Neuroimaging the Effects of Intravenous Anesthetic on Amygdala Dependent Memory Processes

Phase 4

Terminated

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.

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.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo given in low dose to gauge subject's responses to visual stimuli.
Propofol	Propofol	Propofol given at 0.90 μgml-1 to gauge subject's responses to visual stimuli.
Thiopental	Thiopental	Thiopental given at 3.0 μgml-1 to gauge subject's responses to visual stimuli.

Primary Outcome Measures

Name	Time	Method
Blood-oxygen-level-dependent Significant Activation Cluster	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

Name	Time	Method
Blood-oxygen-level-dependent Significant Activation Cluster for Positive Sequential Memory	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.