Neuroimaging the Effects of Intravenous Anesthetic on Amygdala Dependent Memory Processes (Amygdala)

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.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Propofol; Drug: Thiopental

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo given in low dose to gauge subject's responses to visual stimuli.	Drug: Placebo; A low dose given intravenously one time for just under an hour while the subject is shown visually stimulating images in an MRI machine.
Active Comparator: Propofol; Propofol given at 0.90 μgml-1 to gauge subject's responses to visual stimuli.	Drug: Propofol; A low dose of propofol 0.90 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine.
Active Comparator: Thiopental; Thiopental given at 3.0 μgml-1 to gauge subject's responses to visual stimuli.	Drug: Thiopental; A low dose of thiopental 3.0 μgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood-oxygen-level-dependent Significant Activation Cluster	Three anatomical regions for which there was an a priori mechanistic hypothesis were assessed using standard small volume correction: (i) the amygdala, bilaterally; (ii) the hippocampus, bilaterally; and (iii) the parahippocampus, bilaterally. Using single-tailed t tests, a priori regions were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons in the hypothesized anatomical region. For non-hypothesized regions outside the medial temporal lobe, findings were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons across the whole brain. Clusters containing voxel maxima at these thresholds are reported.	for 90 minutes after the drug/placebo was commenced

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood-oxygen-level-dependent Significant Activation Cluster for Positive Sequential Memory	Three anatomical regions for which there was an a priori mechanistic hypothesis were assessed using standard small volume correction: (i) the amygdala, bilaterally; (ii) the hippocampus, bilaterally; and (iii) the parahippocampus, bilaterally. Using single-tailed t tests, a priori regions were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons in the hypothesized anatomical region. For non-hypothesized regions outside the medial temporal lobe, findings were reported as significant if the initial uncorrected voxel-wise P value was < 0.001, and then the P value was < 0.05 after family-wise error correction for multiple comparisons across the whole brain. Clusters containing voxel maxima at these thresholds are reported.	for 90 minutes after the drug/placebo was commenced

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Kane Pryor, M.D., Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Pryor KO, Root JC, Mehta M, Stern E, Pan H, Veselis RA, Silbersweig DA. Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects. Br J Anaesth. 2015 Jul;115 Suppl 1(Suppl 1):i104-i113. doi: 10.1093/bja/aev038.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2007
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: July 19, 2007
• First Submitted That Met QC Criteria: July 19, 2007
• First Posted (Estimate): July 20, 2007

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: June 21, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: N/A healthy volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Anticonvulsants; Propofol; Thiopental
• Other Study ID Numbers: 0701008933; K08GM083213 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO