Neuroimaging the Effects of Intravenous Anesthetic on Amygdala Dependent Memory Processes

Weill Cornell Medicine (WCM)

Status and phase: Terminated; Phase 4

Conditions: Healthy

Treatments: Drug: Propofol; Drug: Thiopental; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00504894

0701008933

K08GM083213 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study involves 60 healthy volunteers aged between 18 and 50 recruited from the general community. It involves doing a set of simple memory tests while inside a fMRI machine. The subject is given a very low dose of an anesthetic drug intravenously while in the scanner. The subject then sees a sequence of pictures on a screen, and presses a button if they remember seeing the picture before. While this is happening, the scanner will be capturing images that tell us what parts of the brain are active. Hypothesis: patterns of hippocampal and amygdala activation during the encoding and retrieval of memory,as measured by fMRI, will be altered by intravenous anesthetics such that suppression of hippocampal and amygdala activities will be dissociable. This dissociation pattern will be different between the drugs propofol and thiopental.

Full description

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: Sixty healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 μgml-1, thiopental, at an estimated brain concentration of 3.0 μgml-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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• age b/w 18 and 50
• right-handed
• minimum of high school education
• fluent in English
• normal vocabulary

Exclusion criteria

• any significant medical/psychiatric comorbidity
• deficit in vision or hearing that would impede the study
• allergies to any of the study drugs, to soybeans, or eggs.
• history of head trauma
• family history of major psychiatric illness
• body mass index > 30 kg/m2
• claustrophobia
• prior exposure to IAPS pictures
• pregnancy
• permanent metal objects anywhere in the body
• a personal/family history of any porphyria

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo given in low dose to gauge subject's responses to visual stimuli.

Treatment:

Drug: Placebo

Propofol

Active Comparator group

Description:

Propofol given at 0.90 μgml-1 to gauge subject's responses to visual stimuli.

Treatment:

Drug: Propofol

Thiopental

Active Comparator group

Description:

Thiopental given at 3.0 μgml-1 to gauge subject's responses to visual stimuli.

Treatment:

Drug: Thiopental