Neuroimaging the Effects of Intravenous Anesthetic on Amygdala Dependent Memory Processes

Healthy Clinical Trial

— Amygdala  

Official title:

Neuroimaging the Effects of Intravenous Anesthetic on Amygdala Dependent Memory Processes

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00504894
• Other study ID #: 0701008933
• Secondary ID: K08GM083213
• Status: Terminated
• Phase: Phase 4
• Start date: March 2007
• Est. completion date: November 2013

Study information

• Verified date: June 2021
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 60
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

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.
• Propofol
A low dose of propofol 0.90 µgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine.
• Thiopental
A low dose of thiopental 3.0 µgml-1, given intravenously while the subject is shown visually stimulating images in an MRI machine.

Locations

Country	Name	City	State
United States	Weill Cornell Medical College	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Institute of General Medical Sciences (NIGMS), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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