression of the hippocampal response. Propofol caused memory performance to become uncoupled from amygdalar activation, but it remained correlated with activation in the posterior hippocampus, which decreased in proportion to amnesia.

CONCLUSIONS: Propofol is relatively ineffective at suppressing amygdalar activation at sedative doses, but abolishes emotional modulation and causes amnesia via mechanisms that commonly involve hyporesponsiveness of the hippocampus. These findings raise the possibility that amygdala-dependent fear systems may remain intact even when a patient has diminished memory of events. This may be of clinical importance in the perioperative development of fear-based psychopathologies, such as post-traumatic stress disorder.

CLINICAL TRIAL REGISTRATION: NCT00504894.

DOI10.1093/bja/aev038
Alternate JournalBr J Anaesth
PubMed ID26174294
PubMed Central IDPMC4501915
Grant ListK08 GM083213 / GM / NIGMS NIH HHS / United States