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

• ClinicalTrials.gov Identifier: NCT00504894
• Recruitment Status: Terminated
• First Posted: July 20, 2007
• Results First Posted: May 18, 2017
• Last Update Posted: July 15, 2021
• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Placebo; Drug: Propofol; Drug: Thiopental	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Other
• Official Title: Neuroimaging the Effects of Intravenous Anesthetic on Amygdala Dependent Memory Processes
• Actual Study Start Date: March 2007
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: November 2013

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Blood-oxygen-level-dependent Significant Activation Cluster [ Time Frame: for 90 minutes after the drug/placebo was commenced ]
   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.

Secondary Outcome Measures :

1. Blood-oxygen-level-dependent Significant Activation Cluster for Positive Sequential Memory [ Time Frame: for 90 minutes after the drug/placebo was commenced ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New York

Weill Cornell Medical College

New York, New York, United States, 10065

Sponsors and Collaborators

Weill Medical College of Cornell University

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:i104-i113. doi: 10.1093/bja/aev038.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00504894
• Other Study ID Numbers: 0701008933; K08GM083213 ( U.S. NIH Grant/Contract )
• First Posted: July 20, 2007
• Results First Posted: May 18, 2017
• Last Update Posted: July 15, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Weill Medical College of Cornell University:

N/A healthy volunteers

Additional relevant MeSH terms:

Thiopental; Propofol; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anticonvulsants; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action