The purpose of this research is to understand how some of the drugs commonly used in
anesthesia impair memory. We are particularly interested in whether the emotion associated
with a memory influences how well these drugs are able to block memory. We are studying four
commonly used drugs—propofol, thiopental, midazolam, and dexmedetomidine, all of which may
have slightly differing effects. We will also study an inactive substance, called a placebo,
that should have no effect. The results of this study will provide information that will be
useful in understanding how memory works, how these drugs affect memory, and possibly why
some people don't have their memory blocked as easily as others.
The protocol "Effect of Affective Content on Drug Induced Amnesia of Episodic Memory"
investigates the relationship between the ability of affective ('emotional') content to
modulate the formation of episodic memory, and the memory impairment ('amnestic') effects of
several common intravenous anesthetic drugs. Because memory modulation by affective content
appears to be a distinct memory process, the underlying question is whether drugs that
impair memory via different mechanisms will have differing effects on memory modulation.
Specifically, the objectives are: (1) To study the influence of three GABAergic agents
(thiopental, propofol, and midazolam) and one α2-adrenergic agent (dexmedetomidine) on the
ability of affective content to modulate the strength of episodic memory; and (2) To study
whether the subliminal ('consciously imperceptible') presentation of emotional words can
influence memory for visual stimuli shown immediately after the subliminal presentation.
A maximum of eighty volunteers will receive sub-anesthetic doses of one of the four study
drugs, or placebo, while performing a visual continuous recognition task ('CRT') of pictures
with randomly varying affective load. Drug effect on affective modulation of working and
early long-term memory behavior will be examined by analyzing which images are and are not
recognized during the CRT. Drug effect on affective modulation of later long-term memory
will be examined by analyzing which images are recognized several hours after presentation.
In a second experiment, emotive and non-emotive words are subliminally presented immediately
before the presentation of a 'bland' picture. The ability of the subliminally presented word
to influence memory will be examined by analyzing which bland images are recognized several
Three hypotheses are tested:
The memory impairment effected by GABAergic drugs will be stronger for memory of emotively
positive images than for memory of emotively negative images
The memory impairment effected by dexmedetomidine will be similar for memory of emotively
positive and negative images
Recognition memory for neutral, non-arousing images will be greater if the image is
immediately preceded by the subliminal presentation of an emotively arousing word than if it
is preceded by an emotively non-arousing word
- Healthy normal volunteers, age 18 to 50 years *,who show no evidence of neurologic
deficit on questionnaire and physical examination.
- Females must be non-pregnant as demonstrated using a serum pregnancy test.
- Right hand dominant.
- High school education or above.
- English as native language or equivalent degree of fluency. *Age group selected based
on pharmacokinetic models for drug infusion, and norms for standardized memory tests.
- Any evidence of neurologic deficit including seizures, severe head trauma resulting
in unconsciousness, or any previously abnormal study of CNS - (e.g. MRI, EEG, etc.)
- Any deficit in auditory or visual ability.
- Any history of hypertension (resting BP >150 systolic, >100 diastolic) or taking
anti- hypertensive medication or cardiovascular disease.
- Significant pulmonary, renal, gastrointestinal, or endocrine metabolic disease which
in the opinion of the investigator would complicate the goals of this study.
- Allergy to propofol or eggs.
- History of acute intermittent porphyria in subject or subject's blood relatives.
- History of substance abuse
- Currently taking centrally acting medications (e,g, benzodiazepines or anti
- Subjects whose body weight relative to their height exceeds accepted criteria for
defining obesity in the general population (Body Mass Index > 30). Excess weight can
affect the pharmacodynamics of the drug in the body.
- Anyone who, in the opinion of the investigators, would be unwilling or unable to
tolerate the procedures and/or comply with the task instructions.