About this trial
This is a multi-visit which will collect MRI (pictures of the brain) and EEG (brain waves) data to determine changes in brain connectivity and brain activity for memory formation and pain perception while receiving the commonly-used anesthetic agents ketamine and propofol, both alone and in combination.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
have none of the specific
Disqualifiers
have a valid email address and valid phone number throughout the study
free from any non-MRI compatible implants
are pregnant or attempting to conceive
body mass index (BMI) > 35
Trial design
Crossover
Treatments tested in this trial
Propofol
DrugSubjects will receive an intravenous infusion of this drug, during portions of the study.
Ketamine
DrugSubjects will receive an intravenous infusion of this drug, during portions of the study.
Peripheral Nerve Stimulation
DeviceExperimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired with specific experimental events.
Treatment groups
Trial outcomes
Primary outcomes
Explicit Memory Performance, comparing single-drug to drug-combination condition
Recognition memory testing, using the Remember-Know procedure, in which subjects indicate whether they recognize previously experienced experimental items among novel items (not previously in the experiment). This allows calculation of interdependent measures of recollection \& familiarity using the signal detection statistic, d'. d' is calculated as the cumulative Gaussian distribution of false positive responses subtracted from the cumulative Gaussian distribution of correctly identified previously-experienced items. d' is on a (theoretically infinite) scale of standard deviation units, with negative values representing performance worse than chance guessing and positive values representing stand deviations of performance above chance.
Pain intensity and unpleasantness ratings, comparing single-drug to drug-combination condition
Numerical rating scale (0-10) pain score difference, comparing the single-drug condition to the steady-state dose of the drug-combination condition. Higher pain scores indicate more pain; a positive difference between pain scores during the single-drug condition minus the value during the steady-state dose of the combination-drug condition indicates pain reduction (a better outcome).
Secondary outcomes
MRI-based activation during memory formation, comparing the single-drug condition to the combination-drug condition
The Z-score is calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate a larger difference in brain activity, with positive values indicating decreases under the combination-drug condition, while negative Z-scores indicate increases under the combination-drug condition, compared to the single-drug condition. This outcome is reported as a number, as it is calculated using all the data across subjects combined into one statistical measure for the overall strength of difference in MRI signal change between two groups of data. Dispersion measures cannot be calculated for the summary Z-score.
MRI-based activation during painful stimulation, comparing the single-drug condition to the combination-drug condition
The Z-score is calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate a larger difference in brain activity, with positive values indicating decreases under the combination-drug condition, while negative Z-scores indicate increases under the combination-drug condition, compared to the single-drug conditions. This outcome is reported as a number, as it is calculated using all the data across subjects combined into one statistical measure for the overall strength of difference in MRI signal change between two groups of data. Dispersion measures cannot be calculated for the summary Z-score.
MRI-based changes in functional connectivity, comparing the single-drug condition to the combination-drug condition
Functional connectivity (FC) measures the correlation of MRI signal time-series between brain regions. Changes in FC reflect differences in brain state, in this case between single-drug and combination-drug conditions. A T-statistic of 0 indicates no change; more positive scores mean stronger connectivity in the single-drug condition, and more negative scores mean stronger connectivity with the combination-drug condition. This outcome is a number reflecting the overall magnitude of difference between two datasets, calculated in one summary statistic. Dispersion measures cannot be calculated for the T-statistic in this analysis framework.
EEG-based changes in functional connectivity, comparing single-drug to combination-drug condition.
Functional connectivity (FC) measures the correlation of MRI signal time-series between brain regions. Changes in FC reflect differences in brain state, in this case between single-drug and combination-drug conditions. A T-statistic of 0 indicates no change; more positive scores mean stronger connectivity in the single-drug condition, and more negative scores mean stronger connectivity with the combination-drug condition. This outcome is a number reflecting the overall magnitude of difference between two datasets, calculated in one summary statistic. Dispersion measures cannot be calculated for the T-statistic in this analysis framework.
Sponsors and contacts
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Keith M Vogt
Lead sponsor
University of Pittsburgh
Sponsor institution
National Institute of General Medical Sciences (NIGMS)
Collaborator